The contribution of PM2.5 to cardiovascular disease in China

China is experiencing rapid urbanization and industrialization with correspondingly high levels of air pollution. Although the harm of PM2.5 has been long reported, it is only quite recently that there is increasing concern in China for its possible adverse health effects on cardiovascular disease. We reviewed the epidemiologic evidence of potential health effects of PM2.5 on cardiovascular disease reported from recent studies in China (2013 onwards). There is clear evidence for the contribution of PM2.5 to cardiovascular outcomes, including mortality, ischemic heart disease, and stroke from studies based in various regions in China. This evidence adds to the global evidence that PM2.5 contributes to adverse cardiovascular health risk and highlights the need for improved air quality in China

The rodent uterotrophic assay: Critical protocol features, studies with nonyl phenols, and comparison with a yeast estrogenicity assay

The major protocol features of the immature rat uterotrophic assay have been evaluated using a range of reference chemicals. The protocol variables considered include the selection of the test species and route of chemical administration, the age of the test animals, the maintenance diet used, and the specificity of the assay for estrogens. It is concluded that three daily oral administrations of test chemicals to 21- to 22-day-old rats, followed by determination of absolute uterus weights on the fourth day, provide a sensitive and toxicologically relevant in vivo estrogenicity assay. Rats are favored over mice for reasons of toxicological practice, but the choice of test species is probably not a critical protocol variable, as evidenced by the similar sensitivity of rats and mice to the uterotrophic activity of methoxychlor. Vaginal opening is shown to be a useful, but nondefinitive, adjunct to the uterotrophic assay. The ability of test chemicals to reduce or abolish the uterotrophic response of estradiol is suggested to provide a useful extension of the uterotrophic assay for the purpose of detecting antiestrogens. The results of a series of studies on the environmental estrogen nonyl phenol (NP), and its linear isomer n -nonyl phenol, confirm that branching of the aliphatic side chain is important for activity. 17beta-Desoxyestradiol is shown to be of similar activity to estradiol in the uterotrophic assay and is suggested to represent the "parent" estrogen of NP. Benzoylation of NP and 17-desoxyestradiol did not affect their uterotrophic activity, in contrast to the enhancing effect of benzoylation on estradiol. Selected chemicals shown to be active in the immature rat uterotrophic assay were also evaluated in an in vitro yeast human estrogen receptor transactivation assay. Most of the chemicals gave similar qualitative responses to those seen in the uterotrophic assay, and the detection of the estrogen methoxychlor by the yeast assay evidenced a degree of intrinsic metabolic competence. However, the assay had a reduced ability (compared to rodents) to hydrolyze the benzoate ester of estradiol, and the estrogenic benzoate derivative of NP was not active in the yeast assay. These last results indicate that current metabolic deficiencies of in vitro estrogenicity assays will limit the value of negative data for the immediate future. The results described illustrate the intrinsic complexity of evaluating chemicals for estrogenic activities and confirm the need for rigorous attention to experimental design and criteria for assessing estrogenic activity

Automatic Detection of Expanding HI Shells Using Artificial Neural Networks

The identification of expanding HI shells is difficult because of their variable morphological characteristics. The detection of HI bubbles on a global scale therefore never has been attempted. In this paper, an automatic detector for expanding HI shells is presented. The detection is based on the more stable dynamical characteristics of expanding shells and is performed in two stages. The first one is the recognition of the dynamical signature of an expanding bubble in the velocity spectra, based on the classification of an artificial neural network. The pixels associated with these recognized spectra are identified on each velocity channel. The second stage consists in looking for concentrations of those pixels that were firstly pointed out, and to decide if they are potential detections by morphological and 21-cm emission variation considerations. Two test bubbles are correctly detected and a potentially new case of shell that is visually very convincing is discovered. About 0.6% of the surveyed pixels are identified as part of a bubble. These may be false detections, but still constitute regions of space with high probability of finding an expanding shell. The subsequent search field is thus significantly reduced. We intend to conduct in the near future a large scale HI shells detection over the Perseus Arm using our detector.Comment: 39 pages, 11 figures, accepted by PAS

Epistasis between 5-HTTLPR and ADRA2B polymorphisms influences attentional bias for emotional information in healthy volunteers

Individual differences in emotional processing are likely to contribute to vulnerability and resilience to emotional disorders such as depression and anxiety. Genetic variation is known to contribute to these differences but they remain incompletely understood. The serotonin transporter (5-HTTLPR) and alpha(2B)-adrenergic autoreceptor (ADRA2B) insertion/deletion polymorphisms impact on two separate but interacting monaminergic signalling mechanisms that have been implicated in both emotional processing and emotional disorders. Recent studies suggest that the 5-HTTLPR s allele is associated with a negative attentional bias and an increased risk of emotional disorders. However, such complex behavioural traits are likely to exhibit polygenicity, including epistasis. This study examined the contribution of the 5-HTTLPR and ADRA2B insertion/deletion polymorphisms to attentional biases for aversive information in 94 healthy male volunteers and found evidence of a significant epistatic effect (p < 0.001). Specifically, in the presence of the 5-HTTLPR s allele, the attentional bias for aversive information was attenuated by possession of the ADRA2B deletion variant whereas in the absence of the s allele, the bias was enhanced. These data identify a cognitive mechanism linking genotype-dependent serotonergic and noradrenergic signalling that is likely to have implications for the development of cognitive markers for depression/anxiety as well as therapeutic drug effects and personalized approaches to treatment

Prevalence and Exposure Assessment of Aflatoxins Through Black Tea Consumption in the Multan City of Pakistan and the Impact of Tea Making Process on Aflatoxins

Aflatoxins are the highly toxic secondary metabolites of certain fungi, being mainly produced by Aspergillus flavus and Aspergillus parasiticus. Aflatoxins are classified as group 1 category carcinogens by the International Agency for Research on Cancer (IARC). A large number of food commodities are reported to be contaminated with aflatoxins. Tea is the world’s second most consumed beverage and the consumption of tea is increasing day by day. Besides being a source of several health promoting substances, tea leaves are also reported to be contaminated with aflatoxins. However, not a single study is reported from Pakistan regarding the level of aflatoxins in commercially available black tea samples. The current study aimed to quantify the level of aflatoxins in commercially available branded and non-branded black tea samples. The estimated daily intake (EDI) of aflatoxins through branded and non-branded black tea consumption and the health risk assessment based on margin of exposure (MOE) approach was assessed. Furthermore, the impact of local tea making processes on the concentration of aflatoxins in tea beverage (filtrate) was also investigated

Common aquatic pollutants modify hemocyte immune responses in Biomphalaria glabrata.

Funding The studentship supporting this research was awarded by the UK Natural Environment Research Council (NERC). Acknowledgments We are grateful to Dr. David Rollinson (Natural History Museum) for providing B. glabrata snails and to Drs. Nuha Mansour and Quentin Bickle (London School of Hygiene and Tropical Medicine) for providing parasite material. We thank the UK Natural Environment Research Council (NERC) for funding.Peer reviewedPublisher PD

Competition between Intramolecular and Intermolecular Interactions in an Amyloid-Forming Protein

Despite much progress in understanding the folding and the aggregation processes of proteins, the rules defining their interplay have yet to be fully defined. This problem is of particular importance since many diseases are initiated by protein unfolding and hence the propensity to aggregate competes with intramolecular collapse and other folding events. Here, we describe the roles of intramolecular and intermolecular interactions in defining the length of the lag time and the apparent rate of elongation of the 100-residue protein human β2-microglobulin at pH&nbsp;2.5, commencing from an acid-denatured state that lacks persistent structure but contains significant non-random hydrophobic interactions. Using a combination of site-directed mutagenesis, quantitative kinetic analysis and computational methods, we show that only a single region of about 10 residues in length, determines the rate of fibril formation, despite the fact that other regions exhibit a significant intrinsic propensity for aggregation. We rationalise these results by analysing the effect of incorporating the conformational properties of acid-unfolded β2-microglobulin and its variants at pH&nbsp;2.5 as measured by NMR spectroscopy into the Zyggregator aggregation prediction algorithm. These results demonstrate that residual structure in the precursor state modulates the intrinsic propensity of the polypeptide chain to aggregate and that the algorithm developed here allows the key regions for aggregation to be more clearly identified and the rates of their self-association to be predicted. Given the common propensity of unfolded chains to form non-random intramolecular interactions as monomers and to self-assemble subsequently into amyloid fibrils, the approach developed should find widespread utility for the prediction of regions important in amyloid formation and their rates of self-assembly. © 2009 Elsevier Ltd. All rights reserved

Inference of malaria reproduction numbers in three elimination settings by combining temporal data and distance metrics

Individual-level geographic information about malaria cases, such as the GPS coordinates of residence or health facility, is often collected as part of surveillance in near-elimination settings, but could be more effectively utilised to infer transmission dynamics, in conjunction with additional information such as symptom onset time and genetic distance. However, in the absence of data about the flow of parasites between populations, the spatial scale of malaria transmission is often not clear. As a result, it is important to understand the impact of varying assumptions about the spatial scale of transmission on key metrics of malaria transmission, such as reproduction numbers. We developed a method which allows the flexible integration of distance metrics (such as Euclidian distance, genetic distance or accessibility matrices) with temporal information into a single inference framework to infer malaria reproduction numbers. Twelve scenarios were defined, representing different assumptions about the likelihood of transmission occurring over different geographic distances and likelihood of missing infections (as well as high and low amounts of uncertainty in this estimate). These scenarios were applied to four individual level datasets from malaria eliminating contexts to estimate individual reproduction numbers and how they varied over space and time. Model comparison suggested that including spatial information improved models as measured by second order AIC (ΔAICc), compared to time only results. Across scenarios and across datasets, including spatial information tended to increase the seasonality of temporal patterns in reproduction numbers and reduced noise in the temporal distribution of reproduction numbers. The best performing parameterisations assumed long-range transmission (> 200 km) was possible. Our approach is flexible and provides the potential to incorporate other sources of information which can be converted into distance or adjacency matrices such as travel times or molecular markers

Training Load and Carbohydrate Periodization Practices of Elite Male Australian Football Players: Evidence of Fueling for the Work Required.

The authors aimed to quantify (a) the periodization of physical loading and daily carbohydrate (CHO) intake across an in-season weekly microcycle of Australian Football and (b) the quantity and source of CHO consumed during game play and training. Physical loading (via global positioning system technology) and daily CHO intake (via a combination of 24-hr recall, food diaries, and remote food photographic method) were assessed in 42 professional male players during two weekly microcycles comprising a home and away fixture. The players also reported the source and quantity of CHO consumed during all games (n = 22 games) and on the training session completed 4 days before each game (n = 22 sessions). The total distance was greater (p < .05) on game day (GD; 13 km) versus all training days. The total distance differed between training days, where GD-2 (8 km) was higher than GD-1, GD-3, and GD-4 (3.5, 0, and 7 km, respectively). The daily CHO intake was also different between training days, with reported intakes of 1.8, 1.4, 2.5, and 4.5 g/kg body mass on GD-4, GD-3, GD-2, and GD-1, respectively. The CHO intake was greater (p < .05) during games (59 ± 19 g) compared with training (1 ± 1 g), where in the former, 75% of the CHO consumed was from fluids as opposed to gels. Although the data suggest that Australian Football players practice elements of CHO periodization, the low absolute CHO intakes likely represent considerable underreporting in this population. Even when accounting for potential underreporting, the data also suggest Australian Football players underconsume CHO in relation to the physical demands of training and competition