Postural Changes in Blood Pressure Associated with Interactions between Candidate Genes for Chronic Respiratory Diseases and Exposure to Particulate Matter

BACKGROUND. Fine particulate matter [aerodynamic diameter ≤ 2.5 μm (PM2.5)] has been associated with autonomic dysregulation. OBJECTIVE. We hypothesized that PM2.5 influences postural changes in systolic blood pressure (ΔSBP) and in diastolic blood pressure (ΔDBP) and that this effect is modified by genes thought to be related to chronic lung disease. METHODS. We measured blood pressure in participants every 3-5 years. ΔSBP and ΔDBP were calculated as sitting minus standing SBP and DBP. We averaged PM2.5 over 48 hr before study visits and analyzed 202 single nucleotide polymorphisms (SNPs) in 25 genes. To address multiple comparisons, data were stratified into a split sample. In the discovery cohort, the effects of SNP x PM2.5 interactions on ΔSBP and ΔDBP were analyzed using mixed models with subject-specific random intercepts. We defined positive outcomes as p < 0.1 for the interaction; we analyzed only these SNPs in the replicate cohort and confirmed them if p < 0.025 with the same sign. Confirmed associations were analyzed within the full cohort in models adjusted for anthropometric and lifestyle factors. RESULTS. Nine hundred forty-five participants were included in our analysis. One interaction with rs9568232 in PHD finger protein 11 (PHF11) was associated with greater ΔDBP. Interactions with rs1144393 in matrix metalloprotease 1 (MMP1) and rs16930692, rs7955200, and rs10771283 in inositol 1,4,5-triphosphate receptor, type 2 (ITPR2) were associated with significantly greater ΔSBP. Because SNPs associated with ΔSBP in our analysis are in genes along the renin-angiotensin pathway, we then examined medications affecting that pathway and observed significant interactions for angiotensin receptor blockers but not angiotensin-converting enzyme inhibitors with PM2.5. CONCLUSIONS. PM2.5 influences blood pressure and autonomic function. This effect is modified by genes and drugs that also act along this pathway.National Institute of Environmental Health Sciences (T32 ES07069, ES0002, ES015172-01, ES014663, P01 ES09825); United States Environmental Protection Agency (R827353, R832416); National Institutes of Health/National Institute of Aging (AG027014); United States Department of Veterans Affairs; Massachusetts Veterans Epidemiology Research and Information Cente

An evaluation of indices for quantifying tuberculosis transmission using genotypes of pathogen isolates

BACKGROUND: Infectious diseases are often studied by characterising the population structure of the pathogen using genetic markers. An unresolved problem is the effective quantification of the extent of transmission using genetic variation data from such pathogen isolates. METHODS: It is important that transmission indices reflect the growth of the infectious population as well as account for the mutation rate of the marker and the effects of sampling. That is, while responding to this growth rate, indices should be unresponsive to the sample size and the mutation rate. We use simulation methods taking into account both the mutation and sampling processes to evaluate indices designed to quantify transmission of tuberculosis. RESULTS: Previously proposed indices generally perform inadequately according to the above criteria, with the partial exception of the recently proposed Transmission-Mutation Index. CONCLUSION: Any transmission index needs to take into account mutation of the marker and the effects of sampling. Simple indices are unlikely to capture the full complexity of the underlying processes

Genomic Assemblies of Members of Burkholderia and Related Genera as a Resource for Natural Product Discovery.

The genomes of 450 members of Burkholderiaceae, isolated from clinical and environmental sources, were sequenced and assembled as a resource for genome mining. Genomic analysis of the collection has enabled the identification of multiple metabolites and their biosynthetic gene clusters, including the antibiotics gladiolin, icosalide A, enacyloxin, and cepacin A

High levels of engagement with testing for HIV and sexually transmissible infection among gay Asian men in Sydney and Melbourne: An observational study

Gay and other men who have sex with men of Asian background (GAM) have been identified as a key population in efforts to eradicate HIV in New South Wales. The aims of the present study were to evaluate current levels of engagement with HIV and sexually transmissible infection (STI) testing services, assess knowledge of pre- and post-exposure prophylaxis and to identify factors associated with service engagement in this group. Methods: A survey of 604 GAM residing in Sydney and Melbourne was undertaken. Results: The data identified that a significant proportion of non-HIV-positive men (i.e. HIV-negative men and men whose HIV status was unknown) surveyed (n = 567; 93.9%) had engaged in frequent HIV testing and comprehensive STI testing in the 12 months prior to the survey (n = 180; 31.7%). There were significant differences (P < 0.05) in sexual practices at the bivariate level between those who reported frequent and comprehensive HIV/STI testing and those who did not. Those who tested regularly were substantially more sexually active, were more likely to have multiple partners (P = 0.001) and were more likely to engage in condomless anal intercourse with both casual (P < 0.001) and regular (P = 0.002) partners. Those who engaged with testing initiatives were more likely to discuss HIV status with both regular (P = 0.008) and casual (P < 0.001) partners, and identified more reasons to test than their counterparts (P < 0.001). The data also highlighted key service venues, with gay men most likely to have used public sexual health clinics (46.9%) as their most recent testing venue. Conclusions: The data demonstrate an association between high levels of male-to-male sexual activity and engagement in frequent and comprehensive HIV and STI testing. This likely derives from both self-perceived notions of risk and current reliance on established gay community organisations to convey information around testing. Increasing engagement with testing initiatives beyond GAM who self-identify as being at high HIV and STI risk will require the use of novel routes by which to disseminate this information

Obstetric anal sphincter injury: a systematic review of information available on the internet.

OBJECTIVE: There is no systematic evaluation of online health information pertaining to obstetric anal sphincter injury. Therefore, we evaluated the accuracy, credibility, reliability, and readability of online information concerning obstetric anal sphincter injury. MATERIALS AND METHODS: Multiple search engines were searched. The first 30 webpages were identified for each keyword and considered eligible if they provided information regarding obstetric anal sphincter injury. Eligible webpages were assessed by two independent researchers for accuracy (prioritised criteria based upon the RCOG Third and Fourth Degree Tear guideline); credibility; reliability; and readability. RESULTS: Fifty-eight webpages were included. Seventeen webpages (30%) had obtained Health On the Net certification, or Information Standard approval and performed better than those without such approvals (p = 0.039). The best overall performing website was http://www.pat.nhs.uk (score of 146.7). A single webpage (1%) fulfilled the entire criteria for accuracy with a score of 18: www.tamesidehospital.nhs.uk . Twenty-nine webpages (50%) were assessed as credible (scores ≥7). A single webpage achieved a maximum credibility score of 10: www.meht.nhs.uk . Over a third (21 out of 58) were rated as poor or very poor. The highest scoring webpage was http://www.royalsurrey.nhs.uk (score 62). No webpage met the recommended Flesch Reading Ease Score above 70. The intra-class coefficient between researchers was 0.98 (95% CI 0.96-0.99) and 0.94 (95% CI 0.89-0.96) for accuracy and reliability assessments. CONCLUSION: Online information concerning obstetric anal sphincter injury often uses language that is inappropriate for a lay audience and lacks sufficient accuracy, credibility, and reliability

Interactions and potential implications of Plasmodium falciparum-hookworm coinfection in different age groups in south-central Côte d'Ivoire

BACKGROUND: Given the widespread distribution of Plasmodium and helminth infections, and similarities of ecological requirements for disease transmission, coinfection is a common phenomenon in sub-Saharan Africa and elsewhere in the tropics. Interactions of Plasmodium falciparum and soil-transmitted helminths, including immunological responses and clinical outcomes of the host, need further scientific inquiry. Understanding the complex interactions between these parasitic infections is of public health relevance considering that control measures targeting malaria and helminthiases are going to scale.METHODOLOGY: A cross-sectional survey was carried out in April 2010 in infants, young school-aged children, and young non-pregnant women in south-central Côte d'Ivoire. Stool, urine, and blood samples were collected and subjected to standardized, quality-controlled methods. Soil-transmitted helminth infections were identified and quantified in stool. Finger-prick blood samples were used to determine Plasmodium spp. infection, parasitemia, and hemoglobin concentrations. Iron, vitamin A, riboflavin, and inflammation status were measured in venous blood samples.PRINCIPAL FINDINGS: Multivariate regression analysis revealed specific association between infection and demographic, socioeconomic, host inflammatory and nutritional factors. Non-pregnant women infected with P. falciparum had significantly lower odds of hookworm infection, whilst a significant positive association was found between both parasitic infections in 6- to 8-year-old children. Coinfected children had lower odds of anemia and iron deficiency than their counterparts infected with P. falciparum alone.CONCLUSIONS/SIGNIFICANCE: Our findings suggest that interaction between P. falciparum and light-intensity hookworm infections vary with age and, in school-aged children, may benefit the host through preventing iron deficiency anemia. This observation warrants additional investigation to elucidate the mechanisms and consequences of coinfections, as this information could have important implications when implementing integrated control measures against malaria and helminthiases

Genome mining identifies cepacin as a plant-protective metabolite of the biopesticidal bacterium Burkholderia ambifaria.

Beneficial microorganisms are widely used in agriculture for control of plant pathogens, but a lack of efficacy and safety information has limited the exploitation of multiple promising biopesticides. We applied phylogeny-led genome mining, metabolite analyses and biological control assays to define the efficacy of Burkholderia ambifaria, a naturally beneficial bacterium with proven biocontrol properties but potential pathogenic risk. A panel of 64 B. ambifaria strains demonstrated significant antimicrobial activity against priority plant pathogens. Genome sequencing, specialized metabolite biosynthetic gene cluster mining and metabolite analysis revealed an armoury of known and unknown pathways within B. ambifaria. The biosynthetic gene cluster responsible for the production of the metabolite cepacin was identified and directly shown to mediate protection of germinating crops against Pythium damping-off disease. B. ambifaria maintained biopesticidal protection and overall fitness in the soil after deletion of its third replicon, a non-essential plasmid associated with virulence in Burkholderia cepacia complex bacteria. Removal of the third replicon reduced B. ambifaria persistence in a murine respiratory infection model. Here, we show that by using interdisciplinary phylogenomic, metabolomic and functional approaches, the mode of action of natural biological control agents related to pathogens can be systematically established to facilitate their future exploitation.A.J.M. is funded by a Biotechnology and Biological Sciences Research Council (BBSRC) South West doctoral training partnership award (BY1910 7007). E.M., G.L.C., T.R.C. and J.P. acknowledge additional support for genome mining from BBSRC award BB/L021692/1; C.J. and M.J. were funded by this award. M.J. is currently the recipient of a BBSRC Future Leader Fellowship (BB/R01212/1). The Bruker maXis II UHPLC-ESI-Q-TOF-MS system used in this research was funded by the BBSRC (BB/M017982/1). G.W. was supported by awards to E.M. from the Life Sciences Bridging Fund and Wellcome Trust Institutional Strategic Support Fund held at Cardiff University. T.R.C. and M.J.B. acknowledge funding support from the Medical Research Council’s Cloud Infrastructure for Microbial Bioinformatics (MR/L015080/1), which provided the computational resources to undertake the analyses for this work. D.R.N. and A.E.G. acknowledge funding from a Wellcome Trust and Royal Society Sir Henry Dale Fellowship awarded to D.R.N. (grant number 204457/Z/16/Z). G.L.C. is the recipient of a Wolfson Research Merit Award from the Royal Society (WM130033)