An automated micro solid phase extraction gas chromatography-mass spectrometry (µSPE-GC-MS) detection method for geosmin and 2-methylisoborneol in drinking water.

Geosmin and 2-methylisoborneol (2-MIB) are amongst the most common earthy and musty taste and odour (T&O) compounds found in drinking water. With low odour threshold detection limits below 10 ng L-1, and the complexity of raw water matrices, these two compounds provide a significant challenge for water companies globally. In this research, for the first time, a novel and fully automated micro-solid phase-extraction (µSPE) method coupled with gas chromatography (GC)-mass spectrometry (MS) has been developed for the detection of geosmin and 2-MIB for drinking water analysis. The new automated method described herein is environmentally friendly requiring low raw water sample volumes, of 25 mL, and only 50 µL of elution solvent. Our µSPE-GC-MS method exhibits excellent linearity for both compounds (R2 > 0.999) and low limits of detection of 2.0 ng L-1 and 4.3 ng L-1 for geosmin and 2-MIB, respectively. The method showed excellent recovery rates (95.1-100.1%) and good precision (RSD < 7%) in raw sample matrices. Our approach is fully automated onto a robotic workstation which can be readily integrated into a laboratory workflow for routine water analysis. Furthermore, the method has excellent potential to be incorporated within a portable system for onsite analysis.

Carbohydrate quantity is more closely associated with glycaemic control than weight in pregnant women with type 1 diabetes: Insights from the Diabetes and Pre-eclampsia Intervention Trial (DAPIT).

BACKGROUND: The present study aimed to explore the relationships between carbohydrate intake, body mass index (BMI) and glycaemic control (HbA1c) in pregnant women with type 1 diabetes mellitus (T1DM) METHODS: Secondary analysis of data was undertaken to assess dietary intake in a cohort of women who participated in a randomised controlled trial (RCT) of antioxidant supplementation to prevent preeclampsia (DAPIT10 ). Study-specific peripheral venous blood samples were obtained for HbA1c at 26 and 34 weeks. Diet was collected using a validated semiquantitative food frequency questionnaire at 26-28 weeks of gestation which assessed dietary intake over 2 weeks. Mean daily average nutrient intakes were analysed using Q Builder nutritional software and SPSS, version 25. RESULTS: Dietary data were available for 547 pregnant women (72% of cohort) aged 29 years (95% confidence interval [CI] = 28.9-29.9) with average diabetes duration 11.8 years (95% confidence interval = 11.1-12.6). Average body mass index (BMI) (<16 weeks of gestation) was 26.7 kg/m2 (95% CI = 26.3 -27, range 18.8-45.6 kg/m2 ); 43% (n = 234) were overweight (BMI = 25.0-29.9 kg/m2 ) and 20% (n = 112) were obese (BMI ≥ 30 kg/m2 ). Differences in HbA1c and carbohydrate quantity and quality were found when adjusted for age and insulin dose. No differences between BMI group were observed for total carbohydrate and glycaemic control; however, differences were noted in fibre and glycaemic index. CONCLUSIONS: Average quantity of dietary carbohydrate influenced HbA1c when adjusted for insulin dose however, BMI had less impact. More research is required on the relationship between carbohydrate consumption and glycaemic control in pregnancy.

Clinical utility of ultrasonography-measured visceral adipose tissue depth as a tool in early pregnancy screening for gestational diabetes: a proof-of-concept study.

AIM: To examine, in a proof-of-concept study, the ability of visceral adipose tissue depth and subcutaneous fat depth measured in early pregnancy to predict subsequent gestational diabetes, and to assess the performance of these measures as screening tests for gestational diabetes compared with use of the current UK criteria. METHODS: A total of 100 women in early pregnancy were recruited from a maternity hospital in Belfast, UK. Visceral adipose tissue depth and subcutaneous fat depth were measured, and each participant underwent a 75-g oral glucose tolerance test at 28 weeks' gestation for the diagnosis of gestational diabetes using WHO 2013 criteria. RESULTS: Eighty women completed the study, of whom 15 (19%) developed gestational diabetes. Increasing visceral adipose tissue depth, but not subcutaneous fat depth, was associated with greater gestational diabetes risk after adjusting for confounding factors (odds ratio for a 1-sd rise 2.09, 95% CI 1.06-4.12; P=0.03). Visceral adipose tissue depth ≥4.27 cm had greater sensitivity compared with current National Institute of Health and Care Excellence criteria (87% vs 40%, respectively; P=0.02) and similar specificity (62% vs 74%, respectively; P=0.15) for identifying gestational diabetes. CONCLUSIONS: Ultrasonography-measured visceral adipose tissue in early pregnancy is a potential clinical tool for improving sensitivity of selective screening for gestational diabetes, which, compared with universal oral glucose tolerance testing, is likely to reduce by half the numbers requiring this test. Further larger studies are now required for confirmation, including investigation into impact on clinical outcomes.

Maternal vitamin D and markers of glycaemia during pregnancy in the Belfast centre of the Hyperglycaemia and Adverse Pregnancy Outcome study.

AIMS: To measure total 25-hydroxyvitamin D levels in women in mid-pregnancy who participated in the Belfast centre of the Hyperglycaemia and Adverse Pregnancy Outcome (HAPO) observational study, and to investigate the associations between levels of 25-hydroxyvitamin D and markers of gestational diabetes mellitus and lipid biomarkers. METHODS: A total of 1585 pregnant women had serum samples available for measurement. Participants were recruited from the Royal Jubilee Maternity Hospital, Belfast, Northern Ireland, at 24-32 weeks' gestation, as part of the HAPO study. 25-hydroxyvitamin D concentrations were measured using liquid chromatography tandem mass spectrometry. Glucose, C-peptide and lipid levels were previously analysed in a central laboratory. Statistical analysis was performed. RESULTS: The median (interquartile range) 25-hydroxyvitamin D concentration during pregnancy was 38.6 (24.1-60.7) nmol/l, with 65.8% of women being vitamin D-deficient (≤50 nmol/l). In regression analysis, the association between maternal 25-hydroxyvitamin D and fasting plasma glucose levels approached significance [regression coefficient -0.017 (95% CI -0.034 to 0.001); P=0.06], and a significant positive association was observed between maternal 25-hydroxyvitamin D and ß-cell function [1.013 (95% CI 1.001 to 1.024); P=0.031]. Maternal 25-hydroxyvitamin D level was positively associated with HDL [0.047 (95% CI 0.021 to 0.073) P≤ 0.001] and total cholesterol [0.085 (95% CI 0.002 to 0.167); P=0.044] in regression analysis. CONCLUSIONS: These results indicate a high prevalence of vitamin D deficiency during pregnancy, which requires identification and treatment; however, only weak associations were observed between 25-hydroxyvitamin D level and markers of glucose and insulin metabolism. This would suggest that these are of doubtful clinical significance.

Barriers to adopting a Mediterranean diet in Northern European adults at high risk of developing cardiovascular disease.

BACKGROUND: Strong evidence links the consumption of a Mediterranean diet (MD) with a reduced cardiovascular disease (CVD) risk; however, there is uncertainty as to whether non-Mediterranean regions will adopt this diet. The present qualitative research aimed to investigate attitudes towards a MD in individuals at high CVD risk in a Northern European population. This information is needed to inform development of MD interventions in non-Mediterranean high-risk populations. METHODS: Focus groups (n = 12) were held with individuals at high CVD risk from Northern Europe (≥2 CVD risk factors, aged ≥50 years, no established CVD/type 2 diabetes). Attitudes to dietary change towards a MD were explored. Data were analysed using inductive thematic analysis. RESULTS: Sixty-seven adults participated (60% female, mean age 64 years). There was some awareness of the term MD but limited knowledge of its composition. Barriers to general dietary change were evident, including perception of expense, concern over availability, expectation of time commitment, limited knowledge, lack of cooking skills, amount and conflicting nature of media information on diets, changing established eating habits and resistance to dietary change. Barriers specific to MD adoption were also identified, including perceived difficulty living in a colder climate, perceived impact on body weight, acceptability of a MD and cultural differences. CONCLUSIONS: Knowledge of a MD was limited in this Northern European sample at high CVD risk. In addition to general barriers to dietary change, barriers specific to a MD were identified. These findings have implications for the development of interventions aiming to promote MD adoption in non-Mediterranean populations.

Effect of pregnancy planning on maternal and neonatal outcomes in women with Type 1 diabetes.

AIMS: To assess the effect of pregnancy planning on maternal and neonatal outcomes in women with Type 1 diabetes. METHODS: Pregnancy planning was assessed retrospectively in a cohort of women who participated in the Diabetes and Pre-eclampsia Intervention Trial (DAPIT). Pregnancy planning was determined based on self-report as to whether pregnancy was planned or unplanned. The effect of pregnancy planning on maternal and neonatal outcomes was examined, controlling for confounding variables. RESULTS: A total of 747 women were included in the study, of whom 39% considered their pregnancy unplanned. Characteristics associated with unplanned pregnancy included being younger (P<0.001), being a current smoker (P<0.001), being from a lower social class (P<0.001) and having higher HbA1c values prior to and throughout pregnancy (P≤0.005). Significantly fewer women with unplanned vs planned pregnancies received pre-pregnancy counselling (24% vs 64%; P<0.001). Infants of women with unplanned pregnancies were more likely to be small for gestational age (<5th centile; P=0.004), to be admitted to the neonatal care unit (P=0.001) and to have a longer stay in hospital (P=0.01). Outcomes did not differ between the groups in relation to pre-eclampsia, congenital malformations or a composite adverse outcome. CONCLUSIONS: Risks associated with diabetes in pregnancy need to be highlighted to all women, their partners and families, and healthcare professionals. Further research is required to determine if these groups are fully aware of the risks associated with diabetes in pregnancy.

Evaluation of the predictive value of placental vascularisation indices derived from 3-Dimensional power Doppler whole placental volume scanning for prediction of pre-eclampsia: A systematic review and meta-analysis.

Pre-eclampsia remains a leading cause of maternal and fetal morbidity and mortality. This systematic review aims to evaluate the ability of placental vascularisation indices (PVIs) derived from 3D power Doppler whole placental volume scanning to predict early, late and any-onset pre-eclampsia (PE). The following databases were searched: MEDLINE, EMBASE and Web of Science. Studies selected for inclusion measured PVIs: Vascularisation Index (%) (VI) and/or Flow Index (FI) and/or Vascularisation Flow Index (VFI) derived from 3D power Doppler whole placental volume scanning via Virtual Organ Computer-aided Analysis (VOCAL) technique prior to diagnosis of PE. A total of 667 records were screened with five eligible studies included. A narrative review of all studies was undertaken and three studies with sufficient data were included in a meta-analysis. This review, the first of its kind to evaluate the predictive value of PVIs for PE, reports significantly lower first trimester PVIs across a range of studies in women who develop PE. Mean differences in vascularisation indices in PE and non-PE pregnancies were: VI -2.93% (95% CI -5.84,-0.01), FR -2.83 (95% CI -3.97,-1.69) and VFI -0.93 (95% CI -1.6,-0.25), respectively. While only two studies reported sensitivity and specificity data, VI and VFI most accurately predicted early onset PE, and VFI predicted PE in high risk women. Further research is required to validate these findings in different study populations and to examine the performance of PVIs within combined screening models for PE.

How much is '5-a-day'? A qualitative investigation into consumer understanding of fruit and vegetable intake guidelines.

BACKGROUND: Despite the known health benefits of fruit and vegetables (FV), population intakes remain low. One potential contributing factor may be a lack of understanding surrounding recommended intakes. The present study aimed to explore the understanding of FV intake guidelines among a sample of low FV consumers. METHODS: Six semi-structured focus groups were held with low FV consumers (n = 28, age range 19-55 years). Focus groups were recorded digitally, transcribed verbatim and analysed thematically using nvivo (QSR International, Melbourne, Australia) to manage the coded data. Participants also completed a short questionnaire assessing knowledge on FV intake guidelines. Descriptive statistics were used to analyse responses. RESULTS: The discussions highlighted that, although participants were aware of FV intake guidelines, they lacked clarity with regard to the meaning of the '5-a-day' message, including what foods are included in the guideline, as well as what constitutes a portion of FV. There was also a sense of confusion surrounding the concept of achieving variety with regard to FV intake. The sample highlighted a lack of previous education on FV portion sizes and put forward suggestions for improving knowledge, including increased information on food packaging and through health campaigns. Questionnaire findings were generally congruent with the qualitative findings, showing high awareness of the '5-a-day' message but a lack of knowledge surrounding FV portion sizes. CONCLUSIONS: Future public health campaigns should consider how best to address the gaps in knowledge identified in the present study, and incorporate evaluations that will allow the impact of future initiatives on knowledge, and ultimately behaviour, to be investigated.

Serum 25-hydroxyvitamin D and insulin resistance in people at high risk of cardiovascular disease: a euglycaemic hyperinsulinaemic clamp study.

CONTEXT: In observational studies, low serum 25-hydroxyvitamin D (25-OHD) concentration is associated with an increased risk of type 2 diabetes mellitus (DM). Increasing serum 25-OHD may have beneficial effects on insulin resistance or beta-cell function. Cross-sectional studies utilizing suboptimal methods for assessment of insulin sensitivity and serum 25-OHD concentration provide conflicting results. OBJECTIVE: This study examined the relationship between serum 25-OHD concentration and insulin resistance in healthy overweight individuals at increased risk of cardiovascular disease, using optimal assessment techniques. METHODS: A total of 92 subjects (mean age 56·0, SD 6·0 years), who were healthy but overweight (mean body mass index 30·9, SD 2·3 kg/m(2) ), underwent assessments of insulin sensitivity (two-step euglycaemic hyperinsulinaemic clamp, HOMA2-IR), beta-cell function (HOMA2%B), serum 25-OHD concentration and body composition (DEXA). RESULTS: Mean total 25-OHD concentration was 32·2, range 21·8-46·6 nmol/l. No association was demonstrated between serum 25-OHD concentration and insulin resistance. CONCLUSIONS: In this study using optimal assessment techniques to measure 25-OHD concentration, insulin sensitivity and body composition, there was no association between serum 25-OHD concentration and insulin resistance in healthy, overweight individuals at high risk of developing cardiovascular disease. This study suggests the documented inverse association between serum 25-OHD concentration and risk of type 2 DM is not mediated by a relationship between serum 25-OHD concentration and insulin resistance.

Increasing fruit and vegetable intake has no effect on retinal vessel caliber in adults at high risk of developing cardiovascular disease.

BACKGROUND AND AIM: Retinal vessel abnormalities are associated with cardiovascular disease (CVD) risk. To date, there are no trials investigating the effect of dietary factors on the retinal microvasculature. This study examined the dose response effect of fruit and vegetable (FV) intake on retinal vessel caliber in overweight adults at high CVD risk. METHODS AND RESULTS: Following a 4 week washout period, participants were randomized to consume either 2 or 4 or 7 portions of FV daily for 12 weeks. Retinal vessel caliber was measured at baseline and post-intervention. A total of 62 participants completed the study. Self-reported FV intake indicated good compliance with the intervention, with serum concentrations of zeaxanthin and lutein increasing significantly across the groups in a dose-dependent manner (P for trend < 0.05). There were no significant changes in body composition, 24-h ambulatory blood pressure or fasting blood lipid profiles in response to the FV intervention. Increasing age was a significant determinant of wider retinal venules (P = 0.004) whereas baseline systolic blood pressure was a significant determinant of narrower retinal arterioles (P = 0.03). Overall, there was no evidence of any short-term dose-response effect of FV intake on retinal vessel caliber (CRAE (P = 0.92) or CRVE (P = 0.42)). CONCLUSIONS: This study demonstrated no effect of increasing FV intake on retinal vessel caliber in overweight adults at high risk of developing primary CVD. CLINICAL TRIAL REGISTRATION: NCT00874341.

The chromosome 3q25 locus associated with fetal adiposity is not associated with childhood adiposity.

Increased newborn adiposity is associated with later adverse metabolic outcomes. Previous genome-wide association studies (GWAS) demonstrated strong association of a locus on chromosome 3 (3q25.31) with newborn sum of skinfolds, a measure of overall adiposity. Whether this locus is associated with childhood adiposity is unknown. Genotype and sum of skinfolds data were available for 293 children at birth and age 2, and for 350 children at birth and age 6 from a European cohort (Belfast, UK) who participated in the Hyperglycemia and Adverse Pregnancy Outcome GWAS. We examined single nucleotide polymorphisms (SNPs) at the 3q25.31 locus associated with newborn adiposity. Linear regression analyses under an additive genetic model adjusting for maternal body mass index were performed. In both cohorts, a positive association was observed between all SNPs and sum of skinfolds at birth (P=2.3 × 10(-4), ß=0.026 and P=4.8 × 10(-4), ß=0.025). At the age of 2 years, a non-significant negative association was observed with sum of skinfolds (P=0.06; ß =-0.015). At the age of 6 years, there was no evidence of association (P=0.86; ß=0.002). The 3q25.31 locus strongly associated with newborn adiposity had no significant association with childhood adiposity suggesting that its impact may largely be limited to fetal fat accretion.

Adolescents' views about a proposed rewards intervention to promote healthy food choice in secondary school canteens.

Using rewards may be an effective method to positively influence adolescent eating behaviour, but evidence regarding this approach is limited. The aim of this study was to explore young adolescent views about a proposed reward intervention associated with food choice in school canteens. Focus groups were held in 10 schools located in lower socioeconomic areas within Northern Ireland and involved 90 pupils aged 11-12 years (54 girls, 36 boys). Our findings indicated a high degree of acceptability for a reward scheme but there was major diversity in the type of rewards valued by pupils, largely defined by geographical area and socio-cultural differences. Pupils from rural areas tended to emphasize group-based and longer-term rewards, whereas pupils from urban-city schools tended to suggest individualistic and immediate rewards. The major factors influencing food choice were food price, value for money, taste and visual appearance. Pupils felt that factors outside of their control, such as being assigned to the second lunch sitting placed considerable constraints on their food choice. This research not only indicated a high degree of acceptability for a rewards-based intervention but also highlighted a number of socio-cultural and environmental factors that should be considered by researchers when developing such an intervention.

On the antioxidant properties of erythropoietin and its association with the oxidative-nitrosative stress response to hypoxia in humans.

AIM: The aim of this study was to examine if erythropoietin (EPO) has the potential to act as a biological antioxidant and determine the underlying mechanisms. METHODS: The rate at which its recombinant form (rHuEPO) reacts with hydroxyl (HO˙), 2,2-diphenyl-1-picrylhydrazyl (DPPH˙) and peroxyl (ROO˙) radicals was evaluated in-vitro. The relationship between the erythopoietic and oxidative-nitrosative stress response to poikilocapneic hypoxia was determined separately in-vivo by sampling arterial blood from eleven males in normoxia and following 12 h exposure to 13% oxygen. Electron paramagnetic resonance spectroscopy, ELISA and ozone-based chemiluminescence were employed for direct detection of ascorbate (A(˙-) ) and N-tert-butyl-α-phenylnitrone spin-trapped alkoxyl (PBN-OR) radicals, 3-nitrotyrosine (3-NT) and nitrite (NO2-). RESULTS: We found rHuEPO to be a potent scavenger of HO˙ (kr = 1.03-1.66 × 10(11) m(-1) s(-1) ) with the capacity to inhibit Fenton chemistry through catalytic iron chelation. Its ability to scavenge DPPH˙ and ROO˙ was also superior compared to other more conventional antioxidants. Hypoxia was associated with a rise in arterial EPO and free radical-mediated reduction in nitric oxide, indicative of oxidative-nitrosative stress. The latter was confirmed by an increased systemic formation of A˙(-) , PBN-OR, 3-NT and corresponding loss of NO2- (P < 0.05 vs. normoxia). The erythropoietic and oxidative-nitrosative stress responses were consistently related (r = -0.52 to 0.68, P < 0.05). CONCLUSION: These findings demonstrate that EPO has the capacity to act as a biological antioxidant and provide a mechanistic basis for its reported cytoprotective benefits within the clinical setting.

Polycystic ovary syndrome influences the level of serum amyloid A and activity of phospholipid transfer protein in HDL2 and HDL3.

STUDY QUESTION: Is polycystic ovary syndrome (PCOS) associated with altered levels of pro-inflammatory high-density lipoproteins (HDL) and activity of HDL-associated enzymes? SUMMARY ANSWER: In PCOS, HDL contained increased levels of the inflammatory marker serum amyloid A (SAA) and altered functioning of HDL-associated phospholipid transfer protein (PLTP), with these changes being independent of BMI, body fat and insulin resistance (IR). WHAT IS KNOWN ALREADY: PCOS is associated with adipocyte-derived inflammation, which potentially increases the risk of cardiovascular disease and diabetes. SAA is an inflammatory marker that is released from hypertrophic adipocytes and interacts with HDL, reducing their anti-atherogenic properties. No studies have previously investigated if SAA-associated HDL influences the HDL-associated enzymes namely, PLTP and cholesterol ester transfer protein (CETP) in women with PCOS. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: Obese women with PCOS were matched with controls for BMI and percentage body fat (n = 100/group; cohort-1); a subset of these women (n = 64/group; cohort-2) were further matched for IR. HDL in blood samples was subfractionated into HDL2 and HDL3 by rapid ultracentrifugation. SAA was measured in serum, HDL2 and HDL3 by an enzyme-linked immunosorbent assay and the activities of PLTP and CETP were measured in HDL2 and HDL3 by fluorimetric assays. MAIN RESULTS AND THE ROLE OF CHANCE: In the PCOS women from cohort-1, SAA was increased in serum, HDL2 and HDL3 (P = 0.038, 0.008 and 0.001 versus control, respectively), as was the activity of PLTP in HDL2 and HDL3 (P = 0.006 and 0.009 versus controls, respectively). In the PCOS women from cohort-2, SAA was increased in serum, HDL2 and HDL3, although only significantly in HDL3 (P = 0.083, 0.120 and 0.034 versus controls, respectively), as was the activity of PLTP in HDL2 and HDL3, although this was only significant in HDL2 (P = 0.045 and 0.070 versus controls, respectively). LIMITATIONS, REASONS FOR CAUTION: First, insulin sensitivity was not determined by the euglycaemic-hyperinsulinaemic clamp. Secondly, the method used to estimate body fat was not able to discriminate between visceral and peripheral fat. Thirdly, larger study groups would be required to confirm if PCOS independently contributed to SAA-related HDL and functional changes to this lipoprotein, independent of BMI, percentage body fat and IR. WIDER IMPLICATIONS OF THE FINDINGS: This is the first study to highlight the usefulness of HDL-associated SAA as a marker to identify increased inflammation in women with PCOS. This study also identified that the functioning of HDL was altered in women with PCOS. These findings illustrate a mechanism through which cardiovascular disease may increase in PCOS. STUDY FUNDING/COMPETING INTERESTS: Funded by the Irish Endocrinology Society. No competing interests. CLINICAL TRIAL REGISTRATION NUMBER: NCT001195168.

The impact of endovascular repair of ruptured abdominal aortic aneurysm on the gastrointestinal and renal function.

Introduction. Systemic effects of ruptured abdominal aortic aneurysm (rAAA) may be altered by the mode of surgery. This study aimed to determine systemic effects of endovascular aneurysm repair (EVAR) compared to open repair (OR). Patients and Methods. Consecutive patients with rAAA were repaired by OR or EVAR according to computerised tomographic (CT) findings. Renal function was monitored by estimated glomerular filtration rate (eGFR), serum urea and creatinine, and urinary albumin creatinine ratio (ACR). Hepatic function was assessed postoperatively for 5 days. Intestinal function was determined by the paracetamol absorption test. Intestinal permeability was assessed by urinary lactulose/mannitol ratio. Results. 30 rAAA patients were included. Fourteen had eEVAR and sixteen eOR. Serum urea were higher in eOR, while creatinine was similar between groups. Hepatic function showed no intergroup difference. Paracetamol absorption was increased in eEVAR group at day 3 compared to day 1 (P = 0.03), with no similar result in eOR (P = 0.24). Peak lactulose/mannitol ratio was higher in eOR (P = 0.03), with higher urinary L/M ratio in eOR at day 3 (P = 0.02). Clinical intestinal function returned quicker in eEVAR (P = 0.02). Conclusion. EVAR attenuated the organ dysfunction compared to open repair. However, a larger comparative trial would be required to validate this. The clinical trial is registered with reference number EUDRACT: 2013-003373-12.

Effect of increased fruit and vegetable consumption on bone turnover in older adults: a randomised controlled trial.

UNLABELLED: Evidence suggests that increased fruit and vegetable (FV) intake may be associated with improved bone health, but there is limited evidence from intervention trials to support this. This 16-week study showed that increased FV consumption (five or more portions per day) does not have any effect on the markers of bone health in older adults. INTRODUCTION: Observational evidence suggests that increased FV consumption may be associated with improved bone health. However, there is lack of evidence from intervention trials to support this. This study examined the effect of increased FV consumption on bone markers among healthy, free-living older adults. METHODS: A randomised controlled trial was undertaken. Eighty-three participants aged 65-85 years, habitually consuming less than or equal to two portions of FV per day, were randomised to continue their normal diet or to consume five or more portions of FV per day for 16 weeks. FV were delivered to all participants each week, free of charge. Compliance was assessed at baseline and at 6, 12 and 16 weeks by diet histories and biomarkers of micronutrient status. Fasting serum bone markers (osteocalcin (OC) and C-terminal telopeptide of type 1 collagen (CTX)) were measured using enzyme-linked immunosorbent assay. RESULTS: Eighty-two participants completed the intervention. The five portions per day group showed a significantly greater change in daily FV consumption compared to the two portions per day group (p < 0.001), and this was reflected in significant increases in micronutrient status. No significant differences were evident in change in bone markers between the two portions per day group and the five portions per day group over the 16 weeks (geometric mean of week 16 to baseline ratio (95% confidence interval): OC-0.95 (0.89-1.02) and 1.04 (0.91-1.18), respectively, p = 0.25; CTX-1.06 (0.95-1.19) and 0.98 (0.90-1.06) respectively, p = 0.20). CONCLUSIONS: Increased FV consumption had no effect on bone markers in older adults. Larger intervention studies of longer duration are warranted to establish whether long-term FV consumption can benefit bone health.

Disordered vascular compliance in haemochromatosis.

BACKGROUND: A relationship may exist between body iron stores, endothelial dysfunction and overall cardiovascular risk. AIMS: To compare vascular compliance, biochemical endothelial function and antioxidant status between patients with homozygous hereditary haemochromatosis and healthy controls. METHODS: Haemochromatosis patients and healthy controls were recruited. Measures of vascular compliance were assessed by applanation tonometry. Serological markers of endothelial function (plasma lipid hydroperoxides, cell adhesion molecules), antioxidant levels (ascorbate, lipid soluble antioxidants) and high-sensitivity C-reactive protein (CRP) were also measured. RESULTS: Thirty-five hereditary haemochromatosis patients (ten females, mean age 54.6) and 36 controls (27 female, mean age 54.0) were recruited. Haemochromatosis patients had significantly higher systolic and diastolic blood pressures. Pulse wave velocity (PWV) was significantly higher in male haemochromatosis patients (9.90 vs. 8.65 m/s, p = 0.048). Following adjustment for age and blood pressure, male haemochromatosis patients continued to have a trend for higher PWVs (+1.37 m/s, p = 0.058). Haemochromatosis patients had significantly lower levels of ascorbate (46.11 vs. 72.68 µmol/L, p = 0.011), retinol (1.17 vs. 1.81 µmol/L, p = 0.001) and g-tocopherol (2.51 vs. 3.14 µmol/L, p = 0.011). However, there was no difference in lipid hydroperoxides (0.46 vs. 0.47 nmol/L, p = 0.94), cell adhesion molecule levels (ICAM: 348.12 vs. 308.03 ng/mL, p = 0.32 and VCAM: 472.78 vs. 461.31 ng/mL, p = 0.79) or high-sensitivity CRP (225.01 vs. 207.13 mg/L, p = 0.32). CONCLUSIONS: Haemochromatosis is associated with higher PWVs in males and diminished antioxidants across the sexes but no evidence of endothelial dysfunction or increased lipid peroxidation.

A randomised controlled trial evaluating the effect of potassium supplementation on vascular function and the renin-angiotensin-aldosterone system.

There is limited evidence on the effect of potassium supplementation on the vasculature in patients at increased cardiovascular risk. Potassium increases aldosterone and there is a strong association of hyperaldosteronism with poor cardiac outcomes. We aimed to determine whether potassium supplementation has a significant medium-term effect on aldosterone levels and, if so, what the overall effect of this is on vascular function in patients at moderate cardiovascular disease risk. Forty patients at moderate cardiovascular disease risk were included in a randomised placebo-controlled crossover study. Patients were assigned to 64 mmol potassium chloride or placebo for 6 weeks. Vascular function was assessed using pulse-wave analysis including the detection of a change in augmentation index to salbutamol and nitroglycerine-induced vasodilation. There was no change in augmentation index with potassium vs placebo (25.2±1.4 vs. 26.0±1.3%, respectively). Potassium improved brachial systolic blood pressure (131.8±2.2 vs. 137.1±2.4 mm Hg; P=0.013), central systolic blood pressure (123.2±2.3 vs. 128.4±2.3 mm Hg; P=0.011) and central diastolic blood pressure (80.3±1.3 vs. 83.7±1.4 mm Hg; P=0.019). Plasma renin activity and serum aldosterone both increased with potassium (P=0.001 and P=0.048 respectively). We found that potassium supplementation had no effect on endothelial function or pulse-wave analysis. It lowered brachial systolic and central blood pressure. It was associated with increased plasma renin activity and serum aldosterone.

The inflammatory response to ruptured abdominal aortic aneurysm is altered by endovascular repair.

Introduction. Ruptured abdominal aortic aneurysm (rAAA) causes a significant inflammatory response. The study aims to investigate this response following endovascular and open repair of ruptured AAA. Patients and Methods. Consecutive rAAA patients had either endovascular aneurysm repair (EVAR) or open repair (OR). Blood samples were taken for cytokines, lipid hydroperoxides (LOOH), antioxidants, and neutrophil elastase/ α 1-anti-trypsin complexes (NE/AAT) before surgery, 6 hours after clamp release and 1, 3, 5 days postoperatively. Results. 30 patients were included in the study, with 14 undergoing eEVAR and 16 eOR, with comparable baseline comorbidities, age, and parameters. IL-6 peaked higher in eOR patients (P = 0.04), while p75TNFr was similar between groups except at day 5 (P = 0.04). The NE/AAT concentrations were higher in eOR patients (P = 0.01), particularly in the first postoperative day, and correlated with blood (r = 0.398, P = 0.029) and platelet (r = 0.424, P = 0.020) volume transfused. C-reactive protein rose and lipid hydroperoxide fell in both groups without significant intergroup difference. Vitamins C and E, lycopene, and ß -carotene levels were similar between groups. Conclusion. EVAR is associated with lower systemic inflammatory response compared to OR. Its increased future use may thereby improve outcomes for patients.

Haptoglobin phenotype, pre-eclampsia, and response to supplementation with vitamins C and E in pregnant women with type-1 diabetes.

OBJECTIVE: The phenotype of the antioxidant and pro-angiogenic protein haptoglobin (Hp) predicts cardiovascular disease risk and treatment response to antioxidant vitamins in individuals with diabetes. Our objective was to determine whether Hp phenotype influences pre-eclampsia risk, or the efficacy of vitamins C and E in preventing pre-eclampsia, in women with type-1 diabetes. DESIGN: This is a secondary analysis of a randomised controlled trial in which women with diabetes received daily vitamins C and E, or placebo, from 8 to 22 weeks of gestation until delivery. SETTING: Twenty-five antenatal metabolic clinics across the UK (in north-west England, Scotland, and Northern Ireland). POPULATION: Pregnant women with type-1 diabetes. METHODS: Hp phenotype was determined in white women who completed the study and had plasma samples available (n = 685). MAIN OUTCOME MEASURE: Pre-eclampsia. RESULTS: Compared with Hp 2-1, Hp 1-1 (OR 0.59, 95% CI 0.30-1.16) and Hp 2-2 (OR 0.93, 95% CI 0.60-1.45) were not associated with significantly decreased pre-eclampsia risk after adjusting for treatment group and HbA1c at randomisation. Our study was not powered to detect an interaction between Hp phenotype and treatment response; however, our preliminary analysis suggests that vitamins C and E did not prevent pre-eclampsia in women of any Hp phenotype (Hp 1-1, OR 0.77, 95% CI 0.22-2.71; Hp 2-1, OR 0.81, 95% CI 0.46-1.43; Hp 2-2, 0.67, 95% CI 0.34-1.33), after adjusting for HbA1c at randomisation. CONCLUSIONS: The Hp phenotype did not significantly affect pre-eclampsia risk in women with type-1 diabetes.