Mycoprotein represents a bioavailable and insulinotropic non-animal-derived dietary protein source: a dose-response study

This is the final version of the article. Available from CUP via the DOI in this record.The anabolic potential of a dietary protein is determined by its ability to elicit postprandial rises in circulating essential amino acids and insulin. Minimal data exist regarding the bioavailability and insulinotropic effects of non-animal-derived protein sources. Mycoprotein is a sustainable and rich source of non-animal-derived dietary protein. We investigated the impact of mycoprotein ingestion, in a dose-response manner, on acute postprandial hyperaminoacidaemia and hyperinsulinaemia. In all, twelve healthy young men completed five experimental trials in a randomised, single-blind, cross-over design. During each trial, volunteers consumed a test drink containing either 20 g milk protein (MLK20) or a mass matched (not protein matched due to the fibre content) bolus of mycoprotein (20 g; MYC20), a protein matched bolus of mycoprotein (40 g; MYC40), 60 g (MYC60) or 80 g (MYC80) mycoprotein. Circulating amino acid, insulin and uric acid concentrations, and clinical chemistry profiles, were assessed in arterialised venous blood samples during a 4-h postprandial period. Mycoprotein ingestion resulted in slower but more sustained hyperinsulinaemia and hyperaminoacidaemia compared with milk when protein matched, with overall bioavailability equivalent between conditions (P>0·05). Increasing the dose of mycoprotein amplified these effects, with some evidence of a plateau at 60-80 g. Peak postprandial leucine concentrations were 201 (sem 24) (30 min), 118 (sem 10) (90 min), 150 (sem 14) (90 min), 173 (sem 23) (45 min) and 201 (sem 21 (90 min) µmol/l for MLK20, MYC20, MYC40, MYC60 and MYC80, respectively. Mycoprotein represents a bioavailable and insulinotropic dietary protein source. Consequently, mycoprotein may be a useful source of dietary protein to stimulate muscle protein synthesis rates.The project was sponsored by Marlow Foods Ltd (B. T. W. as grant holder). The University of Exeter (B. T. W.) were responsible for the study design, data collection and analysis, decision to publish and preparation of the manuscript. The private partners have contributed to the project through regular discussion. M. V. D. is supported through the aforementioned grant, S. P. K. is supported from an internal studentship grant in collaboration with Maastricht University

Repeatability and sensitivity of T2* measurements in patients with head and neck squamous cell carcinoma at 3T.

Purpose To determine whether quantitation of T2* is sufficiently repeatable and sensitive to detect clinically relevant oxygenation levels in head and neck squamous cell carcinoma (HNSCC) at 3T.Materials and methods Ten patients with newly diagnosed locally advanced HNSCC underwent two magnetic resonance imaging (MRI) scans between 24 and 168 hours apart prior to chemoradiotherapy treatment. A multiple gradient echo sequence was used to calculate T2* maps. A quadratic function was used to model the blood transverse relaxation rate as a function of blood oxygenation. A set of published coefficients measured at 3T were incorporated to account for tissue hematocrit levels and used to plot the dependence of fractional blood oxygenation (Y) on T2* values, together with the corresponding repeatability range. Repeatability of T2* using Bland-Altman analysis, and calculation of limits of agreement (LoA), was used to assess the sensitivity, defined as the minimum difference in fractional blood oxygenation that can be confidently detected.Results T2* LoA for 22 outlined tumor volumes were 13%. The T2* dependence of fractional blood oxygenation increases monotonically, resulting in increasing sensitivity of the method with increasing blood oxygenation. For fractional blood oxygenation values above 0.11, changes in T2* were sufficient to detect differences in blood oxygenation greater than 10% (Δ T2* > LoA for ΔY > 0.1).Conclusion Quantitation of T2* at 3T can detect clinically relevant changes in tumor oxygenation within a wide range of blood volumes and oxygen tensions, including levels reported in HNSCC. J. Magn. Reson. Imaging 2016;44:72-80

Characterizing Ligand-Gated Ion Channel Receptors with Genetically Encoded Ca++ Sensors

We present a cell based system and experimental approach to characterize agonist and antagonist selectivity for ligand-gated ion channels (LGIC) by developing sensor cells stably expressing a Ca2+ permeable LGIC and a genetically encoded Förster (or fluorescence) resonance energy transfer (FRET)-based calcium sensor. In particular, we describe separate lines with human α7 and human α4β2 nicotinic acetylcholine receptors, mouse 5-HT3A serotonin receptors and a chimera of human α7/mouse 5-HT3A receptors. Complete concentration-response curves for agonists and Schild plots of antagonists were generated from these sensors and the results validate known pharmacology of the receptors tested. Concentration-response relations can be generated from either the initial rate or maximal amplitudes of FRET-signal. Although assaying at a medium throughput level, this pharmacological fluorescence detection technique employs a clonal line for stability and has versatility for screening laboratory generated congeners as agonists or antagonists on multiple subtypes of ligand-gated ion channels. The clonal sensor lines are also compatible with in vivo usage to measure indirectly receptor activation by endogenous neurotransmitters

Severity of Giardia infection associated with post-infectious fatigue and abdominal symptoms two years after

<p>Abstract</p> <p>Background</p> <p>A high rate of post-infectious fatigue and abdominal symptoms two years after a waterborne outbreak of giardiasis in Bergen, Norway in 2004 has previously been reported. The aim of this report was to identify risk factors associated with such manifestations.</p> <p>Methods</p> <p>All laboratory confirmed cases of giardiasis (n = 1262) during the outbreak in Bergen in 2004 received a postal questionnaire two years after. Degree of post-infectious abdominal symptoms and fatigue, as well as previous abdominal problems, was recorded. In the statistical analyses number of treatment courses, treatment refractory infection, delayed education and sick leave were used as indices of protracted and severe <it>Giardia </it>infection. Age, gender, previous abdominal problems and symptoms during infection were also analysed as possible risk factors. Simple and multiple ordinal logistic regression models were used for the analyses.</p> <p>Results</p> <p>The response rate was 81% (1017/1262), 64% were women and median age was 31 years (range 3-93), compared to 61% women and 30 years (range 2-93) among all 1262 cases. Factors in multiple regression analysis significantly associated with abdominal symptoms two years after infection were: More than one treatment course, treatment refractory infection, delayed education, bloating and female gender. Abdominal problems prior to <it>Giardia </it>infection were not associated with post-infectious abdominal symptoms. More than one treatment course, delayed education, sick leave more than 2 weeks, and malaise at the time of infection, were significantly associated with fatigue in the multiple regression analysis, as were increasing age and previous abdominal problems.</p> <p>Conclusion</p> <p>Protracted and severe <it>giardiasis </it>seemed to be a risk factor for post-infectious fatigue and abdominal symptoms two years after clearing the <it>Giardia </it>infection.</p

Effectiveness and cost-effectiveness of a patient-initiated botulinum toxin treatment model for blepharospasm and hemifacial spasm: a study protocol for a randomised controlled trial

Background Blepharospasm and hemifacial spasm are debilitating conditions that significantly impact on patient quality of life. Cyclical treatment with botulinum toxin injections offers temporary relief, but the duration of treatment efficacy is variable. The standard model of patient care defines routine fixed-time based scheduled treatment cycles which may lead to unnecessarily frequent treatment for some patients and experience of distressing symptoms in others, if symptoms return before the scheduled follow-up period. Methods/Design A randomised controlled trial will compare a patient-initiated model of care, where patients determine botulinum toxin treatment timing, to the standard model of care in which care is scheduled by the clinical team. A sample of 266 patients with blepharospasm or hemifacial spasm will be recruited from Moorfields Eye Hospital (MEH), London. The trial will be accompanied by a mixed methods evaluation of acceptability of the new service. Patients who meet eligibility criteria will be assessed at baseline and those in the intervention group will be provided instructions on how to book their own treatment appointments. Patients in both groups will be followed up 3 and 9 months into the trial and all patients will be returned to usual care after 9 months to meet safety protocols. Primary outcome measures include disease severity (questionnaire), functional disability (questionnaire) and patient satisfaction with care (questionnaire). Secondary outcomes include disease-specific quality of life (questionnaire), mood (questionnaire), illness and treatment perceptions (questionnaire and semi-structured interviews), economic impact (questionnaire) and acceptability (questionnaire and semi-structured interviews). Discussion This trial will assess the effectiveness and cost-effectiveness of a patient-led care model for botulinum toxin therapy. If the new model is shown to be effective in reducing distress and disability in these populations and is found to be acceptable to patients, whilst being cost-effective, this will have significant implications for service organisation across the NHS. Trial registration UK Clinical Research Network (UKCRN) Portfolio 18660. Clinicaltrials.gov ID NCT102577224 (registered 29th October 2015

Rapidity and Centrality Dependence of Proton and Anti-proton Production from Au+Au Collisions at sqrt(sNN) = 130GeV

We report on the rapidity and centrality dependence of proton and anti-proton transverse mass distributions from Au+Au collisions at sqrt(sNN) = 130GeV as measured by the STAR experiment at RHIC. Our results are from the rapidity and transverse momentum range of |y|<0.5 and 0.35 <p_t<1.00GeV/c. For both protons and anti-protons, transverse mass distributions become more convex from peripheral to central collisions demonstrating characteristics of collective expansion. The measured rapidity distributions and the mean transverse momenta versus rapidity are flat within |y|<0.5. Comparisons of our data with results from model calculations indicate that in order to obtain a consistent picture of the proton(anti-proton) yields and transverse mass distributions the possibility of pre-hadronic collective expansion may have to be taken into account.Comment: 4 pages, 3 figures, 1 table, submitted to PR

Chlamydia trachomatis antigens in enteroendocrine cells and macrophages of the small bowel in patients with severe irritable bowel syndrome

<p>Abstract</p> <p>Background</p> <p>Inflammation and immune activation have repeatedly been suggested as pathogentic factors in irritable bowel syndrome (IBS). The driving force for immune activation in IBS remains unknown. The aim of our study was to find out if the obligate intracellular pathogen <it>Chlamydia </it>could be involved in the pathogenesis of IBS.</p> <p>Methods</p> <p>We studied 65 patients (61 females) with IBS and 42 (29 females) healthy controls in which IBS had been excluded. Full thickness biopsies from the jejunum and mucosa biopsies from the duodenum and the jejunum were stained with a monoclonal antibody to <it>Chlamydia </it>lipopolysaccharide (LPS) and species-specific monoclonal antibodies to <it>C. trachomatis </it>and <it>C. pneumoniae</it>. We used polyclonal antibodies to chromogranin A, CD68, CD11c, and CD117 to identify enteroendocrine cells, macrophages, dendritic, and mast cells, respectively.</p> <p>Results</p> <p><it>Chlamydia </it>LPS was present in 89% of patients with IBS, but in only 14% of healthy controls (p < 0.001) and 79% of LPS-positive biopsies were also positive for <it>C. trachomatis </it>major outer membrane protein (MOMP). Staining for <it>C. pneumoniae </it>was negative in both patients and controls. <it>Chlamydia </it>LPS was detected in enteroendocrine cells of the mucosa in 90% of positive biopsies and in subepithelial macrophages in 69% of biopsies. Biopsies taken at different time points in 19 patients revealed persistence of <it>Chlamydia </it>LPS up to 11 years. The odds ratio for the association of <it>Chlamydia </it>LPS with presence of IBS (43.1; 95% CI: 13.2-140.7) is much higher than any previously described pathogenetic marker in IBS.</p> <p>Conclusions</p> <p>We found <it>C. trachomatis </it>antigens in enteroendocrine cells and macrophages in the small bowel mucosa of patients with IBS. Further studies are required to clarify if the presence of such antigens has a role in the pathogenesis of IBS.</p

Change in physical activity level and clinical outcomes in older adults with knee pain: a secondary analysis from a randomised controlled trial

BACKGROUND: Exercise interventions improve clinical outcomes of pain and function in adults with knee pain due to osteoarthritis and higher levels of physical activity are associated with lower severity of pain and higher levels of physical functioning in older adults with knee osteoarthritis in cross-sectional studies. However, to date no studies have investigated if change in physical activity level during exercise interventions can explain clinical outcomes of pain and function. This study aimed to investigate if change in physical activity during exercise interventions is associated with future pain and physical function in older adults with knee pain. METHODS: Secondary longitudinal data analyses of a three armed exercise intervention randomised controlled trial. Participants were adults with knee pain attributed to osteoarthritis, over the age of 45 years old (n = 514) from Primary Care Services in the Midlands and Northwest regions of England. Crude and adjusted associations between absolute change in physical activity from baseline to 3 months (measured by the self-report Physical Activity Scale for the Elderly (PASE)) and i) pain ii) physical function (Western Ontario and McMaster Universities Osteoarthritis Index) and iii) treatment response (OMERACT-OARSI responder criteria) at 3 and 6 months follow-up were investigated using linear and logistic regression. RESULTS: Change in physical activity level was not associated with future pain, function or treatment response outcomes in crude or adjusted models at 3 or 6 months (P > 0.05). A 10 point increase in PASE was not associated with pain β = - 0.01 (- 0.05, 0.02), physical function β = - 0.09 (- 0.19, 0.02) or likelihood (odds ratio) of treatment response 1.02 (0.99, 1.04) at 3 months adjusting for sociodemographics, clinical covariates and the trial intervention arm. Findings were similar for 6 month outcome models. CONCLUSIONS: Change in physical activity did not explain future clinical outcomes of pain and function in this study. Other factors may be responsible for clinical improvements following exercise interventions. However, the PASE may not be sufficiently responsive to measure change in physical activity level. We also recommend further investigation into the responsiveness of commonly used physical activity measures. TRIAL REGISTRATION: ( ISRCTN93634563 ). Registered 29th September 2011