A single-particle characterization of a mobile Versatile Aerosol Concentration Enrichment System for exposure studies

BACKGROUND: An Aerosol Time-of-Flight Mass Spectrometer (ATOFMS) was used to investigate the size and chemical composition of fine concentrated ambient particles (CAPs) in the size range 0.2–2.6 μm produced by a Versatile Aerosol Concentration Enrichment System (VACES) contained within the Mobile Ambient Particle Concentrator Exposure Laboratory (MAPCEL). The data were collected during a study of human exposure to CAPs, in Edinburgh (UK), in February-March 2004. The air flow prior to, and post, concentration in the VACES was sampled in turn into the ATOFMS, which provides simultaneous size and positive and negative mass spectral data on individual fine particles. RESULTS: The particle size distribution was unaltered by the concentrator over the size range 0.2–2.6 μm, with an average enrichment factor during this study of ~5 (after dilution of the final air stream). The mass spectra from single particles were objectively grouped into 20 clusters using the multivariate K-means algorithm and then further grouped manually, according to similarity in composition and time sequence, into 8 main clusters. The particle ensemble was dominated by pure and reacted sea salt and other coarse inorganic dusts (as a consequence of the prevailing maritime-source climatology during the study), with relatively minor contributions from carbonaceous and secondary material. Very minor variations in particle composition were noted pre- and post-particle concentration, but overall there was no evidence of any significant change in particle composition. CONCLUSION: These results confirm, via single particle analysis, the preservation of the size distribution and chemical composition of fine ambient PM in the size range 0.2–2.6 μm after passage through the VACES concentration instrumentation

Chemosensory abilities in consumers of a western-style diet

People vary in their habitual diet and also in their chemosensory abilities. In this study we examined whether consumption of a Western-style diet, rich in saturated fat and added sugar, is associated with either poorer or different patterns of chemosensory perception, relative to people who consume a healthier diet. Participants were selected based on a food frequency questionnaire, which established whether they were likely to consume a diet either higher or lower in saturated fat and added sugar. Eighty-seven participants were tested for olfactory ability (threshold, discrimination, identification), gustatory ability (PROP sensitivity, taste intensity, quality and hedonics), and flavour processing (using dairy fat-sugar-odour mixtures). A Western-style diet was associated with poorer odour identification ability, greater PROP sensitivity, poorer fat discrimination, different patterns of sweetness taste enhancement, and hedonic differences in taste and flavour perception. No differences were evident for odour discrimination or threshold, in perception of taste intensity/quality (excluding PROP) or the ability of fats to affect flavour perception. The significant relationships were of small to moderate effect size, and would be expected to work against consuming a healthier diet. The discussion focuses on whether these diet-related differences precede adoption of a Western-style diet and/or are a consequence of it

Fibrin clot structure remains unaffected in young, healthy individuals after transient exposure to diesel exhaust

Exposure to urban particulate matter has been associated with an increased risk of cardiovascular disease and thrombosis. We studied the effects of transient exposure to diesel particles on fibrin clot structure of 16 healthy individuals (age 21- 44). The subjects were randomly exposed to diesel exhaust and filtered air on two separate occasions. Blood samples were collected before exposure, and 2 and 6 hours after exposure. There were no significant changes on clot permeability, maximum turbidity, lag time, fibre diameter, fibre density and fibrinogen level between samples taken after diesel exhaust exposure and samples taken after filtered air exposure. These data show that there are no prothrombotic changes in fibrin clot structure in young, healthy individuals exposed to diesel exhaust

Early computed tomography coronary angiography in adults presenting with suspected acute coronary syndrome:the RAPID-CTCA RCT

Abstract Background Acute coronary syndrome is a common medical emergency. The optimal strategy to investigate patients who are at intermediate risk of acute coronary syndrome has not been fully determined. Objective To investigate the role of early computed tomography coronary angiography in the investigation and treatment of adults presenting with suspected acute coronary syndrome. Design A prospective, multicentre, open, parallel-group randomised controlled trial with blinded end-point adjudication. Setting Thirty-seven hospitals in the UK. Participants Adults (aged ≥ 18 years) presenting to the emergency department, acute medicine services or cardiology department with suspected or provisionally diagnosed acute coronary syndrome and at least one of the following: (1) a prior history of coronary artery disease, (2) a cardiac troponin level > 99th centile and (3) an abnormal 12-lead electrocardiogram. Interventions Early computed tomography coronary angiography in addition to standard care was compared with standard care alone. Participants were followed up for 1 year. Main outcome measure One-year all-cause death or subsequent type 1 (spontaneous) or type 4b (stent thrombosis) myocardial infarction, measured as the time to such event adjudicated by two cardiologists blinded to the computerised tomography coronary angiography (CTCA) arm. Cost-effectiveness was estimated as the lifetime incremental cost per quality-adjusted life-year gained. Results Between 23 March 2015 and 27 June 2019, 1748 participants [mean age 62 years (standard deviation 13 years), 64% male, mean Global Registry Of Acute Coronary Events score 115 (standard deviation 35)] were randomised to receive early computed tomography coronary angiography (n = 877) or standard care alone (n = 871). The primary end point occurred in 51 (5.8%) participants randomised to receive computed tomography coronary angiography and 53 (6.1%) participants randomised to receive standard care (adjusted hazard ratio 0.91, 95% confidence interval 0.62 to 1.35; p = 0.65). Computed tomography coronary angiography was associated with a reduced use of invasive coronary angiography (adjusted hazard ratio 0.81, 95% confidence interval 0.72 to 0.92; p = 0.001) but no change in coronary revascularisation (adjusted hazard ratio 1.03, 95% confidence interval 0.87 to 1.21; p = 0.76), acute coronary syndrome therapies (adjusted odds ratio 1.06, 95% confidence interval 0.85 to 1.32; p = 0.63) or preventative therapies on discharge (adjusted odds ratio 1.07, 95% confidence interval 0.87 to 1.32; p = 0.52). Early computed tomography coronary angiography was associated with longer hospitalisations (median increase 0.21 days, 95% confidence interval 0.05 to 0.40 days) and higher mean total health-care costs over 1 year (£561 more per patient) than standard care. Limitations The principal limitation of the trial was the slower than anticipated recruitment, leading to a revised sample size, and the requirement to compromise and accept a larger relative effect size estimate for the trial intervention. Future work The potential role of computed tomography coronary angiography in selected patients with a low probability of obstructive coronary artery disease (intermediate or mildly elevated level of troponin) or who have limited access to invasive cardiac catheterisation facilities needs further prospective evaluation. Conclusions In patients with suspected or provisionally diagnosed acute coronary syndrome, computed tomography coronary angiography did not alter overall coronary therapeutic interventions or 1-year clinical outcomes, but it did increase the length of hospital stay and health-care costs. These findings do not support the routine use of early computed tomography coronary angiography in intermediate-risk patients with acute chest pain

Challenging the obesity paradox: Extreme obesity and COPD mortality in the SUMMIT Trial

Populations with COPD demonstrate higher survival in overweight and obese compared with normal weight; the “obesity paradox”. Relationships in less-severe COPD are unclear, as is the impact of cardiovascular risk, and few studies include individuals at extremes of obesity.  We examined the relationship between body mass index (BMI; defined as underweight: 40 kg·m−2, suggesting that obesity may not remain protective at the extremes in this population

Manganese-Enhanced T₁ Mapping in the Myocardium of Normal and Infarcted Hearts

Background. Manganese-enhanced MRI (MEMRI) has the potential to identify viable myocardium and quantify calcium influx and handling. Two distinct manganese contrast media have been developed for clinical application, mangafodipir and EVP1001-1, employing different strategies to mitigate against adverse effects resulting from calcium-channel agonism. Mangafodipir delivers manganese ions as a chelate, and EVP1001-1 coadministers calcium gluconate. Using myocardial T1 mapping, we aimed to explore chelated and nonchelated manganese contrast agents, their mechanism of myocardial uptake, and their application to infarcted hearts. Methods. T1 mapping was performed in healthy adult male Sprague-Dawley rats using a 7T MRI scanner before and after nonchelated (EVP1001-1 or MnCl2 (22 μmol/kg)) or chelated (mangafodipir (22–44 μmol/kg)) manganese-based contrast media in the presence of calcium channel blockade (diltiazem (100–200 μmol/kg/min)) or sodium chloride (0.9%). A second cohort of rats underwent surgery to induce anterior myocardial infarction by permanent coronary artery ligation or sham surgery. Infarcted rats were imaged with standard gadolinium delayed enhancement MRI (DEMRI) with inversion recovery techniques (DEMRI inversion recovery) as well as DEMRI T1 mapping. A subsequent MEMRI scan was performed 48 h later using either nonchelated or chelated manganese and T1 mapping. Finally, animals were culled at 12 weeks, and infarct size was quantified histologically with Masson’s trichrome (MTC). Results. Both manganese agents induced concentration-dependent shortening of myocardial T1 values. This was greatest with nonchelated manganese, and could be inhibited by 30–43% with calcium-channel blockade. Manganese imaging successfully delineated the area of myocardial infarction. Indeed, irrespective of the manganese agent, there was good agreement between infarct size on MEMRI T1 mapping and histology (bias 1.4%, 95% CI −14.8 to 17.1 P&gt;0.05). In contrast, DEMRI inversion recovery overestimated infarct size (bias 11.4%, 95% CI −9.1 to 31.8 P=0.002), as did DEMRI T1 mapping (bias 8.2%, 95% CI −10.7 to 27.2 P=0.008). Increased manganese uptake was also observed in the remote myocardium, with remote myocardial ∆T1 inversely correlating with left ventricular ejection fraction after myocardial infarction (r=−0.61, P=0.022). Conclusions. MEMRI causes concentration and calcium channel-dependent myocardial T1 shortening. MEMRI with T1 mapping provides an accurate assessment of infarct size and can also identify changes in calcium handling in the remote myocardium. This technique has potential applications for the assessment of myocardial viability, remodelling, and regeneration.</jats:p

Beneficial cardiovascular effects of reducing exposure to particulate air pollution with a simple facemask

<p>Abstract</p> <p>Background</p> <p>Exposure to air pollution is an important risk factor for cardiovascular morbidity and mortality, and is associated with increased blood pressure, reduced heart rate variability, endothelial dysfunction and myocardial ischaemia. Our objectives were to assess the cardiovascular effects of reducing air pollution exposure by wearing a facemask.</p> <p>Methods</p> <p>In an open-label cross-over randomised controlled trial, 15 healthy volunteers (median age 28 years) walked on a predefined city centre route in Beijing in the presence and absence of a highly efficient facemask. Personal exposure to ambient air pollution and exercise was assessed continuously using portable real-time monitors and global positional system tracking respectively. Cardiovascular effects were assessed by continuous 12-lead electrocardiographic and ambulatory blood pressure monitoring.</p> <p>Results</p> <p>Ambient exposure (PM_2.586 ± 61 <it>vs </it>140 ± 113 μg/m³; particle number 2.4 ± 0.4 <it>vs </it>2.3 ± 0.4 × 10⁴particles/cm³), temperature (29 ± 1 <it>vs </it>28 ± 3°C) and relative humidity (63 ± 10 <it>vs </it>64 ± 19%) were similar (P > 0.05 for all) on both study days. During the 2-hour city walk, systolic blood pressure was lower (114 ± 10 <it>vs </it>121 ± 11 mmHg, P < 0.01) when subjects wore a facemask, although heart rate was similar (91 ± 11 <it>vs </it>88 ± 11/min; P > 0.05). Over the 24-hour period heart rate variability increased (SDNN 65.6 ± 11.5 <it>vs </it>61.2 ± 11.4 ms, P < 0.05; LF-power 919 ± 352 <it>vs </it>816 ± 340 ms², P < 0.05) when subjects wore the facemask.</p> <p>Conclusion</p> <p>Wearing a facemask appears to abrogate the adverse effects of air pollution on blood pressure and heart rate variability. This simple intervention has the potential to protect susceptible individuals and prevent cardiovascular events in cities with high concentrations of ambient air pollution.</p