Effects of Tea on Peripheral and Cerebral Micro- and Macrovascular Function in Humans

Cardiovascular disease (CVD) is the leading cause of global mortality, with the incidence of cardiovascular related pathologies remaining a public health burden. CVD encompasses pathologies of the vascular tree and heart, including, for example, peripheral artery disease, coronary heart disease and ischaemic stroke. Atherosclerosis is the primary pathological process leading to CVD and is characterised by a multifactorial pathophysiology that first manifests in the vascular endothelium. Termed endothelial dysfunction, this early marker of atherosclerosis has become a focus of interest for identifying individuals at risk of a profound cardiovascular insult, particularly arising from lifestyle choices such as physical inactivity and calorie-rich diets. Dietary interventions have received increasing attention in recent years as inexpensive strategies to potentially combat the ever-increasing global burden of CVD. A high dietary flavonoid intake is associated with a reduction in CVD risk and several studies have revealed a strong, inverse relation between the regular intake of tea, a major source of dietary flavonoids, and CVD risk. Tea has demonstrated improved conduit artery endothelial function and glucose handling in both healthy individuals and in those with overt CVD. However, the effects of tea on the microvasculature and cerebrovasculature are not yet understood, particularly in relation to lifestyle factors. The primary aim of this thesis was to explore the impact of tea ingestion on peripheral and cerebral micro- and macrovascular function in humans. In an initial methodological study, the day-to-day reproducibility of thermally stimulated cutaneous microvascular function was assessed. Fifteen, healthy males (28 ± 5 yrs, BMI 25 ± 2 kg/m2) attended two experimental trials 2-7 days apart. During each trial, baseline and maximal thermally stimulated forearm skin responses were examined simultaneously at four sites on the dominant forearm using laser Doppler flowmetry (LDF). The following heating protocols were adopted: 1. Rapid 39°C (0.5°C/5-s), 2. Rapid 42°C (0.5°C/5-s) 3. Gradual 42°C (0.5°C/2-min 30-s) and 4. Slow 42°C (0.5°C/5-min). The coefficient of variation (CV) was calculated for absolute flux, cutaneous vascular conductance (CVC; flux/mean arterial pressure, MAP) and CVC expressed as a percentage of maximal CVC at 44°C (%CVCmax) at three different time points; baseline (33°C), plateau (39/42°C) and maximal (44°C). Reproducibility of baseline flux, CVC and %CVCmax was 17-29% across all protocols. During the plateau, Rapid, Gradual and Slow 42°C demonstrated a reproducibility of 13-18% for flux and CVC and 5-11% for %CVCmax. However, Rapid 39°C demonstrated a lower reproducibility for flux, CVC and %CVCmax (21%). Reproducibility at 44°C was 12-15% for flux and CVC across all protocols. The good-to-moderate reproducibility of the Rapid, Gradual and Slow 42°C protocols supported their (simultaneous) use to assess peripheral microvascular function. The aim of Chapter 5 was to examine the acute (2-hour) cutaneous vascular responses to local skin heating following ingestion of black tea in a healthy adult population. Twenty healthy participants (58 ± 5 yrs, BMI 26 ± 4 kg/m2, 9 men) attended two experimental trials (tea, placebo), 7-days apart in a randomised, controlled, double-blind, cross-over design. Participants ingested a single dose of 200 ml black tea or placebo, followed by assessment of forearm cutaneous microvascular function using LDF and three distinct local skin heating protocols to distinguish between axon- and endothelium-dependent vasodilation: 1. Rapid 42°C, 2. Rapid 39°C and 3. Gradual 42°C. On the contralateral arm, full-field laser perfusion imaging (FLPI) was used to assess forearm cutaneous microvascular function during Gradual 42°C. Data were analysed as CVC and %CVCmax. Rapid local heating to 39°C or 42°C demonstrated no effect of tea for flux, CVC or %CVCmax (all P>0.05). Gradual local heating to 42°C, however, produced a higher skin blood flow following black tea ingestion for absolute CVC (P=0.04) when measured by LDF, and higher absolute flux (P0.05). MAP was increased after UL-Placebo, whereas it was reduced after UL-Tea (P=0.06). LDF responses to rapid local heating demonstrated non-significant reductions in CVC following UL-Placebo but no difference following UL-Tea (P>0.05), with a significant interaction of time*condition*temperature observed following Gradual 42°C (P=0.02). Brachial artery FMD was not different pre vs post or between UL-Placebo and UL-Tea (P>0.05), whereas femoral artery FMD decreased after UL-Placebo, which was prevented during UL-Tea (P0.05). There were no differences in the cerebrovascular responses to CO2 or dynamic autoregulation between (-)-epicatechin and placebo. The findings from this thesis suggest that, firstly, use of simultaneous skin local heating protocols provides a valuable means of interrogating the cutaneous microvessels for mechanistic insight in intervention studies. Secondly, current findings evidence improved cutaneous microvascular function following acute black tea consumption. Furthermore, the research work undertaken in this thesis provides important insight into the effects of tea consumption on peripheral (micro- and macro-) vascular function and insulin sensitivity, particularly its abrogative effects on lifestyle-induced vascular impairments. However, the effects of tea consumption on the cerebrovasculature remain uncertain. Overall, based on the current findings, tea consumption presents a simple, inexpensive, non-pharmacological cardioprotective strategy to help combat the ever-increasing global burden of CVD

The Self-Efficacy for Therapeutic Use of Self Questionnaire (SETUS): psychometric properties of the English version

Purpose The purpose of this paper is to investigate psychometric properties of the Self-Efficacy for Therapeutic Use of Self (SETUS) scales, a questionnaire based on the Intentional Relationship model, and to investigate the factor structure and internal consistency of the English version of three-part SETUS questionnaire in occupational therapy students. Design/methodology/approach The sample of this cross-sectional study included 155 students with age range 18–30 years, of which 95% were women. Principal Components Analysis (PCA) was performed on the questionnaire scales, including the Self-Efficacy for Therapeutic Mode Use (SETMU), Self-Efficacy for Recognizing Interpersonal Characteristics (SERIC) and Self-Efficacy for Managing Interpersonal Events (SEMIE). The internal consistencies were calculated. Pearson correlation analysis was used to evaluate the strength of correlation among the scales. Findings The PCA confirmed that the items of each of the three proposed scales loaded strongly on one factor (self-efficacy for three factors of therapeutic mode use, recognizing interpersonal characteristics and managing interpersonal events). The Cronbach’s alpha for the SETMU, SERIC and SEMIE was 0.85, 0.95 and 0.96, respectively. The three scales significantly inter-correlated strongly (r ranging 0.74–0.83, all p < 0.001). Originality/value The SETUS questionnaire comprises three valid and reliable scales. It can be used by occupational therapy supervisors as a means to reflect on students’ self-efficacy in components of therapeutic use of self.publishedVersio

Fetal Sex and RHD Genotyping with Digital PCR Demonstrates Greater Sensitivity than Real-time PCR.

BACKGROUND: Noninvasive genotyping of fetal RHD (Rh blood group, D antigen) can prevent the unnecessary administration of prophylactic anti-D to women carrying RHD-negative fetuses. We evaluated laboratory methods for such genotyping. METHODS: Blood samples were collected in EDTA tubes and Streck® Cell-Free DNA™ blood collection tubes (Streck BCTs) from RHD-negative women (n = 46). Using Y-specific and RHD-specific targets, we investigated variation in the cell-free fetal DNA (cffDNA) fraction and determined the sensitivity achieved for optimal and suboptimal samples with a novel Droplet Digital™ PCR (ddPCR) platform compared with real-time quantitative PCR (qPCR). RESULTS: The cffDNA fraction was significantly larger for samples collected in Streck BCTs compared with samples collected in EDTA tubes (P < 0.001). In samples expressing optimal cffDNA fractions (≥4%), both qPCR and digital PCR (dPCR) showed 100% sensitivity for the TSPY1 (testis-specific protein, Y-linked 1) and RHD7 (RHD exon 7) assays. Although dPCR also had 100% sensitivity for RHD5 (RHD exon 5), qPCR had reduced sensitivity (83%) for this target. For samples expressing suboptimal cffDNA fractions (<2%), dPCR achieved 100% sensitivity for all assays, whereas qPCR achieved 100% sensitivity only for the TSPY1 (multicopy target) assay. CONCLUSIONS: qPCR was not found to be an effective tool for RHD genotyping in suboptimal samples (<2% cffDNA). However, when testing the same suboptimal samples on the same day by dPCR, 100% sensitivity was achieved for both fetal sex determination and RHD genotyping. Use of dPCR for identification of fetal specific markers can reduce the occurrence of false-negative and inconclusive results, particularly when samples express high levels of background maternal cell-free DNA

Attitudes towards the use and acceptance of eHealth technologies : a case study of older adults living with chronic pain and implications for rural healthcare

Acknowledgements The research described here is supported by the award made by the RCUK Digital Economy programme to the dot.rural Digital Economy Hub; award reference: EP/G066051/1. MC’s time writing the paper is funded by the Scottish Government’s Rural and Environmental Science and Analytical Services Division (RESAS) under Theme 8 ‘Vibrant Rural Communities’ of the Food, Land and People Programme (2011–2016). MC is also an Honorary Research Fellow at the Division of Applied Health Sciences, University of Aberdeen. The input of other members of the TOPS research team, Alastair Mort, Fiona Williams, Sophie Corbett, Phil Wilson and Paul MacNamee who contributed to be wider study and discussed preliminary findings reported here with the authors of the paper is acknowledged. We acknowledge the feedback on earlier versions of this paper provided by members of the Trans-Atlantic Rural Research Network, especially Stefanie Doebler and Carmen Hubbard. We also thank Deb Roberts for her comments.Peer reviewedPublisher PD

Reproducibility of four frequently used local heating protocols to assess cutaneous microvascular function.

BACKGROUND: Skin microvascular responses to local heating are frequently used to assess microvascular function. Several local heating protocols have been developed, all varying slightly in execution. The aim of this study was to determine the inter-day reproducibility of the four most commonly used local heating protocols in healthy young subjects. METHODS: Fifteen, healthy males (28±5yrs, BMI 25±2kg/m(2)) attended two experimental trials 2-7days apart. During each trial, baseline and maximal thermally stimulated forearm skin responses were examined simultaneously at four sites on the dominant forearm using laser Doppler flowmetry (LDF). The following heating protocols were adopted: 1. Rapid 39°C (0.5°C/5s), 2. Rapid 42°C (0.5°C/5s) 3. Gradual 42°C (0.5°C/2min 30s) and 4. Slow 42°C (0.5°C/5min). The coefficient of variation (CV) was calculated for absolute flux, cutaneous vascular conductance (CVC; flux/mean arterial pressure, MAP) and CVC expressed as a percentage of maximal CVC at 44°C (%CVCmax) at three different time points; baseline (33°C), plateau (39/42°C) and maximal (44°C). RESULTS: Reproducibility of baseline flux, CVC and %CVCmax was 17-29% across all protocols. During the plateau, Rapid, Gradual and Slow 42°C demonstrated a reproducibility of 13-18% for flux and CVC and 5-11% for %CVCmax. However, Rapid 39°C demonstrated a lower reproducibility for flux, CVC and %CVCmax (all 21%). Reproducibility at 44°C was 12-15% for flux and CVC across all protocols. CONCLUSION: This is the first study examining inter-day reproducibility across four local heating protocols. The good-to-moderate reproducibility of the Rapid, Gradual and Slow 42°C protocols support their (simultaneous) use to assess microvascular function. Using Rapid 39°C may require a greater number of subjects to detect differences within subjects

New 10Be exposure ages improve Holocene ice sheet thinning history near the grounding line of Pope Glacier, Antarctica

Evidence for the timing and pace of past grounding line retreat of the Thwaites Glacier system in the Amundsen Sea embayment (ASE) of Antarctica provides constraints for models that are used to predict the future trajectory of the West Antarctic Ice Sheet (WAIS). Existing cosmogenic nuclide surface exposure ages suggest that Pope Glacier, a former tributary of Thwaites Glacier, experienced rapid thinning in the early to mid-Holocene. There are relatively few exposure ages from the lower ice-free sections of Mount Murphy (< 300 m asl) that are uncomplicated by either nuclide inheritance or scattering due to localised topographic complexities; this makes the trajectory for the latter stages of deglaciation uncertain. This paper presents 12 new 10Be exposure ages from erratic cobbles collected from the western flank of Mt Murphy, within 160 m of the modern ice surface and 1 km from the present grounding line. The ages comprise two tightly clustered populations with mean deglaciation ages of 7.1 ± 0.1 ka and 6.4 ± 0.1 ka (1SE). Linear regression analysis applied to the age-elevation array of all available exposure ages from Mt Murphy indicates that the median rate of thinning of Pope Glacier was 0.27 m yr-1 between 8.1–6.3 ka, occurring 1.5 times faster than previously thought. Furthermore, this analysis better constrains the uncertainty (95 % confidence interval) in the timing of deglaciation at the base of the Mt Murphy vertical profile (~80 m above the modern ice surface), shifting it to earlier in the Holocene (from 5.2 ± 0.7 ka to 6.3 ± 0.4 ka). Taken together, the results presented here suggest that early–mid Holocene thinning of Pope Glacier occurred over a shorter interval than previously assumed and permit a longer duration over which subsequent late Holocene rethickening could have occurred

Local radio to promote mental health awareness: a public health initiative.

BACKGROUND: Public health strategies have focused largely on physical health. However, there is increasing recognition that raising mental health awareness and tackling stigma is crucial to reduce disease burden. National campaigns have had some success but tackling issues locally is particularly important. AIMS: To assess the public's awareness and perception of the monthly BBC Cornwall mental health phone-in programmes that have run for 8.5 years in Cornwall, UK (population 530 000). METHOD: A consultation, review and feedback process involving a multiagency forum of mental and public health professionals, people with lived experience and local National Health Service trust's media team was used to develop a brief questionnaire. This was offered to all attendees at two local pharmacies covering populations of 27 000 over a 2-week period. RESULTS: In total, 14% (95% CI 11.9-16.5) were aware of the radio show, 11% (95% CI 9.0-13.1) have listened and the majority (76%) of those who listened did so more than once. The estimated reach is 70 000 people in the local population, of whom approximately 60 000 listen regularly. The show is highly valued among respondents with modal and median scores of 4 out of 5. CONCLUSIONS: Local radio is a successful, cost-effective and impactful way to reach a significant proportion of the population and likely to raise awareness, reduce stigma and be well received. The format has been adopted in other regions thus demonstrating easy transferability. It could form an essential part of a public health strategy to improve a population's mental well-being. DECLARATION OF INTEREST: W.H. received support from the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) for the South West Peninsula UK. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. L.R. and D.S. were involved in delivering the programmes but had no role in their evaluation

The self-efficacy for therapeutic use of self-questionnaire (SETUS): Psychometric properties of the English version

Purpose. The purpose of this paper is to investigate psychometric properties of the Self-Efficacy for Therapeutic Use of Self (SETUS) scales, a questionnaire based on the Intentional Relationship model, and to investigate the factor structure and internal consistency of the English version of three-part SETUS questionnaire in occupational therapy students. Design/methodology/approach. The sample of this cross-sectional study included 155 students with age range 18–30 years, of which 95% were women. Principal Components Analysis (PCA) was performed on the questionnaire scales, including the Self-Efficacy for Therapeutic Mode Use (SETMU), Self-Efficacy for Recognizing Interpersonal Characteristics (SERIC) and Self-Efficacy for Managing Interpersonal Events (SEMIE). The internal consistencies were calculated. Pearson correlation analysis was used to evaluate the strength of correlation among the scales. Findings. The PCA confirmed that the items of each of the three proposed scales loaded strongly on one factor (self-efficacy for three factors of therapeutic mode use, recognizing interpersonal characteristics and managing interpersonal events). The Cronbach’s alpha for the SETMU, SERIC and SEMIE was 0.85, 0.95 and 0.96, respectively. The three scales significantly inter-correlated strongly (r ranging 0.74–0.83, all p < 0.001). Originality/value. The SETUS questionnaire comprises three valid and reliable scales. It can be used by occupational therapy supervisors as a means to reflect on students’ self-efficacy in components of therapeutic use of self