LC/MS-based discrimination between plasma and urine metabolomic changes following exposure to ultraviolet radiation by using data modelling.

INTRODUCTION: This study sought to compare between metabolomic changes of human urine and plasma to investigate which one can be used as best tool to identify metabolomic profiling and novel biomarkers associated to the potential effects of ultraviolet (UV) radiation. METHOD: A pilot study of metabolomic patterns of human plasma and urine samples from four adult healthy individuals at before (S1) and after (S2) exposure (UV) and non-exposure (UC) were carried out by using liquid chromatography-mass spectrometry (LC-MS). RESULTS: The best results which were obtained by normalizing the metabolites to their mean output underwent to principal components analysis (PCA) and Orthogonal Partial least squares-discriminant analysis (OPLS-DA) to separate pre-from post-of exposure and non-exposure of UV. This separation by data modeling was clear in urine samples unlike plasma samples. In addition to overview of the scores plots, the variance predicted-Q2 (Cum), variance explained-R2X (Cum) and p-value of the cross-validated ANOVA score of PCA and OPLS-DA models indicated to this clear separation. Q2 (Cum) and R2X (Cum) values of PCA model for urine samples were 0.908 and 0.982, respectively, and OPLS-DA model values were 1.0 and 0.914, respectively. While these values in plasma samples were Q2 = 0.429 and R2X = 0.660 for PCA model and Q2 = 0.983 and R2X = 0.944 for OPLS-DA model. LC-MS metabolomic analysis showed the changes in numerous metabolic pathways including: amino acid, lipids, peptides, xenobiotics biodegradation, carbohydrates, nucleotides, Co-factors and vitamins which may contribute to the evaluation of the effects associated with UV sunlight exposure. CONCLUSIONS: The results of pilot study indicate that pre and post-exposure UV metabolomics screening of urine samples may be the best tool than plasma samples and a potential approach to predict the metabolomic changes due to UV exposure. Additional future work may shed light on the application of available metabolomic approaches to explore potential predictive markers to determine the impacts of UV sunlight.

Reduced nitric oxide synthesis in winter: A potential contributing factor to increased cardiovascular risk.

BACKGROUND: Nitric oxide is a key signalling molecule that elicits a range of biological functions to maintain vascular homeostasis. A reduced availability of nitric oxide is implicated in the progression of cardiovascular diseases and increases the risk of pathogenic events. AIMS: To compare the concentration of nitric oxide metabolites in healthy adults between winter and summer months. DESIGN: An observational study of healthy adults (age 32 ± 9 years) living in central Scotland. METHODS: Thirty-four healthy adults (13 females) were monitored for 7 days in summer and winter to record sunlight exposure (ultraviolet-A (UV-A) radiation), diet, and physical activity. At the end of each phase, blood pressure was measured, and samples of blood and saliva collected. The samples were analysed to determine the concentrations of plasma and salivary nitrate and nitrite and serum 25-hydroxyvitamin D (25(OH)D). RESULTS: The participants maintained similar diets in each measurement phase but were exposed to more UV-A radiation (550%) and undertook more moderate-vigorous physical activity (23%) in the summer than in winter. Plasma nitrite (46%) and serum 25(OH)D (59%) were higher and blood pressure was lower in the summer compared to winter months. Plasma nitrite concentration was negatively associated with systolic, diastolic, and mean arterial blood pressure. CONCLUSIONS: Plasma nitrite, an established marker of nitric oxide synthesis, is higher in healthy adults during the summer than in winter. This may be mediated by a greater exposure to UV-A which stimulates the release of nitric oxide metabolites from skin stores. While it is possible that seasonal variation in nitric oxide availability may contribute to an increased blood pressure in the winter months, the overall impact on cardiovascular health remains to be determined.

Venous occlusion during blood collection decreases plasma nitrite but not nitrate concentration in humans.

BACKGROUND: To maintain vascular tone and blood flow when tissue oxygenation is reduced, nitrite anions are reduced to nitric oxide (NO). From a practical perspective, it is unclear how the application of a tourniquet during blood collection might influence measurement of NO metabolites. Accordingly, this study evaluated the effect of venous occlusion on plasma nitrite and nitrate during venous blood collection. METHODS: Fifteen healthy participants completed two trials that were preceded by the ingestion of nitrate-rich beetroot juice (BRJ; total of ~8.4 mmol nitrate) or no supplementation (control). In both trials, blood was collected using a venepuncture needle while a tourniquet was applied to the upper arm and using an indwelling intravenous cannula, from the opposing arm. The venepuncture samples were collected at 35 s post occlusion. Changes in the oxygenation of forearm flexor muscles were assessed using near-infrared spectroscopy. Plasma nitrite and nitrate were analysed using gas-phase chemiluminescence. RESULTS: In the control trial, plasma nitrite was significantly elevated when collected via the cannula (179 ± 67 nM) compared to venepuncture (112 ± 51 nM, P = 0.03). The ingestion of BRJ increased plasma nitrite and values remained higher when sampled from the cannula (473 ± 164 nM) compared to venepuncture (387 ± 136 nM, P < 0.001). Plasma nitrate did not differ between collection methods in either trial (all P > 0.05). The delta changes in total-, deoxy-, and oxy-haemoglobin were all significantly greater during venepuncture sample compared to the cannula sample at the point of blood collection (all P < 0.05). CONCLUSIONS: Venous occlusion during venepuncture blood collection lowers plasma nitrite concentration, potentially due to localised changes in haemoglobin concentration and/or a suppression of endogenous NO synthesis. Accordingly, the method of blood collection to enable measurements of NO metabolites should be carefully considered and consistently reported by researchers.

Dietary nitrate supplementation alters the oral microbiome but does not improve the vascular responses to an acute nitrate dose.

Nitrate (NO3-) contained in food and beverages can transiently increase nitric oxide (NO) availability following a stepwise reduction to nitrite (NO2-) by commensal bacteria in the oral cavity. We tested the hypothesis that regular ingestion of dietary NO3- would influence the oral microbiome, the capacity to reduce NO3- to NO2- in saliva, and the vascular responses to an acute dose of NO3-. The abundance of bacterial species on the tongue, the availability of NO markers, and vascular function were assessed in 11 healthy males before and after 7 days of supplementation with NO3--rich beetroot juice and a NO3--depleted placebo. As expected, saliva and plasma NO2- and NO3- were significantly elevated after NO3- supplementation (all P < 0.05) but not placebo. We found that NO3- supplementation increased salivary pH (7.13 ±â€¯0.54 to 7.39 ±â€¯0.68, P = 0.043) and altered the abundance of some bacteria previously implicated in NO3- reduction: Neisseria (from 2% ±â€¯3%-9% ±â€¯5%, P < 0.001), Prevotella (from 34% ±â€¯17%-23% ±â€¯11%, P = 0.001) and Actinomyces (from 1% ±â€¯1%-0.5% ±â€¯0.4%). Despite these alterations to the oral microbiota, an acute dose of NO3- increased salivary and plasma NO2-, reduced systolic blood pressure and increased the response to flow mediated dilation to a similar extent before and after 7 days of supplementation (P > 0.05). Our study establishes that supplementing the diet with NO3- for a sustained period can alter the oral environment in favour of health but does not impact the response to an acute NO3- dose. Acute ingestion of NO3- results in transient improvements in vascular function but the dietary induced adaptations to the oral bacteria did not enhance these effects.

Variability in nitrate-reducing oral bacteria and nitric oxide metabolites in biological fluids following dietary nitrate administration: An assessment of the critical difference.

There is conflicting evidence on whether dietary nitrate supplementation can improve exercise performance. This may arise from the complex nature of nitric oxide (NO) metabolism which causes substantial inter-individual variability, within-person biological variation (CVB), and analytical imprecision (CVA) in experimental endpoints. However, no study has quantified the CVA and CVB of NO metabolites or the factors that influence their production. These data are important to calculate the critical difference (CD), defined as the smallest difference between sequential measurements required to signify a true change. The main aim of the study was to evaluate the CVB, CVA, and CD for markers of NO availability (nitrate and nitrite) in plasma and saliva before and after the ingestion of nitrate-rich beetroot juice (BR). We also assessed the CVB of nitrate-reducing bacteria from the dorsal surface of the tongue. It was hypothesised that there would be substantial CVB in markers of NO availability and the abundance of nitrate-reducing bacteria. Ten healthy male participants (age 25 ±â€¯5 years) completed three identical trials at least 6 days apart. Blood and saliva were collected before and after (2, 2.5 and 3 h) ingestion of 140 ml of BR (∼12.4 mmol nitrate) and analysed for [nitrate] and [nitrite]. The tongue was scraped and the abundance of nitrate-reducing bacterial species were analysed using 16S rRNA next generation sequencing. There was substantial CVB for baseline concentrations of plasma (nitrate 11.9%, nitrite 9.0%) and salivary (nitrate 15.3%, nitrite 32.5%) NO markers. Following BR ingestion, the CVB for nitrate (plasma 3.8%, saliva 12.0%) and salivary nitrite (24.5%) were lower than baseline, but higher for plasma nitrite (18.6%). The CD thresholds that need to be exceeded to ensure a meaningful change from baseline are 25, 19, 37, and 87% for plasma nitrate, plasma nitrite, salivary nitrate, and salivary nitrite, respectively. The CVB for selected nitrate-reducing bacteria detected were: Prevotella melaninogenica (37%), Veillonella dispar (35%), Haemophilus parainfluenzae (79%), Neisseria subflava (70%), Veillonella parvula (43%), Rothia mucilaginosa (60%), and Rothia dentocariosa (132%). There is profound CVB in the abundance of nitrate-reducing bacteria on the tongue and the concentration of NO markers in human saliva and plasma. Where these parameters are of interest following experimental intervention, the CD values presented in this study will allow researchers to interpret the meaningfulness of the magnitude of the change from baseline.

An acute dose of inorganic dietary nitrate does not improve high-intensity, intermittent exercise performance in temperate or hot and humid conditions.

PURPOSE: Dietary nitrate (NO3-) has repeatedly been shown to improve endurance and intermittent, high-intensity events in temperate conditions. However, the ergogenic effects of dietary NO3- on intermittent exercise performance in hot conditions have yet to be investigated. METHODS: In a randomised, counterbalanced, double-blind crossover study, 12 recreationally trained males ingested a nitrate-rich beetroot juice shot (BRJ) (6.2 mmol NO3-) or a nitrate-depleted placebo (PLA) (< 0.004 mmol NO3-) 3 h prior to an intermittent sprint test (IST) in temperate (22 °C, 35% RH) and hot conditions (30 °C, 70% RH). The cycle ergometer IST consisted of twenty maximal 6 s sprints interspersed by 114 s of active recovery. Work done, power output, heart rate and RPE were measured throughout; tympanic temperature was measured prior to and upon completion. RESULTS: There were no significant effects of supplement on sprint performance in either temperate or hot, humid conditions (p > 0.05). There was a reduced peak (BRJ: 659 ± 100W vs. PLA: 693 ± 139W; p = 0.056) and mean power (BRJ: 543 ± 29W vs. PLA: 575 ± 38W; p = 0.081) following BRJ compared to PLA in the hot and humid condition, but this was not statistically significant. There was no effect of supplement on total work done irrespective of environmental condition. However, ~ 75% of participants experienced performance decreases following BRJ in the hot and humid environment. No differences were observed between trials for tympanic temperature measured at the conclusion of the exercise trial. CONCLUSION: In conclusion, an acute dose of inorganic dietary NO3- does not improve repeated-sprint performance in either temperate, or hot and humid conditions.

Changes in body posture alter plasma nitrite but not nitrate concentration in humans.

PURPOSE: This study evaluated the change (Δ) in plasma volume (PV), nitrate [NO3-], and nitrite [NO2-] concentration following changes in posture in the presence and absence of elevated plasma [NO3-] and [NO2-] METHODS: Fourteen healthy participants completed two trials that were preceded by either supplementation with NO3--rich beetroot juice (BR; total of ∼31 mmol NO3-) or no supplementation (CON). Both trials comprised 30 min of lying supine followed by 2 min of standing, 2 min of sitting and 5 min of sub-maximal cycling. Measurements of plasma [NO3-] and [NO2-] were made by gas-phase chemiluminescence and ΔPV was estimated using the Dill and Costill method. RESULTS: Plasma [NO2-] decreased from baseline (CON: 120 ± 49 nM, BR: 357 ± 129 nM) after lying supine for 30 min (CON 77 ± 30 nM; BR 231 ± 92 nM, both P < 0.01) before increasing during standing (CON 109 ± 42 nM; BR 297 ± 105 nM, both P < 0.01) and sitting (CON 131 ± 43 nM; BR 385 ± 125 nM, both P < 0.01). Plasma [NO2-] remained elevated following exercise only in CON (125 ± 61 nM P = 0.02). Plasma [NO3-] was not different between measurement points in either condition (P > 0.05). PV increased from baseline during the supine phase before decreasing upon standing, sitting, and exercise in both trials (all P<0.05). CONCLUSIONS: Changing body posture causes rapid and consistent alterations in plasma [NO2-]. Researchers should therefore carefully consider the effect of posture when measuring this variable.

The effects of two different doses of ultraviolet-A light exposure on nitric oxide metabolites and cardiorespiratory outcomes.

PURPOSE: The present study investigated different doses of ultraviolet-A (UV-A) light on plasma nitric oxide metabolites and cardiorespiratory variables. METHODS: Ten healthy male participants completed three experimental conditions, 7 days apart. Participants were exposed to no light (CON); 10 J cm2 (15 min) of UV-A light (UVA10) and 20 J cm2 (30 min) of UV-A light (UVA20) in a randomized order. Plasma nitrite [NO2-] and nitrate [NO3-] concentrations, blood pressure (BP), and heart rate (HR) were recorded before, immediately after exposure and 30 min post-exposure. Whole body oxygen utilization ([Formula: see text]), resting metabolic rate (RMR) and skin temperature were recorded continuously. RESULTS: None of the measured parameters changed significantly during CON (all P > 0.05). [Formula: see text] and RMR were significantly reduced immediately after UVA10 (P < 0.05) despite no change in plasma [NO2-] (P > 0.05). Immediately after exposure to UVA20, plasma [NO2-] was higher (P = 0.014) and [Formula: see text] and RMR tended to be lower compared to baseline (P = 0.06). There were no differences in [NO2-] or [Formula: see text] at the 30 min time point in any condition. UV-A exposure did not alter systolic BP, diastolic BP or MAP (all P > 0.05). UV-A light did not alter plasma [NO3-] at any time point (all P > 0.05). CONCLUSIONS: This study demonstrates that a UV-A dose of 20 J cm2 is necessary to increase plasma [NO2-] although a smaller dose is capable of reducing [Formula: see text] and RMR at rest. Exposure to UV-A did not significantly reduce BP in this cohort of healthy adults. These data suggest that exposure to sunlight has a meaningful acute impact on metabolic function.

Beetroot juice versus chard gel: A pharmacokinetic and pharmacodynamic comparison of nitrate bioavailability.

Dietary supplementation with inorganic nitrate (NO3-) has been shown to induce a multitude of advantageous cardiovascular and metabolic responses during rest and exercise. While there is some suggestion that pharmacokinetics may differ depending on the NO3- source ingested, to the best of our knowledge this has yet to be determined experimentally. Here, we compare the plasma pharmacokinetics of NO3-, nitrite (NO2-), and total nitroso species (RXNO) following oral ingestion of either NO3- rich beetroot juice (BR) or chard gels (GEL) with the associated changes in blood pressure (BP). Repeated samples of venous blood and measurements of BP were collected from nine healthy human volunteers before and after ingestion of the supplements using a cross-over design. Plasma concentrations of RXNO and NO2- were quantified using reductive gas-phase chemiluminescence and NO3- using high pressure liquid ion chromatography. We report that, [NO3-] and [NO2-] were increased and systolic BP reduced to a similar extent in each experimental arm, with considerable inter-individual variation. Intriguingly, there was a greater increase in [RXNO] following ingestion of BR in comparison to GEL, which may be a consequence of its higher polyphenol content. In conclusion, our data suggests that while differences in circulating NO2- and NO3- concentrations after oral administration of distinct NO3--rich supplementation sources are moderate, concentrations of metabolic by-products may show greater-than-expected variability; the significance of the latter observation for the biological effects under study remains to be investigated.

Acute whole body UVA irradiation combined with nitrate ingestion enhances time trial performance in trained cyclists.

Dietary nitrate supplementation has been shown to increase nitric oxide (NO) metabolites, reduce blood pressure (BP) and enhance exercise performance. Acute exposure to ultraviolet (UV)-A light also increases NO bioavailability and reduces BP. We conducted a randomized, counterbalanced placebo-controlled trial to determine the effects of UV-A light alone and in combination with nitrate on the responses to sub-maximal steady-state exercise and time trial (TT) performance. Nine cyclists (VO2max 53.1 ± 4.4 ml/kg/min) completed five performance trials comprising 10 min submaximal steady-state cycling followed by a 16.1 km TT. Following a familiarization the final four trials were preceded, in random order, by either (1) Nitrate gels (NIT) + UV-A, (2) Placebo (PLA) + UV-A, (3) NIT + Sham light (SHAM) and (4) PLA + SHAM (control). The NIT gels (2 × 60 ml gels, ~8.1 mmol nitrate) or a low-nitrate PLA were ingested 2.5 h prior to the trial. The light exposure consisted of 20 J/cm(2) whole body irradiation with either UV-A or SHAM light. Plasma nitrite was measured pre- and post-irradiation and VO2 was measured continuously during steady-state exercise. Plasma nitrite was higher for NIT + SHAM (geometric mean (95% CI), 332 (292-377) nM; P = 0.029) and NIT + UV-A (456 (312-666) nM; P = 0.014) compared to PLA + SHAM (215 (167-277) nM). Differences between PLA + SHAM and PLA + UV-A (282 (248-356) nM) were small and non-significant. During steady-state exercise VO2 was reduced following NIT + UVA (P = 0.034) and tended to be lower in NIT + SHAM (P = 0.086) but not PLA + UV-A (P = 0.381) compared to PLA + SHAM. Performance in the TT was significantly faster following NIT + UV-A (mean ± SD 1447 ± 41 s P = 0.005; d = 0.47), but not PLA + UV-A (1450 ± 40 s; d = 0.41) or NIT + SHAM (1455 ± 47 s; d = 0.28) compared to PLA + SHAM (1469 ± 52 s). These findings demonstrate that exposure to UV-A light alone does not alter the physiological responses to exercise or improve performance in a laboratory setting. A combination of UV-A and NIT, however, does improve cycling TT performance in this environment, which may be due to a larger increase in NO availability.

The effects of a single dose of concentrated beetroot juice on performance in trained flatwater kayakers.

The aim of the current study was to determine the effects of dietary nitrate ingestion on parameters of submaximal and supramaximal exercise and time trial (TT) performance in trained kayakers. Eight male kayakers completed four exercise trials consisting of an initial discontinuous graded exercise test to exhaustion and three performance trials using a kayak ergometer. The performance trials were composed of 15 min of paddling at 60% of maximum work rate, five 10-s all-out sprints, and a 1 km TT. The second and third trials were preceded by ingestion of either 70 ml nitrate-rich concentrated beetroot juice (BR) or tomato juice (placebo [PLA]) 3 hr before exercise using a randomized crossover design. Plasma nitrate (PLA: 33.8 ± 1.9 µM, BR: 152 ± 3.5 µM) and nitrite (PLA: 519.8 ± 25.8, BR: 687.9 ± 20 nM) were higher following ingestion of BR compared with PLA (both p < .001). VO2 during steady-state exercise was lower in the BR trial than in the PLA trial (p = .010). There was no difference in either peak power in the sprints (p = .590) or TT performance between conditions (PLA: 277 ± 5 s, BR: 276 ± 5 s, p = .539). Despite a reduction in VO2, BR ingestion appears to have no effect on repeated supramaximal sprint or 1 km TT kayaking performance. A smaller elevation in plasma nitrite following a single dose of nitrate and the individual variability in this response may partly account for these findings.

Performance benchmarking microplate-immunoassays for quantifying target-specific cysteine oxidation reveals their potential for understanding redox-regulation and oxidative stress.

The antibody-linked oxi-state assay (ALISA) for quantifying target-specific cysteine oxidation can benefit specialist and non-specialist users. Specialists can benefit from time-efficient analysis and high-throughput target and/or sample n-plex capacities. The simple and accessible "off-the-shelf" nature of ALISA brings the benefits of oxidative damage assays to non-specialists studying redox-regulation. Until performance benchmarking establishes confidence in the "unseen" microplate results, ALISA is unlikely to be widely adopted. Here, we implemented pre-set pass/fail criteria to benchmark ALISA by robustly evaluating immunoassay performance in diverse biological contexts. ELISA-mode ALISA assays were accurate, reliable, and sensitive. For example, the average inter-assay CV for detecting 20%- and 40%-oxidised PRDX2 or GAPDH standards was 4.6% (range: 3.6-7.4%). ALISA displayed target-specificity. Immunodepleting the target decreased the signal by ∼75%. Single-antibody formatted ALISA failed to quantify the matrix-facing alpha subunit of the mitochondrial ATP synthase. However, RedoxiFluor quantified the alpha subunit displaying exceptional performance in the single-antibody format. ALISA discovered that (1) monocyte-to-macrophage differentiation amplified PRDX2-specific cysteine oxidation in THP-1 cells and (2) exercise increased GAPDH-specific cysteine oxidation in human erythrocytes. The "unseen" microplate data were "seen-to-be-believed" via orthogonal visually displayed immunoassays like the dimer method. Finally, we established target (n = 3) and sample (n = 100) n-plex capacities in ∼4 h with 50-70 min hands-on time. Our work showcases the potential of ALISA to advance our understanding of redox-regulation and oxidative stress.

Exercise decreases PP2A-specific reversible thiol oxidation in human erythrocytes: Implications for redox biomarkers.

New readily accessible systemic redox biomarkers are needed to understand the biological roles reactive oxygen species (ROS) play in humans because overtly flawed, technically fraught, and unspecific assays severely hamper translational progress. The antibody-linked oxi-state assay (ALISA) makes it possible to develop valid ROS-sensitive target-specific protein thiol redox state biomarkers in a readily accessible microplate format. Here, we used a maximal exercise bout to disrupt redox homeostasis in a physiologically meaningful way to determine whether the catalytic core of the serine/threonine protein phosphatase PP2A is a candidate systemic redox biomarker in human erythrocytes. We reasoned that: constitutive oxidative stress (e.g., haemoglobin autoxidation) would sensitise erythrocytes to disrupted ion homeostasis as manifested by increased oxidation of the ion regulatory phosphatase PP2A. Unexpectedly, an acute bout of maximal exercise lasting ~16 min decreased PP2A-specific reversible thiol oxidation (redox ratio, rest: 0.46; exercise: 0.33) without changing PP2A content (rest: 193 pg/ml; exercise: 191 pg/ml). The need for only 3-4 µl of sample to perform ALISA means PP2A-specific reversible thiol oxidation is a capillary-fingertip blood-compatible candidate redox biomarker. Consistent with biologically meaningful redox regulation, thiol reductant-inducible PP2A activity was significantly greater (+10%) at rest compared to exercise. We establish a route to developing new readily measurable protein thiol redox biomarkers for understanding the biological roles ROS play in humans.

Does Connected Health Technology Improve Health-Related Outcomes in Rural Cardiac Populations? Systematic Review Narrative Synthesis.

Individuals living in rural areas are more likely to experience cardiovascular diseases (CVD) and have increased barriers to regular physical activity in comparison to those in urban areas. This systematic review aimed to understand the types and effects of home-based connected health technologies, used by individuals living in rural areas with CVD. The inclusion criteria included technology deployed at the participant's home and could be an mHealth (smart device, fitness tracker or app) or telehealth intervention. Nine electronic databases were searched across the date range January 1990-June 2021. A total of 207 full texts were screened, of which five studies were included, consisting of 603 participants. Of the five studies, four used a telehealth intervention and one used a form of wearable technology. All interventions which used a form of telehealth found a reduction in overall healthcare utilisation, and one study found improvements in CVD risk factors. Acceptability of the technologies was mixed, in some studies barriers and challenges were cited. Based on the findings, there is great potential for implementing connected health technologies, but due to the low number of studies which met the inclusion criteria, further research is required within rural areas for those living with cardiovascular disease.

Clinical and health economic evaluation of a post-stroke arrhythmia monitoring service.

Atrial fibrillation (AF) is a major cause of recurrent stroke and transient ischaemic attack (TIA) in the UK. As many patients can have asymptomatic paroxysmal AF, prolonged arrhythmia monitoring is advised in selected patients following a stroke or TIA. This service evaluation assessed the clinical and potential health economic impact of prolonged arrhythmia monitoring post-stroke using R-TEST monitoring devices. This was a prospective, case-controlled, service evaluation in a single health board in the North of Scotland. Patients were included if they had a recent stroke or TIA, were in sinus rhythm, and did not have another indication for, or contraindication to, oral anticoagulation. A health economic model was developed to estimate the clinical and economic value delivered by the R-TEST monitoring. Approval to use anonymised patient data in this service evaluation was obtained. During the evaluation period, 100 consecutive patients were included. The average age was 70 ± 11 years, 46% were female. Stroke was the presenting complaint in 83% of patients with the other 17% having had a TIA. AF was detected in seven of 83 (8.4%) patients who had had a stroke and one of 17 (5.9%) patients with a TIA. Health economic modelling predicted that adoption of R-TEST monitoring has a high probability of demonstrating both clinical and economic benefits. In conclusion, developing a post-stroke arrhythmia monitoring service using R-TEST devices is feasible, effective at detecting AF, and represents a probable clinical and economic benefit.

CD34+ progenitors are predictive of mortality and are associated with physical activity in cardiovascular disease patients.

BACKGROUND AND AIMS: Circulating progenitor cells (CPCs) play an important role in vascular repair and can influence cardiovascular (CV) health and longevity. Exercise is known to modulate these cells via mobilization from the bone marrow. The primary aims of this study were to evaluate the association of CPCs with mortality and explore the association between physical activity (PA) and CPCs. METHODS: 1751 individuals from the Framingham Offspring cohort (66 ± 9 years [40-92 years], 54% female) were included in the study. CPCs (CD34+, CD34+CD133+, CD34+CD133+KDR+) were measured by flow cytometry. Multivariable Cox regression analyses were performed to investigate relationship of CPCs with future CV event and mortality. Multivariate regression analyses were performed to determine the relationship between self-reported PA and CPC counts. RESULTS: Following adjustment for standard risk factors, there was an inverse association between CD34+ CPCs and all-cause mortality (hazard ratio (HR) per unit increase in CD34+, 0.79; 95% CI 0.64-0.98, p = 0.036). CD34+CD133+ CPCs were inversely associated with CV mortality (HR 0.63, 95% CI 0.44-0.91, p = 0.013). Associations of CD34+ and CD34+CD133+ with mortality were strongest in participants with pre-existing CVD. PA was associated with CD34+ CPCs only in CVD participants (PA Index: ß = 0.176, p = 0.003; moderate-to-vigorous [MVPA]: ß = 0.159, p = 0.007). This relationship was maintained after adjustment for confounding variables. CONCLUSIONS: A higher number of CD34+ and CD34+ CD133+ CPCs was inversely associated with all-cause and CV mortality. These associations were strongest in participants with CVD. PA is independently associated with CD34+ CPCs in individuals with CVD only, suggestive of greater benefit for this population group.

Accuracy of Wrist-Worn Photoplethysmography Devices at Measuring Heart Rate in the Laboratory and During Free-Living Activities.

This study compared heart rate (HR) measurements taken from two wrist-worn devices; the Empatica E4 and the Apple Watch Series 5, to that taken from a Polar H10 chest strap. Ten healthy adult volunteers took part in a laboratory validation study and performed a treadmill exercise protocol. A single-subject validity study was also conducted to evaluate the accuracy of continuous HR measurements obtained during free-living activities. The participant wore both wrist devices, as well as the Polar H10 for 12-hours, as she continued her habitual daily activities. The key findings of the laboratory study were that the Apple Watch was accurate at assessing HR compared to the Polar H10 with Mean Absolute Percentage Error (MAPE) values < 5% during treadmill exercise. The accuracy of the E4 however was generally poor with MAPE values > 15%. Findings from the single-subject validity study indicate that the Apple Watch produces accurate measurements of HR, whereas the E4 device overestimated HR, except for during the more strenuous activities undertaken where HR was underestimated.Clinical Relevance- The Apple Watch has acceptable accuracy in measuring HR during treadmill exercise and during free-living activities in healthy adult volunteers.

Measurement of Heart Rate Using the Polar OH1 and Fitbit Charge 3 Wearable Devices in Healthy Adults During Light, Moderate, Vigorous, and Sprint-Based Exercise: Validation Study.

BACKGROUND: Accurate, continuous heart rate measurements are important for health assessment, physical activity, and sporting performance, and the integration of heart rate measurements into wearable devices has extended its accessibility. Although the use of photoplethysmography technology is not new, the available data relating to the validity of measurement are limited, and the range of activities being performed is often restricted to one exercise domain and/or limited intensities. OBJECTIVE: The primary objective of this study was to assess the validity of the Polar OH1 and Fitbit Charge 3 devices for measuring heart rate during rest, light, moderate, vigorous, and sprint-type exercise. METHODS: A total of 20 healthy adults (9 female; height: mean 1.73 [SD 0.1] m; body mass: mean 71.6 [SD 11.0] kg; and age: mean 40 [SD 10] years) volunteered and provided written informed consent to participate in the study consisting of 2 trials. Trial 1 was split into 3 components: 15-minute sedentary activities, 10-minute cycling on a bicycle ergometer, and incremental exercise test to exhaustion on a motorized treadmill (18-42 minutes). Trial 2 was split into 2 components: 4 × 15-second maximal sprints on a cycle ergometer and 4 × 30- to 50-m sprints on a nonmotorized resistance treadmill. Data from the 3 devices were time-aligned, and the validity of Polar OH1 and Fitbit Charge 3 was assessed against Polar H10 (criterion device). Validity was evaluated using the Bland and Altman analysis, Pearson moment correlation coefficient, and mean absolute percentage error. RESULTS: Overall, there was a very good correlation between the Polar OH1 and Polar H10 devices (r=0.95), with a mean bias of -1 beats·min-1 and limits of agreement of -20 to 19 beats·min-1. The Fitbit Charge 3 device underestimated heart rate by 7 beats·min-1 compared with Polar H10, with a limit of agreement of -46 to 33 beats·min-1 and poor correlation (r=0.8). The mean absolute percentage error for both devices was deemed acceptable (<5%). Polar OH1 performed well across each phase of trial 1; however, validity was worse for trial 2 activities. Fitbit Charge 3 performed well only during rest and nonsprint-based treadmill activities. CONCLUSIONS: Compared with our criterion device, Polar OH1 was accurate at assessing heart rate, but the accuracy of Fitbit Charge 3 was generally poor. Polar OH1 performed worse during trial 2 compared with the activities in trial 1, and the validity of the Fitbit Charge 3 device was particularly poor during our cycling exercises.