•A suite of flame retardants were measured in paired samples of handwipes and dust.•FR levels in handwipes were significantly correlated with house dust levels.•PBDE levels in house dust was ...significantly correlated over a 2 year time frame.•Children’s age, handwashing behavior and dust levels predicted handwipe levels.•Siblings living in the same home had very similar FR exposure levels.
Polybrominated diphenyl ether (PBDE), flame retardants (FRs) have been ubiquitously detected at high concentrations in indoor environments; however, with their recent phase-out, more attention is being focused on measurements of exposure to alternative FRs such as organophosphate FRs (OPFRs). In our previous research, we found that PBDE residues measured on children’s handwipes were a strong predictor of serum PBDE levels. Here we build upon this research to examine longitudinal changes in PBDEs in indoor dust and children’s handwipes, and explore the associations between handwipes and dust for alternative FRs. Children from our previous study were re-contacted after approximately two years and new samples of indoor dust and handwipes were collected. PBDE dust-levels were significantly correlated between two different sampling rounds separated by two years; however, PBDE levels in handwipes were not correlated, perhaps suggesting that the sources of PBDEs remained relatively constant in the home, but that behavioral differences in children are changing with age and influencing handwipe levels. OPFRs i.e. tris(1,3-dichloroisopropyl) phosphate (TDCPP), tris(2-chloroethyl) phosphate (TCEP), tris(2-chloroisopropyl) phosphate (TCIPP), 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB, also known as TBB), di(2-ethylhexyl) tetrabromophthalate (BEH-TEBP, also known as TBPH), and 1,2,5,6,9,10-hexabromocyclododecane (HBCD) were also ubiquitously detected in house dust samples and geometric mean levels were similar to PBDE levels, or higher in the case of the OPFRs. Significant associations between handwipes and house dust were observed for these alternative FRs, particularly for EH-TBB (rs=0.54; p<0.001). Increasing house dust levels and age were associated with higher levels of FRs in handwipes, and high hand washing frequency (>5timesd−1) was associated with lower FR levels in handwipes. Overall these data suggest that exposure to these alternative FRs will be similar to PBDE exposure, and the influence of hand-to-mouth behavior in children’s exposure needs to be further examined to better estimate exposure potential.
Relationships between total soil or bioaccessible lead (Pb), measured using an in vitro bioaccessibility assay, and children’s blood lead levels (BLL) were investigated in an urban neighborhood in ...Philadelphia, PA, with a history of soil Pb contamination. Soil samples from 38 homes were analyzed to determine whether accounting for the bioaccessible Pb fraction improves statistical relationships with children’s BLLs. Total soil Pb concentration ranged from 58 to 2821 mg/kg; the bioaccessible Pb concentration ranged from 47 to 2567 mg/kg. Children’s BLLs ranged from 0.3 to 9.8 μg/dL. Hierarchical models were used to compare relationships between total or bioaccessible Pb in soil and children’s BLLs. Total soil Pb concentration as the predictor accounted for 23% of the variability in child BLL; bioaccessible soil Pb concentration as the predictor accounted for 26% of BLL variability. A bootstrapping analysis confirmed a significant increase in R 2 for the model using bioaccessible soil Pb concentration as the predictor with 99.0% of bootstraps showing a positive increase. Estimated increases of 1.3 μg/dL and 1.5 μg/dL in BLL per 1000 mg/kg Pb in soil were observed for this study area using total and bioaccessible Pb concentrations, respectively. Children’s age did not contribute significantly to the prediction of BLLs.
The storage of coal combustion residue (CCR) in surface water impoundments may have an impact on nearby water quality and aquatic ecosystems. CCR contains leachable trace elements that can enter ...nearby waters through spills and monitored discharge. It is important, therefore, to understand their environmental fate in affected systems. This experiment examined trace element leachability into freshwater from fly ash (FA), the most common form of CCR. The effects on water quality of FA derived from both high and low sulfur coal sources as well as the influences of two different emergent macrophytes,
Juncus effusus
and
Eleocharis quadrangulata
, were evaluated in wetland microcosms. FA leachate dosings increased water electric conductivity (EC), altered pH, and, most notably, elevated the concentrations of boron (B), molybdenum (Mo), and manganese (Mn). The presence of either macrophyte species helped reduce elevated EC, and B, Mo, and Mn concentrations over time, relative to microcosms containing no plants. B and Mo appeared to bioaccumulate in the plant tissue from the water when elevated by FA dosing, while Mn was not higher in plants dosed with FA leachates. The results of this study indicate that emergent macrophytes could help ameliorate downstream water contamination from CCR storage facilities and could potentially be utilized in wetland filtration systems to treat CCR wastewater before discharge. Additionally, measuring elevated B and Mo in aquatic plants may have potential as a monitoring tool for downstream CCR contamination.
Interest in improved understanding of relationships among soil properties and arsenic (As) bioaccessibility has motivated the use of regression models for As bioaccessibility prediction. However, ...limits in the numbers and types of soils included in previous studies restrict the usefulness of these models beyond the range of soil conditions evaluated, as evidenced by reduced predictive performance when applied to new data. In response, hierarchical models that consider variability in relationships among soil properties and As bioaccessibility across geographic locations and contaminant sources were developed to predict As bioaccessibility in 139 soils on both a mass fraction (mg/kg) and % basis. The hierarchical approach improved the estimation of As bioaccessibility in studied soils. In addition, the number of soil elements identified as statistically significant explanatory variables increased when compared to previous investigations. Specifically, total soil Fe, P, Ca, Co, and V were significant explanatory variables in both models, while total As, Cd, Cu, Ni, and Zn were also significant in the mass fraction model and Mg was significant in the % model. This developed hierarchical approach provides a novel tool to (1) explore relationships between soil properties and As bioaccessibility across a broad range of soil types and As contaminant sources encountered in the environment and (2) identify areas of future mechanistic research to better understand the complexity of interactions between soil properties and As bioaccessibility.
Arsenic (As) and lead (Pb) are two contaminants of concern associated with urban gardening. In Puerto Rico, data currently is limited on As and Pb levels in urban garden soils, soil metal (loid) ...bioaccessibility, and uptake of As and Pb in soil by edible plants grown in the region. This study examined total and bioaccessible soil As and Pb concentrations and accumulation in 10 commonly grown garden plants collected from three urban community gardens in Puerto Rico. Bioavailability values were predicted using bioaccessibility data to compare site-specific bioavailability estimates to commonly used default exposure assumptions. Total and bioaccessible As levels in study soils ranged from 2 to 55 mg/kg and 1 to 18 mg/kg, respectively. Total and bioaccessible Pb levels ranged from 19 to 172 mg/kg and 17 to 97 mg/kg, respectively. Measured bioaccessibility values corresponded to 19 to 42% bioaccessible As and 61 to 100% bioaccessible Pb when expressed as a percent of total As and Pb respectively. Predicted relative percent bioavailability of soil As and Pb based on measured bioaccessibility values ranged from 18 to 36% and 51 to 85% for As and Pb respectively. Transfer factors (TFs) measuring uptake of As in plants from soil ranged from 0 to 0.073 in the edible flesh (fruit or vegetable) of plant tissues analyzed and 0.073 to 0.444 in edible leaves. Pb TFs ranged from 0.002 to 0.012 in flesh and 0.023 to 0.204 in leaves. Consistent with TF values, leaves accumulated higher concentrations of As and Pb than the flesh, with the highest tissue concentrations observed in the culantro leaf (3.2 mg/kg dw of As and 8.9 mg/kg dw of Pb). Leaves showed a general but not statistically-significant (α = 0.05) trend of increased As and Pb concentration with increased soil levels, while no trend was observed for flesh tissues. These findings provide critical data that can improve accuracy and reduce uncertainty when conducting site-specific risk determination of potential As and Pb exposure while gardening or consuming garden produce in the understudied region of Puerto Rico.
Lead (Pb) in soil is an important exposure source for children. Thus, determining bioavailability of Pb in soil is critical in evaluating risk and selecting appropriate strategies to minimize ...exposure. A mouse model was developed to estimate relative bioavailability of Pb in NIST SRM 2710a (Montana 1 Soil). Based on Pb levels in tissues, the mean relative bioavailability of this metal in this soil was 0.5. Estimates of relative bioavailabilities derived from mouse compared favorably with those obtained in juvenile swine. The mouse model is thus an efficient and inexpensive method to obtain estimates of relative bioavailability of soil Pb.
Background: Although heparin possesses multiple mechanisms of action, enhanced factor Xa inhibition by antithrombin is accepted as the predominant therapeutic mechanism. The contribution of FIXa ...inhibition to heparin activity in human plasma remains incompletely defined.
Objectives: To determine the relevance of FIXa as a therapeutic target for heparins, particularly serpin‐independent inhibition of intrinsic tenase (FIXa–FVIIIa) activity.
Patients/Methods: Thrombin generation was detected by fluorogenic substrate cleavage. The inhibitory potencies (EC50s) of low molecular weight heparin (LMWH), super‐sulfated LMWH (ssLMWH), fondaparinux and unfractionated heparin (UFH) were determined by plotting concentration vs. relative velocity index (ratio ± heparin). Inhibition was compared under FIX‐dependent and FIX‐independent conditions (0.2 or 4 pm tissue factor TF, respectively) in normal plasma, and in mock‐depleted or antithrombin/FIX‐depleted plasma supplemented with recombinant FIX.
Results: UFH and fondaparinux demonstrated similar potency under FIX‐dependent and FIX‐independent conditions, whereas LMWH (2.9‐fold) and ssLMWH (5.1‐fold) demonstrated increased potency with limiting TF. UFH (62‐fold) and fondaparinux (42‐fold) demonstrated markedly increased EC50 values in antithrombin‐depleted plasma, whereas LMWH (9.4‐fold) and ssLMWH (two‐fold) were less affected, with an EC50 within the therapeutic range for LMWH. The molecular target for LMWH/ssLMWH was confirmed by supplementing FIX/antithrombin‐depleted plasma with 90 nm recombinant FIX possessing mutations in the heparin‐binding exosite. Mutated FIX demonstrated resistance to inhibition of thrombin generation by LMWH and ssLMWH that paralleled the effect of these mutations on intrinsic tenase inhibition.
Conclusions: Therapeutic LMWH concentrations inhibit plasma thrombin generation via antithrombin‐independent interaction with the FIXa heparin‐binding exosite.
Background
In the recently concluded PARTNER 2 trial, TF‐TAVR cohort was shown to have lower risks of death or disabling strokes as compared to SAVR, whereas the outcomes with transthoracic TAVR were ...comparable with SAVR.
Methods
We searched PubMed, EMBASE, Web of Science, and Google Scholar for all comparison studies between TAVR and SAVR and mortality as an outcome, irrespective of surgical risk. Randomized controlled trials and propensity‐score‐matched cohort studies that used a transfemoral approach exclusively or stratified results by route of access and reported data for TF‐TAVR patients were eligible for inclusion. Outcomes of interest included 30‐day and 1‐year mortality, and 30‐day complications. If significant heterogeneity was found in the random effects meta‐analyses, a sensitivity analysis which individually removed each study was conducted.
Results
Seven studies reported results on TF‐TAVR. Compared with SAVR, TF‐TAVR had comparable 30‐day mortality (RR 0.79, 95% CI 0.58, 1.06), 1‐year mortality (RR 0.91, 95% CI 0.78, 1.08) and 30‐day risk of bleeding (RR 0.70, 95% CI 0.31, 1.57). However, TF‐TAVR was associated with lower 30‐day risks of atrial fibrillation (RR 0.28, 95% CI 0.17, 0.45), acute kidney injury (RR 0.38, 95% CI 0.20, 0.71), and myocardial infarction (RR 0.41, 95% CI 0.23, 0.75) at a cost of higher incidences of vascular complications (RR 6.10, 95% CI 2.92, 12.73) and pacemaker implantations (RR 3.29, 95% CI 1.41, 7.65).
Conclusions
TF‐TAVR is associated with lower 30‐day risks of myocardial infarction compared to SAVR. Further studies are required to investigate the role of myocardial injury on overall TF‐TAVR outcomes.
Factor (F)IXa activity has been detected in human plasma and may impact thrombotic risk. Current FIXa activity assays are complex and cumbersome.
To develop a reproducible enzyme-linked immunosorbent ...assay (ELISA) using a novel monoclonal antibody that detects total FIXa in human plasma.
A monoclonal antibody was raised against the new N-terminus exposed upon activation of FIX to FIXa by cleavage after R226. This antibody is specific for FIXa protease and does not recognize FIX zymogen or FIXα. The antibody was used to develop a FIXa-specific ELISA capable of quantifying total FIXa (free FIXa and FIXa-antithrombin complex) in human plasma. Total FIXa quantified using the ELISA was compared to that of FIXa-antithrombin quantified using modifications of a previously described ELISA.
The FIXa-specific ELISA was reproducible and quantified total FIXa in human plasma. Total FIXa levels correlated with FIXa-antithrombin levels.
A monoclonal antibody was developed that specifically detects human FIXa protease. A FIXa-specific ELISA using the new antibody is capable of reproducibly measuring total FIXa in human plasma (both free FIXa and FIXa-antithrombin). This assay should facilitate the evaluation of total FIXa levels in a variety of clinical circumstances.
•Coagulation factor (F)IXa plasma levels may impact the risk of thrombosis.•A new monoclonal antibody was developed that specifically detects FIXa.•An assay to measure total FIXa levels in human plasma was developed using new antibodies.•The new FIXa assay should be a useful tool for measuring FIXa levels.
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