Recent Submissions

  • The effect of accounting for biarticularity in hip flexor and hip extensor joint torque representations

    Lewis, Martin; Yeadon, M.R.; King, M.A.; Nottingham Trent University (Elsevier, 2017-10-07)
    Subject-specific torque-driven models have ignored biarticular effects at the hip. The aim of this study was to establish the contribution of monoarticular hip flexors and hip extensors to total hip flexor and total hip extensor joint torques for an individual and to investigate whether torque-driven simulation models should consider incorporating biarticular effects at the hip joint. Maximum voluntary isometric and isovelocity hip flexion and hip extension joint torques were measured for a single participant together with surface electromyography. Single-joint and two-joint representations were fitted to the collected torque data and used to determine the maximum voluntary joint torque capacity. When comparing two-joint and single-joint representations, the single-joint representation had the capacity to produce larger maximum voluntary hip flexion torque (larger by around 9% of maximum torque) and smaller maximum voluntary hip extension torque (smaller by around 33% of maximum torque) with the knee extended. Considering the range of kinematics found for jumping movements, the single-joint hip flexors had the capacity to produce around 10% additional torque, while the single joint hip extensors had about 70% of the capacity of the two-joint representation. Two-joint representations may overcome an over-simplification of single-joint representations by accounting for biarticular effects, while building on the strength of determining subject-specific parameters from measurements on the participant.
  • The effect of visual focus on spatio-temporal and kinematic parameters of treadmill running

    Lucas-Cuevas, Ángel G.; Priego Quesada, Jose I; Gooding, Josh; Lewis, Martin; Encarnación-Martínez, Alberto; Perez-Soriano, Pedro; Nottingham Trent University (Elsevier, 2017-07-15)
    The characteristics of a treadmill and the environment where it is based could influence the user’s gaze and have an effect on their running kinematics and lower limb impacts. The aim of this study was to identify the effect of visual focus on spatio-temporal parameters and lower limb kinematics during treadmill running. Twenty six experienced runners ran at 3.33 m s−1 on a treadmill under two visual conditions, either looking ahead at a wall or looking down at the treadmill visual display. Spatio-temporal parameters, impact accelerations of the head and tibia, and knee and ankle kinematics were measured for the final 15 s of a 90 s bout of running under each condition. At the end of the test, participants reported their preference for the visual conditions assessed. Participants’ stride angle, flight time, knee flexion during the flight phase, and ankle eversion during contact time were increased when runners directed visual focus toward the wall compared to the treadmill display (p < 0.05). Whilst head acceleration was also increased in the wall condition (p < 0.05), the other acceleration parameters were unaffected (p > 0.05). However, the effect size of all biomechanical alterations was small. The Treadmill condition was the preferred condition by the participants (p < 0.001; ESw = 1.0). The results of the current study indicate that runners had a greater mass centre vertical displacement when they ran looking ahead, probably with the aim of compensating for reduced visual feedback, which resulted in larger head accelerations. Greater knee flexion during the flight phase and ankle eversion during the contact time were suggested as compensatory mechanisms for lower limb impacts.
  • Optimisation of a machine learning algorithm in human locomotion using principal component and discriminant function analyses

    Bisele, Maria; Bencsik, Martin; Lewis, Martin; Barnett, Cleveland; Nottingham Trent University (Public Library of Science (PLoS), 2017-09-08)
    Assessment methods in human locomotion often involve the description of normalised graphical profiles and/or the extraction of discrete variables. Whilst useful, these approaches may not represent the full complexity of gait data. Multivariate statistical methods, such as Principal Component Analysis (PCA) and Discriminant Function Analysis (DFA), have been adopted since they have the potential to overcome these data handling issues. The aim of the current study was to develop and optimise a specific machine learning algorithm for processing human locomotion data. Twenty participants ran at a self-selected speed across a 15m runway in barefoot and shod conditions. Ground reaction forces (BW) and kinematics were measured at 1000 Hz and 100 Hz, respectively from which joint angles (°), joint moments (N.m.kg-1) and joint powers (W.kg-1) for the hip, knee and ankle joints were calculated in all three anatomical planes. Using PCA and DFA, power spectra of the kinematic and kinetic variables were used as a training database for the development of a machine learning algorithm. All possible combinations of 10 out of 20 participants were explored to find the iteration of individuals that would optimise the machine learning algorithm. The results showed that the algorithm was able to successfully predict whether a participant ran shod or barefoot in 93.5% of cases. To the authors’ knowledge, this is the first study to optimise the development of a machine learning algorithm.
  • Movement velocity as a measure of exercise intensity in three lower limb exercises.

    Conceição, Filipe; Fernandes, Juvenal; Lewis, Martin; Gonzaléz-Badillo, Juan José; Jimenéz-Reyes, Pedro; Nottingham Trent University (Taylor & Francis, 2015-09-22)
    The purpose of this study was to investigate the relationship between movement velocity and relative load in three lower limbs exercises commonly used to develop strength: leg press, full squat and half squat. The percentage of one repetition maximum (%1RM) has typically been used as the main parameter to control resistance training; however, more recent research has proposed movement velocity as an alternative. Fifteen participants performed a load progression with a range of loads until they reached their 1RM. Maximum instantaneous velocity (Vmax) and mean propulsive velocity (MPV) of the knee extension phase of each exercise were assessed. For all exercises, a strong relationship between Vmax and the %1RM was found: leg press (r2adj = 0.96; 95% CI for slope is [−0.0244, −0.0258], P < 0.0001), full squat (r2adj = 0.94; 95% CI for slope is [−0.0144, −0.0139], P < 0.0001) and half squat (r2adj = 0.97; 95% CI for slope is [−0.0135, −0.00143], P < 0.0001); for MPV, leg press (r2adj = 0.96; 95% CI for slope is [−0.0169, −0.0175], P < 0.0001, full squat (r2adj = 0.95; 95% CI for slope is [−0.0136, −0.0128], P < 0.0001) and half squat (r2adj = 0.96; 95% CI for slope is [−0.0116, 0.0124], P < 0.0001). The 1RM was attained with a MPV and Vmax of 0.21 ± 0.06 m s−1 and 0.63 ± 0.15 m s−1, 0.29 ± 0.05 m s−1 and 0.89 ± 0.17 m s−1, 0.33 ± 0.05 m s−1 and 0.95 ± 0.13 m s−1 for leg press, full squat and half squat, respectively. Results indicate that it is possible to determine an exercise-specific %1RM by measuring movement velocity for that exercise.
  • Lung clearance index in detection of post-transplant bronchiolitis obliterans syndrome

    Driskel, Madeleine; Horsley, Alex; Fretwell, Laurice; Clayton, Nigel; Al-Aloul, Mohamed; Lung Function Laboratory, Manchester University NHS Foundation Trust, Manchester, UK; Cardiothoracic Transplant Unit, Manchester University NHS Foundation Trust, Manchester, UK; Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK; School of Human Sciences, University of Derby, Derby, UK (European Respiratory Society, 2019-10-15)
    Long-term outcomes after lung transplantation are often limited by the development of obliterative bronchiolitis (OB), which is clinically defined using spirometry as bronchiolitis obliterans syndrome (BOS). Lung clearance index (LCI), derived from multiple breath washout (MBW) testing, is a global measure of ventilation heterogeneity that has previously been shown to be a more sensitive measure of obstructive small airway diseases than spirometry. We aimed to assess the feasibility of LCI in adult lung transplant patients and to compare LCI to BOS grade. 51 stable adult double-lung transplant recipients performed sulfur hexafluoride MBW in triplicate on a single occasion, using a closed-circuit Innocor device. BOS grades were derived from serial spirometry according to International Society for Heart and Lung Transplantation criteria and, where available, high-resolution computed tomography (HRCT) evidence of OB was recorded. LCI was successfully performed in 98% of patients. The within-visit coefficient of variation for repeat LCI measurements was 3.1%. Mean LCI increased significantly with BOS grades: no BOS (n=15), LCI 7.6; BOS-0p (n=16), LCI 8.3; BOS-1 (n=11), LCI 9.3; BOS-2–3 (n=9), LCI 13.2 (p<0.001). 27 patients had HRCT within 12 months. LCI in those with HRCT evidence of OB was higher than those without OB (11.1 versus 8.2, p=0.006). 47% patients displayed abnormal LCI (>7) despite a normal forced expiratory volume in 1 s (FEV1) (>80% of baseline). LCI measurement in lung transplant recipients is feasible and reproducible. LCI increased with increasing BOS grade. A significant proportion of this cohort had abnormal LCI with preserved FEV1, suggesting early subclinical small airway dysfunction, and supporting a role for MBW in the early identification of BOS.
  • Developing a professional leadership identity during organisational change in professional youth football

    Gibson, Luke; Groom, Ryan; University of Derby; Manchester Metropolitan University (Taylor Francis, 2019-10-09)
    The purpose of this paper is to investigate the construction of a professional leadership identity of an outsider appointed to implement organisational change within the academy of a professional football club. Data were collected through field notes, informal observations and meetings, formal academy team meetings, three in-depth co-worker interviews and four semi-structured in-depth participant interviews, which were subjected to an iterative analysis. Findings highlighted how the appraisal of others and their appraisal of the participant were affected by employment vulnerability, and that ‘identity work’ when leading organisational change was intertwined with micro-political literacy and micro-political action. This study furthers understanding of the development of a leadership identity as a fluid and fragmented struggle, by demonstrating that the process of identity construction is emotional work and is entwined in a complex interplay of micro-political literacy and action, and employment vulnerability.
  • Differences in the semantics of prosocial words: an exploration of compassion and kindness

    Gilbert, Paul; Basran, Jaskaran; MacArthur, Michael; Kirby, James N.; University of Derby; The University of Queensland (Springer, 2019-07-02)
    The study of prosocial behaviour has accelerated greatly in the last 20 years. Researchers are exploring different domains of prosocial behaviour such as compassion, kindness, caring, cooperation, empathy, sympathy, love, altruism and morality. While these constructs can overlap, and are sometimes used interchangeably, they also have distinctive features that require careful elucidation. This paper discusses some of the controversies and complexities of describing different (prosocial) mental states, followed by a study investigating the differences between two related prosocial concepts: compassion and kindness. For the study, a scenario-based questionnaire was developed to assess the degree to which a student (N = 222) and a community (N = 112) sample judged scenarios in terms of compassion or kindness. Subsequently, participants rated emotions (e.g. sadness, anxiety, anger, disgust, joy) associated with each scenario. Both groups clearly distinguished kindness from compassion in the scenarios on the basis of suffering. In addition, participants rated compassion-based scenarios as significantly higher on sadness, anger, anxiety and disgust, whereas kindness-based scenarios had higher levels of joy. As a follow-up, a further sample (29 male, 63 female) also rated compassionate scenarios as involving significantly more suffering compared to the kindness scenarios. Although overlapping concepts, compassion and kindness are clearly understood as different processes with different foci, competencies and emotion textures. This has implications for research in prosocial behaviour, and the cultivation of kindness and compassion for psychotherapy and in general.
  • Functional training of the inspiratory muscles improves load carriage performance

    Faghy, Mark A; Brown, Peter I; University of Derby; Loughborough University (Taylor & Francis, 2019-08-16)
    Inspiratory Muscle Training (IMT) whilst adopting body positions that mimic exercise (functional IMT; IMTF) improves running performance above traditional IMT methods in unloaded exercise. We investigated the effect of IMTF during load carriage tasks. Seventeen males completed 60 min walking at 6.5 km·h-1 followed by a 2.4 km load carriage time-trial (LCTT) whilst wearing a 25 kg backpack. Trials were completed at baseline; post 4 weeks IMT (consisting of 30 breaths twice daily at 50% of maximum inspiratory pressure) and again following either 4 weeks IMTF (comprising four inspiratory loaded core exercises) or maintenance IMT (IMTCON). Baseline LCTT was 15.93 ± 2.30 min and was reduced to 14.73 ± 2.40 min (mean reduction 1.19 ± 0.83 min, p < 0.01) after IMT. Following phase two, LCTT increased in IMTF only (13.59 ± 2.33 min, p < 0.05) and was unchanged in post-IMTCON. Performance was increased following IMTF, providing an additional ergogenic effect beyond IMT alone. Practitioner Summary: We confirmed the ergogenic benefit of Inspiratory Muscle Training (IMT) upon load carriage performance. Furthermore, we demonstrate that functional IMT methods provide a greater performance benefit during exercise with thoracic loads. Abbreviations: [Lac-]B: blood lactate; FEV1: forced expiratory volume in one second; FEV1/FVC: forced expiratory volume in one second/forced vital capacity ratio; FVC: forced vital capacity; HR: heart rate; IMT: inspiratory muscle training; IMTCON: inspiratory muscle training maintenance; IMTF: functional inspiratory muscle training; LC: load carriage; LCTT: load carriage time trial; Pdi: transdiaphragmatic pressure; PEF: peak expiratory flow; PEmax: maximum expiratory mouth pressure; PImax: maximum inspiratory mouth pressure; RPE: rating of perceived exertion; RPEbreating: rating of perceived exertion for the breathing; RPEleg: rating of perceived exertion for the legs; SEPT: sport-specific endurance plank test; V̇ O2: oxygen consumption; V̇ O2peak: peak oxygen consumption.
  • The efficacy of a compassion-focused therapy–based intervention in reducing psychopathic traits and disruptive behavior: a clinical case study with a juvenile detainee

    Ribeiro da Silva, Diana; Rijo, Daniel; Castilho, Paula; Gilbert, Paul; University of Coimbra; University of Derby (SAGE Publications, 2019-05-15)
    Conduct disorder (CD) is the most diagnosed psychopathological disorder in juvenile detainees. The presence of a CD diagnosis, especially when associated with psychopathic traits, contributes to a poor prognosis, high recidivism rates, and low responsivity to treatment in these youth. Although group intervention programs have proven to be effective in decreasing antisocial behavior, studies testing their efficacy in reducing psychopathic traits are scarce and limited. Moreover, there is a lack of research focused on the efficacy of individual treatment approaches specifically designed to reduce psychopathic traits and disruptive behavior in juvenile detainees. Compassion-focused therapy (CFT) shows promising results in the treatment of several psychopathological disorders. Besides, there is some theoretical support to consider CFT a suitable approach to treating juvenile detainees. However, there are no treatment programs based on CFT that are designed to target psychopathic traits and disruptive behavior in these youth. Consequently, treatment outcome research in this area is absent. This clinical case study presents the treatment of a juvenile detainee with CD, a high psychopathic profile, and a very high risk for criminal recidivism using the PSYCHOPATHY.COMP program (a 20-session individual CFT program), which was specially designed to reduce psychopathic traits and disruptive behavior. The treatment outcome data revealed a significant reduction in psychopathic traits and disruptive behavior. The treatment gains were maintained and/or increased over time (3 months after program completion). This clinical case study demonstrates the feasibility and efficacy of the PSYCHOPATHY.COMP program in reducing psychopathic traits and disruptive behavior in a juvenile detainee.
  • Distinguishing shame, humiliation and guilt: an evolutionary functional analysis and compassion focused Interventions

    Gilbert, Paul; Centre for Compassion Research and Training College of Health and Social Care Research Centre, University of Derby; University of Queensland (Springer International Publishing, 2019-04-26)
    The self-conscious emotions of shame, humiliation and guilt are clearly related to our human capacity for self-awareness and sense of self as an ‘object in the minds of others’. However, this chapter will highlight that the emotional and motivational processes that sit behind them are phylogenetically old and rooted in social competition for shame and humiliation, and care-giving for guilt. Insight into their phylogenetic origins and differences helps us to gain insight into the physiological processes that texture them and why they can have such profound effects not only on individual human behaviour but also whole societies and cultures. This chapter will explore the differences between these self-conscious emotions, how they are rooted in different motivational systems and how we can utilise care and compassion based motivational systems for the remediation and change.
  • Accelerometer-based physical activity levels differ between week and weekend ways in British preschool children

    Roscoe, Clare M. P.; James, Rob S.; Duncan, Michael J.; University of Derby; Coventry University (MDPI AG, 2019-09-12)
    Participation in physical activity (PA) is fundamental to children’s future health. Studies examining the temporal pattern of PA between weekdays and weekends in British preschool children are lacking. Therefore, the aim of this study was to compare PA levels between week and weekend days for UK preschool children, using objective measurements. One hundred and eighty-five preschool children (99 boys, 86 girls, aged 4–5 years), from central England wore a triaxial accelerometer (GENEActiv) for 4 days to determine PA. The time (min) and percentage (%) of time spent in light, moderate and vigorous PA (MVPA) was determined using specific cut-points for counts per minute related to 3–5 year olds. Of the sample, none of the children met the UK recommended 180 min or more of PA per day. A significant difference (P < 0.05) was observed between the amount of time that preschool children spent in sedentary behaviours on weekdays (91.9%) compared to weekend days (96.9%). During weekdays and weekend days, 6.3% and 2.0% of time was spent in MVPA, respectively. Therefore, a substantial proportion of British preschool children’s day is spent in sedentary behaviours, with less MVPA accrued during the weekend. Regular engagement during the weekdays provides opportunities to accrue PA, which may not be present on weekend days.
  • Do individuals with Chronic Pain show attentional bias to pain-related information? An early stage systematic review of the eye-tracking evidence.

    Gaffiero, Daniel; Elander, James; Maratos, Frances; University of Derby (British Psychology Society, 2019-03)
  • Treating hoarding disorder with compassion‐focused therapy: A pilot study examining treatment feasibility, acceptability, and exploring treatment effects

    Chou, Chia‐Ying; Tsoh, Janice Y.; Shumway, Martha; Smith, Lauren C.; Chan, Joanne; Delucchi, Kevin; Tirch, Dennis; Gilbert, Paul; Mathews, Carol A.; Department of Psychiatry, University of California, San Francisco, California, USA; et al. (Wiley Online Library, 2019-07-04)
    Hoarding disorder (HD) was recognized as a psychiatric disorder in 2013. Existing literature suggests room for improvement in its treatment. The current pilot study aimed to provide an initial evaluation on the potential of compassion‐focused therapy (CFT) as an intervention for HD, with the primary aim being assessing its feasibility and acceptability, and the secondary being evaluating its effects. Both CFT and a second round of the current standard of treatment and cognitive behavioural therapy (CBT) were investigated in the current study as follow‐up treatment options for individuals who had completed CBT but were still significantly symptomatic. Forty eligible individuals were enrolled (20 in each treatment). Treatment feasibility and acceptability were assessed by quantitative and qualitative measures. To explore treatment effects, HD symptom severity, HD‐related dysfunctions, and their underlying mechanisms were assessed pre‐treatment and post‐treatment. Retention rates were 72% for CFT and 37% for CBT. All participants and 79% of the participants rated CFT and CBT, respectively, as good or excellent. After receiving CFT as a follow‐up treatment, HD symptom severity dropped below the cut‐off point for clinically significant HD for 77% of the treatment completers, and 62% achieved clinically significant reduction in symptom severity. In contrast, after completing a second course of CBT, 23% had HD symptom severity dropped below the cut‐off threshold, and 29% achieved clinically significant symptom reduction. The current study showed satisfactory feasibility and acceptability of CFT. Moreover, it also found promising effects of CFT in addressing hoarding‐related mechanisms that may not have been sufficiently addressed by CBT. The results suggest promising potential of CFT as a treatment for HD. Further investigation on this intervention is needed. CFT may be a promising treatment option, particularly for those who do not respond well to CBT. Improving emotion regulation and negative self‐perception by applying CFT interventions may help relieve hoarding symptoms. Generalization of the findings should be applied with caution given the small convenience sample of the current study. Statistical comparison on treatment effect measures between CFT and CBT as follow‐up treatments was not available due to small sample size. Therefore, the comparative conclusions based on this pilot study should be made with caution.
  • PWE-001 field cancerisation theory in colorectal cancer (crc): what role do fibroblast growth factors have?

    Patel, A; Williams, N; Nwokolo, C; Tripathi, G; Arasaradnam, R; University of Westminster (BMJ, 09/06/2014)
    Characterisation of the molecular field defect around colorectal cancer (CRC) could enable identification of novel biomarkers that could be used for early detection of CRC. Previous studies have suggested fibroblast growth factor 19 (FGF19) may play a role in CRC formation through interaction with the B-catenin/wnt signalling cascade. The role of fibroblast growth factor 7 (FGF7) however remains controversial. The aim of this study was to determine if there are differences in FGF19 and FGF7 gene expression in cancer tissue and the adjacent ‘normal tissue’ compared with normal colonic tissue. Mucosal pinch biopsies were taken from the rectum and caecum at time of colonoscopy for healthy controls. For CRC patients, tissue samples were taken from the tumour, adjacent to the tumour and at the resection margin of the colectomy specimen. Healthy controls were age and sex matched to CRC patients. Quantitative real time PCR was used to determine gene expression of FGF19, its receptor FGFR4, FGF7 and its receptor, FGFR2. Results were further validated using immunohistochemistry. Serum levels of FGF19 were measured using the Quantikine ELISA kit (RandD systems, UK). 49 patients were recruited (28 M: 21 F, median age 71 years (range 48–86 years)); 18 patients with CRC and 32 healthy controls. There was no overall difference in gene expression of FGF19/FGFR4 or FGF7/FGFR2 between cancer patients and healthy controls. There was upregulation of FGFR4 in mucosa adjacent to the tumour (mean fold change 1.23 vs. 0.93, p = 0.38) and the tumour itself (mean fold change 1.49 vs. 1.04, p = 0.700) in patients whose tumour expressed FGF19 compared to those that did not. Patients with upregulation of FGF19/FGFR4 had a significantly lower fasting serum FGF19 level (119 pg/ml versus 208 pg/ml, p = 0.05). FGF7 was upregulated in 6/19 cancers; this was associated with a significant upregulation in FGF7 in adjacent mucosa compared with cancers where FGF7 was downregulated (mean fold change 3.62 vs. 0.95, p = 0.018). There was a non-significant trend towards upregulation of the receptor (FGFR2) in mucosa adjacent to the cancer and the tumour tissue itself. Upregulation of FGFR4 in patients whose tumours expressed FGF19 corresponded inversely with serum FGF19 suggesting its potential as a putative biomarker. Significant upregulation of FGF7 in ‘normal’ mucosa adjacent to only tumours that express FGF7 lends support to the field theory of colorectal carcinogenesis.
  • Systemic triglycerides as a key determinant of TLR regulated inflammatory risk in human adipose tissue post bariatric surgical intervention and weight loss

    Kumsaiyai, W; Al-Daghri, N; Kyrou, I; Vrbikova, J; Hainer, V; Fried, M; Sramkova, P; Barber, T; S Kumar; Tripathi, G; et al. (bioscientifica, 01/03/2014)
    Bariatric surgery can lead to a quick reversal in type 2 diabetes mellitus (T2DM) status. However, despite this reversal inflammatory responses may still persist via activation of Toll-like receptors (TLR) within adipose tissue (AT); with triglycerides (TGs) noted as a potential mediator of such inflammation. Therefore the aims of these studies were to understand the impact of TG changes, pre- and post-bariatric surgery, on TLR expression in ex vivo AT and the in vitro effects of triglyceride rich lipoprotein (VLDL), on TLR expression in isolated human differentiated pre-adipocytes. Obese, T2DM, female subjects (age: 54.6±6.6 years, BMI pre (41.2±5.5 kg/m2) and 6 months post-surgery (36.05±5.16 kg/m2; n=30) underwent bariatric surgery (banding (n=8); plication (n=14); and biliopancreatic diversion (n=8)). Biochemical data and abdominal subcutaneous AT (AbdSc AT) samples were taken during surgery and 6 months post-surgery. Real-time PCR assessed TLR expression. Human differentiated pre-adipocyte Chub S7 cells were used to examine transcriptional effects of VLDL on TLR expression. Following surgical intervention, BMI (P<0.001), blood glucose (P<0.001), insulin (P<0.001), HOMA-IR (P<0.001), TG (P<0.05), cholesterol (P<0.001), and LDL-cholesterol (P<0.05) were significantly improved. There was a significant reduction in TLR4 mRNA post-surgery (P<0.01) irrespective of surgery type. It was also noted that subjects with the greatest drop (55.5% reduction) in TGs post-surgery (P<0.001) showed a significant correlated reduction in TLR4 mRNA expression (P<0.001). In vitro treatment of differentiated Chub S7 cells highlighted VLDL induced TLR4 mRNA expression (P<0.05).There is a reduction in AT inflammation as denoted by TLR expression. The reduction in AT inflammation appears dependent on how successfully subjects reduce their serum triglyceride, which is supported by in vitro studies. These studies suggest that bariatric surgery lead to metabolic improvement with weight loss, whilst dietary intervention is still required to ensure TGs reduce to reduce inflammation.
  • Meal size and frequency influences metabolic endotoxaemia and inflammatory risk but has no effect on diet induced thermogenesis in either lean or obese subjects

    Piya, M; Reddy, N; Campbell, A; Hattersley, J; Halder, L; Tripathi, G; Tahrani, A; Kumar, S; Barber, T; McTernan, P; et al. (bioscientifica, 01/03/2014)
    Small frequent meals are often recommended for weight loss, with supporting evidence often provided from studies in diabetes. Dietary meal content is also relevant, as high fat meals cause systemic inflammation via gut derived bacteria, endotoxin. As such, repeated meals may exacerbate this. In contrast, dietary induced thermogenesis, related to meal size, may reduce with small frequent meals. Therefore, the aim of this study was to compare the effect of 2 vs 5 meals on metabolic endotoxaemia and 24 h (hour) energy expenditure in lean and obese women. In a crossover study, 24 lean (age: 34 (mean±S.D.)±10 years, BMI: 22.9±2 kg/m2) and obese (age: 42±9 years, BMI: 36±8 kg/m2) women were given two or five isocaloric high (50%) fat meals, on two separate days. On both visits, 24 h energy expenditure was measured in whole body room calorimeters and blood samples taken 2 hourly (0900 to 2100 h). Serum endotoxin, glucose, insulin, lipids were measured. The obese subjects had increased area under the curve (AUC) for insulin, glucose, HOMA-IR and triglyceride (TG), with decreased HDL (P<0.01), compared with lean subjects, for both meal visits. For the entire cohort, fasting endotoxin correlated with triglyceride (r=0.32, P<0.05), and AUC for endotoxin and TG correlated in the five meal visit (r=0.44, P<0.05), but not the two meal visit. In the final 2100 h blood test, the endotoxin levels were significantly higher in the five meal visit (P=0.05), but not the two meal visit. Meal frequency did not affect 24 h expenditure, in either the obese group (2124±312 vs 2142±365 Kcal/day) or lean group (1724±160 vs 1683±166 Kcal/day).Our findings suggest in metabolically healthy lean and obese subjects, increased meal frequency may pose an inflammatory risk posed by circulating endotoxin and TGs leading to peak levels at bedtime. As such, small frequent meals may not influence diet induced thermogenesis, but may increase metabolic disease risk.
  • Unfolded protein response in adipose tissue of obese diabetic women significantly improved 6 months post bariatric surgery, irrespective of malabsorptive or bypass operation type and correlates with plasma glucose concentration

    Voyias, P; Antonysunil, A; Kumasaiyai, W; Kyrou, I; Vrbikova, J; Hainer, V; Fried, M; Sramkova, P; Saravanan, P; Kumar, S; et al. (bioscientifica, 01/03/2014)
    In obesity, excess nutrients and an increased demand for protein synthesis contribute to unfolded proteins accumulating within the endoplasmic reticulum and consequent activation of unfolded protein response (UPR). UPR in adipose tissue (AT) is critical to the initiation and integration of inflammation and insulin signalling pathways in obese and type 2 diabetes mellitus (T2DM) patients. The aim of this study was to examine whether novel malabsorptive or bypass bariatric surgery in obese women with T2DM leads to reduction in UPR. Abdominal subcutaneous (AbSc) AT was isolated from 30 Caucasian obese T2DM women aged 54.1±1.3 (mean±S.E.M.) years, BMI 41.21±1.0 kg/m2, that had undergone bariatric surgery of malabsorptive; gastric band (n=9) or novel gastric plication (n=13), or bypass; biliopancreatic diversion (n=8) type. Biopsies and anthropometric data were collected at the time of surgery and 6 months post-surgery. UPR markers were measured by qRT-PCR and western blotting and correlation analysis was performed. Six months post-operation all subjects significantly reduced body weight (P<0.001) with mean excess BMI lost 33.4±2.4%. Anthropometric measurements were significantly improved; fat mass, HbA1c, glucose, insulin, HOMA-IR, and total cholesterol (all P<0.001). ATF6, IRE1α, XBP1s, ATF4, and CHOP10 mRNAs and ATF6, pIRE1α, XBP1s, Calnexin and Bip proteins were all significantly (P<0.05) reduced post-surgery irrespective of operation type. Correlations between UPR mRNAs were strengthened post-surgery for ATF4 and CHOP10 (P=0.041–P<0.001) and IRE1α and ATF6 (P=0.853–P<0.001). Post-surgery plasma glucose correlated significantly (P=0.034) with XBP1s mRNA. This study highlights that bariatric surgery induced weight loss is coupled with improved glucose homeostasis and reduced UPR expression in AT. Furthermore post weight loss there are enhanced associations identified between UPR and XBP1 in AT and plasma glucose which may arise due to improved glucose homeostasis. This suggests UPR regulation in AT is linked to plasma glucose levels which aligns to metabolic health.
  • A 3-month low fat diet leads to significant lipid profile improvement in obese T2DM Saudi subjects, without substantial weight loss, and the capacity to manage a damaging high-fat meal challenge more appropriately post intervention

    Al-Disi, D; Al-Daghri, N; Khan, N; Alsaif, M; Alfadda, A; Sabico, S; Tripathi, G; McTernan, P; University of Westminster (bioscientifica, 01/03/2014)
    Current evidence highlights that dietary cholesterol, trans-fatty acids and saturated fatty acids (SFAs) are all known to increase the levels of systemic atherogenic lipoproteins and cardiovascular disease. The aim of this study was to observe the direct effect of dietary change, via a calorie-restricted diet on i) cardio-metabolic profile and ii) a high-fat meal challenge pre- and post-3-month intervention. T2DM subjects (Saudi female, age: 40.50±6.8years, BMI: 37.28±10.75 kg/m2, n=18) were given a high-fat meal pre- and post-calorie restricted diet (3 months; 500 kcal deficit/day, balanced diet with complex carbohydrate). Baseline (0 h) and post-prandial sera (1–4 h) were taken from subjects, anthropometric and biochemical data was collated at both time points. On baseline comparison of pre- and post-diet interventions, there were modest reductions in anthropometric data, BMI (P<0.001), waist (P<0.001), and waist:hip ratio (WHR; P<0.01). Baseline HDL-cholesterol increased significantly (P<0.01) whilst LDL- and total-cholesterol were significantly reduced (pre-total cholesterol: 5.13 (4.53, 5.93) vs post-total cholesterol: 4.70 (4.01, 5.14); pre-LDL cholesterol: 3.56 (3.07, 4.06) vs post-LDL cholesterol: 2.81 (2.34, 3.56), P<0.05). The findings also showed significant changes in the effects of high-fat meal intake on the metabolic profile pre- and post-diet intervention. At 4 h post-prandially, post-dietary intervention, HDL-cholesterol was 16.6% higher than pre-diet (P<0.05), whilst LDL- and total-cholesterol were 24.2 and 12% lower, respectively, than at the 4 h equivalent pre-diet (P<0.05). These findings suggest that lipid mediators associated with increased cardiometabolic risk can be quickly reversed as a result of a balanced diet, in T2DM subjects without substantial weight loss. As a result, the body is able to cope with the occasional high-fat meal insult, whilst still maintaining a reduced long-term CVD risk. As such, this is a diet that patients with T2DM may be able to adhere to more successfully, longer-term.
  • Vitamin B12 deficiency induces cholesterol biosynthesis by limiting S-adenosyl methionine and altering the methylation of Srebf1 and Ldlr genes

    Adaikalakoteswari, A; Finer, S; Voyias, P.D; McCarthy, C; Moore, J; Smart-Halajko, M; Bawazeer, N; Al-Daghri, N.M; McTernan, P.G; University of Westminster
    Maternal vitamin B12 deficiency affecting one-carbonmetabolism influences metabolic status and the degree of insulinresistance of the offspring in adulthood. But its significance andmechanism in the development of adiposity and adipose tissuedysfunction is unknown. To investigate the role of vitamin B12 in the developmentof adipocyte dysfunction. Human pre-adipocytes were differentiatedin customised media with varying concentrations of B12. Adipo-cytes cultured in low B12 (0.15nM) or no B12 conditions hadincreased cholesterol and homocysteine levels and reduced glucoseuptake capacity compared to control (B12 500nM). Global DNAmethylation profiling and bisulphite pyrosequencing showed thatthe promoter regions of sterol regulatory element-binding tran-scription factor 1 (SREBF1) and low density lipoprotein receptor(LDLR) were hypomethylated in B12 deficient conditions, consis-tent with the increased gene expressions. The S-adenosyl methio-nine/S-adenosyl homocysteine ratio was significantly lower in B12deficient conditions. Inhibition of methylation in high B12 condi-tions by 5-aza-2-deoxycytidine led to increased cholesterol accu-mulation but not homocysteine. In two independent clinicalstudies, women at child bearing age (age: 19–39 years) and inearly pregnancy (16–18 weeks), showed that low B12 was asso-ciated with higher total cholesterol, LDL cholesterol and choles-terol to HDL ratio. Regression analysis in the pregnant cohortadjusting for all confounders showed B12 levels to be indepen-dently associated with total cholesterol and triglyceride levels. Vitamin B12 deficiency leads to adipocyte dysfunc-tion by inducing cholesterol biosynthesis and homocysteine.Induction of cholesterol biosynthesis was due to hypomethylationof SREBF1 and LDLR. Clinical observations support that the B12effect is independent and our findings show this link is probably causal.
  • Elevated cord leptin from low B12 mothers predicts birth weight

    Antonysunil, A; Vatish, M; Lawson, A; Wood, C; Sivakumar, K; Webster, C; Anderson, N; McTernan, P; Tripathi, G; Saravanan, P; et al. (bioscientifica, 01/03/2014)
    Vitamin B12 (B12) insufficiency is common in pregnancy and independently predicts insulin resistance (IR) in the offspring. B12 is an important key nutrient for epigenetic programming through regulating DNA methylation. Such B12 DNA methylation may influence leptin, a strong candidate for methylation, which could impact both insulin resistance (IR) and associated neonatal metabolic risk. Therefore, we hypothesize that leptin can be programmed by maternal B12 which could influence metabolic risk in the offspring. To test this hypothesis, we investigated whether i) maternal B12 is associated with leptin in cord blood and ii) evaluated their association with birth weight. Paired maternal venous and cord blood samples (n=91) were collected at the time of elective caesarean section. Serum vitamin-B12 was determined by electro-chemiluminescent immunoassay. Leptin levels were measured by ELISA. B12 insufficiency (<150 pmol/l) was common (mothers-40%; and neonates-29%). Maternal B12 was inversely associated with neonatal leptin (r=−0.304; P=0.005). In regression analysis, adjusted for all likely confounders, maternal B12 independently predicted neonatal leptin (β=−0.647; P=0.005; R2=12.8%). There was no correlation between maternal and neonatal leptin levels. Cord leptin from mothers with low B12 correlated with birth weight (r=0.366; P=0.036). Regression analysis adjusted for maternal leptin and insulin showed that cord leptin from mothers with low B12 independently predicted birth weight (β=0.024; P=0.049; R2=14.5%). Our study highlights that maternal B12 insufficiency predicts elevated leptin in cord blood and is associated with higher birth weight. Since cord leptin is derived from neonatal adipose tissue and not mother, these findings suggest that maternal B12 might program leptin levels in-utero either directly through the satiety centre or mediated via inducing IR and adiposity in the offspring. Delineating the mechanistic relationship between cord leptin and maternal B12 might provide crucial answers in understanding the molecular mechanisms of adverse metabolic programming.

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