Exposures to Airborne Particulate Matter and Adverse Perinatal Outcomes: A Biologically Plausible Mechanistic Framework for Exploring Potential Effect Modification by Nutrition

OBJECTIVES: The specific objectives are threefold: to describe the biologically plausible mechanistic pathways by which exposure to particulate matter (PM) may lead to the adverse perinatal outcomes of low birth weight (LBW), intrauterine growth retardation (IUGR), and preterm delivery (PTD); review the evidence showing that nutrition affects the biologic pathways; and explain the mechanisms by which nutrition may modify the impact of PM exposure on perinatal outcomes. METHODS: We propose an interdisciplinary conceptual framework that brings together maternal and infant nutrition, air pollution exposure assessment, and cardiopulmonary and perinatal epidemiology. Five possible albeit not exclusive biologic mechanisms have been put forth in the emerging environmental sciences literature and provide corollaries for the proposed framework. CONCLUSIONS: Protecting the environmental health of mothers and infants remains a top global priority. The existing literature indicates that the effects of PM on LBW, PTD, and IUGR may manifest through the cardiovascular mechanisms of oxidative stress, inflammation, coagulation, endothelial function, and hemodynamic responses. PM exposure studies relating mechanistic pathways to perinatal outcomes should consider the likelihood that biologic responses and adverse birth outcomes may be derived from both PM and non-PM sources (e.g., nutrition). In the concluding section, we present strategies for empirically testing the proposed model and developing future research efforts

Criminal and Noncriminal Psychopathy: The Devil is in the Detail

Brooks, NS ORCiD: 0000-0003-1784-099XPsychopathy is prevalent and problematic in criminal populations, but is also found to be present in noncriminal populations. In 1992, Robert Hare declared that psychopaths may also “be found in the boardroom”, which has since been followed by an interest in the issue of noncriminal, or even successful, psychopathy. In this chapter, the paradox of criminal and noncriminal psychopathy is discussed with specific attention given to the similarities and differences that account for psychopathic personality across contexts. That psychopathy is a condition typified by a constellation of traits and behaviours requires wider research across diverse populations, and thus the streams of research related to criminal and noncriminal psychopathy are presented and the implications of these contrasting streams are explored

Access Rate to the Emergency Department for Venous Thromboembolism in Relationship with Coarse and Fine Particulate Matter Air Pollution

Particulate matter (PM) air pollution has been associated with cardiovascular and respiratory disease. Recent studies have proposed also a link with venous thromboembolism (VTE) risk. This study was aimed to evaluate the possible influence of air pollution-related changes on the daily flux of patients referring to the Emergency Department (ED) for VTE, dissecting the different effects of coarse and fine PM. From July 1st, 2007, to June 30th, 2009, data about ED accesses for VTE and about daily concentrations of PM air pollution in Verona district (Italy) were collected. Coarse PM (PM10-2.5) was calculated by subtracting the finest PM2.5 from the whole PM10. During the index period a total of 302 accesses for VTE were observed (135 males and 167 females; mean age 68.3±16.7 years). In multiple regression models adjusted for other atmospheric parameters PM10-2.5, but not PM2.5, concentrations were positively correlated with VTE (beta-coefficient = 0.237; P = 0.020). During the days with high levels of PM10-2.5 (≥75th percentile) there was an increased risk of ED accesses for VTE (OR 1.69 with 95%CI 1.13–2.53). By analysing days of exposure using distributed lag non-linear models, the increase of VTE risk was limited to PM10-2.5 peaks in the short-term period. Consistently with these results, in another cohort of subjects without active thrombosis (n = 102) an inverse correlation between PM10-2.5 and prothrombin time was found (R = −0.247; P = 0.012). Our results suggest that short-time exposure to high concentrations of PM10-2.5 may favour an increased rate of ED accesses for VTE through the induction of a prothrombotic state

Protective Effect of Curcumin on Pulmonary and Cardiovascular Effects Induced by Repeated Exposure to Diesel Exhaust Particles in Mice

Particulate air pollution has been associated with increased risk of cardiopulmonary diseases. However, the underlying mechanisms are not fully understood. We have previously demonstrated that single dose exposure to diesel exhaust particle (DEP) causes lung inflammation and peripheral thrombotic events. Here, we exposed mice with repeated doses of DEP (15µg/animal) every 2nd day for 6 days (a total of 4 exposures), and measured several cardiopulmonary endpoints 48 h after the end of the treatments. Moreover, the potential protective effect of curcumin (the yellow pigment isolated from turmeric) on DEP-induced cardiopulmonary toxicity was assessed. DEP exposure increased macrophage and neutrophil numbers, tumor necrosis factor α (TNF α) in the bronchoalveolar lavage (BAL) fluid, and enhanced airway resistance to methacoline measured invasively using Flexivent. DEP also significantly increased plasma C-reactive protein (CRP) and TNF α concentrations, systolic blood pressure (SBP) as well as the pial arteriolar thrombosis. It also significantly enhanced the plasma D-dimer and plasminogen activator inhibitor-1 (PAI-1). Pretreatment with curcumin by oral gavage (45 mg/kg) 1h before exposure to DEP significantly prevented the influx of inflammatory cells and the increase of TNF α in BAL, and the increased airway resistance caused by DEP. Likewise, curcumin prevented the increase of SBP, CRP, TNF α, D-dimer and PAI-1. The thrombosis was partially but significantly mitigated. In conclusion, repeated exposure to DEP induced lung and systemic inflammation characterized by TNFα release, increased SBP, and accelerated coagulation. Our findings indicate that curcumin is a potent anti-inflammatory agent that prevents the release of TNFα and protects against the pulmonary and cardiovascular effects of DEP

Air pollution and the microvasculature: A cross-sectional assessment of in vivo retinal images in the population-based multi-ethnic study of atherosclerosis (MESA)

10.1371/journal.pmed.1000372PLoS Medicine711

The relationship of air pollution and surrogate markers of endothelial dysfunction in a population-based sample of children

<p>Abstract</p> <p>Background</p> <p>This study aimed to assess the relationship of air pollution and plasma surrogate markers of endothelial dysfunction in the pediatric age group.</p> <p>Methods</p> <p>This cross-sectional study was conducted in 2009-2010 among 125 participants aged 10-18 years. They were randomly selected from different areas of Isfahan city, the second large and air-polluted city in Iran. The association of air pollutants' levels with serum thrombomodulin (TM) and tissue factor (TF) was determined after adjustment for age, gender, anthropometric measures, dietary and physical activity habits.</p> <p>Results</p> <p>Data of 118 participants was complete and was analyzed. The mean age was 12.79 (2.35) years. The mean pollution standards index (PSI) value was at moderate level, the mean particular matter measuring up to 10 μm (PM₁₀) was more than twice the normal level. Multiple linear regression analysis showed that TF had significant relationship with all air pollutants except than carbon monoxide, and TM had significant inverse relationship with ozone. The odds ratio of elevated TF was significantly higher in the upper vs. the lowest quartiles of PM₁₀, ozone and PSI. The corresponding figures were in opposite direction for TM.</p> <p>Conclusions</p> <p>The relationship of air pollutants with endothelial dysfunction and pro-coagulant state can be an important factor in the development of atherosclerosis from early life. This finding should be confirmed in future longitudinal studies. Concerns about the harmful effects of air pollution on children's health should be considered a top priority for public health policy; it should be underscored in primordial and primary prevention of chronic diseases.</p

Polymicrobial Nature of Chronic Diabetic Foot Ulcer Biofilm Infections Determined Using Bacterial Tag Encoded FLX Amplicon Pyrosequencing (bTEFAP)

Diabetic extremity ulcers are associated with chronic infections. Such ulcer infections are too often followed by amputation because there is little or no understanding of the ecology of such infections or how to control or eliminate this type of chronic infection. A primary impediment to the healing of chronic wounds is biofilm phenotype infections. Diabetic foot ulcers are the most common, disabling, and costly complications of diabetes. Here we seek to derive a better understanding of the polymicrobial nature of chronic diabetic extremity ulcer infections. spp. and against difficult to culture bacteria such as anaerobes. While PCR methods also have bias, further work is now needed in comparing traditional culture results to high-resolution molecular diagnostic methods such as bTEFAP

Rare germline variants in DNA repair genes and the angiogenesis pathway predispose prostate cancer patients to develop metastatic disease

Background Prostate cancer (PrCa) demonstrates a heterogeneous clinical presentation ranging from largely indolent to lethal. We sought to identify a signature of rare inherited variants that distinguishes between these two extreme phenotypes. Methods We sequenced germline whole exomes from 139 aggressive (metastatic, age of diagnosis < 60) and 141 non-aggressive (low clinical grade, age of diagnosis ≥60) PrCa cases. We conducted rare variant association analyses at gene and gene set levels using SKAT and Bayesian risk index techniques. GO term enrichment analysis was performed for genes with the highest differential burden of rare disruptive variants. Results Protein truncating variants (PTVs) in specific DNA repair genes were significantly overrepresented among patients with the aggressive phenotype, with BRCA2, ATM and NBN the most frequently mutated genes. Differential burden of rare variants was identified between metastatic and non-aggressive cases for several genes implicated in angiogenesis, conferring both deleterious and protective effects. Conclusions Inherited PTVs in several DNA repair genes distinguish aggressive from non-aggressive PrCa cases. Furthermore, inherited variants in genes with roles in angiogenesis may be potential predictors for risk of metastases. If validated in a larger dataset, these findings have potential for future clinical application