The application of near infrared spectroscopy in nutritional intervention studies

Functional near infrared spectroscopy (NIRS) is a non-invasive optical imaging technique used to monitor cerebral blood flow (CBF) and by proxy neuronal activation. The use of NIRS in nutritional intervention studies is a relatively novel application of this technique, with only a small, but growing, number of trials published to date. These trials—in which the effects on CBF following administration of dietary components such as caffeine, polyphenols and omega-3 polyunsaturated fatty acids are assessed—have successfully demonstrated NIRS as a sensitive measure of change in hemodynamic response during cognitive tasks in both acute and chronic treatment intervention paradigms. The existent research in this area has been limited by the constraints of the technique itself however advancements in the measurement technology, paired with studies endeavoring increased sophistication in number and locations of channels over the head should render the use of NIRS in nutritional interventions particularly valuable in advancing our understanding of the effects of nutrients and dietary components on the brain

The development of clothing concepts in response to analysis of changing gendered social attitudes

The relationship of gender and clothing were widely discussed by theorists, and fashion collections illustrated this thinking. This study aimed to address one area of this relationship, by conducting practice-based research to develop garments for women who wear men’s clothing. The study responds to real insights from the women themselves through qualitative interviews. This study aimed to understand why women choose to wear men’s clothing and to use this to question gender assignment in clothing, in order to develop design concepts for the development of clothing for this specific group of women. This interdisciplinary practice-based study combined phenomenological thinking and practice with theory to engage more deeply with why women choose to wear men’s clothing. The Victorian square cut shirt became pivotal to the process of design and accorded with preferences for large shapes and interesting proportion. The Pit brow study highlighted how historical gender roles can aid in the understanding of gendered clothing now. Surveys asking about the gendered perception of clothing on and off the body found significantly that clothing is perceived differently when not on a body. Qualitative interviews were conducted with 10 women answering a call for women who wear men’s clothing. Experimental design concepts were developed though combining, research inputs and an output culminating in a selection of garments was produced. The practice found that space between the body and clothing provides feelings of well-being, through comfort, space and coverage of the body. This study contributes to knowledge of garment design practice, by recording and analysing the complex thinking behind garment design for women who wear men’s clothing for fashion. Experimental responsive making, can create new and effective design methods through an intra-active relationship with fabric and an openness to the haphazard. The process of research and design combined with theory has defined preferences for the development of clothing for the group of women. The conceptual model, Women’s clothing preferences. Wellbeing in relation to gender and body image, records the final preferences and is a resource for future use for the design of clothing for all people. Gender assignment in clothing from the perspective of the viewer was found to be variable and influenced by personal and situational aspects, which were 4 | P a g e changeable. For the women participants, gendered clothing for the wearer, was found to be selected primarily by merit of wear properties. Women who wear men’s clothing do not wish to be defined by their gendered body, but by a sense of who they are

DHA-rich oil modulates the cerebral haemodynamic response to cognitive tasks in healthy young adults: a near IR spectroscopy pilot study

The impact of dietary n-3 PUFA on behavioural outcomes has been widely researched; however, very little attention has been given to their impact on brain functioning in physiological terms. A total of twenty-two healthy adults took part in this double-blind, placebo-controlled study, wherein the cerebral haemodynamic effects of 12 weeks of daily dietary supplementation with either 1 g DHA-rich or 1 g EPA-rich fish oil (FO) or placebo (1 g olive oil) were assessed. Relative changes in the concentration of oxygenated Hb (oxy-Hb) and deoxygenated Hb were assessed in the prefrontal cortex using near IR spectroscopy (NIRS) during the performance of four computerised cognitive tasks. Supplementation with DHA-rich FO, in comparison with placebo, resulted in a significant increase in the concentrations of oxy-Hb and total levels of Hb, indicative of increased cerebral blood flow (CBF), during the cognitive tasks. In comparison, no effect on CBF was observed following supplementation with EPA-rich FO, where concentration changes in the chromophores followed the same pattern as placebo. These encouraging pilot data warrant further application of NIRS in this area

Biobehavioural and cerebral hemodynamic effects of omega-3 polyunsaturated fatty acids in healthy individuals

The omega-3 polyunsaturated fatty acids (n-3 PUFAs) are a unique class of fatty acids that cannot be manufactured by the body, and must be acquired via dietary sources. In the UK, as well as in other Western nations, these ‘essential’ fatty acids are consumed in quantities that fall below government guidelines. This thesis examined the relationship between n-3 PUFAs and cognitive function and mood in healthy children (8-10 years) and adults (18-35 years), with a view to evaluate their efficacy for cognitive and mood enhancement in these populations. A second aim was to evaluate the effects of n-3 PUFAs on cerebral hemodynamics, a novel line of enquiry. Chapters 2 and 4 describe novel intervention studies that assessed the effects of n- 3 PUFA supplements on cognitive function and mood in healthy children and adults, respectively. In Chapter 3, the relationship between peripheral PUFA concentrations, a correlate of dietary PUFA intake, and cognitive and function and mood was examined for the first time in healthy adults. Chapter 5 describes a pilot trial in which Near Infrared Spectroscopy (NIRS) imaging technique was applied to investigate the cerebral hemodynamic effects of n-3 PUFA supplements. The results of this study were explored in more detail in Chapter 6, with the additional inclusion of parallel cognitive measures. Most notably, the behavioural data from the intervention studies described herein do not support the use of n-3 PUFA supplements for cognitive and mood enhancement in healthy children and adults not consuming appreciable amounts of oily fish. However, the results do suggest that supplementation with dietary n-3 PUFAs has an impact on peripheral fatty acid status and cerebral hemodynamics in healthy adults. Taken together, these findings suggest that, in healthy, cognitively intact individuals, short-term use of n-3 PUFA supplements has a minimal effect on behaviour; the impact of long-term n-3 PUFA dietary intake or supplement use over the course of the entire lifespan on behaviour should be addressed further

Investigating the role of DNA methylation in pluripotency and differentiation using an embryoid body model

Epigenetics is the study of heritable alterations in phenotype caused by changes in cellular properties, but where the genotype is unchanged. At the molecular level these changes include chemical modifications of DNA and histones in chromatin. Specific chromatin states are associated with gene activity or silencing. The proper functioning of these mechanisms is critical for mammalian survival, particularly during embryonic development. One of the best studied epigenetic modifications is DNA methylation, wherein methyl-groups are placed on cytosines in CpG dinucleotide contexts by DNA methyltransferases to form 5mC. The malfunction of this mechanism is associated with failure of embryogenesis and many adult human disease pathologies, including cancer. However, questions remain about how the 5mC patterns are established de novo, how the patterns can change between different cell types, and why some cell types can tolerate the absence of 5mC but not others. Genetic removal of the de novo (Dnmt3a and Dnmt3b) or maintenance methyltransferases (Dnmt1) in somatic cells can lead to cell death. However, mouse embryonic stem cells (ESCs) can proliferate normally in the absence of all three of these proteins. This suggests that DNA methylation becomes essential at some point after the cells exit pluripotency and begin differentiation. Being able to identify this window of time during development is important for better understanding the dynamics of recruitment of these proteins and deposition of the mark and could therefore provide insight into how their misregulation contributes to disease. In this thesis I investigate the role of DNA methylation during ESC differentiation using a combination of conditional and reporter cell lines, in vitro differentiation models, RNA sequencing, genetic engineering, and high-resolution imaging. The ESC lines include those in which i) the expression of Dnmt1 and key pluripotency genes can be tuned separately and in combination, ii) contain germ layer differentiation reporters, and iii) contain reporters of 5mC distribution. I allow these cells to differentiate to form embryoid bodies (EBs), a validated embryogenesis-like model that enables simulation of the pluripotent-to-differentiated transition in vitro. By combining these approaches, I was able to investigate the impact of loss of Dnmt1 on gene expression pathways including apoptosis, primordial germ cell (PGC) and 2C-like cell formation, germ layer differentiation, and changes in transposable element expression. I was also able to delineate differentiation trajectories by comparing my bulk RNA sequencing data with published single cell RNA sequencing data. Overall, I observed that inhibition of Dnmt1 activity consistently led to a significant reduction in EB size though germ layer differentiation was still able to occur. Likewise, EBs were still able to form in the absence of master pluripotency factor Oct4, although to a reduced capacity. Loss of both proteins led to smaller EBs than the wild type. Interestingly Oct4-/-, Dnmt1+/+ EBs were the most affected. There were no significant changes in frequency of apoptotic cells, and only LTR-family transposable elements were de-repressed. By comparing data, I was able to identify that loss of Dnmt1 enriched EBs for PGC-like cell marker genes at late stages of differentiation. I conclude that under normal differentiation initiation conditions the two systems, the pluripotency network and the DNA methylation network, work synergistically to control the gradual switch of cells from the pluripotent to the differentiated state enabling the formation of a limited population of PGC-like cells prior to advanced differentiation of germ layer cell lineages. The purpose of this may be to protect emerging PGC-like cells from Transposon Element activity. It may also be to allow the number of pluripotent cells to reach a threshold level prior to initiating differentiation to prevent the EB size being limited in a mechanism similar to that suggested for primordial dwarfism

Acute and Chronic Effects of Green Oat (Avena sativa) Extract on Cognitive Function and Mood during a Laboratory Stressor in Healthy Adults: A Randomised, Double-Blind, Placebo-Controlled Study in Healthy Humans

Green oat (Avena sativa) extracts contain several groups of potentially psychoactive phytochemicals. Previous research has demonstrated improvements in cognitive function following a single dose of these extracts, but not following chronic supplementation. Additionally, whilst green oat extracts contain phytochemicals that may improve mood or protect against stress, for instance species-specific triterpene saponins, to date this possibility has not been examined. The current study investigated the effects of a single dose and four weeks of administration of a novel, Avena sativa herbal extract (cognitaven®) on cognitive function and mood, and changes in psychological state during a laboratory stressor. The study adopted a dose-ranging, double-blind, randomised, parallel groups design in which 132 healthy males and females (35 to 65 years) received either 430 mg, 860 mg, 1290 mg green oat extract or placebo for 29 days. Assessments of cognitive function, mood and changes in psychological state during a laboratory stressor (Observed Multitasking Stressor) were undertaken pre-dose and at 2 h and 4 h post-dose on the first (Day 1) and last days (Day 29) of supplementation. The results showed that both a single dose of 1290 mg and, to a greater extent, supplementation for four weeks with both 430 mg and 1290 mg green oat extract resulted in significantly improved performance on a computerised version of the Corsi Blocks working memory task and a multitasking task (verbal serial subtractions and computerised tracking) in comparison to placebo. After four weeks, the highest dose also decreased the physiological response to the stressor in terms of electrodermal activity. There were no treatment-related effects on mood. These results confirm the acute cognitive effects of Avena sativa extracts and are the first to demonstrate that chronic supplementation can benefit cognitive function and modulate the physiological response to a stressor

Diurnal rhythm of plasma EPA and DHA in healthy adults

Knowledge of the diurnal variation in circulating omega-3 polyunsaturated fatty acids (n-3 PUFAs) may be an important consideration for the development of dosing protocols designed to optimise tissue delivery of these fatty acids. The objective of the current study was to examine the variation in plasma concentrations of eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3) over a 24-h period in healthy adults under eating and sleeping conditions generally approximate to a free-living environment. Twenty-one healthy participants aged 25–44 years took part in a single laboratory visit encompassing an overnight stay. EPA and DHA were measured in plasma samples collected every two hours from 22:00 until 22:00 the following day, with all meals being provided at conventional times. Cosinor analysis was used to estimate the diurnal variation in each fatty acid from pooled data across all participants. A significant diurnal variation in the pooled plasma concentrations of both fatty acids was detected. However, evidence of distinct rhythmicity was strongest for DHA. The timing of the peak concentration of DHA was 17:43 with a corresponding nadir at 05:43. In comparison, the observed acrophase for EPA was delayed by three hours, occurring at 20:41, with a nadir at 08:41. This is the first time that the diurnal variation in these important bioactive fatty acids has been described in a sample of healthy adults following a normal pattern of eating and sleeping. In the absence of any dietary intake of EPA and DHA, circulating levels of these fatty acids fall during the overnight period and reach their lowest point in the morning. Consumption of n-3 PUFAs at night time, which counteracts this pattern, may have functional significance

Acute and chronic effects of multivitamin/mineral supplementation on objective and subjective energy measures

Background: Vitamins and minerals play an essential role within many cellular processes including energy production and metabolism. Previously, supplementation with a multivitamin/mineral (MVM) for ≥28 days resulted in improvements to cognition and subjective state. We have also demonstrated shifts in metabolism during cognitively demanding tasks following MVM in females, both acutely and following 8-week supplementation. The current study aimed to assess these effects further in males and females using metabolically challenging exercise and cognitive tasks. Methods: The current randomised, placebo-controlled, parallel groups study investigated the effects of a MVM complex in 82 healthy young (18-35y) exercisers. Subjective ratings and substrate metabolism were assessed during 30 min each of increasingly effortful incremental exercise and demanding cognitive tasks. Assessments took place on acute study days following a single dose (Day 1) of MVM, containing 3 times recommended daily allowance of water-soluble vitamins plus CoQ10, and following 4-week supplementation (Day 28). Results: Energy expenditure (EE) was increased during cognitive tasks following MVM across Day 1 and Day 28, with greater effects in males. In males, MVM also increased carbohydrate oxidation and energy expenditure during exercise across Day 1 and Day 28. In females, mental tiredness was lower during exercise; increases in physical tiredness following 30 min of exercise were attenuated; and stress ratings following cognitive tasks were reduced following MVM. In males, MVM only lowered mental tiredness following 10 min of exercise. These effects were apparent irrespective of day, but effects on mental tiredness were greater on Day 28. Ferritin levels were also higher on Day 28 in those receiving MVM. Conclusion: These findings extend on existing knowledge, demonstrating increased carbohydrate oxidation and increased energy expenditure in males following MVM supplementation for the first time. Importantly, they show modulation of energy expenditure and subjective tiredness following a single dose, providing further evidence for acute effects of MVM. Differential effects in men and women suggest that sex may play an important role in the effects of MVM on energy metabolism and should be considered in future research. Trial registration: ClinicalTrials.gov, NCT03003442. Registered 22nd November 2016 – retrospectively registere

Biobehavioural and cerebral hemodynamic effects of omega-3 polyunsaturated fatty acids in healthy individuals

The omega-3 polyunsaturated fatty acids (n-3 PUFAs) are a unique class of fatty acids that cannot be manufactured by the body, and must be acquired via dietary sources. In the UK, as well as in other Western nations, these ‘essential’ fatty acids are consumed in quantities that fall below government guidelines. This thesis examined the relationship between n-3 PUFAs and cognitive function and mood in healthy children (8-10 years) and adults (18-35 years), with a view to evaluate their efficacy for cognitive and mood enhancement in these populations. A second aim was to evaluate the effects of n-3 PUFAs on cerebral hemodynamics, a novel line of enquiry. Chapters 2 and 4 describe novel intervention studies that assessed the effects of n- 3 PUFA supplements on cognitive function and mood in healthy children and adults, respectively. In Chapter 3, the relationship between peripheral PUFA concentrations, a correlate of dietary PUFA intake, and cognitive and function and mood was examined for the first time in healthy adults. Chapter 5 describes a pilot trial in which Near Infrared Spectroscopy (NIRS) imaging technique was applied to investigate the cerebral hemodynamic effects of n-3 PUFA supplements. The results of this study were explored in more detail in Chapter 6, with the additional inclusion of parallel cognitive measures. Most notably, the behavioural data from the intervention studies described herein do not support the use of n-3 PUFA supplements for cognitive and mood enhancement in healthy children and adults not consuming appreciable amounts of oily fish. However, the results do suggest that supplementation with dietary n-3 PUFAs has an impact on peripheral fatty acid status and cerebral hemodynamics in healthy adults. Taken together, these findings suggest that, in healthy, cognitively intact individuals, short-term use of n-3 PUFA supplements has a minimal effect on behaviour; the impact of long-term n-3 PUFA dietary intake or supplement use over the course of the entire lifespan on behaviour should be addressed further.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

The Acute and Chronic Cognitive and Cerebral Blood-Flow Effects of Nepalese Pepper (Zanthoxylum armatum DC.) Extract—A Randomized, Double-Blind, Placebo-Controlled Study in Healthy Humans

Background: Zanthoxylum armatum DC. (ZA) is a traditional Asian culinary spice and medicinal compound, which is rich in monoterpenes and hydroxy α-sanshool. Mechanistic interactions with the monoamine, cholinergic and cannabinoid neurotransmission systems, as well as transient receptor potential (TRP) and potassium ion channels, may predispose ZA to modulate human brain function. Objectives: To investigate the effects of a single dose and 56-days supplementation with a lipid extract of ZA on cognitive function, mood and cerebral blood-flow (CBF) parameters in the pre-frontal cortex during cognitive task performance. Design: Double-blind, randomized, parallel groups study with N = 82 healthy males and females between the ages of 30 and 55 years. Assessments were undertaken pre-dose and at 1, 3 and 5 hours post-dose on the first (Day 1) and last (Day 56) days of supplementation. Results: A single dose of ZA (Day 1) resulted in acute improvements on a ‘Speed of Attention’ factor and the Rapid Visual Information Processing (RVIP) task, in comparison to placebo. However, following ZA participants were less accurate on the name-to-face recall task. After 56 days of ZA consumption (Day 56), speed was enhanced on a global ‘Speed of Performance’ measure, comprising data from all of the timed tasks in the computerized battery. Participants also completed more correct Serial 3s Subtractions at the 3 hours assessment and were less mentally fatigued throughout the day than participants consuming placebo. These effects were complemented on both Day 1 and Day 56 by modulation of CBF parameters, as assessed by Near Infrared Spectroscopy (NIRS). The primary finding here was a reduced hemodynamic response during the RVIP task. Conclusion: ZA improves aspects of cognitive performance, in particular the speed of performing tasks, in healthy humans and results in concomitant reductions in hemodynamic responses in the frontal cortex during task performance. The findings suggest an increase in neural efficiency following ZA