754 resultados para cross-over study


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Background: The Early Development Instrument (EDI) is a population-level measure of five developmental domains at school-entry age. The overall aim of this thesis was to explore the potential of the EDI as an indicator of early development in Ireland. Methods: A cross-sectional study was conducted in 47 primary schools in 2011 using the EDI and a linked parental questionnaire. EDI (teacher completed) scores were calculated for 1,344 children in their first year of full-time education. Those scoring in the lowest 10% of the sample population in one or more domains were deemed to be 'developmentally vulnerable'. Scores were correlated with contextual data from the parental questionnaire and with indicators of area and school-level deprivation. Rasch analysis was used to determine the validity of the EDI. Results: Over one quarter (27.5%) of all children in the study were developmentally vulnerable. Individual characteristics associated with increased risk of vulnerability were being male; under 5 years old; and having English as a second language. Adjusted for these demographics, low birth weight, poor parent/child interaction and mother’s lower level of education showed the most significant odds ratios for developmental vulnerability. Vulnerability did not follow the area-level deprivation gradient as measured by a composite index of material deprivation. Children considered by the teacher to be in need of assessment also had lower scores, which were not significantly different from those of children with a clinical diagnosis of special needs. all domains showed at least reasonable fit to the Rasch model supporting the validity of the instrument. However, there was a need for further refinement of the instrument in the Irish context. Conclusion: This thesis provides a unique snapshot of early development in Ireland. The EDI and linked parental questionnaires are promising indicators of the extent, distribution and determinants of developmental vulnerability.

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Malnutrition, sarcopenia and cancer cachexia (CC) are prevalent among cancer patients and can have detrimental effects on clinical outcomes such as quality of life (QoL) and overall survival. Cachexia is associated with lower tolerance for chemotherapy, which limits the total dose that can be delivered, the number of symptomatic responses and any survival advantage that might be accrued. Moreover, for the majority who do not respond, cachexia may be exacerbated by systemic chemotherapy, thus increasing the net symptom burden experienced by patients. The multitude of interactions between cancer location, treatments, nutritional status and QoL has never been thoroughly explored in an Irish cancer cohort. The objectives of this thesis were to further understand nutritional status, especially body composition in ambulatory cancer patients and determine the relationship between nutritional status using different assessment criteria and QoL, chemotherapy toxicity and survival among cancer patients undergoing chemotherapy. Results aimed to identify baseline factors that may be predictive of poor outcome, toxicities to chemotherapy and disease-free and overall survival. This thesis broadly divides into two sections. The first section (Chapters 3 & 4) focuses on improving our knowledge of the nutritional status of Irish cancer outpatients using a cross sectional study design. A study of 517 patients referred for chemotherapy was conducted using computed tomography (CT) imaging (body composition) and a survey that documented oncologic data, weight loss (WL) data and QoL data. We revealed that a significant proportion of Irish cancer patients undergoing chemotherapy experience unintentional WL over the previous 6 months (62%), sarcopenia (45%) and CC (43%), and the distribution of WL and nutritional risk were associated with site of primary tumour and treatment intent. Patients that had sarcopenia, nutritional risk, or CC had significantly reduced functional abilities, more symptoms and adverse global QoL. In the second section of this thesis (Chapters 5 & 6) the potential link between developing toxicity to antineoplastic regimens in patients with sarcopenia was conducted by way of retrospective studies. A retrospective serial CT analysis defined the prevalence of sarcopenia in patients with metastatic renal cell carcinoma (mRCC) and metastatic castrate resistant prostate cancer (mCRPC), which was then correlated with dose limiting toxicities of sunitinib and docetaxel respectively. Sarcopenia was prevalent in patients with mRCC and mCRPC, was an occult condition in patients with normal/high BMI, was associated with less treatment days, was a significant predictor of DLT in patients receiving sunitinib and a significant predictor of neutropenia and neurosensory toxicities in patients receiving docetaxel. This thesis attempted to address the underlying research deficiencies in Irish oncology nutritional data at national level. The findings from this thesis have implications for the planning of cancer care interventions and indicate that further research is required to improve nutritional screening, in particular for CC and sarcopenia, in the hope that timely intervention can improve both patient-centered and oncologic outcomes.

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OBJECTIVE: Strict lifelong compliance to a gluten-free diet (GFD) minimizes the long-term risk of mortality, especially from lymphoma, in adult celiac disease (CD). Although serum IgA antitransglutaminase (IgA-tTG-ab), like antiendomysium (IgA-EMA) antibodies, are sensitive and specific screening tests for untreated CD, their reliability as predictors of strict compliance to and dietary transgressions from a GFD is not precisely known. We aimed to address this question in consecutively treated adult celiacs. METHODS: In a cross-sectional study, 95 non-IgA deficient adult (median age: 41 yr) celiacs on a GFD for at least 1 yr (median: 6 yr) were subjected to 1) a dietician-administered inquiry to pinpoint and quantify the number and levels of transgressions (classified as moderate or large, using as a cutoff value the median gluten amount ingested in the overall noncompliant patients of the series) over the previous 2 months, 2) a search for IgA-tTG-ab and -EMA, and 3) perendoscopic duodenal biopsies. The ability of both antibodies to discriminate celiacs with and without detected transgressions was described using receiver operating characteristic curves and quantified as to sensitivity and specificity, according to the level of transgressions. RESULTS: Forty (42%) patients strictly adhered to a GFD, 55 (58%) had committed transgressions, classified as moderate (< or = 18 g of gluten/2 months; median number 6) in 27 and large (>18 g; median number 69) in 28. IgA-tTG-ab and -EMA specificity (proportion of correct recognition of strictly compliant celiacs) was 0.97 and 0.98, respectively, and sensitivity (proportion of correct recognition of overall, moderate, and large levels of transgressions) was 0.52, 0.31, and 0.77, and 0.62, 0.37, and 0.86, respectively. IgA-tTG-ab and -EMA titers were correlated (p < 0.001) to transgression levels (r = 0.560 and R = 0.631, respectively) and one to another (p < 0.001) in the whole patient population (r = 0.834, N = 84) as in the noncompliant (r = 0.915, N = 48) group. Specificity and sensitivity of IgA-tTG-ab and IgA-EMA for recognition of total villous atrophy in patients under a GFD were 0.90 and 0.91, and 0.60 and 0.73, respectively. CONCLUSIONS: In adult CD patients on a GFD, IgA-tTG-ab are poor predictors of dietary transgressions. Their negativity is a falsely secure marker of strict diet compliance.

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BACKGROUND: Edoxaban, an oral direct factor Xa inhibitor, is in development for thromboprophylaxis, including prevention of stroke and systemic embolism in patients with atrial fibrillation (AF). P-glycoprotein (P-gp), an efflux transporter, modulates absorption and excretion of xenobiotics. Edoxaban is a P-gp substrate, and several cardiovascular (CV) drugs have the potential to inhibit P-gp and increase drug exposure. OBJECTIVE: To assess the potential pharmacokinetic interactions of edoxaban and 6 cardiovascular drugs used in the management of AF and known P-gp substrates/inhibitors. METHODS: Drug-drug interaction studies with edoxaban and CV drugs with known P-gp substrate/inhibitor potential were conducted in healthy subjects. In 4 crossover, 2-period, 2-treatment studies, subjects received edoxaban 60 mg alone and coadministered with quinidine 300 mg (n = 42), verapamil 240 mg (n = 34), atorvastatin 80 mg (n = 32), or dronedarone 400 mg (n = 34). Additionally, edoxaban 60 mg alone and coadministered with amiodarone 400 mg (n = 30) or digoxin 0.25 mg (n = 48) was evaluated in a single-sequence study and 2-cohort study, respectively. RESULTS: Edoxaban exposure measured as area under the curve increased for concomitant administration of edoxaban with quinidine (76.7 %), verapamil (52.7 %), amiodarone (39.8 %), and dronedarone (84.5 %), and exposure measured as 24-h concentrations for quinidine (11.8 %), verapamil (29.1 %), and dronedarone (157.6 %) also increased. Administration of edoxaban with amiodarone decreased the 24-h concentration for edoxaban by 25.7 %. Concomitant administration with digoxin or atorvastatin had minimal effects on edoxaban exposure. CONCLUSION: Coadministration of the P-gp inhibitors quinidine, verapamil, and dronedarone increased edoxaban exposure. Modest/minimal effects were observed for amiodarone, atorvastatin, and digoxin.

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© 2016, Serdi and Springer-Verlag France.Objectives: The association between cognitive function and cholesterol levels is poorly understood and inconsistent results exist among the elderly. The purpose of this study is to investigate the association of cholesterol level with cognitive performance among Chinese elderly. Design: A cross-sectional study was implemented in 2012 and data were analyzed using generalized additive models, linear regression models and logistic regression models. Setting: Community-based setting in eight longevity areas in China. Subjects: A total of 2000 elderly aged 65 years and over (mean 85.8±12.0 years) participated in this study. Measurements: Total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) concentration were determined and cognitive impairment was defined as Mini-Mental State Examination (MMSE) score≤23. Results: There was a significant positive linear association between TC, TG, LDL-C, HDL-C and MMSE score in linear regression models. Each 1 mmol/L increase in TC, TG, LDL-C and HDL-C corresponded to a decreased risk of cognitive impairment in logistic regression models. Compared with the lowest tertile, the highest tertile of TC, LDL-C and HDL-C had a lower risk of cognitive impairment. The adjusted odds ratios and 95% CI were 0.73(0.62–0.84) for TC, 0.81(0.70–0.94) for LDL-C and 0.81(0.70–0.94) for HDL-C. There was no gender difference in the protective effects of high TC and LDL-C levels on cognitive impairment. However, for high HDL-C levels the effect was only observed in women. High TC, LDL-C and HDL-C levels were associated with lower risk of cognitive impairment in the oldest old (aged 80 and older), but not in the younger elderly (aged 65 to 79 years). Conclusions: These findings suggest that cholesterol levels within the high normal range are associated with better cognitive performance in Chinese elderly, specifically in the oldest old. With further validation, low cholesterol may serve a clinical indicator of risk for cognitive impairment in the elderly.

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Solder pastes and isotropic conductive adhesives (ICAs) are widely used as a principal bonding medium in the electronic industry. This study investigates the rheological behaviour of the pastes (solder paste and isotropic conductive adhesives) used for flip-chip assembly. Oscillatory stress sweep test are performed to evaluate solid characteristic and cohesiveness of the lead-free solder pastes and isotropic conductive adhesive paste materials. The results show that the G' (storage modulus) is higher than G '' (loss modulus) for the pastes material indicating a solid like behaviour. It result shows that the linear visco-elastic region for the pastes lies in a very small stress range, below 10 Pa. in addition, the stress at which the value of storage modulus is equal to that of loss modulus can be used as an indicator of the paste cohesiveness. The measured cross-over stress at G'=G '' shows that the solder paste has higher stress at G'=G '' compared to conductive adhesives. Creep-recovery test method is used to study the slump behaviour in the paste materials. The conductive adhesive paste shows a good recovery when compared to the solder pastes. (C) 2008 Elsevier B.V. All rights reserved.

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Exercise can have deleterious effects on the secretion of salivary immunoglobulin A (s-IgA), which appears to be related to perturbations in sympatheticoadrenal activation (Teeuw et al., 2004). Caffeine, commonly used for its ergogenic properties is associated with increased sympathetic nervous system activity, and it has been previously shown that caffeine ingestion before intensive cycling enhances s-IgA responses during exercise (Bishop et al., 2006). Therefore, the aim of the present study was to examine the effect of a performance cereal bar, containing caffeine, before and during prolonged exhaustive cycling on exercise performance and the salivary secretion of IgA, alpha-amylase activity and cortisol. Using a randomised cross-over design and following a 10 – 12 hour overnight fast, 12 trained cyclists, mean (SEM) age: 21(1) yr; height: 179(2) cm; body mass: 73.6(2.5) kg; maximal oxygen uptake, VO2max: 57.9(1.2) completed 2.5 h of cycling at 60%VO2max (with regular water ingestion) on a stationary ergometer, which was followed by a ride to exhaustion at 75% VO2max. Immediately before exercise, and after 55 min and 115 min of exercise participants ingested a 0.9 MJ cereal bar containing 45 g carbohydrate, 5 g protein, 3 g fat and 100 mg of caffeine (CAF) or an isocaloric noncaffeine bar (PLA). Unstimulated timed saliva samples were collected immediately before exercise, after 70 min and 130 min of exercise, and immediately after the exhaustive exercise bout. Saliva was analysed for s-IgA, alpha-amylase activity and cortisol concentration. Saliva flow rates were determined to calculate the s-IgA secretion rate. Data were analysed using a 2-way repeated measures ANOVA and post-hoc t-tests with Holm Bonferroni adjustments applied where appropriate. Time to exhaustion was 35% longer in CAF compared with PLA ((2177 (0.2) vs 1615 (0.16) s; P < 0.05)). Saliva flow rate did not change significantly during the exercise protocol. Exercise was associated with elevations in s-IgA concentration (9% increase), s-IgA secretion rate (24% increase) and alpha-amylase activity (224% increase) post-exhaustion (P < 0.01), but there was no effect of CAF on these responses. Salivary cortisol concentration increased by 64% post-exhaustion in the CAF trial only (P < 0.05), indicating an increase in adrenal activity following caffeine ingestion. Values were 35.7 (5.5) and 19.6 (3.4) nmol/L post-exhaustion for CAF and PLA, respectively. These findings show that ingestion of a caffeine containing cereal bar during prolonged exhaustive cycling enhances endurance performance, increases salivary cortisol secretion post-exhaustion, but does not affect the exercise-induced increases in s-IgA or alpha-amylase activity.

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Recent electrophysiological studies have suggested that there is a subpopulation of cells in lymphatic vessels which act as pacemakers controlling the characteristic spontaneous contractile activity in this tissue. In this study, electron microscopy and immunohistochemical techniques were used on sheep mesenteric lymphatic vessels to investigate the morphology of the cells comprising the lymphatic wall. The smooth muscle cells were not orientated in circular and longitudinal layers as is seen in the gastrointestinal tract, but were arranged in bundles which interlock and cross over in a basket-weave fashion. Antibodies to Kit and vimentin, which are widely used to label specialised pacemaking cells in the gastrointestinal tract (known as interstitial cells of Cajal), demonstrated the existence of an axially orientated subpopulation of cells lying between the endothelium and the bulk of the smooth muscle. Examination of this area using electron microscopy showed cells which were electron dense compared to the underlying smooth muscle and contained caveolae, Golgi complexes, mitochondria, 10-nm filaments, a well-developed endoplasmic reticulum and a basal lamina. The smooth muscle cells typically contained caveolae, dense bodies, mitochondria, abundant filaments, sER and basal laminae. Cells dispersed for patch-clamp studies were also stained for vimentin and myosin. Myosin-staining cells had the typical spindle appearance of smooth muscle cells whereas the vimentin-positive cells could either be branched or more closely resemble the smooth muscle cells. The present study provides the first morphological evidence that specialised cells exist within the vascular system which have the ultrastructural characteristics of pacemaker cells in other tissues and are vimentin and Kit positive.

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Small changes of diet may reduce CVD risk. One example is the inclusion of nuts. They are rich in fibre, unsaturated fatty acids and phytonutrients. However, their fat content and energy density raise concerns that chronic consumption will promote weight gain. Randomised intervention studies are required to evaluate whether this concern is well founded. This study's aim was to determine if the inclusion of a 1440 kJ serving of almonds in the daily diet results in positive energy balance, and body composition change. During a 23-week cross-over design study, participants were required to consume almonds for 10 weeks and were provided no advice on how to include them in their diet. For another 10 weeks (order counter-balanced), participants followed their customary diet and there was a 3-week washout between. The study group consisted of twenty women. Potential mechanisms of energy dissipation were measured. Ten weeks of daily almond consumption did not cause a change in body weight. This was predominantly due to compensation for the energy contained in the almonds through reduced food intake from other sources. Moreover, inefficiency in the absorption of energy from almonds was documented (P <0·05). No changes in resting metabolic rate, thermic effect of food or total energy expenditure were noted. A daily 1440 kJ serving of almonds, sufficient to provide beneficial effects on cardiovascular risk factors, may be included in the diet with limited risk of weight gain. Whether this can be generalised to other high-fat energy dense foods warrants evaluation.

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This experiment investigated the effects of providing access to grass silage on the welfare of sows introduced to a large dynamic group. Two treatments were applied: (1) access to racks containing grass silage (offering an average of 1.9 kg silage/sow/day), and (2) control treatment with no grass silage racks. Treatments 1 and 2 were applied to two separate dynamic groups, each containing 37 (2) sows. Approximately 9 sows were replaced in both groups at 3-week intervals, and each of these replacements constituted a replicate of the study. The study was replicated six times using a total of 108 sows. In a time-based cross-over design, treatments were swapped between the two dynamic groups after three replicates. Highest levels of rack usage were shown between 08:00 and 14:00 h. During peak periods, 9.8% of sows were observed at the racks at a given time. On average, 78.5% of sows observed at the racks were newly-introduced animals. Overall levels of aggression to which newly-introduced sows were exposed on the day of introduction to the group were low, and did not differ significantly between treatments (P > 0.05). In addition, injury levels measured 1-week post-introduction to the group did not differ significantly between treatments (P > 0.05). Sham chewing behaviour was more prevalent in the post-rather than the pre-feeding yard (P

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This study assessed the effect of increasing fibre levels in the concentrate ration on the welfare of sows housed in a large dynamic group. One hundred and twelve Large White x Landrace sows were allocated to one of two treatments over six replicates. Treatments were as follows: (i) High Fibre diet (similar to 15% CF [Crude Fibre]), and (ii) Control diet (similar to 5% CF). Treatments were applied to two separate dynamic groups each containing 33 (+/- 3) sows in a cross-over design, after three replicates the treatments were switched between the groups. Approximately nine sows were replaced in each of these groups at 3-week intervals (each replacement constituting a replicate of the study). Sows on the high fibre diet spent a greater percentage of time lying (High Fibre: 43.8, Control. 28.0, SEM 3.25%), while sows on the control diet spent more time sham chewing (High Fibre: 7.2, Control: 28.8, SEM 1.55%). Sows newly introduced to the group on the high fibre treatment spent proportionally more time in the kennel areas compared to newly introduced sows in the control treatment (High Fibre. 0.893, Control. 0 788, SEM 5 10) In general, aggression occurred at a very low frequency and overall levels did not differ between treatments (High Fibre: 0.005, Control: 0.003, SEM 0.0007 [occurrences per min)). However, sows in the control treatment performed head thrusting (High Fibre: 0.02, Control: 0.00, SEM 0.001 [occurrences per mini), and biting behaviour (High Fibre. 002, Control. 0.01, SEM 0.002 [occurrences per min]) more frequently than sows on the high fibre diet. There was no effect of treatment on physiological parameters such as plasma cortisol (High Fibre: 1.34, Control: 1.44, SEM 0.114 ng ml(-1)) or haptoglobin levels (High Fibre. 0.73, Control. 0.64, SEM 0.080 mg ml(-1)). In summary, provision of a high fibre diet had a positive effect on the welfare of group-housed dry sows Sows on the high fibre treatment spent more time resting in the kennel areas, less time performing stereotypic behaviours and showed a reduction in some aggressive behaviours relative to sows fed the control diet.

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Objectives
To evaluate how involvement in life situations (participation) in children with cerebral palsy varies with type and severity of impairment and to investigate geographical variation in participation.

Design
Cross sectional study. Trained interviewers visited parents of children with cerebral palsy; multilevel multivariable regression related participation to impairments, pain, and sociodemographic characteristics.

Setting
Eight European regions with population registers of children with cerebral palsy; one further region recruited children from multiple sources.

Participants
1174 children aged 8-12 with cerebral palsy randomly selected from the population registers, 743 (63%) joined in the study; the further region recruited 75 children.

Main outcome measure
Children’s participation assessed by the Life-H questionnaire covering 10 main areas of daily life. Scoring ignored adaptations or assistance required for participation.

Results
Children with pain and those with more severely impaired walking, fine motor skills, communication, and intellectual abilities had lower participation across most domains. Type of cerebral palsy and problems with feeding and vision were associated with lower participation for specific domains, but the sociodemographic factors examined were not. Impairment and pain accounted for up to a sixth of the variation in participation. Participation on all domains varied substantially between regions: children in east Denmark had consistently higher participation than children in other regions. For most participation domains, about a third of the unexplained variation could be ascribed to variation between regions and about two thirds to variation between individuals.

Conclusions
Participation in children with cerebral palsy should be assessed in clinical practice to guide intervention and assess its effect. Pain should be carefully assessed. Some European countries facilitate participation better than others, implying some countries could make better provision. Legislation and regulation should be directed to ensuring this happens.

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Background: Co-localisation is a widely used measurement in immunohistochemical analysis to determine if fluorescently labelled biological entities, such as cells, proteins or molecules share a same location. However the measurement of co-localisation is challenging due to the complex nature of such fluorescent images, especially when multiple focal planes are captured. The current state-of-art co-localisation measurements of 3-dimensional (3D) image stacks are biased by noise and cross-overs from non-consecutive planes.

Method: In this study, we have developed Co-localisation Intensity Coefficients (CICs) and Co-localisation Binary Coefficients (CBCs), which uses rich z-stack data from neighbouring focal planes to identify similarities between image intensities of two and potentially more fluorescently-labelled biological entities. This was developed using z-stack images from murine organotypic slice cultures from central nervous system tissue, and two sets of pseudo-data. A large amount of non-specific cross-over situations are excluded using this method. This proposed method is also proven to be robust in recognising co-localisations even when images are polluted with a range of noises.

Results: The proposed CBCs and CICs produce robust co-localisation measurements which are easy to interpret, resilient to noise and capable of removing a large amount of false positivity, such as non-specific cross-overs. Performance of this method of measurement is significantly more accurate than existing measurements, as determined statistically using pseudo datasets of known values. This method provides an important and reliable tool for fluorescent 3D neurobiological studies, and will benefit other biological studies which measure fluorescence co-localisation in 3D.

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In this study we compared the pharmacokinetics and pharmacodynamics of captopril after sublingual and peroral administration. Single 25 mg doses of captopril were administered sublingually and perorally on two different occasions in a randomised cross-over fashion to eight healthy volunteers aged 22-35 years. The kinetics of unchanged captopril, plasma renin activity (PRA), BP and heart rate were studied over three hours after both peroral and sublingual administration of captopril.

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Mitochondria produce cellular energy but also free-radicals, which damage cells despite an array of endogenous anti-oxidants. In Northern Europe, the mitochondrial haplogroup J has been related to longevity in nonagenarians and centenarians but also with age-related disease. Hypertension is an important contributor to atherosclerotic-related diseases and its pathogenesis is associated with increased oxidative stress. In this study, we questioned whether J haplogroup octo/nonagenarians from the Belfast Elderly Longitudinal Free-living Elderly STudy (BELFAST) study showed evidence of protective blood pressure or anti-oxidant profile which might explain their longevity advantage. Briefly, in a cross-sectional study, community-living, mentally alert (Folstein >25/30), octo/nonagenarian subjects, recruited for good health, were enlisted and consented as part of the BELFAST study, for blood pressure, anthropometric measurements and blood sampling. DNA typing for mitochondrial haplotypes was carried out with measurements for enzymatic and non-enzymatic antioxidants. J haplogroup carriers showed lower systolic blood pressure and glutathione peroxidase activity (Gpx) with higher folate measurements. There was no change in urate, bilirubin, albumin or nutrition-related antioxidants-selenium or vitamins A, C and a and ß carotene. BELFAST study mtDNA J haplogroup octo/nonagenarians showed lower blood pressure and reduced glutathione peroxidase activity and higher folate, but no change for other antioxidants. These findings are of interest in view of mtDNA J haplogroup's association with increased age in some previous studies.