-
1.
Predispose, precipitate, perpetuate, and protect: how diet and the gut influence mental health in emerging adulthood.
Warren, M, O'Connor, C, Lee, JE, Burton, J, Walton, D, Keathley, J, Wammes, M, Osuch, E
Frontiers in nutrition. 2024;:1339269
Abstract
Medicine often employs the 4Ps of predisposing, precipitating, perpetuating, and protective factors to identify salient influences on illness states, and to help guide patient care. Mental illness is a significant cause of morbidity and mortality worldwide. Mental health is a complex combination of biological, psychological, environmental, and social factors. There is growing interest in the gut-brain-microbiome (GBM) axis and its impact on mental health. We use the medical model of the 4Ps to explore factors involving the connection between nutrition and the GBM axis and their associated risks with mental health problems in emerging adults (EAs), a life stage when mental illness onset is the most common. We review the impact of current dietary trends on the GBM and on mental health, and the role that gut microbiome-based interventions can have in modulating the GBM axis of EAs. We discuss the implications of gut health on the GBM and areas for clinical intervention.
-
2.
A randomised study of nurse collected venous blood and self-collected dried blood spots for the assessment of cardiovascular risk factors in the Understanding Society Innovation Panel.
Kumari, M, Andrayas, A, Al Baghal, T, Burton, J, Crossley, TF, Jones, KS, Parkington, DA, Koulman, A, Benzeval, M
Scientific reports. 2023;(1):13008
Abstract
Dried blood spot (DBS) sample collection has been suggested as a less invasive, cheaper and more convenient alternative to venepuncture, which requires trained personnel, making it a potentially viable approach for self-collection of blood on a large scale. We examine whether participants in a longitudinal survey were willing to provide a DBS sample in different interview settings, and how resulting cardiovascular risk biomarkers compared with those from venous blood to calculate clinical risk. Participants of the Understanding Society Innovation Panel, a representative sample of UK households, were randomly assigned to three modes of interview. Most participants (84%) were interviewed in their allocated mode. Participants (n = 2162) were interviewed by a nurse who collected both a blood sample by venepuncture and a DBS card ('nurse collection') or participants were seen by an interviewer or took part in the survey online to self-collect a DBS card ('self-collection'). All DBS cards were returned in the post after the sample had dried. Lipids (total cholesterol, HDL-cholesterol, triglycerides), HbA1c and C-reactive protein were measured in venous and DBS samples and equivalence was calculated. The resultant values were used to confirm equivalent prevalence of risk of cardiovascular disease in each type of blood sample by mode of participation. Of participants interviewed by a nurse 69% consented to venous blood sample and 74% to a DBS sample, while in the self-collection modes, 35% consented to DBS collection. Demographic characteristics of participants in self-collection mode was not different to those in nurse collection mode. The percentage of participants with clinically raised biomarkers did not significantly differ between type of blood collection (for example, 62% had high cholesterol (> 5 mmol/l) measured by venepuncture and 67% had high cholesterol within the self-collected DBS sample (p = 0.13)). While self-collected DBS sampling had a lower response rate to DBS collected by a nurse, participation did not vary by key demographic characteristics. This study demonstrates that DBS collection is a feasible method of sample collection that can provide acceptable measures of clinically relevant biomarkers, enabling the calculation of population levels of cardiovascular disease risk.
-
3.
The effect of intravenous iron supplementation on exercise capacity in iron-deficient but not anaemic patients with chronic kidney disease: study design and baseline data for a multicentre prospective double-blind randomised controlled trial.
Greenwood, SA, Beckley-Hoelscher, N, Asgari, E, Ayis, S, Baker, LA, Banerjee, D, Bhandari, S, Bramham, K, Chilcot, J, Burton, J, et al
BMC nephrology. 2022;(1):268
Abstract
BACKGROUND Many people living with chronic kidney disease (CKD) are iron deficient, even though they may not be anaemic. The Iron and Muscle study aims to evaluate whether iron supplementation reduces symptoms of fatigue, improves muscle metabolism, and leads to enhanced exercise capacity and physical function. We report here the trial design and baseline characteristics. METHODS This is a prospective, double-blind multicentre randomised controlled trial (RCT) including 75 non-dialysis stage 3-4 CKD patients with iron deficiency but without anaemia. Patients were randomly (1:1) assigned to either: i) intravenous iron therapy, or ii) placebo, with concurrent recruitment of eight CKD non-iron deficient participants and six healthy volunteers. The primary outcome of the study is the six-minute walk test (6MWT) distance between baseline and four-weeks. An additional exercise training programme for patients in both groups was initiated and completed between 4 and 12 weeks, to determine the effect of iron repletion compared to placebo treatment in the context of patients undertaking an exercise programme. Additional secondary outcomes include fatigue, physical function, muscle strength, muscle metabolism, quality of life, resting blood pressure, clinical chemistry, safety and harms associated with the iron therapy intervention and the exercise training intervention, and hospitalisations. All outcomes were conducted at baseline, 4, and 12 weeks, with a nested qualitative study, to investigate the experience of living with iron deficiency and intervention acceptability. The cohort have been recruited and baseline assessments undertaken. RESULTS Seventy-five individuals were recruited. 44% of the randomised cohort were male, the mean (SD) age was 58 (14) years, and 56% were White. Body mass index was 31 (7) kg/m2; serum ferritin was 59 (45) μg/L, transferrin saturation was 22 (10) %, and haemoglobin was 125 (12) g/L at randomisation for the whole group. Estimated glomerular filtration rate was 35 (12) mL/min/1.73 m2 and the baseline 6MWT distance was 429 (174) m. CONCLUSION The results from this study will address a substantial knowledge gap in the effects of intravenous iron therapy, and offer potential clinical treatment options, to improve exercise capacity, physical function, fatigue, and muscle metabolism, for non-dialysis patients with CKD who are iron-deficient but not anaemic. It will also offer insight into the potential novel effects of an 8-week exercise training programme. TRIAL REGISTRATION EudraCT: 2018-000,144-25 Registered 28/01/2019.
-
4.
The Two-Way Interaction between the Molecules That Cause Vaginal Malodour and Lactobacilli: An Opportunity for Probiotics.
Puebla-Barragan, S, Akouris, PP, Al, KF, Carr, C, Lamb, B, Sumarah, M, van der Veer, C, Kort, R, Burton, J, Reid, G
International journal of molecular sciences. 2021;(22)
Abstract
Vaginal malodour is a sign of dysbiosis. The biogenic amines (BAs) cadaverine, putrescine and tyramine are known to be causative compounds. Recent reports suggest these compounds produced by pathogens might have a role beyond causing malodour; namely inhibiting the growth of lactobacilli bacteria that are crucial in the maintenance of vaginal homeostasis. The aim of this study was to identify whether certain lactobacilli strains could reduce BAs and to evaluate how Lactobacillus species were affected by these compounds. Using LC-MS and HPLC-UV, five Lactobacillus crispatus strains were identified as being capable of significantly reducing BAs from the media under in vitro conditions. Through 16S rRNA gene sequencing of vaginal swabs exposed to Bas, cadaverine was found to reduce the relative abundance of lactobacilli. When L. crispatus was exposed to media supplemented with BAs with an HCl adjusted lower pH, its growth was enhanced, demonstrating the relevance of the maintenance of an acidic vaginal environment. If strains are to be developed for probiotic application to alleviate bacterial vaginosis and other conditions affecting large numbers of women worldwide, their ability to adapt to Bas and regulate pH should be part of the experimentation.
-
5.
Response to "A randomized controlled trial of the ketogenic diet in refractory childhood epilepsy".
Almomen, M, Burton, J
Acta neurologica Scandinavica. 2017;(6):677
-
6.
Effectiveness of SmartMoms, a Novel eHealth Intervention for Management of Gestational Weight Gain: Randomized Controlled Pilot Trial.
Redman, LM, Gilmore, LA, Breaux, J, Thomas, DM, Elkind-Hirsch, K, Stewart, T, Hsia, DS, Burton, J, Apolzan, JW, Cain, LE, et al
JMIR mHealth and uHealth. 2017;(9):e133
Abstract
BACKGROUND Two-thirds of pregnant women exceed gestational weight gain (GWG) recommendations. Because excess GWG is associated with adverse outcomes for mother and child, development of scalable and cost-effective approaches to deliver intensive lifestyle programs during pregnancy is urgent. OBJECTIVE The aim of this study was to decrease the proportion of women who exceed the Institute of Medicine (IOM) 2009 GWG guidelines. METHODS In a parallel-arm randomized controlled trial, 54 pregnant women (age 18-40 years) who were overweight (n=25) or obese (n=29) were enrolled to test whether an intensive lifestyle intervention (called SmartMoms) decreased the proportion of women with excess GWG, defined as exceeding the 2009 IOM guidelines, compared to no intervention (usual care group). The SmartMoms intervention was delivered through mobile phone (remote group) or in a traditional in-person, clinic-based setting (in-person group), and included a personalized dietary intake prescription, self-monitoring weight against a personalized weight graph, activity tracking with a pedometer, receipt of health information, and continuous personalized feedback from counselors. RESULTS A significantly smaller proportion of women exceeded the IOM 2009 GWG guidelines in the SmartMoms intervention groups (in-person: 56%, 10/18; remote: 58%, 11/19) compared to usual care (85%, 11/13; P=.02). The remote intervention was a lower cost to participants (mean US $97, SD $6 vs mean US $347, SD $40 per participant; P<.001) and clinics (US $215 vs US $419 per participant) and with increased intervention adherence (76.5% vs 60.8%; P=.049). CONCLUSIONS An intensive lifestyle intervention for GWG can be effectively delivered via a mobile phone, which is both cost-effective and scalable. TRIAL REGISTRATION Clinicaltrials.gov NCT01610752; https://clinicaltrials.gov/ct2/show/NCT01610752 (Archived by WebCite at http://www.webcitation.org/6sarNB4iW).
-
7.
The effects of exercise on the lipoprotein subclass profile: A meta-analysis of 10 interventions.
Sarzynski, MA, Burton, J, Rankinen, T, Blair, SN, Church, TS, Després, JP, Hagberg, JM, Landers-Ramos, R, Leon, AS, Mikus, CR, et al
Atherosclerosis. 2015;(2):364-72
-
-
Free full text
-
Abstract
OBJECTIVE The goal was to examine lipoprotein subclass responses to regular exercise as measured in 10 exercise interventions derived from six cohorts. METHODS Nuclear magnetic resonance spectroscopy was used to quantify average particle size, total and subclass concentrations of very low-density lipoprotein, low-density lipoprotein, and high-density lipoprotein particles (VLDL-P, LDL-P, and HDL-P, respectively) before and after an exercise intervention in 1555 adults from six studies, encompassing 10 distinct exercise programs: APOE (N = 106), DREW (N = 385), GERS (N = 79), HERITAGE (N = 715), STRRIDE I (N = 168) and II (N = 102). Random-effects meta-analyses were performed to evaluate the overall estimate of mean change across the unadjusted and adjusted mean change values from each exercise group. RESULTS Meta-analysis of unadjusted data showed that regular exercise induced significant decreases in the concentration of large VLDL-P, small LDL-P, and medium HDL-P and mean VLDL-P size, with significant increases in the concentration of large LDL-P and large HDL-P and mean LDL-P size. These changes remained significant in meta-analysis with adjustment for age, sex, race, baseline body mass index, and baseline trait value. CONCLUSIONS Despite differences in exercise programs and study populations, regular exercise produced putatively beneficial changes in the lipoprotein subclass profile across 10 exercise interventions. Further research is needed to examine how exercise-induced changes in lipoprotein subclasses may be associated with (concomitant changes in) cardiovascular disease risk.
-
8.
Gastrointestinal microbiome modulator improves glucose tolerance in overweight and obese subjects: A randomized controlled pilot trial.
Rebello, CJ, Burton, J, Heiman, M, Greenway, FL
Journal of diabetes and its complications. 2015;(8):1272-6
-
-
Free full text
-
Abstract
OBJECTIVE The objective of this study was to examine the effects of a gastrointestinal microbiome modulator (GIMM) containing inulin, β-glucan, blueberry anthocyanins, and blueberry polyphenols on metabolic parameters, fecal markers of gut microbiota, and satiety. DESIGN AND METHODS Thirty overweight or obese individuals aged 18 to 70years, were enrolled in a randomized controlled trial. Participants consumed the test product or placebo daily for four weeks. Stool samples were collected and blood was drawn at baseline and week four for assessments of gut microbiota, satiety hormones, glucose control, and lipid measures. Subjective satiety was assessed weekly. Linear models were used to compare differences from baseline to week four. RESULTS GIMM consumption improved blood glucose tolerance (p=0.008), and increased satiety (p=0.03). There were no statistically significant differences in insulin sensitivity, fecal markers of gut microbiota, plasma satiety hormones, or serum lipid concentrations between the groups. However, plasma satiety hormones and fecal short chain fatty acid concentrations increased in the test group compared to the placebo. CONCLUSIONS GIMM consumption for four weeks, increases satiety, and improves glucose tolerance possibly through insulin-independent pathways.
-
9.
Structural basis and targeting of the interaction between fibroblast growth factor-inducible 14 and tumor necrosis factor-like weak inducer of apoptosis.
Dhruv, H, Loftus, JC, Narang, P, Petit, JL, Fameree, M, Burton, J, Tchegho, G, Chow, D, Yin, H, Al-Abed, Y, et al
The Journal of biological chemistry. 2013;(45):32261-32276
Abstract
Deregulation of the TNF-like weak inducer of apoptosis (TWEAK)-fibroblast growth factor-inducible 14 (Fn14) signaling pathway is observed in many diseases, including inflammation, autoimmune diseases, and cancer. Activation of Fn14 signaling by TWEAK binding triggers cell invasion and survival and therefore represents an attractive pathway for therapeutic intervention. Based on structural studies of the TWEAK-binding cysteine-rich domain of Fn14, several homology models of TWEAK were built to investigate plausible modes of TWEAK-Fn14 interaction. Two promising models, centered on different anchoring residues of TWEAK (tyrosine 176 and tryptophan 231), were prioritized using a data-driven strategy. Site-directed mutagenesis of TWEAK at Tyr(176), but not Trp(231), resulted in the loss of TWEAK binding to Fn14 substantiating Tyr(176) as the anchoring residue. Importantly, mutation of TWEAK at Tyr(176) did not disrupt TWEAK trimerization but failed to induce Fn14-mediated nuclear factor κ-light chain enhancer of activated B cell (NF-κB) signaling. The validated structural models were utilized in a virtual screen to design a targeted library of small molecules predicted to disrupt the TWEAK-Fn14 interaction. 129 small molecules were screened iteratively, with identification of molecules producing up to 37% inhibition of TWEAK-Fn14 binding. In summary, we present a data-driven in silico study revealing key structural elements of the TWEAK-Fn14 interaction, followed by experimental validation, serving as a guide for the design of small molecule inhibitors of the TWEAK-Fn14 ligand-receptor interaction. Our results validate the TWEAK-Fn14 interaction as a chemically tractable target and provide the foundation for further exploration utilizing chemical biology approaches focusing on validating this system as a therapeutic target in invasive cancers.
-
10.
Scintigraphic study to investigate the effect of food on a HPMC modified release formulation of UK-294,315.
Davis, J, Burton, J, Connor, AL, Macrae, R, Wilding, IR
Journal of pharmaceutical sciences. 2009;(4):1568-76
Abstract
The objective of the study was to use the combined approach of gamma scintigraphy and pharmacokinetics, in order to understand the mechanisms explaining the pharmacokinetic differences observed for a modified release (MR) formulation, when administered either in the fed or fasted state. Ten healthy subjects were recruited into a randomized three period single dose study, each subject receiving UK-294,315 40 mg IR (fasted), 100 mg MR (fasted) or 100 mg MR (after a high fat meal). C(max) values were markedly higher for the MR tablet in the fed state versus fasted and mean residence time was about 3 h longer for fasted versus fed; there was little difference in apparent oral clearance. In the fasted state, average gastric emptying of the intact tablet occurred at 1.2 h postdose, with gastric emptying of intact tablet observed in all subjects. In the fed state, rapid disintegration of the MR tablet was observed by scintigraphy, with 7/9 subjects showing complete disintegration in the stomach. Complete disintegration occurred 10.1 h postdose in the fasted state versus 5.9 h after a high fat meal. The study showed that in the fed state, the MR tablet eroded more rapidly than in the fasted state, leading to an overall increase in the rate of absorption.