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Background: Several studies have demonstrated associations between daily mortality and ambient particulate matter less than 2.5 microns in diameter (fine particles or PM2.5). Few, however, have examined the relative toxicities of PM2.5 constituents, including elemental carbon and organic carbon (EC and OC, respectively), nitrates and transition metals. There is also little information about whether associations between PM2.5 constituents and mortality are modified by socioeconomic and demographic factors. Aim: To examine associations of daily cardiovascular mortality with PM2.5 and its constituents after stratification by gender, race/ethnicity and education, using data from six California counties during 2000 to 2003. Methods: The association of daily counts of cardiovascular mortality with PM2.5 components was analysed using time-series regression analyses. Poisson models with natural splines were used to control for time-varying covariates such as season and weather. Separate models were run after stratification by gender, race/ethnicity (White, Hispanic, Black) and education (high school graduation or not). Models were run for each county and results were combined using random effects meta-analysis. Results: Daily counts of cardiovascular mortality were associated with PM2.5 and several of its species including EC, OC, nitrates, sulphates, potassium, copper and iron. For many of these species, there were significantly higher effect estimates among those with lower educational attainment and Hispanic individuals. For example, while essentially no association was observed for individuals who graduated from high school, an interquartile change in several of the components of PM2.5 was associated with a 3–5% increase in daily mortality among non-high school graduates. Conclusion: There is evidence that several PM2.5 constituents may represent important contributors to cardiovascular mortality. Many of these constituents are generated by motor vehicles, especially those with diesel engines, and by residential wood combustion. In addition, factors associated with low educational attainment may increase susceptibility to PM2.5 and its components.

Objective: Several epidemiologic studies provide evidence of an association between daily mortality and particulate matter$< 2.5 \\mu m$in diameter (PM2.5). Little is known, however, about the relative effects of PM2.5constituents. We examined associations between 19 PM2.5components and daily mortality in six California counties. Design: We obtained daily data from 2000 to 2003 on mortality and PM2.5mass and components, including elemental and organic carbon (EC and OC), nitrates, sulfates, and various metals. We examined associations of PM2.5and its constituents with daily counts of several mortality categories: all-cause, cardiovascular, respiratory, and mortality age > 65 years. Poisson regressions incorporating natural splines were used to control for time-varying covariates. Effect estimates were determined for each component in each county and then combined using a random-effects model. Results: PM2.5mass and several constituents were associated with multiple mortality categories, especially cardiovascular deaths. For example, for a 3-day lag, the latter increased by 1.6, 2.1, 1.6, and 1.5% for PM2.5, EC, OC, and nitrates based on interquartile ranges of 14.6, 0.8, 4.6, and$5.5 \\mu g/m^3$, respectively. Stronger associations were observed between mortality and additional pollutants, including sulfates and several metals, during the cool season. Conclusion: This multicounty analysis adds to the growing body of evidence linking PM2.5with mortality and indicates that excess risks may vary among specific PM2.5components. Therefore, the use of regression coefficients based on PM2.5mass may underestimate associations with some PM2.5components. Also, our findings support the hypothesis that combustion-associated pollutants are particularly important in California.

Many epidemiologic studies provide evidence of an association between daily counts of mortality and ambient particulate matter < 10 μm in diameter ( PM10). Relatively few studies, however, have investigated the relationship of mortality with fine particles [PM < 2.5 μm in diameter ( PM2.5)], especially in a multicity setting. We examined associations between PM2.5and daily mortality in nine heavily populated California counties using data from 1999 through 2002. We considered daily counts of all-cause mortality and several cause-specific subcategories (respiratory, cardiovascular, ischemic heart disease, and diabetes). We also examined these associations among several subpopulations, including the elderly (> 65 years of age), males, females, non-high school graduates, whites, and Hispanics. We used Poisson multiple regression models incorporating natural or penalized splines to control for covariates that could affect daily counts of mortality, including time, seasonality, temperature, humidity, and day of the week. We used meta-analyses using random-effects models to pool the observations in all nine counties. The analysis revealed associations of PM2.5levels with several mortality categories. Specifically, a 10-μ g/ m3change in 2-day average PM2.5concentration corresponded to a 0.6% (95% confidence interval, 0.2-1.0%) increase in all-cause mortality, with similar or greater effect estimates for several other subpopulations and mortality subcategories, including respiratory disease, cardiovascular disease, diabetes, age > 65 years, females, deaths out of the hospital, and non-high school graduates. Results were generally insensitive to model specification and the type of spline model used. This analysis adds to the growing body of evidence linking PM2.5with daily mortality.

Objective: Studies have identified associations between household secondhand tobacco smoke (SHS) exposure and induction of childhood asthma. However, the true nature and strength of this association remains confounded in many studies, producing inconsistent evidence. To look for sources of potential bias and try to uncover consistent patterns of relative risk estimates (RRs), we conducted a meta-analysis of studies published between 1970 and 2005. Data sources: Through an extensive literature search, we identified 38 epidemiologic studies of SHS exposure and the development of childhood asthma (that also controlled for atopy history) from 300 potentially relevant articles. Data synthesis: We observed substantial heterogeneity within initial summary RRs of 1.48 [95% confidence interval (CI), 1.32-1.65], 1.25 (1.21-1.30), and 1.21 (1.08-1.36), for ever, current, and incident asthma, respectively. Lack of control for type of atopy history (familial or child) and child's own smoking status within studies and age category altered summary RRs in separate metaregressions. After adjusting for these confounding characteristics, consistent patterns of association emerged between SHS exposure and childhood asthma induction. Our summary RR of 1.33 (95% CI, 1.14-1.56) from studies of incident asthma among older children (6-18 years of age) is 1.27 times the estimate from studies of younger children and higher than estimates reported in earlier meta-analyses. Conclusions: This new finding indicates that exposure duration may be a more important factor in the induction of asthma than previously understood, and suggests that SHS could be a more fundamental and widespread cause of childhood asthma than some previous meta-analyses have indicated.

Many epidemiological studies provide evidence of an association between ambient particles, measured as PM10, and daily mortality. Most of these studies have been conducted in urban areas where PM10 is highly correlated with and dominated by fine particles less than 2.5 microm in diameter (PM2.5). Fewer studies have investigated impacts associated with the fraction of coarse mode particles (between 2.5 and 10 microm in diameter). In a previous study using data from 1989 through 1992 in the Coachella Valley, a desert resort and retirement area east of Los Angeles, we reported associations between PM10 and several different measures of mortality [Ostro B.D., Hurley S., and Lipsett M.J. Air pollution and daily mortality in the Coachella Valley, California: a study of PM10 dominated by coarse particles. Environ. Res. 1999: 81: 231-238]. In this arid environment, coarse particles of geologic origin are highly correlated with and comprise approximately 60% of PM10, increasing to >90% during wind events. This study was intended to repeat the earlier investigation using 10 years (1989-1998) of daily data on mortality and PM10. The last 2.5 years of data also included daily measures of PM2.5, allowing examination of size-specific impacts. To ensure adequate statistical power, we attempted to develop predictive models for both fine and coarse particles to use in analyses of the full 10-year period. An acceptable fit was found only for coarse particles, which were found to be a cubic function of PM10 (R2 = 0.95). Outcome variables included several measures of daily mortality, including all-cause (minus accidents and homicides), cardiovascular and respiratory mortality. Multivariate Poisson regression analyses using generalized additive models were employed to explain the variation in these endpoints, controlling for temperature, humidity, day of the week, season, and time, using locally weighted smoothing techniques. Pollution lags of up to 4 days were examined. Several pollutants were associated with all-cause mortality, including PM2.5, carbon monoxide and nitrogen dioxide. More consistent results were found for cardiovascular-specific mortality, for which associations were found for coarse particles (RR = 1.02; 95% C.I., 1.01-1.04), PM10 (RR = 1.03; 95% C.I., 1.01-1.05). None of the pollutants was associated with respiratory-specific mortality. Ozone was not associated with any of the mortality outcomes. These findings are generally consistent with those we previously reported for the Coachella Valley for the period 1989-1992, demonstrating associations between several measures of particulate matter and daily mortality in an environment in which particulate concentrations are dominated by the coarse fraction.

Application of the concentration inducing a 50% decrease in respiratory frequency (RD sub(50)) for determining acceptable exposure levels of airborne sensory irritants for the general public was evaluated. Exposure guidelines to protect workers and the public focused on mild irritating signs or symptoms. The availability of RD sub(50)s in male mice for 89 chemicals, and their correlation with occupational exposure levels (OELs) suggested potential applicability to air exposure guidelines for the public. A strong correlation was found between RD sub(50)s and lowest observed adverse effect levels (LOAELs), threshold limit values (TLVs), and California reference exposure levels (RELs). The correlation remained close to 0.8 after conducting various subanalyses, indicating that the strains of mice or the RD sub(50) exposure time did not substantially affect the correlation.

Cardiovascular disease (CVD) remains the leading cause of mortality worldwide. In particular, patients who suffer from ischemic heart disease (IHD) that is not amenable to surgical or percutaneous revascularization techniques have limited treatment options. Furthermore, after revascularization is successfully implemented, there are a number of pathophysiological changes to the myocardium, including but not limited to ischemia-reperfusion injury, necrosis, altered inflammation, tissue remodeling, and dyskinetic wall motion. Electrospinning, a nanofiber scaffold fabrication technique, has recently emerged as an attractive option as a potential therapeutic platform for the treatment of cardiovascular disease. Electrospun scaffolds made of biocompatible materials have the ability to mimic the native extracellular matrix and are compatible with drug delivery. These inherent properties, combined with ease of customization and a low cost of production, have made electrospun scaffolds an active area of research for the treatment of cardiovascular disease. In this review, we aim to discuss the current state of electrospinning from the fundamentals of scaffold creation to the current role of electrospun materials as both bioengineered extracellular matrices and drug delivery vehicles in the treatment of CVD, with a special emphasis on the potential clinical applications in myocardial ischemia.

Introduction. Recent national guidelines recommending mitral valve replacement (MVR) for severe secondary mitral regurgitation have resulted in an increased utilization of mitral bioprosthesis. There is a paucity of data on how longitudinal clinical outcomes vary by prosthesis type. We examined long-term survival and risk of reoperation between patients having bovine vs. porcine MVR. Study Design. A retrospective analysis of MVR or MVR + coronary artery bypass graft (CABG) from 2001 to 2017 among seven hospitals reporting to a prospectively maintained clinical registry was conducted. The analytic cohort included 1,284 patients undergoing MVR (801 bovine and 483 porcine). Baseline comorbidities were balanced using 1 : 1 propensity score matching with 432 patients in each group. The primary end point was all-cause mortality. Secondary end points included in-hospital morbidity, 30-day mortality, length of stay, and risk of reoperation. Results. In the overall cohort, patients receiving porcine valves were more likely to have diabetes (19% bovine vs. 29% porcine; p<0.001), COPD (20% bovine vs. 27% porcine; p=0.008), dialysis or creatinine >2 mg/dL (4% bovine vs. 7% porcine; p=0.03), and coronary artery disease (65% bovine vs. 77% porcine; p<0.001). There was no difference in stroke, acute kidney injury, mediastinitis, pneumonia, length of stay, in-hospital morbidity, or 30-day mortality. In the overall cohort, there was a difference in long-term survival (porcine HR 1.17 (95% CI: 1.00–1.37; p=050)). However, there was no difference in reoperation (porcine HR 0.56 (95% CI: 0.23–1.32; p=0.185)). In the propensity-matched cohort, patients were matched on all baseline characteristics. There was no difference in postoperative complications or in-hospital morbidity and 30-day mortality. After 1 : 1 propensity score matching, there was no difference in long-term survival (porcine HR 0.97 (95% CI: 0.81–1.17; p=0.756)) or risk of reoperation (porcine HR 0.54 (95% CI: 0.20–1.47; p=0.225)). Conclusions. In this multicenter analysis of patients undergoing bioprosthetic MVR, there was no difference in perioperative complications and risk of reoperation of long-term survival after matching.

The extracellular matrix (ECM) is a three-dimensional, acellular network of diverse structural and nonstructural proteins embedded within a gel-like ground substance composed of glycosaminoglycans and proteoglycans. The ECM serves numerous roles that vary according to the tissue in which it is situated. In the myocardium, the ECM acts as a collagen-based scaffold that mediates the transmission of contractile signals, provides means for paracrine signaling, and maintains nutritional and immunologic homeostasis. Given this spectrum, it is unsurprising that both the composition and role of the ECM has been found to be modulated in the context of cardiac pathology. Myocardial infarction (MI) provides a familiar example of this; the ECM changes in a way that is characteristic of the progressive phases of post-infarction healing. In recent years, this involvement in infarct pathophysiology has prompted a search for therapeutic targets: if ECM components facilitate healing, then their manipulation may accelerate recovery, or even reverse pre-existing damage. This possibility has been the subject of numerous efforts involving the integration of ECM-based therapies, either derived directly from biologic sources or bioengineered sources, into models of myocardial disease. In this paper, we provide a thorough review of the published literature on the use of the ECM as a novel therapy for ischemic heart disease, with a focus on biologically derived models, of both the whole ECM and the components thereof.