Perfluorinated alkyl acids in the serum and follicular fluid of UK women with and without polycystic ovarian syndrome undergoing fertility treatment and associations with hormonal and metabolic parameters

© 2018 Women with polycystic ovarian syndrome (PCOS) undergoing treatment for infertility could be a sensitive subpopulation for endocrine effects of exposure to perfluorinated alkyl acids (PFAAs), persistent organic pollutants with potential endocrine activity. Women with, PCOS (n = 30) and age- and BMI-matched controls (n = 29) were recruited from a UK fertility clinic in 2015. Paired serum and follicular fluid samples were collected and analysed for 13 PFAAs. Sex steroid and thyroid hormones, and metabolic markers were measured and assessed for associations with serum PFAAs. Four PFAAs were detected in all serum and follicular fluid samples and concentrations in the two matrices were highly correlated (R2 > 0.95): perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonate (PFHxS), and perfluorononanoic acid (PFNA). Serum PFOS was positively associated with age (1 ng/mL per yr, p < 0.05) and was higher in PCOS cases than controls (geometric mean [GM] 3.9 vs. 3.1 ng/mL, p < 0.05) and in women with irregular vs. regular menstrual cycles (GM 3.9 vs. 3.0 ng/mL, p = 0.01). After adjustment for confounders, serum testosterone was significantly associated with PFOA, PFHxS, PFNA, and the molar sum of the four frequently detected serum PFAAs (approximately 50 percent increase per ln-unit) among controls but not PCOS cases. HbA1c in PCOS cases was inversely associated with serum PFOA, PFHxs, and sum of PFAAs (2–3 mmol/mol per ln-unit). In controls, fasting glucose was positively associated with serum PFOA and sum of PFAAs (0.25 nmol/L per ln-unit increase in PFAAs). Few other associations were observed. The analyses and findings here should be considered exploratory in light of the relatively small sample sizes and large number of statistical comparisons conducted. However, the data do not suggest increased sensitivity to potential endocrine effects of PFAAs in PCOS patients

Long-distance dispersal and recolonization of a fire-destroyed niche by a mite-associated fungus

The Fynbos Biome in the Core Cape Subregion of South Africa is prone to recurrent fires that can clear vast areas of vegetation. Between periods of fire, ophiostomatoid fungi colonize the fruiting structures of serotinous Protea species through arthropod-mediated dispersal. Using microsatellite markers, this study considered the process whereby a Protea-associated ophiostomatoid fungus, Knoxdaviesia proteae, recolonizes a burnt area. The genetic diversity, composition and structure of fungal populations from young P. repens plants in a recently burnt area were compared to populations from the adjacent, unburnt Protea population. The only difference between K. proteae populations from the two areas was found in the number of private alleles, which was significantly higher in the unburnt population. The population structure, although weak, indicated that most K. proteae individuals from recently burnt areas originated from the unburnt population. However, individuals from unsampled source populations were also detected. This, together with the lack of isolation-by-distance across the landscape, suggested that long-distance dispersal is important for K. proteae to recolonize burnt areas. Similarly, the high level of gene flow and low differentiation observed between two distantly separated K. proteae populations also supported the existence of long-distance dispersal. The genetic cohesiveness of populations over long distances and the genetic diversity within populations could be attributed to frequent multiple fungal migration events mediated primarily by arthropods but, potentially, also by birds.National Research Foundation (NRF) and the Department of Science and Technology (DST)-NRF Centre of Excellence in Tree Health Biotechnology (CTHB).http://www.elsevier.com/locate/funbiohb2016Microbiology and Plant Patholog

Development of polymorphic microsatellite markers for the genetic characterisation of Knoxdaviesia proteae (Ascomycota: Microascales) using ISSR-PCR and pyrosequencing

Knoxdaviesia proteae is one of the first native ophiostomatoid fungi discovered in South Africa, where it consistently occurs in the infructescences of the iconic Cape Biome plant, Protea repens. Although numerous studies have been undertaken to better understand the ecology of K. proteae, many questions remain to be answered, particularly given its unique niche and association with arthropods for dispersal.We describe the development and distribution of microsatellite markers in K. proteae through Interspersed Simple Sequence Repeat-Polymerase Chain Reaction (ISSR-PCR) enrichment and pyrosequencing. A large proportion of the 31492 sequences obtained from sequencing the enriched genomic DNA were characterised by microsatellites consisting of short tandem repeats and di- and tri-nucleotide motifs. Seventeen percent of these microsatellites contained flanking regions sufficient for primer design. Twenty-three primer pairs were tested, of which 12 amplified and 10 generated polymorphic fragments in K. proteae. Half of these could be transferred to the sister species, K. capensis. The developedmarkers will be used to investigate the reproductive system, genetic diversity and dispersal strategies of K. proteae.National Research Foundation (NRF) and the Department of Science and Technology (DST)/NRF Centre of Excellence in Tree Health Biotechnology (CTHB).http://link.springer.com/journal/11557hb201

Genome sequences of Knoxdaviesia capensis and K. proteae (Fungi : Ascomycota) from Protea trees in South Africa

Two closely related ophiostomatoid fungi, Knoxdaviesia capensis and K. proteae, inhabit the fruiting structures of certain Protea species indigenous to southern Africa. Although K. capensis occurs in several Protea hosts, K. proteae is confined to P. repens. In this study, the genomes of K. capensis CBS139037 and K. proteae CBS140089 are determined. The genome of K. capensis consists of 35,537,816 bp assembled into 29 scaffolds and 7940 predicted protein-coding genes of which 6192 (77.98 %) could be functionally classified. K. proteae has a similar genome size of 35,489,142 bp that is comprised of 133 scaffolds. A total of 8173 protein-coding genes were predicted for K. proteae and 6093 (74.55 %) of these have functional annotations. The GC-content of both genomes is 52.8 %.Additional file 1: Table S1. Associated MIGS record for K. capensis.Additional file 2: Table S2. Associated MIGS record for K. proteae.Additional file 3: Table S3. Sequenced Sordariomycete fungi used as evidence for genome annotations.The National Research Foundation (NRF) and the Department of Science and Technology/NRF Centre of Excellence in Tree Health Biotechnology.http://www.sherpa.ac.uk/romeo/issn/1944-3277/am2016GeneticsMicrobiology and Plant Patholog

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

The Application of Internal Dose Measures, Biokinetics, and Biomonitoring Data in the Risk Assessment of Dioxin-Like Compounds

This thesis presents a series of investigations into the biokinetic behavior of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related compounds and the application of biokinetic modeling and biomonitoring data in quantitative risk assessment for these compounds. The biokinetic properties of TCDD and related compounds affect nearly every facet of the typical risk assessment procedure as applied to these compounds. Qualitative and quantitative differences in the distribution and elimination of TCDD exist between high and low doses, between species, and even between bolus vs. subchronic dosing administration regimens; similarly, differences exist between TCDD and other dioxin, furan, and PCB compounds of interest. These factors should be considered in risk assessments for dioxins. Because of these complexities, preference should be given to studies most easily interpretable in the context of current human exposure tracking and assessment, which is dominated by the use of biomonitoring efforts. Where possible, use of human studies that rely upon biomonitoring data for exposure quantification concurrent with the measurement of outcome of interest may provide the most reliable basis for risk assessment. Where such data are judged to be unavailable or insufficient, animal studies conducted under chronic or subchronic dosing regimens with measured tissue concentrations may provide the most relevant dose-response data. The substantial uncertainties and interindividual variability in human biokinetics suggests that exposure-response assessments relying on extensive back-calculation of serum TCDD levels should be used only with a great deal of caution, perhaps as supportive analyses rather than the main basis for quantitative risk assessment. Research presented here uses newly-available data sets on elimination of TCDD in highly-exposed human populations to modify and implement a previously-developed model of distribution and elimination for TCDD and to examine the sources of variability and uncertainty involved in the application of such modeling to human occupational cohorts. This research demonstrates that the resulting uncertainty and variations in estimated cumulative exposures may substantially impact a quantitative risk assessment derived based on such estimated exposures. Other research presented in this dissertation demonstrates a variety of approaches for using human biomonitoring and response data in risk assessment for cancer and non-cancer endpoints. Finally, remaining issues related to the role of biokinetics in interspecies extrapolation and risk assessment for dioxins and related compounds are identified. These include the need for assessment of relative potencies on a tissue concentration (rather than intake) basis and the need for further understanding of the role of lactational transfer and interspecies correspondence in critical developmental windows in the occurrence of developmental effects of dioxin-like compounds

Per- and polyfluoroalkyl substances (PFAS) in Australia: Current levels and estimated population reference values for selected compounds

Background Increased public awareness of PFAS contamination in Australia has resulted in serum biomonitoring efforts in individuals in potentially affected communities. However, population-based reference values for assessing whether individual results exceed the typical range in the Australian general population are not currently available. Objective Estimate population upper bound reference values based on updated serum PFAS concentrations in pooled samples from southeast Queensland, Australia and population variation observed in the US National Health and Nutrition Examination Survey (NHANES) datasets. Methods We calculated ratios of 95th percentile to arithmetic mean (P95:AM ratios) using data from the NHANES 2013–14 and 2015–16 cycle samples for frequently detected PFASs: PFOA, linear and branched PFOS, perfluorononanoate (PFNA), perfluorodecanoate (PFDA), and perfluorohexanesulfonate (PFHxS). We estimated Australian age-specific means for PFAS using pooled serum samples collected in 2014–15 and 2016–17. We used the P95:AM ratios to estimate 95th percentile concentrations in the Australian population based on the results of the 2016–17 pooled samples. Results and conclusions P95:AM ratios for each PFAS were similar across NHANES cycle and age group, so overall compound-specific ratios were estimated for PFOA (2.1), PFNA (2.4), PFDA (2.7), PFHxS (2.7), and linear (2.4) and summed PFOS (2.3). Australian mean PFAS concentrations continued previously reported declining trends. The estimated P95 values can be used as preliminary substitutes for more rigorous population reference values to identify samples with clearly elevated serum PFAS concentrations in Australian biomonitoring efforts. Given uncertainties and variability inherent in this evaluation, the estimated P95 values should be interpreted with caution. Mean and estimated P95 serum PFAS concentrations in Australia should continue to be monitored to document declining trends in population serum concentrations.The Queensland Alliance for Environmental Health Sciences (QAEHS), The University of Queensland, gratefully acknowledges the financial support of the Queensland Department of Health. All laboratory staff are gratefully acknowledged for their assistance and provision of sample pools. This project was partly funded by an Australian Research Council Discovery grant (DP180101475) and QAEHS seed funding. MDK receives salary support from the Australian National Health & Medical Research Council (GNT1136112). MDK, JFM, and JB have received funds from the Australian Government Department of Health to conduct the PFAS Health Study. Dr. Sara Broomhall is gratefully acknowledged for ongoing discussion and assistance to the QAEHS researchers