Aerosol Oxidative Potential in the Greater Los Angeles Area: Source Apportionment and Associations with Socioeconomic Position.

Oxidative potential (OP) has been proposed as a possible integrated metric for particles smaller than 2.5 µm in diameter (PM2.5) to evaluate adverse health outcomes associated with particulate air pollution exposure. Here, we investigate how OP depends on sources and chemical composition and how OP varies by land use type and neighborhood socioeconomic position in the Los Angeles area. We measured OH formation (OPOH), dithiothreitol loss (OPDTT), black carbon, and 52 metals and elements for 54 total PM2.5 samples collected in September 2019 and February 2020. The Positive Matrix Factorization source apportionment model identified four sources contributing to volume-normalized OPOH: vehicular exhaust, brake and tire wear, soil and road dust, and mixed secondary and marine. Exhaust emissions contributed 42% of OPOH, followed by 21% from brake and tire wear. Similar results were observed for the OPDTT source apportionment. Furthermore, by linking measured PM2.5 and OP with census tract level socioeconomic and health outcome data provided by CalEnviroScreen, we found that the most disadvantaged neighborhoods were exposed to both the most toxic particles and the highest particle concentrations. OPOH exhibited the largest inverse social gradients, followed by OPDTT and PM2.5 mass. Finally, OPOH was the metric most strongly correlated with adverse health outcome indicators.

The impact of household air cleaners on the oxidative potential of PM2.5 and the role of metals and sources associated with indoor and outdoor exposure.

The health effects associated with human exposure to airborne fine particulate matter (PM2.5) have been linked to the ability of PM2.5 to facilitate the production of excess cellular reactive oxygen species (oxidative potential). Concern about the adverse human health impacts of PM2.5 has led to the increased use of indoor air cleaners to improve indoor air quality, which can be an important environment for PM2.5 exposure. However, the degree to which the oxidative potential of indoor and personal PM2.5 can be influenced by an indoor air cleaner remains unclear. In this study we enrolled 43 children with physician diagnosed asthma in suburban Shanghai, China and collected two paired-sets of 48-h indoor, outdoor, and personal PM2.5 exposure samples. One set of samples was collected under "real filtration" during which a functioning air cleaner was installed in the child's bedroom, and the other ("false filtration") with an air cleaner without internal filters. The PM2.5 samples were characterized by inductively coupled plasma mass spectroscopy for elements, and by an alveolar macrophage assay for oxidative potential. The sources of metals contributing to our samples were determined by the EPA Positive Matrix Factorization model. The oxidative potential was lower under real filtration compared to sham for indoor (median real/sham ratio: 0.260) and personal exposure (0.813) samples. Additionally, the sources of elements in PM2.5 that were reduced indoors and personal exposure samples by the air cleaner (e.g. regional aerosol and roadway emissions) were found by univariate multiple regression models to be among those contributing to the oxidative potential of the samples. An IQR increase in the regional aerosol and roadway emissions sources was associated with a 107% (95% CI: 80.1-138%) and 38.1% (17.6-62.1%) increase in measured oxidative potential respectively. Our results indicate that indoor air cleaners can reduce the oxidative potential of indoor and personal exposure to PM2.5, which may lead to improved human health.

Semi-volatile components of PM2.5 in an urban environment: volatility profiles and associated oxidative potential.

The volatility profiles of PM2.5 semi-volatile compounds and relationships to the oxidative potential of urban airborne particles were investigated in central Los Angeles, CA. Ambient and thermodenuded fine (PM2.5) particles were collected during both warm and cold seasons by employing the Versatile Aerosol Concentration Enrichment System (VACES) combined with a thermodenuder. When operated at 50 °C and 100 °C, the VACES/thermodenuder system removed about 50% and 75% of the PM2.5 volume concentration, respectively. Most of the quantified PM2.5 semi-volatile species including organic carbon (OC), water soluble organic carbon (WSOC), polycyclic aromatic hydrocarbons (PAHs), organic acids, n-alkanes, and levoglucosan, as well as inorganic ions (i.e., nitrate, sulfate, and ammonium) exhibited concentration losses in the ranges of 40-66% and 67-92%, respectively, as the thermodenuder temperature increased to 50 °C and 100 °C. Species in the PM2.5 such as elemental carbon (EC) and inorganic elements (including trace metals) were minimally impacted by the heating process - thus can be considered refractory. On average, nearly half of the PM2.5 oxidative potential (as measured by the dichlorodihydrofluorescein (DCFH) alveolar macrophage in vitro assay) was associated with the semi-volatile species removed by heating the aerosols to only 50 °C, highlighting the importance of this quite volatile compartment to the ambient PM2.5 toxicity. The fraction of PM2.5 oxidative potential lost upon heating the aerosols to 100 °C further increased to around 75-85%. Furthermore, we document statistically significant correlations between the PM2.5 oxidative potential and different semi-volatile organic compounds originating from primary and secondary sources, including OC (Rwarm, and Rcold) (0.86, and 0.74), WSOC (0.60, and 0.98), PAHs (0.88, and 0.76), organic acids (0.76, and 0.88), and n-alkanes (0.67, and 0.83) in warm and cold seasons, respectively, while a strong correlation between oxidative potential and levoglucosan, a tracer of biomass burning, was observed only during the cold season (Rcold=0.81).

Urinary Magnesium and Other Elements in Relation to Mammographic Breast Density, a Measure of Breast Cancer Risk.

PURPOSE: Heavy metals and other elements may act as breast carcinogens due to estrogenic activity. We investigated associations between urine concentrations of a panel of elements and breast density. METHODS: Mammographic density categories were abstracted from radiology reports of 725 women aged 40-65 yr in the Avon Army of Women. A panel of 27 elements was quantified in urine using high resolution magnetic sector inductively coupled plasma mass spectrometry. We applied LASSO (least absolute shrinkage and selection operator) logistic regression to the 27 elements and calculated odds ratios (OR) and 95% confidence intervals (CI) for dense vs. nondense breasts, adjusting for potential confounders. RESULTS: Of the 27 elements, only magnesium (Mg) was selected into the optimal regression model. The odds ratio for dense breasts associated with doubling the Mg concentration was 1.24 (95% CI 1.03-1.49). Doubling the calcium-to-magnesium ratio was inversely associated with dense breasts (OR 0.83, 95% CI 0.70-0.98). CONCLUSIONS: Our cross-sectional study found that higher levels of urinary magnesium were associated with greater breast density. Prospective studies are needed to confirm whether magnesium as evaluated in urine is prospectively associated with breast density and, more importantly, breast cancer.

Urinary Cadmium and Risk of Invasive Breast Cancer in the Women's Health Initiative.

Cadmium is a widespread heavy metal pollutant that may act as an exogenous estrogenic hormone. Environmental cadmium exposure has been associated with risk of breast cancer in retrospective studies. We prospectively assessed the relationship between cadmium exposure, evaluated by creatinine-normalized urinary cadmium concentration, and invasive breast cancer among 12,701 postmenopausal women aged ≥50 years in a Women's Health Initiative study of bone mineral density. After a median of 13.2 years of follow-up (1993-2010), 508 cases of invasive breast cancer and 1,050 comparison women were identified for a case-cohort analysis. Multivariable Cox regression was used to calculate hazard ratios and 95% confidence intervals. Risk of breast cancer was not associated with urinary cadmium parameterized either in quartiles (comparing highest quartile with lowest, hazard ratio = 0.80, 95% confidence interval: 0.56, 1.14; P for trend = 0.20) or as a log-transformed continuous variable (per 2-fold higher urinary cadmium concentration, hazard ratio = 0.94, 95% confidence interval: 0.86, 1.03). We did not observe an association between urinary cadmium and breast cancer risk in any subgroup examined, including never smokers and women with body mass index (weight (kg)/height (m)(2)) less than 25. Results were consistent in both estrogen receptor-positive and estrogen receptor-negative tumors. Our results do not support the hypothesis that environmental cadmium exposure is associated with risk of postmenopausal breast cancer.

Oxidative potential of size-fractionated atmospheric aerosol in urban and rural sites across Europe.

In this study we applied several assays, an in vitro rat alveolar macrophage model, a chemical ROS probe (DTT, dithiothreitol), and cytokine induction (TNFα) to examine relationships between PM-induced generation of reactive oxygen species (ROS) and PM composition, using a unique set of size-resolved PM samples obtained from urban and rural environments across Europe. From April-July 2012, we collected PM from roadside canyon, roadside motorway, and background urban sites in each of six European cities and from three rural sites spanning the continent. A Hi-Vol sampler was used to collect PM in three size classes (PM>7, PM7-3, PM3) and PM was characterized for total elements, and oxidative activity quantified in unfiltered and filtered PM extracts. We measured a remarkable uniformity in air concentrations of ROS and especially DTT activity across the continent. Only a 4-fold difference was documented for DTT across the urban sites and a similar variance was documented for ROS, implying that chemical drivers of oxidative activity are relatively similar between sites. The ROS and DTT specific activity was greater at urban background sites (and also rural sites) than at urban canyon locations. PM3 dominated the size distribution of both ROS activity (86% of total) and DTT activity (76% of total), reflecting both the large contribution of PM3 to total PM mass levels and importantly the higher specific oxidative activity of the PM3 in comparison with the larger particles. The soluble fraction of total activity was very high for DTT (94%) as well as for ROS (64%) in the PM3. However in the larger PM size fractions the contributions of the insoluble components became increasingly significant. The dominance of the insoluble PM drivers of activity was particularly evident in the TNFα data, where the insoluble contribution to cytokine production could be 100-fold greater than that from soluble components. ROS and DTT activity were strongly correlated in the PM3 (r = 0.93), however oxidative activity was not correlated with any measured inorganic element in this size cut. In contrast, significant correlations of both ROS and DTT oxidative activity with specific groups of chemical elements were documented in the larger PM size fractions.

The relative importance of tailpipe and non-tailpipe emissions on the oxidative potential of ambient particles in Los Angeles, CA.

This study examines the associations between the oxidative potential of ambient PM2.5 and PM0.18, measured by means of the dithiothreitol (DTT) assay, and their chemical constituents and modeled sources. Particulate matter (PM) samples were collected from 2012-2013 in Central Los Angeles (LA) and 2013-2014 in Anaheim, California, USA. Detailed chemical analyses of the PM samples, including carbonaceous species, inorganic elements and water-soluble ions, were conducted. Univariate analysis indicated a high correlation (R > 0.60) between the DTT activity and the concentrations of carbonaceous species at both sites. The strongest correlations were observed between DTT and organic tracers of primary vehicle tailpipe emissions including polycyclic aromatic hydrocarbons (PAHs) and hopanes as well as EC, with higher correlations for PM0.18versus PM2.5 components. Moreover, metals and trace elements (e.g., Ba, Cu, Fe, Mn, Pb and Sb) in both size ranges were also associated with DTT activity. Multiple linear regression (MLR) analysis was performed on DTT activity and PM sources identified by a Molecular Marker-Chemical Mass Balance (MM-CMB) model (i.e. major carbonaceous sources: vehicle tailpipe emissions, wood smoke, primary biogenic and secondary organic carbon) together with other typical sources of ambient PM (i.e. crustal material, vehicular abrasion, secondary ions and sea salt). Overall, our findings illustrate the relative importance of different traffic sources on the oxidative potential of ambient PM. Despite major reductions of tailpipe emissions, the lack of similar reductions (and possibly an increase) in non-tailpipe emissions makes them an important source of traffic-related PM in Los Angeles and their increasing role in the overall PM toxicity raises concerns for public health.

ROS-generating/ARE-activating capacity of metals in roadway particulate matter deposited in urban environment.

In this study we investigated the possible causal role for soluble metal species extracted from roadway traffic emissions in promoting particulate matter (PM)-induced reactive oxygen species (ROS) production and antioxidant response element (ARE) promoter activation. To this end, these responses have been evaluated in alveolar macrophage and epithelial lung cells that have been exposed to 'Unfiltered', 'Filtered' and 'Filtered+Chelexed' water extracts of PM samples collected from the roadway urban environments of Thessaloniki, Milan and London. Except for Thessaloniki, our results demonstrate that filtration resulted in a minor decrease in ROS activity of the fine PM fraction, suggesting that ROS activity is attributed mainly to water-soluble PM species. In contrast to ROS, ARE activity was mediated predominantly by the water-soluble component of PM present in both the fine and coarse extracts. Further removal of metals by Chelex treatment from filtered water extracts showed that soluble metal species are the major factors mediating ROS and ARE activities of the soluble fraction, especially in the London PM extracts. Finally, utilizing step-wise multiple-regression analysis, we show that 87% and 78% of the total variance observed in ROS and ARE assays, respectively, is accounted for by changes in soluble metal concentration. Using a statistical analysis we find that As, Zn and Fe best predict the ROS-generating/ARE-activating capacity of the near roadway particulate matter in the pulmonary cells studied. Collectively, our findings imply that soluble metals present in roadside PM are potential drivers of both pro- and anti-oxidative effects of PM in respiratory tract.

Associations of oxidative stress and inflammatory biomarkers with chemically-characterized air pollutant exposures in an elderly cohort.

BACKGROUND: Exposure to air pollution has been associated with cardiorespiratory morbidity and mortality. However, the chemical constituents and pollution sources underlying these associations remain unclear. METHOD: We conducted a cohort panel study involving 97 elderly subjects living in the Los Angeles metropolitan area. Airway and circulating biomarkers of oxidative stress and inflammation were measured weekly over 12 weeks and included, exhaled breath condensate malondialdehyde (EBC MDA), fractional exhaled nitric oxide (FeNO), plasma oxidized low-density lipoprotein (oxLDL), and plasma interleukin-6 (IL-6). Exposures included 7-day personal nitrogen oxides (NOx), daily criteria-pollutant data, five-day average particulate matter (PM) measured in three size-fractions and characterized by chemical components including transition metals, and in vitro PM oxidative potential (dithiothreitol and macrophage reactive oxygen species). Associations between biomarkers and pollutants were assessed using linear mixed effects regression models. RESULTS: We found significant positive associations of airway oxidative stress and inflammation with traffic-related air pollutants, ultrafine particles and transition metals. Positive but nonsignificant associations were observed with PM oxidative potential. The strongest associations were observed among PM variables in the ultrafine range (PM <0.18µm). It was estimated that an interquartile increase in 5-day average ultrafine polycyclic aromatic hydrocarbons was associated with a 6.3% (95% CI: 1.1%, 11.6%) increase in EBC MDA and 6.7% (95% CI: 3.4%, 10.2%) increase in FeNO. In addition, positive but nonsignificant associations were observed between oxLDL and traffic-related pollutants, ultrafine particles and transition metals while plasma IL-6 was positively associated with 1-day average traffic-related pollutants. CONCLUSION: Our results suggest that exposure to pollutants with high oxidative potential (traffic-related pollutants, ultrafine particles, and transition metals) may lead to increased airway oxidative stress and inflammation in elderly adults. This observation was less clear with circulating biomarkers.

Associations between microvascular function and short-term exposure to traffic-related air pollution and particulate matter oxidative potential.

BACKGROUND: Short-term exposure to ambient air pollution has been associated with acute increases in cardiovascular hospitalization and mortality. However, causative chemical components and underlying pathophysiological mechanisms remain to be clarified. We hypothesized that endothelial dysfunction would be associated with mobile-source (traffic) air pollution and that pollutant components with higher oxidative potential to generate reactive oxygen species (ROS) would have stronger associations. METHODS: We carried out a cohort panel study in 93 elderly non-smoking adults living in the Los Angeles metropolitan area, during July 2012-February 2014. Microvascular function, represented by reactive hyperemia index (RHI), was measured weekly for up to 12 weeks (N = 845). Air pollutant data included daily data from regional air-monitoring stations, five-day average PM chemical components and oxidative potential in three PM size-fractions, and weekly personal nitrogen oxides (NOx). Linear mixed-effect models estimated adjusted changes in microvascular function with exposure. RESULTS: RHI was inversely associated with traffic-related pollutants such as ambient PM2.5 black carbon (BC), NOx, and carbon monoxide (CO). An interquartile range change increase (1.06 µg/m(3)) in 5-day average BC was associated with decreased RHI, -0.093 (95 % CI: -0.151, -0.035). RHI was inversely associated with other mobile-source components/tracers (polycyclic aromatic hydrocarbons, elemental carbon, and hopanes), and PM oxidative potential as quantified in two independent assays (dithiothreitol and in vitro macrophage ROS) in accumulation and ultrafine PM, and transition metals. CONCLUSIONS: Our findings suggest that short-term exposures to traffic-related air pollutants with high oxidative potential are major components contributing to microvascular dysfunction.

Influence of Acidification on the Partitioning of Steroid Hormones among Filtrate, Filter Media, and Retained Particulate Matter.

Hormone contamination of aquatic systems has been shown to have deleterious effects on aquatic biota. However, the assessment of hormone contamination of aquatic environments requires a quantitative evaluation of the potential effects of sample preservation on hormone concentrations. This study investigated the influence of acidification (pH 2) of surface water samples on the partitioning of hormones among filtrate, filter media, and filter-retained particulate matter. Hormones were spiked into unpreserved and sulfuric acid-preserved ultrapure water and surface water runoff samples. The samples were filtered, and hormones were extracted from the filter and filtrate and analyzed by high-performance liquid chromatography. Acidification did not influence the partitioning of hormones onto the filter media. For the majority of the hormones investigated in this study, the partitioning of hormones to the filter-retained particulate matter was not influenced by acidification. Acidification increased the partitioning of progesterone and melengestrol acetate onto the retained particulate matter (about 25% for both analytes). Incorporation of an isotopically labeled internal standard (ISTD) for progesterone accounted for the loss of progesterone to the filter-retained particulates and resulted in accurate concentrations of progesterone in the filtrate. The incorporation of an ISTD for melengestrol acetate, however, was unable to account for the loss of melengestrol acetate to the retained particulates and resulted in underestimations of melengestrol acetate in the filtrate. Our results indicate that the analysis of melengestrol acetate in acid preserved surface runoff samples should be conducted on the filter-retained particulates as well as the filtrate.

Genetic variation in metallothionein and metal-regulatory transcription factor 1 in relation to urinary cadmium, copper, and zinc.

BACKGROUND: Metallothionein (MT) proteins play critical roles in the physiological handling of both essential (Cu and Zn) and toxic (Cd) metals. MT expression is regulated by metal-regulatory transcription factor 1 (MTF1). Hence, genetic variation in the MT gene family and MTF1 might influence excretion of these metals. METHODS: 321 women were recruited in Seattle, WA and Las Cruces, NM and provided demographic information, urine samples for measurement of metal concentrations by mass spectrometry and creatinine, and blood or saliva for extraction of DNA. Forty-one single nucleotide polymorphisms (SNPs) within the MTF1 gene region and the region of chromosome 16 encoding the MT gene family were selected for genotyping in addition to an ancestry informative marker panel. Linear regression was used to estimate the association of SNPs with urinary Cd, Cu, and Zn, adjusted for age, urinary creatinine, smoking history, study site, and ancestry. RESULTS: Minor alleles of rs28366003 and rs10636 near the MT2A gene were associated with lower urinary Cd, Cu, and Zn. Minor alleles of rs8044719 and rs1599823, near MT1A and MT1B, were associated with lower urinary Cd and Zn, respectively. Minor alleles of rs4653329 in MTF1 were associated with lower urinary Cd. CONCLUSIONS: These results suggest that genetic variation in the MT gene region and MTF1 influences urinary Cd, Cu, and Zn excretion.

Single Exposure to near Roadway Particulate Matter Leads to Confined Inflammatory and Defense Responses: Possible Role of Metals.

Inhalation of traffic-associated atmospheric particulate matter (PM2.5) is recognized as a significant health risk. In this study, we focused on a single ("subclinical response") exposure to water-soluble extracts from PM collected at a roadside site in a major European city to elucidate potential components that drive pulmonary inflammatory, oxidative, and defense mechanisms and their systemic impacts. Intratracheal instillation (IT) of the aqueous extracts induced a 24 h inflammatory response characterized by increased broncho-alveolar lavage fluid (BALF) cells and cytokines (IL-6 and TNF-α), increased reactive oxygen species production, but insignificant lipids and proteins oxidation adducts in mouse lungs. This local response was largely self-resolved by 48 h, suggesting that it could represent a subclinical response to everyday-level exposure. Removal of soluble metals by chelation markedly diminished the pulmonary PM-mediated response. An artificial metal solution (MS) recapitulated the PM extract response. The self-resolving nature of the response is associated with activating defense mechanisms (increased levels of catalase and glutathione peroxidase expression), observed with both PM extract and MS. In conclusion, metals present in PM collected near roadways are largely responsible for the observed transient local pulmonary inflammation and oxidative stress. Simultaneous activation of the antioxidant defense response may protect against oxidative damage.

Assessing the role of chemical components in cellular responses to atmospheric particle matter (PM) through chemical fractionation of PM extracts.

In order to further our understanding of the influence of chemical components and ultimately specific sources of atmospheric particulate matter (PM) on pro-inflammatory and other adverse cellular responses, we promulgate and apply a suite of chemical fractionation tools to aqueous aerosol extracts of PM samples for analysis in toxicity assays. We illustrate the approach with a study that used water extracts of quasi-ultrafine PM (PM0.25) collected in the Los Angeles Basin. Filtered PM extracts were fractionated using Chelex, a weak anion exchanger diethylaminoethyl (DEAE), a strong anion exchanger (SAX), and a hydrophobic C18 resin, as well as by desferrioxamine (DFO) complexation that binds iron. The fractionated extracts were then analyzed using high-resolution sector field inductively coupled plasma mass spectrometry (SF-ICPMS) to determine elemental composition. Cellular responses to the fractionated extracts were probed in an in vitro rat alveolar macrophages model with measurement of reactive oxygen species (ROS) production and the cytokine tumor necrosis factor-α (TNF-α). The DFO treatment that chelates iron was very effective at reducing the cellular ROS activity but had only a small impact on the TNF-α production. In contrast, the hydrophobic C18 resin treatment had a small impact on the cellular ROS activity but significantly reduced the TNF-α production. The use of statistical methods to integrate the results across all treatments led to the conclusion that sufficient iron must be present to participate in the chemistry needed for ROS activity, but the amount of ROS activity is not proportional to the iron solution concentration. ROS activity was found to be most related to cationic mono- and divalent metals (i.e., Mn and Ni) and oxyanions (i.e., Mo and V). Although the TNF-α production was not significantly affected by the chelexation of iron, it was greatly impacted by the removal of organics with the C18 resin and all other metal removal methods, suggesting that iron is not a critical pathway leading to TNF-α production, but a wide range of soluble metals and organic compounds in particulate matter play a role. Although the results are specific to the Los Angeles Basin, where the samples used in the study were collected, the method employed in the study can be widely employed to study the role of components of particulate matter in in vitro or in vivo assays.

An in vitro alveolar macrophage assay for the assessment of inflammatory cytokine expression induced by atmospheric particulate matter.

Exposures to air pollution in the form of particulate matter (PM) can result in excess production of reactive oxygen species (ROS) in the respiratory system, potentially causing both localized cellular injury and triggering a systemic inflammatory response. PM-induced inflammation in the lung is modulated in large part by alveolar macrophages and their biochemical signaling, including production of inflammatory cytokines, the primary mechanism via which inflammation is initiated and sustained. We developed a robust, relevant, and flexible method employing a rat alveolar macrophage cell line (NR8383) which can be applied to routine samples of PM from air quality monitoring sites to gain insight into the drivers of PM toxicity that lead to oxidative stress and inflammation. Method performance was characterized using extracts of ambient and vehicular engine exhaust PM samples. Our results indicate that the reproducibility and the sensitivity of the method are satisfactory and comparisons between PM samples can be made with good precision. The average relative percent difference for all genes detected during 10 different exposures was 17.1%. Our analysis demonstrated that 71% of genes had an average signal to noise ratio (SNR) ≥ 3. Our time course study suggests that 4 h may be an optimal in vitro exposure time for observing short-term effects of PM and capturing the initial steps of inflammatory signaling. The 4 h exposure resulted in the detection of 57 genes (out of 84 total), of which 86% had altered expression. Similarities and conserved gene signaling regulation among the PM samples were demonstrated through hierarchical clustering and other analyses. Overlying the core congruent patterns were differentially regulated genes that resulted in distinct sample-specific gene expression "fingerprints." Consistent upregulation of Il1f5 and downregulation of Ccr7 was observed across all samples, while TNFα was upregulated in half of the samples and downregulated in the other half. Overall, this PM-induced cytokine expression assay could be effectively integrated into health studies and air quality monitoring programs to better understand relationships between specific PM components, oxidative stress activity and inflammatory signaling potential.

Isotope concentrations from 24-h urine and 3-h serum samples can be used to measure intestinal magnesium absorption in postmenopausal women.

Studies suggest a link between magnesium status and osteoporosis. One barrier to more conclusive research on the potential relation is measuring intestinal magnesium absorption (MgA), which requires the use of stable isotopes and a ≥6-d stool or 3-d urine collection. We evaluated alternative methods of measuring MgA. We administered 2 stable magnesium isotopes to 15 postmenopausal women (cohort 1) aged 62 ± 8 y with a dietary magnesium intake of 345 ± 72 mg/d. Participants fasted from 1200 h to 0700 h and then consumed breakfast with ∼23 mg of oral ²6Mg and ∼11 mg of i.v. ²5Mg. We measured magnesium isotope concentrations in 72-h urine, spot urine (36, 48, 60, and 72 h), and spot serum (1, 3, and 5 h) samples collected after isotope dosing. We calculated MgA using the dose-corrected fraction of isotope concentrations from the 72-h urine collection. We validated new methods in 10 postmenopausal women (cohort 2) aged 59 ± 5 y with a dietary magnesium intake of 325 ± 122 mg/d. In cohort 1, MgA based on the 72-h urine collection was 0.28 ± 0.08. The 72-h MgA correlated most highly with 0-24 h urine MgA value alone (ρ = 0.95, P < 0.001) or the mean of the 0-24 h urine and the 3-h (ρ = 0.93, P < 0.001) or 5-h (ρ = 0.96, P < 0.001) serum MgA values. In cohort 2, Bland-Altman bias was lowest (-0.003, P = 0.82) using means of the 0-24 h urine and 3-h serum MgA values. We conclude that means of 0-24 h urine and 3-h serum MgA provide a reasonable estimate of 72-h MgA. However, if researchers seek to identify small changes in MgA, we recommend a 3-d urine or extended stool collection.

Global perspective on the oxidative potential of airborne particulate matter: a synthesis of research findings.

An emerging hypothesis in the field of air pollution is that oxidative stress is one of the important pathways leading to adverse health effects of airborne particulate matter (PM). To advance our understanding of sources and chemical elements contributing to aerosol oxidative potential and provide global comparative data, we report here on the biological oxidative potential associated with size-segregated airborne PM in different urban areas of the world, measured by a biological (cell-based) reactive oxygen species (ROS) assay. Our synthesis indicates a generally greater intrinsic PM oxidative potential as well as higher levels of exposure to redox-active PM in developing areas of the world. Moreover, on the basis of our observations, smaller size fractions are generally associated with higher intrinsic ROS activity compared with larger PM size fractions. Another important outcome of our study is the identification of major species and sources that are associated with ROS activity. Water-soluble transition metals (e.g., Fe, Ni, Cu, Cr, Mn, Zn and V) and water-soluble organic carbon (WSOC) showed consistent correlations with the oxidative potential of airborne PM across different urban areas and size ranges. The major PM sources associated with these chemical species include residual/fuel oil combustion, traffic emissions, and secondary organic aerosol formation, indicating that these sources are major drivers of PM-induced oxidative potential. Moreover, comparison of ROS activity levels across different seasons indicated that photochemical aging increases the intrinsic oxidative potential of airborne PM.

Local structure and speciation of platinum in fresh and road-aged North American sourced vehicle emissions catalysts: an X-ray absorption spectroscopic study.

Given emerging concerns about the bioavailability and toxicity of anthropogenic platinum compounds emitted into the environment from sources including vehicle emission catalysts (VEC), the platinum species present in selected North American sourced fresh and road-aged VEC were determined by Pt and Cl X-ray absorption spectroscopy. Detailed analysis of the Extended X-ray Absorption Fine Structure at the Pt L3 and L2 edges of the solid phase catalysts revealed mainly oxidic species in the fresh catalysts and metallic components dominant in the road-aged catalysts. In addition, some bimetallic components (Pt-Ni, Pt-Pd, Pt-Rh) were observed in the road-aged catalysts from supporting Ni-, Pd-, and Rh-K edge XAS studies. These detailed analyses allow for the significant conclusion that this study did not find any evidence for the presence of chloroplatinate species in the investigated solid phase of a Three Way Catalyst or Diesel Oxidation Catalysts.

Seasonal and spatial variation in dithiothreitol (DTT) activity of quasi-ultrafine particles in the Los Angeles Basin and its association with chemical species.

A year-long sampling campaign of quasi-ultrafine particles (dp < 0.25 µm) was conducted at 10 distinct sites representing source, urban and/or near-freeway, rural receptor and desert locations across the Los Angeles air basin. Redox activity of the PM samples was measured by means of the Dithiothreitol (DTT) assay and detailed chemical analysis was performed to measure the concentrations of chemical species. DTT activity per unit air volume and unit PM mass (expressed in nmol min(-1) m(-3) and nmol/min/µg PM, respectively) showed similar trends across sites and seasons. DTT activity was generally higher during cold seasons (winter and fall) compared to warm seasons (summer and spring). Noticeable peaks were observed at urban near-freeway locations representing "source" sites impacted by fresh traffic emissions. Regression analysis indicated strong association (R > 0.7) between the DTT activity and the concentrations of carbonaceous species (OC, EC, WSOC and WIOC) across all seasons and strong winter-time correlations with organic tracers of primary vehicular emissions including polycyclic aromatic hydrocarbons (PAHs), alkanes, hopanes and steranes. Strong correlations were also observed, particularly during winter, between DTT activity and transition metals (e.g., Cr, Mn, V, Fe, Cu, Cd and Zn), which share similar vehicular sources with primary organics. A multivariate linear regression analysis indicated that the variability in DTT activity is best explained by the variability in concentrations of WSOC, WIOC, EC and hopanes. Combined contributions from these species explained 88% of the DTT activity. The appearance of WSOC as a typical tracer of secondary organic aerosol, along with EC, WIOC and hopanes, all markers of emissions from primary combustion sources, emphasizes the contributions of both primary and secondary sources to the overall oxidative potential of quasi-ultrafine particles. Supplemental materials are available for this article. Go to the publisher's online edition of the Journal of Environmental Science and Health, Part A, to view the supplemental file.

Tracing the origin of SARS-CoV-2 omicron-like spike sequences detected in an urban sewershed: a targeted, longitudinal surveillance study of a cryptic wastewater lineage.

BACKGROUND: The origin of novel SARS-CoV-2 spike sequences found in wastewater, without corresponding detection in clinical specimens, remains unclear. We sought to determine the origin of one such cryptic wastewater lineage by tracking and characterising its persistence and genomic evolution over time. METHODS: We first detected a cryptic lineage, WI-CL-001, in municipal wastewater in Wisconsin, USA, in January, 2022. To determine the source of WI-CL-001, we systematically sampled wastewater from targeted sub-sewershed lines and maintenance holes using compositing autosamplers. Viral concentrations in wastewater samples over time were measured by RT digital PCR. In addition to using metagenomic 12s rRNA sequencing to determine the virus's host species, we also sequenced SARS-CoV-2 spike receptor binding domains, and, where possible, whole viral genomes to identify and characterise the evolution of this lineage. FINDINGS: We traced WI-CL-001 to its source at a single commercial building. There we detected the cryptic lineage at concentrations as high as 2·7 × 109 genome copies per L. The majority of 12s rRNA sequences detected in wastewater leaving the identified source building were human. Additionally, we generated over 100 viral receptor binding domain and whole-genome sequences from wastewater samples containing the cryptic lineage collected over the 13 consecutive months this virus was detectable (January, 2022, to January, 2023). These sequences contained a combination of fixed nucleotide substitutions characteristic of Pango lineage B.1.234, which circulated in humans in Wisconsin at low levels from October, 2020, to February, 2021. Despite this, mutations in the spike gene and elsewhere resembled those subsequently found in omicron variants. INTERPRETATION: We propose that prolonged detection of WI-CL-001 in wastewater indicates persistent shedding of SARS-CoV-2 from a single human initially infected by an ancestral B.1.234 virus. The accumulation of convergent omicron-like mutations in WI-CL-001's ancestral B.1.234 genome probably reflects persistent infection and extensive within-host evolution. People who shed cryptic lineages could be an important source of highly divergent viruses that sporadically emerge and spread. FUNDING: The Rockefeller Foundation, Wisconsin Department of Health Services, Centers for Disease Control and Prevention, National Institute on Drug Abuse, and the Center for Research on Influenza Pathogenesis and Transmission.