Polyaromatic hydrocarbons in pollution: a heart-breaking matter.

Air pollution is associated with detrimental effects on human health, including decreased cardiovascular function. However, the causative mechanisms behind these effects have yet to be fully elucidated. Here we review the current epidemiological, clinical and experimental evidence linking pollution with cardiovascular dysfunction. Our focus is on particulate matter (PM) and the associated low molecular weight polycyclic aromatic hydrocarbons (PAHs) as key mediators of cardiotoxicity. We begin by reviewing the growing epidemiological evidence linking air pollution to cardiovascular dysfunction in humans. We next address the pollution-based cardiotoxic mechanisms first identified in fish following the release of large quantities of PAHs into the marine environment from point oil spills (e.g. Deepwater Horizon). We finish by discussing the current state of mechanistic knowledge linking PM and PAH exposure to mammalian cardiovascular patho-physiologies such as atherosclerosis, cardiac hypertrophy, arrhythmias, contractile dysfunction and the underlying alterations in gene regulation. Our aim is to show conservation of toxicant pathways and cellular targets across vertebrate hearts to allow a broad framework of the global problem of cardiotoxic pollution to be established. AhR; Aryl hydrocarbon receptor. Dark lines indicate topics discussed in this review. Grey lines indicate topics reviewed elsewhere.

Cardiovascular benefits of reducing personal exposure to traffic-related noise and particulate air pollution: A randomized crossover study in the Beijing subway system.

To assess the cardiovascular benefits of protecting against particulate air pollution and noise, we conducted a randomized crossover study with 40 young healthy college students from March to May 2017 in the underground subway, Beijing. Participants each received 4 treatments (no intervention phase [NIP], respirator intervention phase [RIP], headphone intervention phase [HIP], respirator plus headphone intervention phase [RHIP]) in a randomized order during 4 different study periods with 2-week washout intervals. We measured personal exposure to particulate matter (PM), noise and electrocardiogram (ECG) parameters (heart rate variability (HRV), heart rate (HR) and ST segment changes), ambulatory blood pressure (BP) continuously for 4 hours to investigate the cardiovascular effects. Compared with NIP, most of the HRV parameters increased, especially high frequency (HF) [21.1% (95% CI: 15.7%, 26.9%), 18.2% (95% CI: 12.8%, 23.9%), and 35.5% (95% CI: 29.3%, 42.0%) in RIP, HIP, and RHIP, respectively], whereas ST segment elevation and HR decreased for all 3 modes of interventions. However, no significant differences were observed in BP among the 4 treatments. In summary, short-term wearing of a respirator and/or headphone may be an effective way to minimize cardiovascular risk induced by air pollution in the subway by improving autonomic nervous function.

Association of size-fractionated indoor particulate matter and black carbon with heart rate variability in healthy elderly women in Beijing.

Associations between size-fractionated indoor particulate matter (PM) and black carbon (BC) and heart rate variability (HRV) and heart rate (HR) in elderly women remain unclear. Twenty-nine healthy elderly women were measured for 24-hour HRV/HR indices. Real-time size-fractionated indoor PM and BC were monitored on the same day and on the preceding day. Mixed-effects models were applied to investigate the associations between pollutants and HRV/HR indices. Increases in size-fractionated indoor PM were significantly associated with declines in power in the high-frequency band (HF), power in the low-frequency band (LF), and standard deviation of all NN intervals (SDNN). The largest decline in HF was 19% at 5-minute moving average for an interquartile range (IQR) increase (24 µg/m3 ) in PM0.5 . The results showed that smaller particles could lead to greater reductions in HRV indices. The reported associations were modified by body mass index (BMI): Declines in HF at 5-minute average for an IQR increase in PM0.5 were 34.5% and 1.0% for overweight (BMI ≥25 kg/m2 ) and normal-weight (BMI <25 kg/m2 ) participants, respectively. Moreover, negative associations between BC and HRV indices were found to be significant in overweight participants. Increases in size-fractionated indoor PM and BC were associated with compromised cardiac autonomic function in healthy elderly women, especially overweight ones.

On the origins and genetic diversity of South American chickens: one step closer.

Local chicken populations are a major source of food in the rural areas of South America. However, very little is known about their genetic composition and diversity. Here, we analyzed five populations from South America to investigate their maternal genetic origin and diversity, hoping to mitigate the lack of information on local chicken populations from this region. We also included three populations of chicken from the Iberian Peninsula and one from Easter Island, which are potential sources of the first chickens introduced in South America. The obtained sequencing data from South American chickens indicate the presence of four haplogroups (A, B, E and D) that can be further subdivided into nine sub-haplogroups. Of these, four (B1, D1a, E1a(b), E1b) were absent from local Iberian Peninsula chickens and one (D1a) was present only on Easter Island. The presence of the sub-haplogroups A1a(b) and E1a(b) in South America, previously only observed in Eastern Asia, and the significant population differentiation between Iberian Peninsula and South American populations, suggest a second maternal source of the extant genetic pool in South American chickens.

Whole-eye transplantation: a look into the past and vision for the future.

Blindness afflicts ~39 million people worldwide. Retinal ganglion cells are unable to regenerate, making this condition irreversible in many cases. Whole-eye transplantation (WET) provides the opportunity to replace diseased retinal ganglion cells, as well as the entire optical system and surrounding facial tissue, if necessary. Recent success in face transplantation demonstrates that this may be a promising treatment for what has been to this time an incurable condition. An animal model for WET must be established to further enhance our knowledge of nerve regeneration, immunosuppression, and technical aspects of surgery. A systematic review of the literature was performed to evaluate studies describing animal models for WET. Only articles in which the eye was completely enucleated and reimplanted were included. Study methods and results were compared. In the majority of published literature, WET can result in recovery of vision in cold-blooded vertebrates. There are a few instances in which mammalian WET models demonstrate survival of the transplanted tissue following neurovascular anastomosis and the ability to maintain brief electroretinogram activity in the new host. In this study we review in cold-blooded vertebrates and mammalian animal models for WET and discuss prospects for future research for translation to human eye transplantation.

A fast click-slow release strategy towards the HPLC-free synthesis of RNA.

A general strategy for purification of oligonucleotides synthesized by solid phase synthesis is described. It is based on a recently developed concept involving a bio-orthogonal inverse electron demand Diels-Alder reaction between trans-cyclooctene and tetrazine, termed 'click-to-release'. The strategy has been applied towards the synthesis and purification of a model hairpin RNA strand, as well as a 34 nt long aptamer.

Implementation of feeding guidelines in infants at risk of intestinal failure.

OBJECTIVE: To implement feeding guidelines to reduce advancement time and the incidence of parenteral nutrition-associated liver disease (PNALD) among intestinal surgical infants requiring parenteral nutrition (PN). STUDY DESIGN: Feeding guidelines with higher initial enteral nutrition (EN) volume and specific advancement criteria were implemented for surgical infants aged <6 months. Preimplementation and postimplementation outcomes were compared. RESULTS: There were 57 preimplementation and 33 postimplementation infants. The initial EN volume improved from 10 to 20 ml kg(-1) day(-1) (P<0.001). Time to reach 50% of goal calories from EN decreased by a median of 6 days (P=0.012) without a change in necrotizing enterocolitis incidence after resuming feeding. PNALD incidence decreased from 70% to 48% (P=0.046), and median peak direct bilirubin (DB) decreased from 5.6 to 2.3 mg dl(-1) (P=0.011). CONCLUSION: Feeding guideline implementation with higher initial feeding volume was well tolerated and resulted in faster achievement of 50% goal EN calories. PNALD incidence and peak DB were reduced.

The development and characterization of a 57K single nucleotide polymorphism array for rainbow trout.

In this study, we describe the development and characterization of the first high-density single nucleotide polymorphism (SNP) genotyping array for rainbow trout. The SNP array is publically available from a commercial vendor (Affymetrix). The SNP genotyping quality was high, and validation rate was close to 90%. This is comparable to other farm animals and is much higher than previous smaller scale SNP validation studies in rainbow trout. High quality and integrity of the genotypes are evident from sample reproducibility and from nearly 100% agreement in genotyping results from other methods. The array is very useful for rainbow trout aquaculture populations with more than 40 900 polymorphic markers per population. For wild populations that were confounded by a smaller sample size, the number of polymorphic markers was between 10 577 and 24 330. Comparison between genotypes from individual populations suggests good potential for identifying candidate markers for populations' traceability. Linkage analysis and mapping of the SNPs to the reference genome assembly provide strong evidence for a wide distribution throughout the genome with good representation in all 29 chromosomes. A total of 68% of the genome scaffolds and contigs were anchored through linkage analysis using the SNP array genotypes, including ~20% of the genome assembly that has not been previously anchored to chromosomes.

NICU medication errors: identifying a risk profile for medication errors in the neonatal intensive care unit.

OBJECTIVE: To identify a risk profile for harmful medication errors in the neonatal intensive care unit (NICU). STUDY DESIGN: A retrospective cross-sectional study on NICU medication error reports submitted to MEDMARX between 1 January 1999, and 31 December 2005. The Rao-Scott modified chi(2) test was used for analysis. RESULT: 6749 NICU medication error reports were submitted by 163 health-care facilities. Administering errors accounted for approximately one half of errors, and human factors were the most frequently cited cause of error. Patient age was not associated with an increased likelihood of an error being harmful (P=0.11). Error reports involving Institute for Safe Medication Practices (ISMP) High-Alert Medications, occurring in the prescribing phase of medication processing, or involving equipment/delivery device failures were more likely to be harmful (P< or =0.05). CONCLUSION: Risk factors for harmful medication error reports include use of ISMP High-Alert Medications, the prescribing phase of the medication use process, and failure of equipment/delivery devices.

New concepts for expressing forced expiratory volume in 1 s arising from survival analysis.

Spirometric lung function is partly determined by sex, age and height (Ht). Commonly, lung function is expressed as a percentage of the predicted value (PP) in order to account for these effects. Since the PP method retains sex, age and Ht bias, forced expiratory volume in 1 s (FEV(1)) standardised by powers of Ht and by a new sex-specific lower limit (FEV(1) quotient (FEV(1)Q)) were investigated to determine which method best predicted all-cause mortality in >26,967 patients and normal subjects. On multivariate analysis, FEV(1)Q was the best predictor, with a hazard ratio for the worst decile of 6.9 compared to 4.1 for FEV(1)PP. On univariate analysis, the hazard ratios were 18.8 compared to 6.1, respectively; FEV(1) x Ht(-3) was the next-best predictor of survival. Median survival was calculated for simple cut-off values of FEV(1)Q and FEV(1) x Ht(-3). These survival curves were accurately fitted (r(2) = 1.0) by both FEV(1)Q and FEV(1) x Ht(-3) values expressed polynomially, and so an individual's test result could be used to estimate survival (with sd for median survival of 0.22 and 0.61 yrs, respectively). It is concluded that lung function impairment should be expressed in a new way, here termed the FEV(1)Q, or, alternatively, as FEV(1) x Ht(-3), since these indices best relate spirometric lung function to all-cause mortality and survival.

Airflow obstruction and metabolic syndrome: the Guangzhou Biobank Cohort Study.

There is some evidence that chronic obstructive pulmonary disease (COPD) and metabolic syndrome may be related, perhaps through systemic inflammation, which is common to both. However, the association between the two conditions has not yet been clearly shown. The present study involved 7,358 adults aged > or =50 yrs from a population-based survey who underwent spirometry, a structured interview and measurement of fasting metabolic marker levels. Airflow obstruction (forced expiratory volume in 1 s/forced vital capacity ratio of less than the lower limit of normal) was present in 6.7%, and the International Diabetes Federation metabolic syndrome criteria were met by 20.0%. The risk of metabolic syndrome was higher in those with airflow obstruction than in those without (odds ratio (OR) 1.47; 95% confidence interval (CI) 1.12-1.92), after controlling for potential confounders. Of the five components of metabolic syndrome, only central obesity was significantly associated with airflow obstruction (OR 1.43; 95% CI 1.09-1.88) after adjusting for body mass index. A similar association was observed in both never and current smokers. In this Chinese sample, airflow obstruction was associated with metabolic syndrome, and, in particular, its central obesity component. This may help explain the increased risk of cardiovascular diseases in COPD, and so could guide future clinical practice.

Loss of protein kinase C delta alters mammary gland development and apoptosis.

As apoptotic pathways are commonly deregulated in breast cancer, exploring how mammary gland cell death is regulated is critical for understanding human disease. We show that primary mammary epithelial cells from protein kinase C delta (PKCδ) -/- mice have a suppressed response to apoptotic agents in vitro. In the mammary gland in vivo, apoptosis is critical for ductal morphogenesis during puberty and involution following lactation. We have explored mammary gland development in the PKCδ -/- mouse during these two critical windows. Branching morphogenesis was altered in 4- to 6-week-old PKCδ -/- mice as indicated by reduced ductal branching; however, apoptosis and proliferation in the terminal end buds was unaltered. Conversely, activation of caspase-3 during involution was delayed in PKCδ -/- mice, but involution proceeded normally. The thymus also undergoes apoptosis in response to physiological signals. A dramatic suppression of caspase-3 activation was observed in the thymus of PKCδ -/- mice treated with irradiation, but not mice treated with dexamethasone, suggesting that there are both target- and tissue-dependent differences in the execution of apoptotic pathways in vivo. These findings highlight a role for PKCδ in both apoptotic and nonapoptotic processes in the mammary gland and underscore the redundancy of apoptotic pathways in vivo.

Using the lower limit of normal for the FEV1/FVC ratio reduces the misclassification of airway obstruction.

AIM: The prevalence of airway obstruction varies widely with the definition used. OBJECTIVES: To study differences in the prevalence of airway obstruction when applying four international guidelines to three population samples using four regression equations. METHODS: We collected predicted values for forced expiratory volume in 1 s/forced vital capacity (FEV(1)/FVC) and its lower limit of normal (LLN) from the literature. FEV(1)/FVC from 40 646 adults (including 13 136 asymptomatic never smokers) aged 17-90+years were available from American, English and Dutch population based surveys. The prevalence of airway obstruction was determined by the LLN for FEV(1)/FVC, and by using the Global Initiative for Chronic Obstructive Lung Disease (GOLD), American Thoracic Society/European Respiratory Society (ATS/ERS) or British Thoracic Society (BTS) guidelines, initially in the healthy subgroup and then in the entire population. RESULTS: The LLN for FEV(1)/FVC varied between prediction equations (57 available for men and 55 for women), and demonstrated marked negative age dependency. Median age at which the LLN fell below 0.70 in healthy subjects was 42 and 48 years in men and women, respectively. When applying the reference equations (Health Survey for England 1995-1996, National Health and Nutrition Examination Survey (NHANES) III, European Community for Coal and Steel (ECCS)/ERS and a Dutch population study) to the selected population samples, the prevalence of airway obstruction in healthy never smokers aged over 60 years varied for each guideline: 17-45% of men and 7-26% of women for GOLD; 0-18% of men and 0-16% of women for ATS/ERS; and 0-9% of men and 0-11% of women for BTS. GOLD guidelines caused false positive rates of up to 60% when applied to entire populations. CONCLUSIONS: Airway obstruction should be defined by FEV(1)/FVC and FEV(1) being below the LLN using appropriate reference equations.

Down-regulation of vinculin upon MK886-induced apoptosis in LN18 glioblastoma cells.

Glioblastomas are a type of malignant brain tumor and are among the most difficult cancers to treat. One strategy to treat aggressive cancers is the use of drugs that target multiple signaling pathways. MK886 is a drug known to inhibit both 5- lipoxygenase-activating-protein (FLAP) and peroxisome proliferator activated receptor-alpha (PPAR-alpha). The objectives of this study were to investigate the ability of MK886 to induce apoptotic cell death in LN18 glioblastoma cells and to characterize the cell death mechanisms. MK886 induced massive apoptotic LN18 cell death that was manifested by the release of nucleosomes, annexinV binding to phosphatidylserine in the absence of nuclear staining, and changes in the fluorescent intensity of Mito Tracker Deep Red 633 indicating changes in mitochondrial oxidative function and mass. The alteration of the mitochondrial function implied that MK886 induced apoptosis in LN18 cells via a mitochondrial pathway. The broad caspases inhibitor ZVAD-FMK inhibited MK886-induced nucleosome release, but not annexinV binding or MK886-altered mitochondrial function. Real time RT-PCR demonstrated that LN18 cells expressed significant levels of FLAP and PPAR- alpha mRNAs. A low level of arachidonate 5-lipoxygenase (ALOX-5) mRNA was detected, but little, if any, arachidonate 12- lipoxygenase (ALOX-12) mRNA was present. In addition, MK886-induced apoptosis in LN18 cells was accompanied by a decrease in the protein and mRNA levels of vinculin, but not other focal adhesion proteins. In summary, the data presented here indicate that disruption of the actin-vinculin-cell-cytoskeleton matrix of the LN18 glioblastoma is a component of the MK886 induced apoptosis. In addition, MK886 treated LN18 cells could provide one model in which to investigate drugs that target lipoxygenase and PPAR-alpha pathways in the chemotherapeutic treatment of glioblastomas.

Passive smoking exposure and risk of COPD among adults in China: the Guangzhou Biobank Cohort Study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality in China, where the population is also exposed to high levels of passive smoking, yet little information exists on the effects of such exposure on COPD. We examined the relation between passive smoking and COPD and respiratory symptoms in an adult Chinese population. METHODS: We used baseline data from the Guangzhou Biobank Cohort Study. Of 20 430 men and women over the age of 50 recruited in 2003-06, 15,379 never smokers (6497 with valid spirometry) were included in this cross-sectional analysis. We measured passive smoking exposure at home and work by two self-reported measures (density and duration of exposure). Diagnosis of COPD was based on spirometry and defined according to the GOLD guidelines. FINDINGS: There was an association between risk of COPD and self-reported exposure to passive smoking at home and work (adjusted odds ratio 1.48, 95% CI 1.18-1.85 for high level exposure; equivalent to 40 h a week for more than 5 years). There were significant associations between reported respiratory symptoms and increasing passive smoking exposure (1.16, 1.07-1.25 for any symptom). INTERPRETATION: Exposure to passive smoking is associated with an increased prevalence of COPD and respiratory symptoms. If this association is causal, we estimate that 1.9 million excess deaths from COPD among never smokers could be attributable to passive smoking in the current population in China. Our findings provide strong evidence for urgent measures against passive smoking in China.