Obesity Is A Modifier of Autonomic Cardiac Responses to Fine Metal Particulates

Background: Increasing evidence suggests that obesity may impart greater susceptibility to adverse effects of air pollution. Particulate matter, especially PM$_{2.5}$ (particulate matter with aero-dynamic diameter ≤2.5 μm), is associated with increased cardiac events and reduction of heart rate variability (HRV).Objectives Our goal was to investigate whether particle-mediated autonomic modulation is aggravated in obese individuals.Methods We examined PM$_{2.5}$-mediated acute effects on HRV and heart rate (HR) using 10 24-hr and 13 48-hr ambulatory electrocardiogram recordings collected from 18 boilermakers (39.5 ± 9.1 years of age) exposed to high levels of metal particulates. Average HR and 5-min HRV [SDNN: standard deviation of normal-to-normal intervals (NN); rMSSD: square-root of mean squared-differences of successive NN intervals; HF: high-frequency power 0.15–0.4 Hz] and personal PM$_{2.5}$ exposures were continuously monitored. Subjects with body mass index ≥ 30 kg/m$^2$ were classified as obese. Mixed-effect models were used for statistical analyses. Results: Half (50%) of the study subjects were obese. After adjustment for confounders, each 1-mg/m$^3$ increase in 4-hr moving average PM$_{2.5}$ was associated with HR increase of 5.9 bpm [95% confidence interval (CI), 4.2 to 7.7] and with 5-min HRV reduction by 6.5% (95% CI, 1.9 to 11.3%) for SDNN, 1.7% (95% CI, –4.9 to 8.4%) for rMSSD, and 8.8% (95% CI, –3.8 to 21.3%) for HF. Obese individuals had greater PM$_{2.5}$-mediated HRV reductions (2- to 3-fold differences) than nonobese individuals, and had more PM$_{2.5}$-mediated HR increases (9-bpm vs. 4-bpm increase in HR for each 1-mg/m$^3$ increase in PM$_{2.5}$; p < 0.001). Conclusions: Our study revealed greater autonomic cardiac responses to metal particulates in obese workers, supporting the hypothesis that obesity may impart greater susceptibility to acute cardiovascular effects of fine particles

Secondhand tobacco smoke exposure and heart rate variability and inflammation among non-smoking construction workers: a repeated measures study

Background: Although it has been well recognized that exposure to secondhand tobacco smoke (SHS) is associated with cardiovascular mortality, the mechanisms and time course by which SHS exposure may lead to cardiovascular effects are still being explored. Methods: Non-smoking workers were recruited from a local union and monitored inside a union hall while exposed to SHS over approximately 6 hours. Participants were fitted with a continuous electrocardiographic monitor upon enrollment which was removed at the end of a 24-hr monitoring period. A repeated measures study design was used where resting ECGs and blood samples were taken from individuals before SHS exposure (baseline), immediately following SHS exposure (post) and the morning following SHS exposure (next-morning). Inflammatory markers, including high sensitivity C-reactive protein (CRP) and white blood cell count (WBC) were analyzed. Heart rate variability (HRV) was analyzed from the ECG recordings in time (SDNN, rMSSD) and frequency (LF, HF) domain parameters over 5-minute periods. SHS exposure was quantified using a personal fine particulate matter (PM2.5) monitor. Linear mixed effects regression models were used to examine within-person changes in inflammatory and HRV parameters across the 3 time periods. Exposure-response relationships with PM2.5 were examined using mixed effects models. All models were adjusted for age, BMI and circadian variation. Results: A total of 32 male non-smokers were monitored between June 2010 and June 2012. The mean PM2.5 from SHS exposure was 132 μg/m3. Immediately following SHS exposure, a 100 μg/m3 increase in PM2.5 was associated with declines in HRV (7.8% [standard error (SE) =3%] SDNN, 8.0% (SE = 3.9%) rMSSD, 17.2% (SE = 6.3%) LF, 29.0% (SE = 10.1%) HF) and increases in WBC count 0.42 (SE = 0.14) k/μl. Eighteen hours following SHS exposure, a 100 μg/m3 increase in PM2.5 was associated with 24.2% higher CRP levels. Conclusions: Our study suggest that short-term SHS exposure is associated with significantly lower HRV and higher levels of inflammatory markers. Exposure-associated declines in HRV were observed immediately following exposure while higher levels of CRP were not observed until 18 hours following exposure. Cardiovascular autonomic and inflammation responses may contribute to the pathophysiologic pathways that link SHS exposure with adverse cardiovascular outcomes

Traffic-related exposures and biomarkers of systemic inflammation, endothelial activation and oxidative stress: a panel study in the US trucking industry

Background: Experimental evidence suggests that inhaled particles from vehicle exhaust have systemic effects on inflammation, endothelial activation and oxidative stress. In the present study we assess the relationships of short-term exposures with inflammatory endothelial activation and oxidative stress biomarker levels in a population of trucking industry workers. Methods: Blood and urine samples were collected pre and post-shift, at the beginning and end of a workweek from 67 male non-smoking US trucking industry workers. Concurrent measurements of microenvironment concentrations of elemental and organic carbon (EC & OC), and fine particulate matter (PM2.5) combined with time activity patterns allowed for calculation of individual exposures. Associations between daily and first and last-day average levels of exposures and repeated measures of intercellular and vascular cell adhesion molecule-1 (ICAM-1 & VCAM-1), interleukin 6 (IL-6) and C-reactive protein (CRP) blood levels and urinary 8-Hydroxy-2′-Deoxyguanosine (8-OHdG) were assessed using linear mixed effects models for repeated measures. Results: There was a statistically significant association between first and last-day average PM2.5 and 8-OHdG (21% increase, 95% CI: 2, 42%) and first and last-day average OC and IL-6 levels (18% increase 95% CI: 1, 37%) per IQR in exposure. There were no significant findings associated with EC or associations suggesting acute cross-shift effects. Conclusion: Our findings suggest associations between weekly average exposures of PM2.5 on markers of oxidative stress and OC on IL-6 levels

Obesity Is A Modifier of Autonomic Cardiac Responses to Fine Metal Particulates

Background: Increasing evidence suggests that obesity may impart greater susceptibility to adverse effects of air pollution. Particulate matter, especially PM$_{2.5}$ (particulate matter with aero-dynamic diameter ≤2.5 μm), is associated with increased cardiac events and reduction of heart rate variability (HRV).Objectives Our goal was to investigate whether particle-mediated autonomic modulation is aggravated in obese individuals.Methods We examined PM$_{2.5}$-mediated acute effects on HRV and heart rate (HR) using 10 24-hr and 13 48-hr ambulatory electrocardiogram recordings collected from 18 boilermakers (39.5 ± 9.1 years of age) exposed to high levels of metal particulates. Average HR and 5-min HRV [SDNN: standard deviation of normal-to-normal intervals (NN); rMSSD: square-root of mean squared-differences of successive NN intervals; HF: high-frequency power 0.15–0.4 Hz] and personal PM$_{2.5}$ exposures were continuously monitored. Subjects with body mass index ≥ 30 kg/m$^2$ were classified as obese. Mixed-effect models were used for statistical analyses. Results: Half (50%) of the study subjects were obese. After adjustment for confounders, each 1-mg/m$^3$ increase in 4-hr moving average PM$_{2.5}$ was associated with HR increase of 5.9 bpm [95% confidence interval (CI), 4.2 to 7.7] and with 5-min HRV reduction by 6.5% (95% CI, 1.9 to 11.3%) for SDNN, 1.7% (95% CI, –4.9 to 8.4%) for rMSSD, and 8.8% (95% CI, –3.8 to 21.3%) for HF. Obese individuals had greater PM$_{2.5}$-mediated HRV reductions (2- to 3-fold differences) than nonobese individuals, and had more PM$_{2.5}$-mediated HR increases (9-bpm vs. 4-bpm increase in HR for each 1-mg/m$^3$ increase in PM$_{2.5}$; p < 0.001). Conclusions: Our study revealed greater autonomic cardiac responses to metal particulates in obese workers, supporting the hypothesis that obesity may impart greater susceptibility to acute cardiovascular effects of fine particles

Heart rate variability and DNA methylation levels are altered after short-term metal fume exposure among occupational welders: a repeated-measures panel study

Background: In occupational settings, boilermakers are exposed to high levels of metallic fine particulate matter (PM2.5) generated during the welding process. The effect of welding PM2.5 on heart rate variability (HRV) has been described, but the relationship between PM2.5, DNA methylation, and HRV is not known. Methods: In this repeated-measures panel study, we recorded resting HRV and measured DNA methylation levels in transposable elements Alu and long interspersed nuclear element-1 (LINE-1) in peripheral blood leukocytes under ambient conditions (pre-shift) and right after a welding task (post-shift) among 66 welders. We also monitored personal PM2.5 level in the ambient environment and during the welding procedure. Results: The concentration of welding PM2.5 was significantly higher than background levels in the union hall (0.43 mg/m3 vs. 0.11 mg/m3, p < 0.0001). The natural log of transformed power in the high frequency range (ln HF) had a significantly negative association with PM2.5 exposure (β = -0.76, p = 0.035). pNN10 and pNN20 also had a negative association with PM2.5 exposure (β = -0.16%, p = 0.006 and β = -0.13%, p = 0.030, respectively). PM2.5 was positively associated with LINE-1 methylation [β = 0.79%, 5-methylcytosince (%mC), p = 0.013]; adjusted for covariates. LINE-1 methylation did not show an independent association with HRV. Conclusions: Acute decline of HRV was observed following exposure to welding PM2.5 and evidence for an epigenetic response of transposable elements to short-term exposure to high-level metal-rich particulates was reported. Electronic supplementary material The online version of this article (doi:10.1186/1471-2458-14-1279) contains supplementary material, which is available to authorized users

Night Heart Rate Variability and Particulate Exposures among Boilermaker Construction Workers

Background: Although studies have documented the association between heart rate variability (HRV) and ambient particulate exposures, the association between HRV, especially at night, and metal-rich, occupational particulate exposures remains unclear. Objective: Our goal in this study was to investigate the association between long-duration HRV, including nighttime HRV, and occupational PM2.5 exposures. Methods: We used 24-hr ambulatory electrocardiograms (ECGs) to monitor 36 male boilermaker welders (mean age of 41 years) over a workday and nonworkday. ECGs were analyzed for HRV in the time domain; rMSSD (square root of the mean squared differences of successive intervals), SDNN (SD of normal-to-normal intervals over entire recording), and SDNNi (SDNN for all 5-min segments) were summarized over 24-hr, day (0730–2130 hours), and night (0000–0700 hours) periods. PM2.5 (particulate matter with an aerodynamic diameter ≤ 2.5 μm) exposures were monitored over the workday, and 8-hr time-weighted average concentrations were calculated. We used linear regression to assess the associations between HRV and workday particulate exposures. Matched measurements from a nonworkday were used to control for individual cardiac risk factors. Results: Mean (± SD) PM2.5 exposure was 0.73 ± 0.50 mg/m3 and ranged from 0.04 to 2.70 mg/m3. We observed a consistent inverse exposure–response relationship, with a decrease in all HRV measures with increased PM2.5 exposure. However, the decrease was most pronounced at night, where a 1-mg/m3 increase in PM2.5 was associated with a change of −8.32 [95% confidence interval (CI), −16.29 to −0.35] msec nighttime rMSSD, −14.77 (95% CI, −31.52 to 1.97) msec nighttime SDNN, and −8.37 (95% CI, −17.93 to 1.20) msec nighttime SDNNi, after adjusting for nonworking nighttime HRV, age, and smoking. Conclusion: Metal-rich particulate exposures were associated with decreased long-duration HRV, especially at night. Further research is needed to elucidate which particulate metal constituent is responsible for decreased HRV

PM2.5 metal exposures and nocturnal heart rate variability: a panel study of boilermaker construction workers

<p>Abstract</p> <p>Background</p> <p>To better understand the mechanism(s) of particulate matter (PM) associated cardiovascular effects, research priorities include identifying the responsible PM characteristics. Evidence suggests that metals play a role in the cardiotoxicity of fine PM (PM_2.5) and in exposure-related decreases in heart rate variability (HRV). We examined the association between daytime exposure to the metal content of PM_2.5and night HRV in a panel study of boilermaker construction workers exposed to metal-rich welding fumes.</p> <p>Methods</p> <p>Twenty-six male workers were monitored by ambulatory electrocardiogram (ECG) on a workday while exposed to welding fume and a non-workday (baseline). From the ECG, rMSSD (square root of the mean squared differences of successive intervals) was summarized over the night (0:00–7:00). Workday, gravimetric PM_2.5samples were analyzed by x-ray fluorescence to determine metal content. We used linear mixed effects models to assess the associations between night rMSSD and PM_2.5metal exposures both with and without adjustment for total PM_2.5. Matched ECG measurements from the non-workday were used to control for individual cardiac risk factors and models were also adjusted for smoking status. To address collinearity between PM_2.5and metal content, we used a two-step approach that treated the residuals from linear regression models of each metal on PM_2.5as surrogates for the differential effects of metal exposures in models for night rMSSD.</p> <p>Results</p> <p>The median PM_2.5exposure was 650 μg/m³; median metal exposures for iron, manganese, aluminum, copper, zinc, chromium, lead, and nickel ranged from 226 μg/m³to non-detectable. We found inverse linear associations in exposure-response models with increased metal exposures associated with decreased night rMSSD. A statistically significant association for manganese was observed, with a decline of 0.130 msec (95% CI: -0.162, -0.098) in night rMSSD for every 1 μg/m³increase in manganese. However, even after adjusting for individual metals, increases in total PM_2.5exposures were associated with declines in night rMSSD.</p> <p>Conclusion</p> <p>These results support the cardiotoxicity of PM_2.5metal exposures, specifically manganese. However the metal component alone did not account for the observed declines in night HRV. Therefore, results suggest the importance of other PM elemental components.</p

Consequences of Cold-Ischemia Time on Primary Nonfunction and Patient and Graft Survival in Liver Transplantation: A Meta-Analysis

Introduction: The ability to preserve organs prior to transplant is essential to the organ allocation process. Objective: The purpose of this study is to describe the functional relationship between cold-ischemia time (CIT) and primary nonfunction (PNF), patient and graft survival in liver transplant. Methods: To identify relevant articles Medline, EMBASE and the Cochrane database, including the non-English literature identified in these databases, was searched from 1966 to April 2008. Two independent reviewers screened and extracted the data. CIT was analyzed both as a continuous variable and stratified by clinically relevant intervals. Nondichotomous variables were weighted by sample size. Percent variables were weighted by the inverse of the binomial variance. Results: Twenty-six studies met criteria. Functionally, PNF%=-6.678281+0.9134701*CIT Mean+0.1250879*(CIT Mean-9.89535) 2 - 0.0067663*(CIT Mean-9.89535) 3, r2=.625, p<.0001. Mean patient survival: 93 % (1 month), 88 % (3 months), 83 % (6 months) and 83 % (12 months). Mean graft survival: 85.9 % (1 month), 80.5 % (3 months), 78.1 % (6 months) and 76.8 % (12 months). Maximum patient and graft survival occurred with CITs between 7.5-12.5 hrs at each survival interval. PNF was also significantly correlated with ICU time, % first time grafts and % immunologic mismatches. Conclusion: The results of this work imply that CIT may be the most important pre-transplant information needed in the decision to accept an organ. © 2008 Stahl et al

Energy Resolution Performance of the CMS Electromagnetic Calorimeter

The energy resolution performance of the CMS lead tungstate crystal electromagnetic calorimeter is presented. Measurements were made with an electron beam using a fully equipped supermodule of the calorimeter barrel. Results are given both for electrons incident on the centre of crystals and for electrons distributed uniformly over the calorimeter surface. The electron energy is reconstructed in matrices of 3 times 3 or 5 times 5 crystals centred on the crystal containing the maximum energy. Corrections for variations in the shower containment are applied in the case of uniform incidence. The resolution measured is consistent with the design goals

Prescribing Prevalence of Medications With Potential Genotype-Guided Dosing in Pediatric Patients

Importance: Genotype-guided prescribing in pediatrics could prevent adverse drug reactions and improve therapeutic response. Clinical pharmacogenetic implementation guidelines are available for many medications commonly prescribed to children. Frequencies of medication prescription and actionable genotypes (genotypes where a prescribing change may be indicated) inform the potential value of pharmacogenetic implementation. Objective: To assess potential opportunities for genotype-guided prescribing in pediatric populations among multiple health systems by examining the prevalence of prescriptions for each drug with the highest level of evidence (Clinical Pharmacogenetics Implementation Consortium level A) and estimating the prevalence of potential actionable prescribing decisions. Design, setting, and participants: This serial cross-sectional study of prescribing prevalences in 16 health systems included electronic health records data from pediatric inpatient and outpatient encounters from January 1, 2011, to December 31, 2017. The health systems included academic medical centers with free-standing children's hospitals and community hospitals that were part of an adult health care system. Participants included approximately 2.9 million patients younger than 21 years observed per year. Data were analyzed from June 5, 2018, to April 14, 2020. Exposures: Prescription of 38 level A medications based on electronic health records. Main outcomes and measures: Annual prevalence of level A medication prescribing and estimated actionable exposures, calculated by combining estimated site-year prevalences across sites with each site weighted equally. Results: Data from approximately 2.9 million pediatric patients (median age, 8 [interquartile range, 2-16] years; 50.7% female, 62.3% White) were analyzed for a typical calendar year. The annual prescribing prevalence of at least 1 level A drug ranged from 7987 to 10 629 per 100 000 patients with increasing trends from 2011 to 2014. The most prescribed level A drug was the antiemetic ondansetron (annual prevalence of exposure, 8107 [95% CI, 8077-8137] per 100 000 children). Among commonly prescribed opioids, annual prevalence per 100 000 patients was 295 (95% CI, 273-317) for tramadol, 571 (95% CI, 557-586) for codeine, and 2116 (95% CI, 2097-2135) for oxycodone. The antidepressants citalopram, escitalopram, and amitriptyline were also commonly prescribed (annual prevalence, approximately 250 per 100 000 patients for each). Estimated prevalences of actionable exposures were highest for oxycodone and ondansetron (>300 per 100 000 patients annually). CYP2D6 and CYP2C19 substrates were more frequently prescribed than medications influenced by other genes. Conclusions and relevance: These findings suggest that opportunities for pharmacogenetic implementation among pediatric patients in the US are abundant. As expected, the greatest opportunity exists with implementing CYP2D6 and CYP2C19 pharmacogenetic guidance for commonly prescribed antiemetics, analgesics, and antidepressants