Design and Characterisation of a Randomized Food Intervention That Mimics Exposure to a Typical UK Diet to Provide Urine Samples for Identification and Validation of Metabolite Biomarkers of Food Intake

Poor dietary choices are major risk factors for obesity and non-communicable diseases, which places an increasing burden on healthcare systems worldwide. To monitor the effectiveness of healthy eating guidelines and strategies, there is a need for objective measures of dietary intake in community settings. Metabolites derived from specific foods present in urine samples can provide objective biomarkers of food intake (BFIs). Whilst the majority of biomarker discovery/validation studies have investigated potential biomarkers for single foods only, this study considered the whole diet by using menus that delivered a wide range of foods in meals that emulated conventional UK eating patterns. Fifty-one healthy participants (range 19–77 years; 57% female) followed a uniquely designed, randomized controlled dietary intervention, and provided spot urine samples suitable for discovery of BFIs within a real-world context. Free-living participants prepared and consumed all foods and drinks in their own homes and were asked to follow the protocols for meal consumption and home urine sample collection. This study also assessed the robustness, and impact on data quality, of a minimally invasive urine collection protocol. Overall the study design was well-accepted by participants and concluded successfully without any drop outs. Compliance for urine collection, adherence to menu plans, and observance of recommended meal timings, was shown to be very high. Metabolome analysis using mass spectrometry coupled with data mining demonstrated that the study protocol was well-suited for BFI discovery and validation. Novel, putative biomarkers for an extended range of foods were identified including legumes, curry, strongly-heated products, and artificially sweetened, low calorie beverages. In conclusion, aspects of this study design would help to overcome several current challenges in the development of BFI technology. One specific attribute was the examination of BFI generalizability across related food groups and across different preparations and cooking methods of foods. Furthermore, the collection of urine samples at multiple time points helped to determine which spot sample was optimal for identification and validation of BFIs in free-living individuals. A further valuable design feature centered on the comprehensiveness of the menu design which allowed the testing of biomarker specificity within a biobank of urine samples

Tricarbonyl M(I) (M = Re, 99mTc) complexes bearing acridine fluorophores : synthesis, characterization, DNA interaction studies and nuclear targeting

© The Royal Society of Chemistry 2010New pyrazolyl-diamine ligands with acridine derivatives at the 4-position of the pyrazolyl ring were synthesized and characterized (L1 and L2). Coordination towards the fac-[M(CO)3]+ (M = Re, 99mTc) led to complexes fac-[M(CO)3(κ3-L)] (L = L1: M = Re1, Tc1; L = L2: M = Re2, Tc2). The interaction of the novel pyrazolyl-diamine ligands (L1 and L2) and rhenium(I) complexes (Re1 and Re2) with calf thymus DNA (CT-DNA) was investigated by a variety of techniques, namely UV-visible , fluorescence spectroscopy and circular and linear dichroism . Compounds L1 and Re1 have moderate affinity to CT-DNA and bind to DNA by intercalation, while L2 and Re2 have a poor affinity for CT-DNA. Moreover, LD measurements showed that L1 and Re1 act as perfect intercalators . By confocal fluorescence microscopy we found that L1 and Re1 internalize and localize in the nucleus of B16F1 murine melanoma cells . The congener Tc1 complex also targets the cell nucleus exhibiting a time-dependent cellular uptake and a fast and high nuclear internalization (67.2% of activity after 30 min). Plasmid DNA studies have shown that Tc1 converts supercoiled (sc) puc19 DNA to the open circular (oc) form.Teresa Esteves and Sofia Gama thank the FCT for a doctoral and postdoctoral research grants (SFRH/BD/29154/2006 and SFRH/BPD/29564/2006, respectively). COST Action D39 is also acknowledge. The QITMS instrument was acquired with the support of the Programa Nacional de Reequipamento Científico (Contract>REDE/1503/REM/2005-ITN) of Fundação para a Ciência e a Tecnologia and is part of RNEM - Rede Nacional de Espectrometria de Massa

The influence of biological maturity on dynamic force–time variables and vaulting performance in young female gymnasts

Purpose: This cross-sectional study investigated dynamic force–time variables and vaulting performance in young female gymnasts of different maturity status. Methods: 120 gymnasts aged 5–14 years were sub-divided into maturity groupings using percent of predicted adult height (%PAH) attained. Participants performed three jumping protocols, the squat jump (SJ), countermovement jump (CMJ) and drop jump (DJ), before completing straight jump vaults that were recorded using two-dimensional video. Results: Jumping performance improved with biological maturity evidenced by the most mature gymnasts’ producing significantly more absolute force (P \u3c 0.05; all d \u3e 0.78), impulse (P \u3c 0.05; all d \u3e 0.75) and power (P \u3c 0.05; all d \u3e 0.91) than the least mature group, resulting in the greater jump heights (P \u3c 0.05; all d \u3e 0.70). While, no significant differences were observed in relative peak force across multiple tests, measures of relative peak power did significantly increase with maturity. Based upon regression analyses, maturation was found to influence vertical take-off velocity during vaulting, explaining 41% of the variance in each jumping protocol. Across all tests, the DJ was found to have the highest predictive ability of vaulting vertical take-off velocity, explaining 55% of the total variance. Conclusion: Biological maturation impacts jump height and underpinning mechanical variables in young female gymnasts. Vaulting vertical take-off velocity appears to be influenced by maturation and various dynamic force–time variables, particularly those during DJ, which had the highest explained total variance

Effects of a 12-Week Training Program on Isometric and Dynamic Force-Time Characteristics in Pre– and Post–Peak Height Velocity Male Athletes

Literature shows that training children and adolescents can enhance strength and power irrespective of their stage of development; however, the development of the kinetic variables that underpin strength and power performance are typically unreported in youth training studies. Twenty-four pre– and 14 post–peak height velocity (PHV) male athletes were divided into maturity-specific experimental (EXP) and control groups (CON), with the EXP groups completing a twice-weekly, 12-week training program. Force-time characteristics during the isometric midthigh pull (IMTP), countermovement jump, and squat jump tests were quantified at both baseline and after the completion of the 12-week program. Alpha level was set at p 0.05). Analysis of IMTP data revealed that only the post-PHV EXP group significantly increased absolute isometric peak force (PFabs) and peak rate of force development within the IMTP after training. Both EXP groups displayed significant increases in isometric PF at time epochs 0–90, 0–150, 0–200, and 0–250 ms. Data from the dynamic tests indicated that the pre-PHV EXP cohort improved concentric qualities as reflected by increased squat jump height and countermovement jump concentric power. There were no significant changes for any variables across all tests within either CON group (p > 0.05). Maturity-related differences in response to short-term training affects the kinetic variables associated with strength and power performance, but not movement competency in young male athletes

Movement competency and measures of isometric and dynamic strength and power in boys of different maturity status

An understanding of how movement competency, strength, and power interacts with natural growth and maturation is required in order to determine meaningful changes with developing athletes. Isometric and dynamic testing in youth athletes provide insight into the natural development of the force‐velocity (F‐V) spectrum. Two‐hundred and six young male athletes, aged 9‐17 years of age were grouped according to stage of maturation based on their maturity offset which was determined as number of years from peak height velocity (PHV). All participants performed the back‐squat assessment (BSA), isometric mid‐thigh pull (IMTP), countermovement jump (CMJ) and squat jump (SJ) tests. Absolute and scaled force‐time variables were collected from the IMTP, CMJ, and SJ. No significant differences were observed between maturational groups for squat movement competency (p > 0.05). One‐way ANOVA with Bonferroni post‐hoc analysis revealed that increasing maturity led to significant, moderate to large increases in allometrically scaled peak force (PFallo) for all tests (p < 0.05). Multiple stepwise linear regression models revealed IMTP PFallo significantly predicted 34.8% and 41.3% of variance in SJ and CMJ jump height, respectively (p < 0.05). Natural growth and maturation induces positive adaptations to movement competency as well as isometric and dynamic strength and power. Trends from the IMTP, SJ, and CMJ tests indicate the largest differences in strength and power may occur around the adolescent growth spurt despite the large variation in rates of change within the circa‐PHV group

Developing a food exposure and urine sampling strategy for dietary exposure biomarker validation in free-living individuals

SCOPE: Dietary choices modulate the risk of chronic diseases and improving diet is a central component of public health strategies. Food-derived metabolites present in urine could provide objective biomarkers of dietary exposure. To assist biomarker validation we aimed to develop a food intervention strategy mimicking a typical annual diet over a short period of time and assessed urine sampling protocols potentially suitable for future deployment of biomarker technology in free-living populations. METHODS AND RESULTS: Six different menu plans representing comprehensively a typical UK annual diet that were split into two dietary experimental periods. Free-living adult participants (n = 15 and n = 36, respectively) were provided with all their food, as a series of menu plans, over a period of 3 consecutive days. Multiple spot urine samples were collected and stored at home. CONCLUSION: We established a successful food exposure strategy following a conventional UK eating pattern, which was suitable for biomarker validation in free-living individuals. The urine sampling procedure was acceptable for volunteers and delivered samples suitable for biomarker quantification. Our study design provides scope for validation of existing biomarker candidates and potentially for discovery of new biomarker-leads and should help inform the future deployment of biomarker technology for habitual dietary exposure measurement

Spot and Cumulative Urine Samples Are Suitable Replacements for 24-Hour Urine Collections for Objective Measures of Dietary Exposure in Adults Using Metabolite Biomarkers

BACKGROUND: Measurement of multiple food intake exposure biomarkers in urine may offer an objective method for monitoring diet. The potential of spot and cumulative urine samples that have reduced burden on participants as replacements for 24-h urine collections has not been evaluated. OBJECTIVE: The aim of this study was to determine the utility of spot and cumulative urine samples for classifying the metabolic profiles of people according to dietary intake when compared with 24-h urine collections in a controlled dietary intervention study. METHODS: Nineteen healthy individuals (10 male, 9 female, aged 21-65 y, BMI 20-35 kg/m2) each consumed 4 distinctly different diets, each for 1 wk. Spot urine samples were collected ∼2 h post meals on 3 intervention days/wk. Cumulative urine samples were collected daily over 3 separate temporal periods. A 24-h urine collection was created by combining the 3 cumulative urine samples. Urine samples were analyzed with metabolite fingerprinting by both high-resolution flow infusion electrospray mass spectrometry (FIE-HRMS) and proton nuclear magnetic resonance spectroscopy (1H-NMR). Concentrations of dietary intake biomarkers were measured with liquid chromatography triple quadrupole mass spectrometry and by integration of 1H-NMR data. RESULTS: Cross-validation modeling with 1H-NMR and FIE-HRMS data demonstrated the power of spot and cumulative urine samples in predicting dietary patterns in 24-h urine collections. Particularly, there was no significant loss of information when post-dinner (PD) spot or overnight cumulative samples were substituted for 24-h urine collections (classification accuracies of 0.891 and 0.938, respectively). Quantitative analysis of urine samples also demonstrated the relation between PD spot samples and 24-h urines for dietary exposure biomarkers. CONCLUSIONS: We conclude that PD spot urine samples are suitable replacements for 24-h urine collections. Alternatively, cumulative samples collected overnight predict similarly to 24-h urine samples and have a lower collection burden for participants

A Standardized Strategy for Simultaneous Quantification of Urine Metabolites to Validate Development of a Biomarker Panel Allowing Comprehensive Assessment of Dietary Exposure

SCOPE: Metabolites derived from individual foods found in human biofluids after consumption could provide objective measures of dietary intake. For comprehensive dietary assessment, quantification methods would need to manage the structurally diverse mixture of target metabolites present at a wide concentration range. METHODS & RESULTS: We developed a strategy for selection of candidate dietary exposure biomarkers, providing comprehensive coverage. An analytical method for 62 food biomarkers was validated by extensive analysis of chromatographic and ionization behaviour characteristics using triple quadrupole mass spectrometry. We used urine samples from two food intervention studies: one controlled, inpatient study (n = 19) and the other a free-living study where individuals (n = 15) were provided with food as a series of menu plans. As proof-of-principle, we demonstrated that the biomarker panel could discriminate between menu plans by detecting distinctive changes in the concentration in urine of targeted metabolites. We showed quantitative relationships between four biomarker concentrations in urine and dietary intake. CONCLUSIONS: We have demonstrated design concepts for an analytical strategy allowing simultaneous quantification of a comprehensive panel of chemically-diverse biomarkers of a wide range of commonly-consumed foods. We propose that integration of self-reported dietary recording tools with biomarker approaches will provide more robust assessment of dietary exposure. This article is protected by copyright. All rights reserved