• Development of anthropometric characteristics in professional Rugby League players: Is there too much emphasis on the pre-season period?

      Morehen, James; Clarke, Jon; Batsford, Jake; Highton, Jamie; Erskine, Robert; Morton, James; Close, Graeme
      Rugby League is a team sport requiring players to experience large impact collisions, thus requiring high amounts of muscle mass. Many players (academy and senior) strive to increase muscle mass during the pre-season, however, quantification of changes during this period have not been thoroughly investigated. We therefore assessed changes in body-composition using Dual X-Ray Absorptiometry (DXA) in eleven academy players over three successive pre-seasons and ninety-three senior players from four different European Super League clubs prior to, and at the end of, a pre-season training period. There was no meaningful change in lean mass of the academy players during any of the pre-season periods (year 1 = 72.3 ± 7.1–73.2 ± 7.2kg; ES 0.05, year 2 = 74.4 ± 6.9–75.5 ± 6.9kg; ES 0.07, year 3 = 75.9 ± 6.7–76.8 ± 6.6kg; ES 0.06) with small changes only occurring over the three-year study period (72.3–75.9kg; ES = 0.22). Senior players showed trivial changes in all characteristics during the pre-season period (total mass = 95.1–95.0kg; ES −0.01, lean mass = 74.6–75.1kg; ES 0.07, fat mass = 13.6–12.9kg; ES −0.17, body fat percentage = 14.8–14.1%; ES −0.19). These data suggest that academy players need time to develop towards profiles congruent with senior players. Moreover, once players reach senior level, body-composition changes are trivial during the pre-season and therefore teams may need to individualise training for players striving to gain muscle mass by reducing other training loads.
    • Combining bioacoustics and occupancy modelling for improved monitoring of rare breeding bird populations

      Abrahams, Carlos; Geary, Matthew; Baker Consultants Ltd; Nottingham Trent University; University of Chester
      Effective monitoring of rare and declining species is critical to enable their conservation, but can often be difficult due to detectability or survey constraints. However, developments in acoustic recorders are enabling an important new approach for improved monitoring that is especially applicable for long-term studies, and for use in difficult environments or with cryptic species. Bioacoustic data may be effectively analysed within an occupancy modelling framework, as presence/absence can be determined, and repeated survey events can be accommodated. Hence, both occupancy and detectability estimates can be produced from large, coherent datasets. However, the most effective methods for the practical detection and identification of call data are still far from established. We assessed a novel combination of automated clustering and manual verification to detect and identify heathland bird vocalizations, covering a period of six days at 44 sampling locations Occupancy (Ψ) and detectability (p ) were modelled for each species, and the best fit models provided values of: nightjar Ψ=0.684, p=0.740, Dartford warbler Ψ=0.449 p=0.196 and woodlark Ψ=0.13 p=0.996. Including environmental covariates within the occupancy models indicated that tree, wetland and heather cover were important variables, particularly influencing detectability. The protocol used here allowed robust and consistent survey data to be gathered, with limited fieldwork resourcing, allowing population estimates to be generated for the target bird species. The combination of bioacoustics and occupancy modelling can provide a valuable new monitoring approach, allowing population trends to be identified, and the effects of environmental change and site management to be assessed.
    • Mangrove and mudflat food webs are segregated across four trophic levels, yet connected by highly mobile top predators

      Marley, Guy; Lawrence, Andrew; Phillip, Dawn; Hayden, Brian; Canadian Rivers Institute
      Seascape connectivity is crucial for healthy, resilient ecosystems and fisheries. Yet, our understanding of connectivity in turbid mangrove-lined estuaries—some of the world’s most productive ecosystems—is limited to macrotidal systems, and rarely incorporates highly mobile top predators. We analysed δ13C and δ15N isotope values of 7 primary producers, 24 invertebrate taxa, 13 fishes, 4 birds and 1 reptile to reveal trophic interactions within and between a mangrove and adjacent mudflat in a microtidal system of the Gulf of Paria, Orinoco River estuary. Primary producers, invertebrates and fishes collected within the mangrove were significantly depleted in 13C and 15N compared to those collected on the mudflat. Stable isotope mixing models showed that mangrove-derived carbon was predominantly assimilated by invertebrates (78 ± 5% SE) and fishes (88 ± 11%) sampled in the mangrove. In contrast, invertebrates and fishes sampled in the mudflat derived <21% of their carbon from mangrove sources. Instead, microphytobenthos and phytoplankton underpinned the mudflat food web. Scarlet ibis Eudocimus ruber and yellow-crowned night heron Nyctanassa violacea were also highly associated with mangrove carbon sources. However, osprey Pandion haliaetus, snowy egret Egretta thula and spectacled caiman Caiman crocodilus obtained carbon from both mangrove and mudflat sources, effectively integrating the food webs. The present study demonstrates simultaneous aspects of food web segregation and connectivity, as well as the importance of surveying the entire food web across a range of tidal systems when investigating seascape connectivity.
    • Improving the practicality of using non-aversive handling methods to reduce background stress and anxiety in laboratory mice.

      Gouveia, Kelly; Hurst, Jane L; orcid: 0000-0002-3728-9624; email: jane.hurst@liverpool.ac.uk (2019-12-30)
      Handling can stimulate stress and anxiety in laboratory animals that negatively impacts welfare and introduces a confounding factor in many areas of research. Picking up mice by the tail is a major source of handling stress that results in strong aversion to the handler, while mice familiarised with being picked up in a tunnel or cupped on the open hand show low stress and anxiety, and actively seek interaction with their handlers. Here we investigate the duration and frequency of handling required for effective familiarisation with these non-aversive handling methods, and test whether this is sufficient to prevent aversion and anxiety when animals then experience immobilisation and a mild procedure (subcutaneous injection). Very brief handling (2 s) was sufficient to familiarise mice with tunnel handling, even when experienced only during cage cleaning. Brief but more frequent handling was needed for familiarisation with cup handling, while pick up by tail induced strong aversion even when handling was brief and infrequent. Experience of repeated immobilisation and subcutaneous injection did not reverse the positive effects of tunnel handling. Our findings demonstrate that replacing tail with tunnel handling during routine cage cleaning and procedures provides a major refinement with little if any cost for familiarisation.
    • The effects of in-season, low-volume sprint interval training with and without sport-specific actions on the physical characteristics of elite academy rugby league players

      Dobbin, Nick; Highton, Jamie M.; Moss, Samantha; Twist, Craig
      Purpose: To determine the utility of a running and rugby-specific, in-season sprint interval interventions in professional rugby league players. Methods: Thirty-one professional academy rugby players were assigned to a rugby-specific (SITr/s, n = 16) or running (SITr, n = 15) sprint interval training group. Measures of speed, power, change of direction (CoD) ability, prone Yo-Yo IR1 performance and heart rate recovery (HRR) were taken before and after the 2-week intervention as were sub-maximal responses to the prone Yo-Yo IR1. Internal, external and perceptual responses were collected during SITr/s/SITr, with wellbeing and neuromuscular function assessed before each session. Results: Despite contrasting (possible to most likely) internal, external and perceptual responses to the SIT interventions, possible to most likely within-group improvements in physical characteristics, HRR and sub-maximal responses to the prone Yo-Yo IR1 were observed after both interventions. Between-group analysis favoured the SITr/s intervention (trivial to moderate) for changes in 10 m sprint time, CMJ, change of direction and medicine ball throw as well as sub-maximal (280-440 m) high metabolic power, PlayerLoad™ and acceleratory distance during the prone Yo-Yo IR1. Overall changes in wellbeing or neuromuscular function were unclear. Conclusion: Two-weeks of SITr/s and SITr was effective for improving physical characteristics, HRR and sub-maximal responses to the prone Yo-Yo IR1, with no clear change in wellbeing and neuromuscular function. Between-group analysis favoured the SITr/s group, suggesting that the inclusion of sport- specific actions should be considered for in-season conditioning of rugby league players.
    • Glutamine supplementation reduces markers of intestinal permeability during running in the heat in a dose-dependent manner

      Pugh, Jamie; Sage, Stephen; Hutson, Mark; Doran, Dominic; Fleming, Simon; Highton, Jamie M.; Morton, James; Close, Graeme
      Purpose To examine the dose–response effects of acute glutamine supplementation on markers of gastrointestinal (GI) permeability, damage and, secondary, subjective symptoms of GI discomfort in response to running in the heat. Methods Ten recreationally active males completed a total of four exercise trials; a placebo trial and three glutamine trials at 0.25, 0.5 and 0.9 g kg−1 of fat-free mass (FFM) consumed 2 h before exercise. Each exercise trial consisted of a 60-min treadmill run at 70% of ̇VO2max in an environmental chamber set at 30 °C. GI permeability was measured using ratio of lactulose to rhamnose (L:R) in serum. Plasma glutamine and intestinal fatty acid binding protein (I-FABP) concentrations were determined pre and post exercise. Subjective GI symptoms were assessed 45 min and 24 h post-exercise. Results Relative to placebo, L:R was likely lower following 0.25 g kg−1 (mean difference: − 0.023; ± 0.021) and 0.5 g kg−1 (− 0.019; ± 0.019) and very likely following 0.9 g kg− 1 (− 0.034; ± 0.024). GI symptoms were typically low and there was no effect of supplementation. Discussion Acute oral glutamine consumption attenuates GI permeability relative to placebo even at lower doses of 0.25 g kg−1, although larger doses may be more effective. It remains unclear if this will lead to reductions in GI symptoms. Athletes competing in the heat may, therefore, benefit from acute glutamine supplementation prior to exercise in order to maintain gastrointestinal integrity.
    • Neferine induces autophagy-dependent cell death in apoptosis-resistant cancers via ryanodine receptor and Ca

      Law, Betty Yuen Kwan; Michelangeli, Francesco; Qu, Yuan Qing; orcid: 0000-0003-3733-3661; Xu, Su-Wei; Han, Yu; Mok, Simon Wing Fai; Dias, Ivo Ricardo De Seabra Rodrigues; Javed, Masood-Ul-Hassan; Chan, Wai-Kit; Xue, Wei-Wei; et al. (2019-12-27)
      Resistance of cancer cells to chemotherapy is a significant clinical concern and mechanisms regulating cell death in cancer therapy, including apoptosis, autophagy or necrosis, have been extensively investigated over the last decade. Accordingly, the identification of medicinal compounds against chemoresistant cancer cells via new mechanism of action is highly desired. Autophagy is important in inducing cell death or survival in cancer therapy. Recently, novel autophagy activators isolated from natural products were shown to induce autophagic cell death in apoptosis-resistant cancer cells in a calcium-dependent manner. Therefore, enhancement of autophagy may serve as additional therapeutic strategy against these resistant cancers. By computational docking analysis, biochemical assays, and advanced live-cell imaging, we identified that neferine, a natural alkaloid from Nelumbo nucifera, induces autophagy by activating the ryanodine receptor and calcium release. With well-known apoptotic agents, such as staurosporine, taxol, doxorubicin, cisplatin and etoposide, utilized as controls, neferine was shown to induce autophagic cell death in a panel of cancer cells, including apoptosis-defective and -resistant cancer cells or isogenic cancer cells, via calcium mobilization through the activation of ryanodine receptor and Ulk-1-PERK and AMPK-mTOR signaling cascades. Taken together, this study provides insights into the cytotoxic mechanism of neferine-induced autophagy through ryanodine receptor activation in resistant cancers.
    • Stent Migration Following Endovascular Sealing of Abdominal Aortic Aneurysms

      Yafawi, Asma; McWilliams, Richard G.; Fisher, Robert K.; England, Andrew; Karouki, Maria; Torella, Francesco (Elsevier, 2019-12-09)
    • Alzheimer’s Amyloidopathy: An Alternative Aspect

      Regland, Björn; McCaddon, Andrew (IOS Press, 2019-03-29)
    • Biochemical assessment of patients following ketogenic diets for epilepsy: current practice in the UK and Ireland

      Schoeler, Natasha; Simpson, Zoe; Whiteley, Victoria; Nguyen, Patty; Meskell, Rachel; Lightfoot, Kathryn; Martin-McGill, Kirsty; Olpin, Simon; Ivison, Fiona
      Objective: Biochemical assessment is recommended for patients prior to initiating and following a ketogenic diet (KD). There is no published literature regarding current practice in the UK and Ireland. We aimed to explore practice in comparison to international guidelines, determine approximate costs of biochemical testing in KD patients across the UK and Ireland, and promote greater consistency in KD services nationally. Methods: A survey was designed to determine the biochemical tests requested for patients at baseline, 3-, 6-, 12-, 18- and 24-months+ on KD. The survey was circulated to 39 centres across the UK and Ireland. Results: 16 centres completed the survey. Full blood count, electrolytes, calcium, liver function tests (LFTs), lipid profile and vitamin D were requested at all centres at baseline, in keeping with international guidelines. Bicarbonate, total protein and urinalysis were less consistently requested. Magnesium and zinc were requested by all centres, despite not being specifically recommended for pre-diet evaluation in guidelines. Urea and electrolyte profiles and some LFTs were consistently requested at follow-up, in accordance with guidelines. Other LFTs and renal tests, full blood count, lipid profile, acylcarnitine profile, selenium, vitamin D and urinalysis were less consistently requested at follow-up. The mean costs of the lowest and highest number of tests requested at baseline in our participating centres was £167.54 and £501.93; the mean costs of the lowest and highest number of tests requested at 3-month follow-up was £19.17 and £450.06. Significance: Biochemical monitoring of KD patients varies widely across the UK and Ireland and does not fully correspond to international best practice guidelines. With an ongoing drive for cost-effectiveness within healthcare, further work is needed to streamline practice whilst ensuring patient safety.
    • Impacts of Reducing UK Beef Consumption Using a Revised Sustainable Diets Framework

      Chalmers, Neil; email: neil.chalmers@abdn.ac.uk; Stetkiewicz, Stacia; email: s.stetkiewicz@lancaster.ac.uk; Sudhakar, Padhmanand; orcid: 0000-0003-1907-4491; email: Padhmanand.Sudhakar@earlham.ac.uk; Osei-Kwasi, Hibbah; orcid: 0000-0001-5084-6213; email: h.oseikwasi@chester.ac.uk; Reynolds, Christian J; orcid: 0000-0002-1073-7394; email: c.reynolds@sheffield.ac.uk (MDPI, 2019-12-02)
      The impact of beef consumption on sustainability is a complex and evolving area, as sustainability covers many areas from human nutrient adequacy to ecosystem stability. Three sustainability assessment frameworks have been created to help policy makers unpack the complexities of sustainable food systems and healthy sustainable dietary change. However, none of these frameworks have yet to be applied to a case study or individual policy issue. This paper uses a hybrid version of the sustainability assessment frameworks to investigate the impact of reducing beef consumption (with a concurrent increase in consumption of plant-based foods, with a focus on legumes) on sustainability at a UK level. The aim of this paper is to understand the applicability of these overarching frameworks at the scale of an individual policy. Such an assessment is important, as this application of previously high-level frameworks to individual policies makes it possible to summarise, at a glance, the various co-benefits and trade-offs associated with a given policy, which may be of particular value in terms of stakeholder decision-making. We find that many of the proposed metrics found within the sustainability assessment frameworks are difficult to implement at an individual issue level; however, overall they show that a reduction in beef consumption and an increase in consumption of general plant-based foods, with a focus around legumes production, would be expected to be strongly beneficial in five of the eight overarching measures which were assessed.
    • A UK consensus on optimising CVD secondary prevention care: perspectives from multidisciplinary team members

      The ICON (Integrating Care Opportunities across the NHS) CVD Secondary Prevention Working Group (2019-10-03)
      Although overall cardiovascular (CV) mortality has declined in recent years, patients with clinically manifest cardiovascular disease (CVD) remain at increased risk of recurrent CV events. To minimise the likelihood of future CV events following an acute myocardial infarction (MI), changes in diet and lifestyle, alongside pharmaceutical interventions, such as dual antiplatelet therapy, a β-blocker, an ACE inhibitor, and a statin, are recommended within current clinical guidelines. The use of cardiac rehabilitation (CR) programmes has been shown to be highly effective in reducing mortality and morbidity following MI, and a cost-benefit analysis suggests that increasing the uptake of CR to 65% among eligible patient would result in potential cost savings of over £30 million annually for the NHS. The involvement of a multidisciplinary team (MDT) of healthcare professionals is central to delivering post-MI care, with initial and/or ongoing input from cardiologists, hospital-based specialist pharmacists, specialist nurses, GPs, dietitians, smoking cessation specialists and practice-based and community pharmacists, among others. This consensus statement was developed based on a meeting of HCPs actively involved in delivering CV secondary prevention care at primary and secondary care centres across the UK. Recognising that HCP team configuration and availability of resources/services vary by location, the authors have focused on three common themes which have broad relevance in CVD secondary prevention, specifically: integration of care, medicines optimisation, and encouraging patient activation. Opportunities for MDT members to improve outcomes in post-MI patients are suggested and examples of best practice models which have been implemented successfully are described.
    • Western diet increases cardiac ceramide content in healthy and hypertrophied hearts.

      Butler, Thomas; University of Chester, University of York, University of Hull (Elsevier, 2017-11-01)
      BACKGROUND AND AIMS: Obesity and cardiac left ventricular hypertrophy (LVH) are recognised independent risk factors in the development of heart failure (HF). However, the combination of these factors may exacerbate the onset of cardiovascular disease by mechanisms as yet unclear. LVH leads to significant cellular remodelling, including alterations in metabolism which may result in an inappropriate accumulation of lipids and eventual lipotoxicity and apoptosis. The aim of the study was to determine the impact of dietary manipulation on cardiac metabolism in the obese and hypertrophied heart. METHODS AND RESULTS: LVH was induced via aortic constriction (AC) in an experimental model of cardiac hypertrophy and animals subjected to 9 weeks of dietary manipulation with either a standard, high fat, or a sucrose containing Western-style diet (SD, HFD and WD, respectively). This latter diet resulted in accelerated weight gain in both LVH/AC and control animals. LVH was greater in AC animals fed a WD, and both control and AC animals from this diet showed a significant reduction in cardiac fatty acid oxidation and increased triacylglycerol content. Ceramide content was significantly increased in the WD groups, with no additional effect of LVH. Comparison with a model of HF induced by exposure to Doxorubicin and WD showed exacerbated remodelling of cardiac ceramide species leading to increased C16 and C18 content. CONCLUSIONS: These findings highlight the inappropriate accumulation and re-distribution of cardiac ceramide species in a diet-induced model of obesity and LVH, potentially increasing susceptibility to cell death. The combination of increased fat and sugar leads to greater pathological remodelling and may explain why this diet pattern is consistently linked with poor cardiovascular outcomes.
    • Sex-related changes in physical performance, wellbeing and neuromuscular function of elite Touch players during a four-day international tournament.

      Dobbin, Nick; Highton, Jamie M.; Thorpe, M.; Twist, Craig; University of Chester; Manchester Metropolitan University
      Purpose: To examine the within- and between-sex physical performance, wellbeing and neuromuscular function responses across a four-day international touch rugby (Touch) tournament. Methods: Twenty females and twenty-one males completed measures of wellbeing (fatigue, soreness, sleep, mood, stress) and neuromuscular function (countermovement jump (CMJ) height, peak power output (PPO) and peak force (PF)) during a 4-day tournament with internal, external and perceptual loads recorded for all matches. Results: Relative and absolute total, low- (females) and high-intensity distance was lower on day 3 (males and females) (ES = -0.37 to -0.71) compared to day 1. Mean heart rate was possibly to most likely reduced during the tournament (except day 2 males) (ES = -0.36 to -0.74), whilst RPE-TL was consistently higher in females (ES = 0.02 to 0.83). The change in mean fatigue, soreness and overall wellbeing were unclear to most likely lower (ES = -0.33 to -1.90) across the tournament for both sexes, with greater perceived fatigue and soreness in females on days 3-4 (ES = 0.39 to 0.78). Jump height and PPO were possibly to most likely lower across days 2-4 (ES = -0.30 to -0.84), with greater reductions in females (ES = 0.21 to 0.66). Wellbeing, CMJ height, and PF were associated with changes in external, internal and perceptual measures of load across the tournament (2 = -0.37 to 0.39). Conclusions: Elite Touch players experience reductions in wellbeing, neuromuscular function and running performance across a 4-day tournament, with notable differences in fatigue and running between males and females, suggesting sex-specific monitoring and intervention strategies are necessary.
    • Size at birth and cognitive ability in late life: A systematic review

      Krishna, Murali; orcid: 0000-0002-5354-9027; Jones, Steven; Maden, Michelle; Du, Bharath; Mc, Ramya; Kumaran, Kalyanaraman; Karat, Samuel Christraprasad; Fall, Caroline H.D. (Wiley, 2019-06-13)
    • Cancerous inhibitor of protein phosphatase 2A (CIP2A) modifies energy metabolism via 5′ AMP-activated protein kinase signalling in malignant cells

      Austin, James A.; orcid: 0000-0002-5384-5221; Jenkins, Rosalind E.; Austin, Gemma M.; Glenn, Mark A.; Dunn, Karen; Scott, Laura; Lucas, Claire M.; Clark, Richard E. (Portland Press Ltd., 2019-08-15)
      Abstract Cancerous inhibitor of protein phosphatase 2A (CIP2A) is an adverse biomarker across many malignancies. Using K562 cells engineered to have high or low CIP2A expression, we show that high CIP2A levels significantly bias cellular energy production towards oxidative phosphorylation (OXPHOS) rather than glycolysis. Mass spectrometric analysis of CIP2A interactors and isobaric tagging for relative and absolute protein quantitation (ITRAQ) experiments identified many associated proteins, several of which co-vary with CIP2A level. Many of these CIP2A associating and co-varying proteins are involved in energy metabolism including OXPHOS, or in 5′ AMP-activated protein kinase (AMPK) signalling, and manipulating AMPK activity mimics the effects of low/high CIP2A on OXPHOS. These effects are dependent on the availability of nutrients, driven by metabolic changes caused by CIP2A. CIP2A level did not affect starvation-induced AMPK phosphorylation of Unc-51 autophagy activating kinase 1 (ULK-1) at Ser555, but autophagy activity correlated with an increase in AMPK activity, to suggest that some AMPK processes are uncoupled by CIP2A, likely via its inhibition of protein phosphatase 2A (PP2A). The data demonstrate that AMPK mediates this novel CIP2A effect on energy generation in malignant cells.
    • The influence of CLA on obesity, lung function, adipokines and inflammation

      Williams, John; Ireland, Elsye; Hamdallah, Hanady (University of ChesterUniversity of Chester, 2019-01-31)
      Obesity is currently widespread in the world; the epidemic and pathogenesis of the disease negatively affect several body systems including cardiovascular, endocrine and respiratory systems. Obesity influences the respiratory functions and this effect could be challenging for women, because the air way and lungs are smaller in women compared to men, as well as obesity itself exerts a negative mechanical effect on the women’s airway. Since inflammation was proposed asthe main link between obesity and lung functions, a natural supplement like conjugated linoleic acid (CLA), which has been proposed as an antiinflammatory and anti-obesity food component, could be a potential supplement that can improve the lung functions in obese women. Therefore, the aim of this thesis is to explore the effect of CLA on obesity, lung function, adipokines and inflammation. Additionally, the effect of CLA on inflammation in the current thesis was explored using novel inflammatory markers, such as adhesion molecules (CD11b and CD62L) and heat shock proteins (HSPA1A and HSPB1). Investigating the evidence about the effect of CLA supplementation on obesity in women was conducted via a systematic review with meta-analysis. The meta- analysis searched randomised control trials (RCTs) supplemented CLA mixture in form of oral capsules for less than 6 months. Two search strategies were applied, and eight eligible trials were included with 330 women. CLA significantly reduced body weight (BW; 1.2±0.26 kg, p<0.001), body mass index (BMI; 0.6 ±0.13 kg/ m², p <0.001) and total body fat (TBF; 0.76± 0.26 kg, p=0.003) when it was supplemented for short durations (6- 16 weeks). Moreover, subgroups meta-analyses were conducted which were based on obesity level, menopausal age and life style of the participants. This meta-analysis suggested a mild anti-obesity effect of CLA. However, it was not clear whether the anti-obesity effect is enough to modulate obesity-induced inflammation and lung functions. Therefore, initially a crosssectional trial was conducted to assess the direct associations between the circulating level of CLA and obesity markers, lung functions and inflammations. To the best of Knowledge, this was the first cross-sectional trial that explored these direct associations. The cross-sectional trial recruited 77 women with average age 39 years old with forced expiratory volume in one-second (FEV1) ≥70%. The level of CLA in plasma was assessed by gas chromatography; the expression of the CD markers and HSPs were assessed using flow cytometry; body composition was assessed using bioelectric impedance; and lung functions were assessed using spirometer. Interestingly, the trial revealed significant positive associations between CLA and BW (R=0.4, p<0.001), BMI (R=0.4, P<0.001) and TBF (R=0.34, P<0.001) in the overall population, and in perimenopause women. A significant inverse correlation between t10, c12-CLA and TBF was detected in overweight women (R=- 0.42, p<0.05). A significant positive association (R=0.45, P<0.04) was detected between the c9, t11-CLA and percentage peak of flow predicted (PEF %) in postmenopausal women, meanwhile t10, c12-CLA was negatively associated with peak of flow (R=-0.44, P<0.04). CLA was inversely associated with adiponectin in both obese (R=-0.55, p<0.1) and morbidly obese (R=0.48, P<0.004) women. C9, t11-CLA was positively associated with the expression of HSPA1A inside the lymphocytes in postmenopausal women (R=0.58, p=0.04). HSPB1 expression in the monocytes were associated with both c9, t11-CLA (R=0.58, p<0.05) and total CLA (R=0.71, p<0.001). The level of expression of CD11b on the pro-inflammatory monocytes (CD14++ CD16+ ) was negatively associated with CLA (R=-0.36, p<0.05). Ultimately, the study did not provide strong evidence regarding the direct relationship between CLA and obesity markers or lung functions. However, it showed a potential immunomodulatory effect of CLA on obesity-induced chronic inflammation, which subsequently could influence multiple obesity compilations. The lack of strong evidencewas primarily due to the nature of the study design (observational study). Therefore, in chapter 5 a randomised double-blind placebo control trial was conducted, for more powerful evidence based. The aim of the RCT was to look at the effect of 12-week CLA supplementation on obesity, lung function, adipokines and inflammation in obese and overweight women. The RCT recruited 56 overweight and obese women with a mean age of 42 years old, participants were randomly assigned either to receive 4.5gm/day of CLA or placebo (High Oleic Safflower oil). Participants had to attend three clinics at base line, after 6 weeks and after 12 weeks. In each clinic body composition, lung functions and inflammatory markers were assessed. The study revealed a significant 1.8% reduction in %BF in the CLA group compared to the baseline. No significant effect of CLA on the lung functions was detected, however, this study found a significant reduction in the expression of CD11b on the stimulated pro-inflammatory monocytes after 12 weeks compared to baseline in the CLA group. CLA caused a significant reduction in the expression of intracellular HSPA1A in PBMCs at week 12 compared to baseline. The results might suggest a limited anti-obesity effect of CLA, and a potential positive effect on obesity induced chronic inflammation. Ultimately, no evidence was demonstrated on the direct effect of CLA on lung functions or adipokines. The effect of CLA on adhesion molecules and HSPA1A could suggest an indirect impact on the lung function, but more research in clinically diagnosed patients with pulmonary dysfunctions could help to confirm the effect of CLA on the lung function and adipokines.
    • Changes in selective biomarkers after transurethral resection of the bladder tumour (TURBT), and their association with Non-muscle invasive bladder cancer (NMIBC) recurrence and progression

      Ella-Twongiis, Peter (University of ChesterUniversity of Chester, 2019-10-01)
      Introduction Bladder Cancer (BC) is the 10th most common cancer in the UK, with about 10,000 new cases annually. It affects more men than women (ratio 3:1). Major risk factors include tobacco, chemical carcinogens, schistosomiasis infection and age. About 75-85% of BC are non-muscle invasive (NMIBC), which is associated with high recurrence and progression rates (50-60% within 7-10 years). Currently, diagnosis, treatment and management of BC is via clinical procedures such as transurethral resection of the bladder tumour (TURBT) and endoscopy. Concerning laboratory investigations, there are no routine biomarkers currently available for identifying BC patients at increased risk of developing recurrence and progression. By monitoring changes in selective biomarkers post-TURBT, any sustained changes may be a predictor of cancer recurrence or progression. The main-focus of this research study was to evaluate changes in selective novel biomarkers and their association with recurrence and progression in BC. Materials & Methods In this research, 40 patients (n=40) scheduled for TURBT at the Wrexham Maelor Hospital, North Wales were recruited after written informed consent. Ethical approval for the project was granted via IRAS (REC4: 14/WA/0033). Venous blood samples were taken at baseline (pre-operative) and following TURBT surgery at 1, 3 and 6 months post-operatively. Bladder tumour samples were also taken during TURBT according to standard procedure. Selective biomarkers to assess inflammation, angiogenesis and tumour growth, were measured using commercially available ELISA and BioPlex multiplex assay kits. Tissue immunoreactivity of novel biomarkers were also assessed in BC tissues using immunohistochemistry, with clinical outcome measures being recorded for all patients. Results Significant increases in serum Cluster of differentiation 31 (CD31) (p=0.003) and Stem Cell Factor (SCF) (p=0.032) concentration, as well as trends of increasing concentration of serum basic Fibroblast Growth Factor (bFGF) (p=0.14), Vascular Endothelial Growth Factor Receptor-1 and 2 (VEGFR-1) (p=0.15), VEGFR-2 (p=0.15) and Follistatin (p=0.40) were observed in BC patients up to 6 months post-operative. There were also significant decreases in serum Macrophage Inflammatory Protein -2 (MIP-2) (p=0.001), Platelet Derived Growth Factor (PDGF) (p=0.012), Matrix Metalloproteinase-9 (MMP-9) (p=0.002) and Vascular Endothelial Growth Factor C (VEGF-C) (p=0.04) serum concentration. Trends of decreasing concentration in MMP-2 (p=0.79), MMP-3 (p=0.15), interleukin-6 (IL-6) (p=0.26), interleukin-8 (IL-8) (p=0.15) and tumour necrosis factor-α (TNF-α) (p=0.69) were observed in BC patients up to 6 months post-operative. There was significant immunoreactivity of CD31 (p< 0.001), CD34 (p< 0.001), Human epidermal growth factor receptor-2 (HER-2) (p=0.032), S100P (p< 0.001), Cyclooxygenase-2 (COX-2) (p< 0.001), VEGFR-3 (p< 0.001), SOX-2 (p< 0.001) and thrombomodulin (p=0.010) in bladder tumours. Although recurrence was significantly associated with cancer grade, there was no association with antibody immunoreactivity. Conclusion Findings from the present study may indicate an alternative approach in the monitoring and management of patients with BC. It is proposed that by allowing urological surgeons access to laboratory markers such as MIP-2, MMP-9, PDGF, SCF, HER-2, Thrombomodulin and CD31 (biomarker profile), potentially, in the future, these biomarkers may be used in addition to, or in combination with, currently used scoring systems to predict cancer recurrence and progression. However, verification and validation of these biomarkers are needed using larger cohorts.
    • Clobazam add-on therapy for drug-resistant epilepsy

      Bresnahan, Rebecca; Williamson, John; Martin-McGill, Kirsty J.; Michael, Benedict D.; Marson, Anthony G. (Wiley, 2019-10-22)
    • The effects of intake of bread with treated corn bran inclusion on postprandial glycaemic response

      Cui, Zhiming; Li, Weili; Kennedy, Lynne; Department of Clinical Sciences and Nutrition, University of Chester
      In the current study, corn bran was treated with hydrothermal processing and then incorporated into bread. The consumption of bread with inclusion of treated corn bran (TCB) and control bread (CB) on postprandial glycaemic response was investigated in a randomised crossover intervention trial with eleven healthy participants and one hyperglycaemicparticipant, capillary blood samples were measured at 0, 15, 30, 45, 60, 75, 90, 105 and 120 minutes after consuming the bread. The results showed the baseline-adjusted peak value of postprandial blood glucose with consumption of CB, containing 75 g carbohydrate was 4.27 mmol/L at 60 min after meal, but with consumption of treated corn bran bread (TCBB), containing 75 g carbohydrate was 3.88 mmol/L at 45 min after meal. In addition, the postprandial blood glucose concentration with consumption of CB is consistently higher than that with the consumption of TCBB since the peak time to 120 min. However, there was no significant differences, in turn, the incremental area under the curves (IAUC) with baseline-adjusted for CB consumption is consistently higher than that of TCBB consumption, but not any significant difference either (p>0.05). However, it is interesting to notice that more considerable difference in rise of blood sugar at peak time and thereafter for hyperglycaemicparticipant between the consumptions of TCBB and CB. In conclusion, the consumption of bread with inclusion of TCB is able to reduce the postprandial glycaemic response to a lower level compared with the consumption of CB and the more obvious difference was observed with the hyperglycaemicparticipant and healthy group Key words: Corn bran, hydrothermal treatment, postprandial glycaemic response. Intervention trial.