Health impact assessment of PM2.5 from uncovered coal trains in the San Francisco Bay Area: Implications for global exposures.

Coal generates almost 40% of the world's electricity with 80 countries throughout the world using coal power. An inherent part of this generation is the rail transport of coal in uncovered cars, often up to a mile long. Existing studies document the subsequent increments of PM2.5 to the near-rail populations, which typically include a large number of economically disadvantaged residents and/or people of color. However, to date there is no assessment of the health implications of this stage in the use of coal. The present study quantifies such impacts on a region in the San Francisco Bay Area. The analysis shows important effects on mortality, hospitalization for cardiovascular and respiratory disease, asthma exacerbation, work loss, and days of restricted activity. Several of these outcomes exhibited a one to six percent increase over baseline. As such, it delineates the implications for the global effects of the transport of coal.

Impact of a Municipal Policy Restricting Trans Fatty Acid Use in New York City Restaurants on Serum Trans Fatty Acid Levels in Adults.

OBJECTIVES: To estimate the impact of the 2006 policy restricting use of trans fatty acids (TFAs) in New York City restaurants on change in serum TFA concentrations in New York City adults. METHODS: Two cross-sectional population-based New York City Health and Nutrition Examination Surveys conducted in 2004 (n = 212) and 2013-2014 (n = 247) provided estimates of serum TFA exposure and average frequency of weekly restaurant meals. We estimated the geometric mean of the sum of serum TFAs by year and restaurant meal frequency by using linear regression. RESULTS: Among those who ate less than 1 restaurant meal per week, geometric mean of the sum of serum TFAs declined 51.1% (95% confidence interval [CI] = 42.7, 58.3)-from 44.6 (95% CI = 39.7, 50.1) to 21.8 (95% CI = 19.3, 24.5) micromoles per liter. The decline in the geometric mean was greater (P for interaction = .04) among those who ate 4 or more restaurant meals per week: 61.6% (95% CI = 55.8, 66.7) or from 54.6 (95% CI = 49.3, 60.5) to 21.0 (95% CI = 18.9, 23.3) micromoles per liter. CONCLUSIONS: New York City adult serum TFA concentrations declined between 2004 and 2014. The indication of greater decline in serum TFAs among those eating restaurant meals more frequently suggests that the municipal restriction on TFA use was effective in reducing TFA exposure. Public Health Implications. Local policies focused on restaurants can promote nutritional improvements.

Impact of internal standard selection on measurement results for long chain fatty acids in blood.

Introduction: Internal standards correct for measurement variation due to sample loss. Isotope labeled analytes are ideal internal standards for the measurement of fatty acids in human plasma but are not always readily available. For this reason, quantification of multiple analytes at once is most often done using only a single or few internal standards. The magnitude of the impact this has on method accuracy and precision is not well studied for gas chromatography-mass spectrometry systems. Objective: This study aims to estimate bias and changes in uncertainty associated with using alternative fatty acid isotopologue internal standards for the estimation of similar or dissimilar long chain fatty acids. Method: Using a previously reported method for the quantification of 27 fatty acids in human plasma using 18 internal standards we obtained estimates of bias and uncertainty at up to three levels of fatty acid concentration. Results: With some notable exceptions, method accuracy remained relatively stable when using an alternative internal standard (Median Relative Absolute Percent Bias: 1.76%, Median Spike-Recovery Absolute Percent Bias: 8.82%), with larger changes in method precision (Median Increase in Variance: 141%). Additionally, the degree of difference between analyte and internal standard structure was related to the magnitude of bias and uncertainty of the measurement. Conclusion: The data presented here show that the choice of internal standard used to estimate fatty acid concentration can affect the accuracy and reliability of measurement results and, therefore, needs to be assessed carefully when developing analytical methods for the measurement of fatty acid profiles.Disclaimer: The findings and conclusions in this report are those of the author(s) and do not necessarily represent the official position of the Centers for Disease Control and Prevention/the Agency for Toxic Substances and Disease Registry. Use of trade names is for identification only and does not imply endorsement by the Centers for Disease Control and Prevention, the Public Health Service, and the US Department of Health and Human Services.

Psychedelic public health: State of the field and implications for equity.

BACKGROUND: Psychedelic Public Health is an emerging discipline uniting the practices of public health with the potential benefits of psychedelics to reduce harm and promote health, wellness, and equity at community and population levels. Little is known regarding the current state of psychedelic public health despite rising psychedelic usage, evidence of its health efficacy, opening policy environments, and concerns regarding equity and potential harms. METHODS: To characterize the current state of psychedelic public health, this survey reviewed relevant webpages from 228 universities housing accredited Schools and Programs in Public Health (SPPHs) and 59 Psychedelic Research Centers (PRCs) in the US and globally. The scan corresponded to the Prisma 2020 checklist, identifying URLs through keyword searches by Beautiful Soup python package and Google search engine web application. Measures were coded through webpage text analysis. FINDINGS: Fewer than 10% (9.6%) of SPPHs engaged with psychedelics (2.6% substantially), while half (52.6%) of universities engaged (28.1% substantially). Among PRCs, only 10% indicated a collaboration with SPPHs, and fewer than 3% of PRC personnel held public health degrees. PRCs were preponderantly affiliated with medical schools. Although Indigeneity significantly contributes to Western therapeutic psychedelic protocols, only approximately one-quarter of active universities, SPPHs, or PRCs visibly addressed Indigeneity and only one PRC included Indigenous leadership. 92% of PRCs were led or co-led by people characterized as White-European and 88% by men. Only 20-43% of SPPHs, universities, and PRCs visibly addressed social determinants of health. CONCLUSIONS: Public health schools, which train, study, and advise the future of public health, showed limited involvement in the growing psychedelic field, signifying a gap in psychedelic science and practice. The absence of public health's population-level approaches signifies a missed opportunity to maximize benefits and protect against potential harms of psychedelics at community and population levels.

The impact of coal trains on PM2.5 in the San Francisco Bay area.

Exposure to fine particulate matter (PM2.5) is associated with adverse health effects, including mortality, even at low concentrations. Rail conveyance of coal, accounting for one-third of American rail freight tonnage, is a source of PM2.5. However, there are limited studies of its contribution to PM2.5, especially in urban settings where residents experience higher exposure and vulnerability to air pollution. We developed a novel artificial intelligence-driven monitoring system to quantify average and maximum PM2.5 concentrations of full and empty (unloaded) coal trains compared to freight and passenger trains. The monitor was close to the train tracks in Richmond, California, a city with a racially diverse population of 115,000 and high rates of asthma and heart disease. We used multiple linear regression models controlling for diurnal patterns and meteorology. The results indicate coal trains add on average 8.32 µg/m3 (95% CI = 6.37, 10.28; p < 0.01) to ambient PM2.5, while sensitivity analysis produced midpoints ranging from 5 to 12 µg/m3. Coal trains contributed 2 to 3 µg/m3 more of PM2.5 than freight trains, and 7 µg/m3 more under calm wind conditions, suggesting our study underestimates emissions and subsequent concentrations of coal train dust. Empty coal cars tended to add 2 µg/m3. Regarding peak concentrations of PM2.5, our models suggest an increase of 17.4 µg/m3 (95% CI = 6.2, 28.5; p < 0.01) from coal trains, about 3 µg/m3 more than freight trains. Given rail shipment of coal occurs globally, including in populous areas, it is likely to have adverse effects on health and environmental justice.

Local health department leadership strategies for healthy built environments.

CONTEXT: The built environment is an important but less-recognized health determinant, and local health departments need expanded guidance to address it. In such situations, leadership is particularly relevant. OBJECTIVE: To assess whether and how local public and environmental health leaders increase their departments' health-promoting impact on built environment design, and what pitfalls they should avoid. DESIGN: Mixed-methods employing cross-sectional surveys and a comparative case study. SETTING: Local public and environmental health departments. PARTICIPANTS SURVEY: A total of 159 (89%) health officers, health directors, and environmental health directors from all 62 local jurisdictions in California. Case-Study: Three departments, 12 cases, 36 health and land-use professionals, and 30 key informants. MAIN OUTCOME MEASURES: The study measured the influence of leadership practices on health departments' built environment-related collaborations, land use activities, policy developments, and contributions to physical changes. Quantitative multivariate linear and logistic regression were used. Case-study content analysis and pattern-matching, which related strong and weak leadership practices to outcomes, were also employed. RESULTS: Departments having highly innovative leaders with positive attitudes had greater odds of achieving physical changes to the built environment (OR: 4.5, 3.4, respectively). Leadership that most prepared their departments for built environment work (by updating staffing, structure, and strategy) tripled interagency and cross-sector collaboration (OR: 3.4). Leadership of successful departments consistently (1) established and managed a healthy built environment vision, (2) cultivated innovation, (3) supported, empowered and protected staff, (4) directly engaged in land use and transportation processes, (5) established direct contacts with directors in other departments, and (6) leveraged their professional reputation. Inconsistency in these practices was twice as common among failure as success cases (80%, 43%). CONCLUSIONS: Local health leadership underlies public and environmental health departments' community design efforts and should receive technical support and targeted resources to do so effectively.

Dietary Sources of Plasma trans Fatty Acids among Adults in the United States: NHANES 2009-2010.

BACKGROUND: Intake of trans fatty acids (TFAs) increases LDL cholesterol, decreases HDL cholesterol, and increases the risk of heart disease morbidity and mortality. Many food products potentially contain industrially produced or ruminant TFAs. However, little is known about the dietary sources of plasma TFA concentrations. OBJECTIVE: The objective of this study was to examine associations between foods consumed and plasma TFA concentrations using 24-h dietary recall data and plasma TFA measures among adults aged ≥20 y who participated in the NHANES 2009-2010 in the United States. METHODS: Over 4400 food products in the dietary interview data were categorized into 32 food and beverage groups/subgroups. Four major plasma TFAs (palmitelaidic acid, elaidic acid, vaccenic acid, linolelaidic acid) and the sum of the 4 TFAs (sumTFAs) were analyzed using GC-MS. Multivariable linear regression analyses were conducted to identify associations of plasma TFAs with all 32 food and beverage groups/subgroups, controlling for the potential confounding effects of 11 demographic, socioeconomic, behavioral, lifestyle, and health-related variables. RESULTS: Consumption of the following food groups/subgroups was significantly associated with elevated plasma TFA concentrations: cream substitutes (P < 0.001 for palmitelaidic acid, elaidic acid, vaccenic acid, and sumTFAs); cakes, cookies, pastries, and pies (P < 0.001 for elaidic acid, vaccenic acid, and sumTFAs; P < 0.05 for linolelaidic acid); milk and milk desserts (P < 0.01 for palmitelaidic acid and vaccenic acid; P < 0.05 for linolelaidic acid and sumTFAs); beef/veal, lamb/goat, and venison/deer (P < 0.01 for vaccenic acid; P < 0.05 for sumTFAs); and butters (P < 0.001 for palmitelaidic acid and vaccenic acid; P < 0.05 for sumTFAs). CONCLUSIONS: The findings suggest that the above 5 food groups/subgroups could be the main dietary sources of plasma TFAs among adults in the United States in 2009-2010.

Cost assessment of a program for laboratory testing of plasma trans-fatty acids in Thailand.

Objectives: Intake of trans fatty acids (TFA) increases the risk of cardiovascular disease. Assessment of TFA exposure in the population is key for determining TFA burden and monitoring change over time. One approach for TFA monitoring is measurement of TFA levels in plasma. Understanding costs associated with this approach can facilitate program planning, implementation and scale-up. This report provides an assessment of costs associated with a pilot program to measure plasma TFA levels in Thailand. Study design: Cost analysis in a laboratory facility in Thailand. Methods: We defined three broad cost modules: laboratory, personnel, and facility costs, which were further classified into sub-components and into fixed and variable categories. Costs were estimated based on the number of processed plasma samples (100-2700 in increments of 50) per year over a certain number of years (1-5), in both USD and Thai Baht. Total cost and average costs per sample were estimated across a range of samples processed. Results: The average cost per sample of analyzing 900 samples annually over 5 years was estimated at USD186. Laboratory, personnel, and facility costs constitute 67%, 23%, and 10% of costs, respectively. The breakdown across fixed costs, such as laboratory instruments and personnel, and variable costs, such as chemical supplies, was 60% and 40%, respectively. Average costs decline as more samples are processed: the cost per sample for analyzing 100, 500, 1500, and 2500 samples per year over 5 years is USD1351, USD301, USD195; and USD177, respectively. Conclusions: Laboratory analysis of plasma TFA levels has high potential for economies of scale, encouraging a long-term approach to TFA monitoring initiatives, particularly in countries that already maintain national biometric repositories.

Impact of community-based maternal health workers on coverage of essential maternal health interventions among internally displaced communities in eastern Burma: the MOM project.

BACKGROUND: Access to essential maternal and reproductive health care is poor throughout Burma, but is particularly lacking among internally displaced communities in the eastern border regions. In such settings, innovative strategies for accessing vulnerable populations and delivering basic public health interventions are urgently needed. METHODS: Four ethnic health organizations from the Shan, Mon, Karen, and Karenni regions collaborated on a pilot project between 2005 and 2008 to examine the feasibility of an innovative three-tiered network of community-based providers for delivery of maternal health interventions in the complex emergency setting of eastern Burma. Two-stage cluster-sampling surveys among ever-married women of reproductive age (15-45 y) conducted before and after program implementation enabled evaluation of changes in coverage of essential antenatal care interventions, attendance at birth by those trained to manage complications, postnatal care, and family planning services. RESULTS: Among 2,889 and 2,442 women of reproductive age in 2006 and 2008, respectively, population characteristics (age, marital status, ethnic distribution, literacy) were similar. Compared to baseline, women whose most recent pregnancy occurred during the implementation period were substantially more likely to receive antenatal care (71.8% versus 39.3%, prevalence rate ratio [PRR] = 1.83 [95% confidence interval (CI) 1.64-2.04]) and specific interventions such as urine testing (42.4% versus 15.7%, PRR = 2.69 [95% CI 2.69-3.54]), malaria screening (55.9% versus 21.9%, PRR = 2.88 [95% CI 2.15-3.85]), and deworming (58.2% versus 4.1%, PRR = 14.18 [95% CI 10.76-18.71]. Postnatal care visits within 7 d doubled. Use of modern methods to avoid pregnancy increased from 23.9% to 45.0% (PRR = 1.88 [95% CI 1.63-2.17]), and unmet need for contraception was reduced from 61.7% to 40.5%, a relative reduction of 35% (95% CI 28%-40%). Attendance at birth by those trained to deliver elements of emergency obstetric care increased almost 10-fold, from 5.1% to 48.7% (PRR = 9.55 [95% CI 7.21-12.64]). CONCLUSIONS: Coverage of maternal health interventions and higher-level care at birth was substantially higher during the project period. The MOM Project's focus on task-shifting, capacity building, and empowerment at the community level might serve as a model approach for similarly constrained settings.

Quantitation of Trans-Fatty Acids in Children from the National Health and Nutrition Examination Survey.

OBJECTIVES: Trans-fatty acids (TFA) are geometric isomers of naturally occurring cis-fatty acids, formed industrially through partial hydrogenation of vegetable oils or naturally in ruminant animals. TFA intake has been associated with risk factors for cardiovascular disease; therefore, reduced TFA consumption is a major public health objective. Food intake studies have provided estimates for TFA levels in the U.S. and we previously assessed TFA blood concentrations in fasting U.S. adults in the National Health and Nutrition Examination Survey (NHANES), finding an average 54% decrease in TFA between 1999-2000 and 2009-2010. The aim of this study was to determine nationally representative estimates for plasma TFA concentrations in children in the U.S. population. METHODS: We used the CDC isotope dilution-gas chromatography-negative chemical ionization-mass spectrometry (ID-GC-NCI-MS) method to quantitate four major TFA, palmitelaidic acid, elaidic acid, trans-vaccenic acid, and linoelaidic acid, in a nationally representative group of children in the U.S. population using NHANES samples. TFA were derivatized with pentafluorobenzyl-bromide and analyzed by GC-MS in selected ion monitoring mode using NCI with methane reagent gas. Separation was carried out on a Select FAME 200 m column with hydrogen carrier gas. The TFA limits of detection ranged from 0.02 µM to 0.43 µM. The intraday and inter-day % coefficients of variation ranged from 1-11% CV and 6-15% CV respectively. The mean accuracy for all four TFA was 102% (95% CI: 98%-107%). RESULTS: The TFA were measured in 916 participants (age: 6-19 years) from NHANES 1999-2000 and 1718 participants (age: 3-19 years) from NHANES 2009-2010, and were detected in all samples. Geometric means for the sum of the 4 TFAs were 80.7 µmol/l (95% CI: 74.6-87.3 µmol/L) and 30.6 µmol/l (95% CI: 29.0-32.3 µmol/L) in the NHANES 1999-2000 and 2009-2010, respectively. Overall TFA concentrations were 62% lower in NHANES 2009-2010 compared to 1999-2000. CONCLUSIONS: TFA levels in children in the U.S. population are notably lower in NHANES 2009-2010 compared to NHANES 1999-2000 suggesting an overall reduction of TFA levels in children. FUNDING SOURCES: N/A.

Ascorbic acid promotes detoxification and elimination of 4-hydroxy-2(E)-nonenal in human monocytic THP-1 cells.

4-Hydroxy-2(E)-nonenal (HNE), a reactive aldehyde derived from oxidized lipids, has been implicated in the pathogenesis of cardiovascular and neurological diseases, in part by its ability to induce oxidative stress and by protein carbonylation in target cells. The effects of intracellular ascorbic acid (vitamin C) on HNE-induced cytotoxicity and protein carbonylation were investigated in human THP-1 monocytic leukemia cells. HNE treatment of these cells resulted in apoptosis, necrosis, and protein carbonylation. Ascorbic acid accumulated in the cells at concentrations of 6.4 or 8.9 mM after treatment with 0.1 or 1 mM ascorbate in the medium for 18 h. Pretreatment of cells with 1.0 mM ascorbate decreased HNE-induced formation of reactive oxygen species and formation of protein carbonyls. The protective effects of ascorbate were associated with an increase in the formation of GSH-HNE conjugate and its phase 1 metabolites, measured by LC-MS/MS, and with increased transport of GSH conjugates from the cells into the medium. Ascorbate pretreatment enhanced the efflux of the multidrug resistant protein (MRP) substrate, carboxy-2',7'-dichlorofluorescein (CDF), and it prevented the HNE-induced inhibition of CDF export from THP-1 cells, suggesting that the protective effect of ascorbate against HNE cytotoxicity is through modulation of MRP-mediated transport of GSH-HNE conjugate metabolites. The formation of ascorbate adducts of HNE was observed in the cell exposure experiments, but it represented a minor pathway contributing to the elimination of HNE and to the protective effects of ascorbate.

The MOM Project: delivering maternal health services among internally displaced populations in eastern Burma.

Alternative strategies to increase access to reproductive health services among internally displaced populations are urgently needed. In eastern Burma, continuing conflict and lack of functioning health systems render the emphasis on facility-based delivery with skilled attendants unfeasible. Along the Thailand-Burma border, local organisations have implemented an innovative pilot, the Mobile Obstetric Maternal Health Workers (MOM) Project, establishing a three-tiered collaborative network of community-based reproductive health workers. Health workers from local organisations received practical training in basic emergency obstetric care plus blood transfusion, antenatal care and family planning at a central facility. After returning to their target communities inside Burma, these first-tier maternal health workers trained a second tier of local health workers and a third tier of traditional birth attendants (TBAs) to provide a limited subset of these interventions, depending on their level of training. In this ongoing project, close communication between health workers and TBAs promotes acceptance and coverage of maternity services throughout the community. We describe the rationale, design and implementation of the project and a parallel monitoring plan for evaluation of the project. This innovative obstetric health care delivery strategy may serve as a model for the delivery of other essential health services in this population and for increasing access to care in other conflict settings.

Quantitation of trans-fatty acids in human blood via isotope dilution-gas chromatography-negative chemical ionization-mass spectrometry.

Trans-fatty acids (TFA) are geometric isomers of naturally occurring cis-fatty acids. High dietary TFA intake has been associated with risk factors for cardiovascular disease. However, little is known about TFA levels in humans. To address this data need, we developed and validated a new isotope dilution-gas chromatography-negative chemical ionization-mass spectrometry (ID-GC-NCI-MS) method for quantitation of 27 fatty acids (FA) including 4 major TFA in human plasma, serum, and red blood cells (RBC) from 66 donors. Quantitation was performed with 18 isotope labeled internal standards and results are presented in µM and % of total FA. This method has high sensitivity and specificity due to use of pentafluorobenzyl-bromide derivatization combined with NCI-MS and a 200m column to optimize positional and geometric FA isomer separation. The four major TFA, palmitelaidic acid, elaidic acid, trans-vaccenic acid, and linoelaidic acid, were detected in all samples, with median total TFA concentrations of 17.7µM in plasma, 19.6µM in serum, and 21.5µM in RBC. The % of total FA for the TFA was 0.20% in plasma, 0.20% in serum, and 0.30% in RBC. Patterns for % FA are similar to those reported in other studies. We developed a highly specific, ID-GC-NCI-MS method to quantitate TFA and other FA in humans.

Plasma trans-fatty acid concentrations in fasting adults declined from NHANES 1999-2000 to 2009-2010.

Background: The consumption of trans fatty acids (TFAs) is associated with an increased risk of cardiovascular disease, and reducing their consumption is a major public health objective. Food intake studies have provided estimates for TFA concentrations in the US population; however, there is a need for data on TFA blood concentrations in the population.Objective: The objective of this study was to determine plasma TFA concentrations in a nationally representative group of fasted adults in the US population in NHANES samples from 1999-2000 and 2009-2010.Design: Four major TFAs [palmitelaidic acid (C16:1n-7t), trans vaccenic acid (C18:1n-7t), elaidic acid (C18:1n-9t), and linoelaidic acid (C18:2n-6t,9t)] were measured in plasma in 1613 subjects from NHANES 1999-2000 and 2462 subjects from NHANES 2009-2010 by gas chromatography-mass spectrometry. Geometric means and distribution percentiles were calculated for each TFA and their sum by age, sex, and race/ethnicity (non-Hispanic white, non-Hispanic black, Mexican American), and covariate-adjusted geometric means were computed by using a model that included these demographic and other dietary factors, as well as survey year and any significant interaction terms.Results: These nationally representative data for the adult US population show that TFA concentrations were 54% lower in NHANES 2009-2010 than in NHANES 1999-2000. Covariate-adjusted geometric means for the sum of the 4 TFAs were 81.4 µmol/L (95% CI: 77.3, 85.6 µmol/L) and 37.8 µmol/L (95% CI: 36.4, 39.4 µmol/L) in NHANES 1999-2000 and 2009-2010, respectively. Even with the large decline in TFA concentrations, differences between demographic subgroups were comparable in the 2 surveys.Conclusion: The results indicate an overall reduction in TFA concentrations in the US population and provide a valuable baseline to evaluate the impact of the recent regulation categorizing TFAs as food additives.

LC-MS/MS quantitation of mercapturic acid conjugates of lipid peroxidation products as markers of oxidative stress.

Oxidative stress-induced lipid peroxidation (LPO) leads to the formation of cytotoxic and genotoxic 2-alkenals. LPO products such as 4-hydroxy-2(E)-nonenal (HNE) and 4-oxo-2(E)-nonenal (ONE) have been the subject of many studies due to their association with the development of cardiovascular and neurodegenerative diseases, as well as cancer. LPO products are excreted in the urine after conjugation with glutathione (GSH) and subsequent metabolism to mercapturic acid (MA) conjugates. Urinary LPO-MA metabolites are stable end-product metabolites and have gained interest as non-invasive in vivo biomarkers of oxidative stress. This protocol describes a method for the quantitative analysis of LPO-MA metabolites in urine using isotope-dilution liquid chromatography coupled with electrospray tandem mass spectrometry (LC-MS/MS). Included are protocols for preparation of labeled LPO-MA conjugates from unlabeled LPO products and deuterium labeled MA.

Vitamin C supplementation lowers urinary levels of 4-hydroperoxy-2-nonenal metabolites in humans.

The lack of suitable biomarkers of oxidative stress is a common problem for antioxidant intervention studies in humans. We evaluated the efficacy of vitamin C supplementation in decreasing biomarkers of lipid peroxidation in nonsmokers and in cigarette smokers, a commonly studied, free-living human model of chronic oxidative stress. Participants received ascorbic acid (500mg twice per day) or placebo for 17 days in a double-blind, placebo-controlled, randomized crossover design study. The urinary biomarkers assessed and reported herein are derived from 4-hydroperoxy-2-nonenal (HPNE) and include the mercapturic acid (MA) conjugates of 4-hydroxy-2(E)-nonenal (HNE), 1,4-dihydroxy-2(E)-nonene (DHN), and 4-oxo-2(E)-nonenol(ONO). Vitamin C supplementation decreased the urinary concentrations of both ONO-MA (p=0.0013) and HNE-MA (p=0.0213) by ~30%; however, neither cigarette smoking nor sex affected these biomarkers. In contrast, vitamin C supplementation decreased urinary concentrations of DHN-MA (three-way interaction p=0.0304) in nonsmoking men compared with nonsmoking women (p<0.05), as well as in nonsmoking men compared with smoking men (p<0.05). Vitamin C supplementation also decreased (p=0.0092) urinary total of metabolites by ~20%. Thus, HPNE metabolites can be reduced favorably in response to improved plasma ascorbic acid concentrations, an effect due to ascorbic acid antioxidant function.

Quantitation of mercapturic acid conjugates of 4-hydroxy-2-nonenal and 4-oxo-2-nonenal metabolites in a smoking cessation study.

The breakdown of polyunsaturated fatty acids (PUFAs) under conditions of oxidative stress results in the formation of lipid peroxidation (LPO) products. These LPO products such as 4-hydroxy-2-nonenal (HNE) and 4-oxo-2-nonenal (ONE) can contribute to the development of cardiovascular and neurodegenerative diseases and cancer. Conjugation with glutathione, followed by further metabolism to mercapturic acid (MA) conjugates, can mitigate the effects of these LPO products in disease development by facilitating their excretion from the body. We have developed a quantitative method to simultaneously assess levels of 4-oxo-2-nonen-1-ol (ONO)-MA, HNE-MA, and 1,4-dihydroxy-2-nonene (DHN)-MA in human urine samples utilizing isotope-dilution mass spectrometry. We are also able to detect 4-hydroxy-2-nonenoic acid (HNA)-MA, 4-hydroxy-2-nonenoic acid lactone (HNAL)-MA, and 4-oxo-2-nonenoic acid (ONA)-MA with this method. The detection of ONO-MA and ONA-MA in humans is significant because it demonstrates that HNE/ONE branching occurs in the breakdown of PUFAs and suggests that ONO may contribute to the harmful effects currently associated with HNE. We were able to show significant decreases in HNE-MA, DHN-MA, and total LPO-MA in a group of seven smokers upon smoking cessation. These data demonstrate the value of HNE and ONE metabolites as in vivo markers of oxidative stress.

Mercapturic acid conjugates of 4-hydroxy-2-nonenal and 4-oxo-2-nonenal metabolites are in vivo markers of oxidative stress.

Oxidative stress-induced lipid peroxidation leads to the formation of cytotoxic and genotoxic 2-alkenals, such as 4-hydroxy-2-nonenal (HNE) and 4-oxo-2-nonenal (ONE). Lipid-derived reactive aldehydes are subject to phase-2 metabolism and are predominantly found as mercapturic acid (MA) conjugates in urine. This study shows evidence for the in vivo formation of ONE and its phase-1 metabolites, 4-oxo-2-nonen-1-ol (ONO) and 4-oxo-2-nonenoic acid (ONA). We have detected the MA conjugates of HNE, 1,4-dihydroxy-2-nonene (DHN), 4-hydroxy-2-nonenoic acid (HNA), the lactone of HNA, ONE, ONO, and ONA in rat urine by liquid chromatography-tandem mass spectrometry comparison with synthetic standards prepared in our laboratory. CCl(4) treatment of rats, a widely accepted animal model of acute oxidative stress, resulted in a significant increase in the urinary levels of DHN-MA, HNA-MA lactone, ONE-MA, and ONA-MA. Our data suggest that conjugates of HNE and ONE metabolites have value as markers of in vivo oxidative stress and lipid peroxidation.

Mortality rates in conflict zones in Karen, Karenni, and Mon states in eastern Burma.

OBJECTIVES: To estimate mortality rates for populations living in civil war zones in Karen, Karenni, and Mon states of eastern Burma. METHODS: Indigenous mobile health workers providing care in conflict zones in Karen, Karenni, and Mon areas of eastern Burma conducted cluster sample surveys interviewing heads of households during 3-month time periods in 2002 and 2003 to collect demographic and mortality data. RESULTS: In 2002 health workers completed 1290 household surveys comprising 7496 individuals. In 2003, 1609 households with 9083 members were surveyed. Estimates of vital statistics were as follows: infant mortality rate: 135 (95% CI: 96-181) and 122 (95% CI: 70-175) per 1000 live births; under-five mortality rate: 291 (95% CI: 238-348) and 276 (95% CI: 190-361) per 1000 live births; crude mortality rate: 25 (95% CI: 21-29) and 21 (95% CI: 15-27) per 1000 persons per year. CONCLUSIONS: Populations living in conflict zones in eastern Burma experience high mortality rates. The use of indigenous mobile health workers provides one means of measuring health status among populations that would normally be inaccessible due to ongoing conflict.