Global control of cellular physiology by biomolecular condensates through modulation of electrochemical equilibria.

Control of the electrochemical environment in living cells is typically attributed to ion channels. Here we show that the formation of biomolecular condensates can modulate the electrochemical environment in cells, which affects processes globally within the cell and interactions of the cell with its environment. Condensate formation results in the depletion or enrichment of certain ions, generating intracellular ion gradients. These gradients directly affect the electrochemical properties of a cell, including the cytoplasmic pH and hyperpolarization of the membrane potential. The modulation of the electrochemical equilibria between the intra- and extra-cellular environments by biomolecular condensates governs charge-dependent uptake of small molecules by cells, and thereby directly influences bacterial survival under antibiotic stress. The shift of the intracellular electrochemical equilibria by condensate formation also drives a global change of the gene expression profile. The control of the cytoplasmic environment by condensates is correlated with their volume fraction, which can be highly variable between cells due to the stochastic nature of gene expression at the single cell level. Thus, condensate formation can amplify cell-cell variability of the environmental effects induced by the shift of cellular electrochemical equilibria. Our work reveals new biochemical functions of condensates, which extend beyond the biomolecules driving and participating in condensate formation, and uncovers a new role of biomolecular condensates in cellular regulation.

In Utero Exposure to Metals and Birth Outcomes in an Artisanal and Small-Scale Gold Mining Birth Cohort in Madre de Dios, Peru.

BACKGROUND: Few birth cohorts in South America evaluate the joint effect of minerals and toxic metals on neonatal health. In Madre de Dios, Peru, mercury exposure is prevalent owing to artisanal gold mining, yet its effect on neonatal health is unknown. OBJECTIVES: We aimed to determine whether toxic metals are associated with lower birth weight and shorter gestational age independently of antenatal care and other maternal well-being factors. METHODS: Data are from the COhorte de NAcimiento de MAdre de Dios (CONAMAD) birth cohort, which enrolled pregnant women in Madre de Dios prior to their third trimester and obtained maternal and cord blood samples at birth. We use structural equation models (SEMs) to construct latent variables for the maternal metals environment (ME) and the fetal environment (FE) using concentrations of calcium, iron, selenium, zinc, magnesium, mercury, lead, and arsenic measured in maternal and cord blood, respectively. We then assessed the relationship between the latent variables ME and FE, toxic metals, prenatal visits, hypertension, and their effect on gestational age and birth weight. RESULTS: Among 198 mothers successfully enrolled and followed at birth, 29% had blood mercury levels that exceeded the U.S. Centers for Disease Control and Prevention threshold of 5.8µg/L and 2 mothers surpassed the former 5-µg/dL threshold for blood lead. The current threshold value is 3.5µg/dL. Minerals and toxic metals loaded onto ME and FE latent variables. ME was associated with FE (ß=0.24; 95% CI: 0.05, 0.45). FE was associated with longer gestational age (ß=2.31; 95% CI: -0.3, 4.51) and heavier birth weight. Mercury exposure was not directly associated with health outcomes. A 1% increase in maternal blood lead shortened gestational age by 0.05 d (ß=-0.75; 95% CI: -1.51, -0.13), which at the 5-µg/dL threshold resulted in a loss of 3.6 gestational days and 76.5g in birth weight for newborns. Prenatal care visits were associated with improved birth outcomes, with a doubling of visits from 6 to 12 associated with 5.5 more gestational days (95% CI: 1.6, 9.4) and 319g of birth weight (95% CI: 287.6, 350.7). DISCUSSION: Maternal lead, even at low exposures, was associated with shorter gestation and lower birth weight. Studies that focus only on harmful exposures or nutrition may mischaracterize the dynamic maternal ME and FE. SEMs provide a framework to evaluate these complex relationships during pregnancy and reduce overcontrolling that can occur with linear regression. https://doi.org/10.1289/EHP10557.

Dissolution Potential of Elemental Mercury in the Presence of Bisulfide and Implications for Mobilization.

Liquid elemental mercury (Hg0L) pollution can remain in soils for decades and, over time, will undergo corrosion, a process in which the droplet surface oxidizes soil constituents to form more reactive phases, such as mercury oxide (HgO). While these reactive coatings may enhance Hg migration in the subsurface, little is known about the transformation potential of corroded Hg0L in the presence of reduced inorganic sulfur species to form sparingly soluble HgS particles, a process that enables the long-term sequestration of mercury in soils and generally reduces its mobility and bioavailability. In this study, we investigated the dissolution of corroded Hg0L in the presence of sulfide by quantifying rates of aqueous Hg release from corroded Hg0L droplets under different sulfide concentrations (expressed as the S:Hg molar ratio). For droplets corroded in ambient air, no differences in soluble Hg release were observed among all sulfide exposure levels (S:Hg mole ratios ranging from 10-4 to 10). However, for droplets oxidized in the presence of a more reactive oxidant (hydrogen peroxide, H2O2), we observed a 10- to 25-fold increase in dissolved Hg when the oxidized droplets were exposed to low sulfide concentrations (S:Hg ratios from 10-4 to 10-1) relative to droplets exposed to high sulfide concentrations. These results suggest two critical factors that dictate the release of soluble Hg from Hg0L in the presence of sulfide: the extent of surface corrosion of the Hg0L droplet and sufficient sulfide concentration for the formation of HgS solids. The mobilization of Hg0L in porous media, therefore, largely depends on aging conditions in the subsurface and chemical reactivity at the Hg0L droplet interface.

Increased cytotoxicity of Pb2+ with co-exposures to a mitochondrial uncoupler and mitochondrial calcium uniporter inhibitor.

Lead (Pb2+) is an important developmental toxicant. The mitochondrial calcium uniporter (MCU) imports calcium ions using the mitochondrial membrane potential (MMP), and also appears to mediate the influx of Pb2+ into the mitochondria. Since our environment contains mixtures of toxic agents, it is important to consider multi-chemical exposures. To begin to develop generalizable, predictive models of interactive toxicity, we developed mechanism-based hypotheses about interactive effects of Pb2+ with other chemicals. To test these hypotheses, we exposed HepG2 (human liver) cells to Pb2+ alone and in mixtures with other mitochondria-damaging chemicals: carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (FCCP), a mitochondrial uncoupler that reduces MMP, and Ruthenium Red (RuRed), a dye that inhibits the MCU. After 24 hours, Pb2+ alone, the mixture of Pb2+ and RuRed, and the mixture of Pb2+ and FCCP caused no decrease in cell viability. However, the combination of all three exposures led to a significant decrease in cell viability at higher Pb2+ concentrations. After 48 hours, the co-exposure to elevated Pb2+ concentrations and FCCP caused a significant decrease in cell viability, and the mixture of all three showed a clear dose-response curve with significant decreases in cell viability across a range of Pb2+ concentrations. We performed ICP-MS analyses on isolated mitochondrial and cytosolic fractions and found no differences in Pb2+ uptake across exposure groups, ruling out altered cellular uptake as the mechanism for interactive toxicity. We assessed MMP following exposure and observed a decrease in membrane potential that corresponds to loss of cell viability but is likely not sufficient to be the causative mechanistic driver of cell death. This research provides a mechanistically-based framework for understanding Pb2+ toxicity in mixtures with mitochondrial toxicants.

Nanoscale heterogeneity of arsenic and selenium species in coal fly ash particles: analysis using enhanced spectroscopic imaging and speciation techniques.

Coal combustion byproducts are known to be enriched in arsenic (As) and selenium (Se). This enrichment is a concern during the handling, disposal, and reuse of the ash as both elements can be harmful to wildlife and humans if mobilized into water and soils. The leaching potential and bioaccessibility of As and Se in coal fly ash depends on the chemical forms of these elements and their association with the large variety of particles that comprise coal fly ash. The overall goal of this research was to determine nanoscale and microscale solid phase mineral associations and oxidation states of As and Se in fly ash. We utilized nanoscale 2D imaging (30-50 nm spot size) with the Hard X-ray Nanoprobe (HXN) in combination with microprobe X-ray capabilities (∼5 µm resolution) to determine the As and Se elemental associations. Speciation of As and Se was also measured at the nano- to microscale with X-ray absorption spectroscopy. The enhanced resolution of HXN showed As and Se as either diffusely located around or comingled with Ca- and Fe-rich particles. The results also showed nanoparticles of Se attached to the surface of fly ash grains. Overall, a comparison of As and Se species across scales highlights the heterogeneity and complexity of chemical associations for these trace elements of concern in coal fly ash.

Crystal lattice defects in nanocrystalline metacinnabar in contaminated streambank soils suggest a role for biogenic sulfides in the formation of mercury sulfide phases.

At mercury (Hg)-contaminated sites, streambank erosion can act as a main mobilizer of Hg into nearby waterbodies. Once deposited into the waters, mercury from these soils can be transformed to MeHg by microorganisms. It is therefore important to understand the solid-phase speciation of Hg in streambanks as differences in Hg speciation will have implications for Hg transport and bioavailability. In this study, we characterized Hg solid phases in Hg-contaminated soils (100-1100 mg per kg Hg) collected from the incised bank of the East Fork Poplar Creek (EFPC) in Oak Ridge, TN (USA). The analysis of the soil samples by scanning electron microscopy-energy dispersive spectroscopy indicated numerous microenvironments where Hg and sulfur (S) are co-located. According to bulk soil analyses by extended X-ray absorption fine structure spectroscopy (EXAFS), the near-neighbor Hg molecular coordination in the soils closely resembled freshly precipitated Hg sulfide (metacinnabar, HgS); however, EXAFS fits indicated the Hg in the HgS structure was undercoordinated with respect to crystalline metacinnabar. This undercoordination of Hg-S observed by spectroscopy is consistent with transmission electron microspy images showing the presence of nanocrystallites with structural defects (twinning, stacking faults, dislocations) in individual HgS-bearing particles. Although the soils were collected from exposed parts of the stream bank (i.e., open to the atmosphere), the presence of reduced forms of S and sulfate-reducing microbes suggests that biogenic sulfides promote the formation of HgS nanoparticles in these soils. Altogether, these data demonstrate the predominance of nanoparticulate HgS with crystal lattice defects in the bank soils of an industrially impacted stream. Efforts to predict the mobilization and bioavailability of Hg associated with nano-HgS forms should consider the impact of nanocrystalline lattice defects on particle surface reactivity, including Hg dissolution rates and bioavailability on Hg fate and transformations.

Risk of lead exposure from wild game consumption from cross-sectional studies in Madre de Dios, Peru.

Background: Studies have shown elevated blood lead levels (BLL) in residents of remote communities in the Amazon, yet sources of lead exposure are not fully understood, such as lead ammunition consumed in wild game. Methods: Data was collected during two cross-sectional studies that enrolled 307 individuals in 26 communities. Regression models with community random effects were used to evaluate risk factors for BLLs, including diet, water source, smoking, sex, age, and indigenous status. The All-Ages Lead Model (AALM) from the Environmental Protection Agency (EPA) was used to estimate background and dose from wild game consumption. Findings: Indigenous status and wild game consumption were associated with increased BLLs. Indigenous participants had 2.52 µg/dL (95% CI: 1.95-3.24) higher BLLs compared to non-indigenous. Eating wild game was associated with a 1.41 µg/dL (95% CI: 1.20-1.70) increase in BLLs. Two or more portions per serving were associated with increased BLLs of 1.66 µg/dL (95% CI: 1.10-2.57), compared to smaller servings. Using the AALM, we estimate background lead exposures to be 20 µg/day with consumption of wild game contributing 500 µg/meal. Lastly, we found a strong association between BLLs and mercury exposure. Interpretation: Consumption of wild game hunted with lead ammunition may pose a common source of lead exposure in the Amazon. Communities that rely on wild game and wild fish may face a dual burden of exposure to lead and mercury, respectively.

Utility of Diffusive Gradient in Thin-Film Passive Samplers for Predicting Mercury Methylation Potential and Bioaccumulation in Freshwater Wetlands.

Mercury is a risk in aquatic ecosystems when the metal is converted to methylmercury (MeHg) and subsequently bioaccumulates in aquatic food webs. This risk can be difficult to manage because of the complexity of biogeochemical processes for mercury and the need for accessible techniques to navigate this complexity. Here, we explored the use of diffusive gradient in thin-film (DGT) passive samplers as a tool to simultaneously quantify the methylation potential of inorganic Hg (IHg) and the bioaccumulation potential of MeHg in freshwater wetlands. Outdoor freshwater wetland mesocosms were amended with four isotopically labeled and geochemically relevant IHg forms that represent a range of methylation potentials (202Hg2+, 201Hg-humic acid, 199Hg-sorbed to FeS, and 200HgS nanoparticles). Six weeks after the spikes, we deployed DGT samplers in the mesocosm water and sediments, evaluated DGT-uptake rates of total Hg, MeHg, and IHg (calculated by difference) for the Hg isotope spikes, and examined correlations with total Hg, MeHg, and IHg concentrations in sediment, water, and micro and macrofauna in the ecosystem. In the sediments, we observed greater relative MeHg concentrations from the initially dissolved IHg isotope spikes and lower MeHg levels from the initially particulate IHg spikes. These trends were consistent with uptake flux of IHg into DGTs deployed in surface sediments. Moreover, we observed correlations between total Hg-DGT uptake flux and MeHg levels in periphyton biofilms, submergent plant stems, snails, and mosquitofish in the ecosystem. These correlations were better for DGTs deployed in the water column compared to DGTs in the sediments, suggesting the importance of vertical distribution of bioavailable MeHg in relation to food sources for macrofauna. Overall, these results demonstrate that DGT passive samplers are a relatively simple and efficient tool for predicting IHg methylation and MeHg bioaccumulation potentials without the need to explicitly delineate IHg and MeHg speciation and partitioning in complex ecosystems.

Lack of Detectable Direct Effects of Silver and Silver Nanoparticles on Mitochondria in Mouse Hepatocytes.

Silver nanoparticles (AgNPs) are well-proven antimicrobial nanomaterials, yet little is elucidated regarding the mechanism underlying cytotoxicity induced by these nanoparticles. Here, we tested the hypothesis that mitochondria are primary intracellular targets of two AgNPs and silver ions in mouse hepatocytes (AML12) cultured in glucose- and galactose-based media. AML12 cells were more sensitive to mitochondrial uncoupling when grown with galactose rather than glucose. However, 24 h treatments with 15 nm AgNPs and 6 nm GA-AgNPs (5 and 10 µg/mL) and AgNO3 (1 and 3 µg/mL), concentrations that resulted in either 10 or 30% cytotoxicity, failed to cause more toxicity to AML12 cells grown on galactose than glucose. Furthermore, colocalization analysis and subcellular Ag quantification did not show any enrichment of silver content in mitochondria in either medium. Finally, the effects of the same exposures on mitochondrial respiration were mild or undetectable, a result inconsistent with mitochondrial toxicity causing cell death. Our results suggest that neither ionic Ag nor the AgNPs that we tested specifically target mitochondria and are inconsistent with mitochondrial dysfunction being the primary cause of cell death after Ag exposure under these conditions.

CoNaMad-Cohorte de Nacimiento de Madre de Dios/Madre de Dios Birth Cohort to Study Effects of in-utero Trace Metals Exposure in the Southern Peruvian Amazon.

Background: In-utero exposure to mercury and other trace metals pose a significant threat to child health and development, but exposures and health impacts in artisanal and small-scale gold mining (ASGM) environments are poorly defined. Objectives: We describe the CONAMAD study design, a prospective birth cohort consisting of multiparous women (18 and over) living in rural and peri-urban Peruvian Amazon communities exposed to ASGM. Methods: Pregnant women are enrolled from health posts across four zones of Madre de Dios, Peru. Data are collected at enrollment, childbirth, and (planned) 36-48 months. At enrollment, hair samples for mercury assessment, demographic and clinical data are obtained. At birth, we obtain venous and cord blood, placenta, hair, toenails, and saliva. Findings: Two hundred seventy mothers were enrolled at an average 20 weeks gestational age with no differences in maternal characteristics across zones. Two hundred fifteen mothers were successfully followed at birth. We obtained 214 maternal and cord blood samples, 211 maternal and 212 infant hair samples, 212 placenta samples, 210 infant saliva samples, and 214 infant dried blood spots. Data collected will allow for testing our primary hypotheses of maternal malnutrition modifying ratios of cord:maternal blood total mercury (tHg), cord blood:maternal hair tHg, and infant:maternal hair tHg, and whether chemical mixtures (Hg, Pb, Cd) have synergistic effects on infant neurodevelopment. Conclusions: CONAMAD is designed to collect and store samples for future processing and hypothesis testing associated with in-utero mercury exposure and child development. We have completed the exposure assessments and will conduct a follow-up of mothers to evaluate early child development outcomes, including developmental delay and growth. These data offer insights into disease mechanisms, exposure prevention, and policy guidance for countries where ASGM is prevalent.

Plastic pellets trigger feeding responses in sea anemones.

Multiple mechanisms for plastic consumption by marine animals have been proposed based on the feeding cues and behavior of the animal studied. We investigated plastic consumption in sea anemones. We found that anemones readily consumed pristine National Institute of Standards and Technology low-density polyethylene and high-density polyethylene II and III pre-production pellets. Anemone weight, crown area, and number of tentacles were measured before and after 12 days of daily pellet consumption. Crown area significantly increased for control anemones only. Fresh anemones were then sequentially fed consumed and egested pellets from two of the earlier daily trials to measure feeding retention time, which decreased over three to four feedings. The concentrations of elements in anemones (zinc, iron, arsenic, manganese, chromium, copper, vanadium, selenium, nickel, cadmium, and cobalt) were similar to control anemones that were not exposed to pellets. Lead concentrations were significantly higher in anemones fed HDPE III pellets as compared to control. Plastic consumption by marine animals might be reduced by reducing the amount of plastic that enters the ocean and understanding the chemical triggers underlying plastic consumption.

Caveats to the use of MTT, neutral red, Hoechst and Resazurin to measure silver nanoparticle cytotoxicity.

The extensive use of silver nanoparticles (AgNPs) in manufactured products will inevitably increase environmental exposure, highlighting the importance of accurate toxicity assessments. A frequent strategy to estimate AgNP cytotoxicity is to use absorbance or fluorescent-based assays. In this study we report that AgNPs - with or without surface functionalizations (polyvinyl pyrrolidone or gum arabic), and of different sizes (2-15 nm) - can interfere with the spectrometric quantification of different dyes commonly used in cytotoxicity assays, such as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), neutral red (NR), Hoechst, and Resazurin. Some AgNP types caused more interference than others, which was dependent on the assay. Overall most AgNPs caused the direct reduction of MTT, as well as Hoechst and NR fluorescence quenching, and absorbed light at the same wavelength as NR. None of the AgNPs tested caused the direct reduction of Resazurin; however, depending on AgNP characteristics and concentration, they may still promote fluorescence quenching of this dye. Our results show that AgNPs with different size and coatings can interfere with spectroscopy-based assays to different degrees, suggesting that their cytotoxicity may be underestimated or overestimated. We suggest that when using any spectroscopy-based assay it is essential that each individual nanoparticle formulation be tested first for potential interferences at all intended concentrations.

Relative Reactivity and Bioavailability of Mercury Sorbed to or Coprecipitated with Aged Iron Sulfides.

The potential for inorganic mercury (Hg) to be converted to methylmercury depends, in part, on the chemical form of Hg and its bioavailability to anaerobic microorganisms that can methylate Hg. In anaerobic settings, Hg can be associated with sulfide phases, including ferrous iron sulfide (FeS), which can sorb or be coprecipitated with Hg. The objective of this study was to determine if the aging state of FeS alters the Hg coordination environment as well as the reactivity and bioavailability of sorbed and coprecipitated Hg species. FeS particles were synthesized with and without Hg2+ and aged in anaerobic conditions for multiple time frames spanning from 1 h to 1 month. For FeS particles synthesized without Hg, Hg2+ was subsequently sorbed to the FeS for 1 day. Analysis of Hg speciation of these materials by X-ray absorption near edge spectroscopy revealed a predominance of four-coordinate Hg-S species in the sorbed Hg-FeS solids and a mixture of two- and four-coordinate Hg-S in the coprecipitated Hg-FeS. The leaching potential of the Hg was assessed by exposing the particles to a solution of dissolved glutathione (a thiolate-based Hg chelator). As expected, the sorbed Hg-FeS released more soluble Hg compared to the coprecipitated Hg-FeS. However, when these particles were exposed to Desulfovibrio desulfuricans ND132 (a known Hg methylator), more Hg was methylated from the coprecipitated Hg-FeS than the sorbed Hg-FeS, consistent with expectations from the Hg-S coordination state and inconsistent with the selective leaching results. Overall, these results suggest that the bioavailability of particulate Hg cannot be easily discerned by its leaching potential into bulk solution. Rather, bioavailability entails more subtle interactions at particle-cell interfaces and perhaps correlates with the local Hg-S coordination state in the particles.

Differences in bulk and microscale yttrium speciation in coal combustion fly ash.

Coal combustion ash is a promising alternative source of rare earth elements (REE; herein defined as the 14 stable lanthanides, yttrium, and scandium). Efforts to extract REE from coal ash will depend heavily on the location and speciation of these elements in the ash. This study sought to identify the major chemical forms of yttrium (Y), as a representative REE in coal fly ash samples selected from major coal sources in the United States. Y speciation was evaluated using both bulk scale analyses (sequential extractions, Y K-edge X-ray absorption near-edge spectroscopy - XANES) and complementary analyses at the micron scale (micro-focus X-ray fluorescence and micro-XANES). Sequential selective extractions revealed that the REE were primarily in the residual (unextracted fraction) of coal fly ash samples. Extraction patterns for yttrium resembled those of the lanthanides, indicating that these elements were collectively dispersed throughout the aluminosilicate glass in fly ash. Bulk XANES analysis indicated that Y coordination states resembled a combination of Y-oxides, Y-carbonate, and Y-doped glass, regardless of ash origin. However, in the microprobe analysis, we observed "hotspots" of Y (∼10-50 µm) in some samples that included different Y forms (e.g., Y-phosphate) not observed in bulk measurements. Overall, this study demonstrated that yttrium (and potentially other REEs) are entrained in the glass phase of fly ash and that microscale investigations of individual high-REE regions in fly ash samples do not necessarily capture the dominant speciation.

Ranking Coal Ash Materials for Their Potential to Leach Arsenic and Selenium: Relative Importance of Ash Chemistry and Site Biogeochemistry.

The chemical composition of coal ash is highly heterogeneous and dependent on the origin of the source coal, combustion parameters, and type and configuration of air pollution control devices. This heterogeneity results in uncertainty in the evaluation of leaching potential of contaminants from coal ash. The goal of this work was to identify whether a single leaching protocol could roughly group high-leaching potential coal ash from low-leaching potential coal ash, with respect to arsenic (As) and selenium (Se). We used four different leaching tests, including the Toxicity Characteristic Leaching Protocol (TCLP), natural pH, aerobic sediment microcosms, and anaerobic sediment microcosms on 10 different coal ash materials, including fly ash, lime-treated ash, and flue gas desulfurization materials. Leaching tests showed promise in categorizing high and low-leaching potential ash materials, indicating that a single point test could act as a first screening measure to identify high-risk ash materials. However, the amount of contaminant leached varied widely across tests, reflecting the importance of ambient conditions (pH, redox state) on leaching. These results demonstrate that on-site geochemical conditions play a critical role in As and Se mobilization from coal ash, underscoring the need to develop a situation-based risk assessment framework for contamination by coal ash pollutants.

Quantification of Mercury Bioavailability for Methylation Using Diffusive Gradient in Thin-Film Samplers.

Mercury-contaminated sediment and water contain various Hg species, with a small fraction available for microbial conversion to the bioaccumulative neurotoxin monomethylmercury (MeHg). Quantification of this available Hg pool is needed to prioritize sites for risk management. This study compared the efficacy of diffusive gradient in thin-film (DGT) passive samplers to a thiol-based selective extraction method with glutathione (GSH) and conventional filtration (<0.2 µm) as indicators of Hg bioavailability. Anaerobic sediment slurry microcosms were amended with isotopically labeled inorganic Hg "endmembers" (dissolved Hg2+, Hg-humic acid, Hg-sorbed to FeS, HgS nanoparticles) with a known range of bioavailability and methylation potentials. Net MeHg production (expressed as percent of total Hg as MeHg) over 1 week correlated with mass accumulation of Hg endmembers on the DGTs and only sometimes correlated with the 0.2 µm filter passing Hg fraction and the GSH-extractable Hg fraction. These results suggest for the first time that inorganic Hg uptake in DGTs may indicate bioavailability for methylating microbes. Moreover, the methylating microbial community assessed by hgcA gene abundance was not always consistent with methylation rates between the experiments, indicating that knowledge of the methylating community should target the transcript or protein level. Altogether, these results suggest that DGTs could be used to quantify the bioavailable Hg fraction as part of a method to assess net MeHg production potential in the environment.

Periphyton uptake and trophic transfer of coal fly-ash-derived trace elements.

To determine whether the bioavailability of trace elements derived from coal ash leachates varies with the geochemical conditions associated with their formation, we quantified periphyton bioaccumulation and subsequent trophic transfer to the mayfly Neocloeon triangulifer. Oxic ash incubations favored periphyton uptake of arsenic, selenium, strontium, and manganese, whereas anoxic incubations favored periphyton uptake of uranium. Mayfly enrichment was strongest for selenium, whereas biodilution was observed for strontium, uranium, and arsenic. Environ Toxicol Chem 2017;36:2991-2996. © 2017 SETAC.

Cost and Expected Visual Effect of Interventions to Improve Follow-up After Cataract Surgery: Prospective Review of Early Cataract Outcomes and Grading (PRECOG) Study.

IMPORTANCE: Some experts recommend increasing low rates of follow-up after cataract surgery in low- and middle-income countries using various interventions. However, little is known about the cost and effect of such interventions. OBJECTIVE: To examine whether promoting follow-up after cataract surgery creates economic value. DESIGN, SETTING, AND PARTICIPANTS: The Prospective Review of Early Cataract Outcomes and Grading (PRECOG) is a cohort study with data from patients undergoing cataract surgery from January 19, 2010, to April 18, 2012. Final follow-up was completed on August 10, 2012. Data were collected before surgery, at discharge, and at follow-up at least 40 days after surgery from 27 centers in 8 countries in Asia, Africa, and Latin America. Each center enrolled 40 to 120 consecutive patients undergoing cataract surgery. If patients did not return to the hospital for the follow-up visit, hospitals could use telephone calls or transportation subsidies to increase follow-up rate. Data were analyzed from December 2013 to January 2016. MAIN OUTCOMES AND MEASURES: Cost of interventions (telephone calls and transportation subsidies) to increase follow-up at least 40 days after surgery, visual acuity (VA) in the eye undergoing cataract surgery, presence of complications, patient and facility costs per visit, and willingness to pay for treatment or glasses if needed. The maximum incremental cost of improving VA in 1 patient (incremental cost-effect ratio [ICER]) was calculated for spontaneous follow-up (compared with no follow-up) and follow-up with the telephone and transportation interventions. Expected ICERs were estimated including only those patients willing to pay. RESULTS: Among 2487 patients (1068 men [42.9%]; 1405 women [56.5%]; 14 missing [0.6%]; mean [SD] age, 68.4 [11.3] years), 2316 (93.1%) received follow-up, of whom 369 (16.0%) were seen in an outside facility or home and were in the cost-effectiveness analysis as unable to follow up. A grand mean (a mean of means of the different countries) of 56.3% of patients needed glasses, of whom 56.9% were willing to pay, and 1.6% had treatable complications, of whom 39.4% were willing to pay. Maximum proportions with improved VA (and corresponding ICERs) were 0.08 for no follow-up, 0.45 ($151.56) for spontaneous follow-up, 0.53 ($164.46) for a telephone intervention, and 0.53 ($133.07) for a transportation intervention. These results were most sensitive to the cost of follow-up. Expected proportions (ICERs) were 0.08, 0.27 ($232.69), 0.30 ($456.22), and 0.30 ($206.47), respectively. CONCLUSIONS AND RELEVANCE: Most patients benefiting from follow-up after cataract surgery returned spontaneously when requested at discharge. Use of telephone calls or transportation subsidies to increase follow-up in low- and middle-income countries may not be cost-effective.

Soil Weathering as an Engine for Manganese Contamination of Well Water.

Manganese (Mn) contamination of well water is recognized as an environmental health concern. In the southeastern Piedmont region of the United States, well water Mn concentrations can be >2 orders of magnitude above health limits, but the specific sources and causes of elevated Mn in groundwater are generally unknown. Here, using field, laboratory, spectroscopic, and geospatial analyses, we propose that natural pedogenetic and hydrogeochemical processes couple to export Mn from the near-surface to fractured-bedrock aquifers within the Piedmont. Dissolved Mn concentrations are greatest just below the water table and decrease with depth. Solid-phase concentration, chemical extraction, and X-ray absorption spectroscopy data show that secondary Mn oxides accumulate near the water table within the chemically weathering saprolite, whereas less-reactive, primary Mn-bearing minerals dominate Mn speciation within the physically weathered transition zone and bedrock. Mass-balance calculations indicate soil weathering has depleted over 40% of the original solid-phase Mn from the near-surface, and hydrologic gradients provide a driving force for downward delivery of Mn. Overall, we estimate that >1 million people in the southeastern Piedmont consume well water containing Mn at concentrations exceeding recommended standards, and collectively, these results suggest that integrated soil-bedrock-system analyses are needed to predict and manage Mn in drinking-water wells.

Population-based study of presbyopia in Nicaragua.

BACKGROUND: Uncorrected presbyopia can greatly impact a person's quality of life and employment prospects. Nicaragua is the poorest country in Latin America and there are no population-based reports of prevalence of presbyopia in Nicaragua. METHODS: A cross-sectional population-based household survey was conducted. The sample was selected through random cluster sampling. Adults 35 years and older were enlisted through a door-to-door method using aged-based sampling. All enumerated household members 35 years and older were asked to attend a free visual acuity screening. Autorefraction was done and then uncorrected distance vision and near visual acuity were measured for all subjects. All those who had distance or near vision that was 6/12 or worse underwent a clinical examination, which included refraction at distance and near. Free spectacles were provided. RESULTS: Of the 3,390 subjects surveyed, 37.1 per cent reported that they wore spectacles on a regular basis. A total of 1,871 (55.2 per cent) of those enumerated were examined. The prevalence of near visual impairment (6/12 [N 6] or worse) was 79.6 per cent for the 35 to 49-year-old group, 97.3 per cent for the 50 to 64-year-old group and 96.7 per cent for the 65 and over group. Of those reporting for the examination, 82.2 per cent did not have glasses. Of those examined, 10 per cent did not need spectacles, four per cent were given spectacles for distance only, 38 per cent spectacles for distance and near, 42 per cent spectacles for near only and seven per cent were referred for medical evaluation due to ocular pathology. During the refractions, 91.5 per cent were corrected to 6/12 or better at distance and 89.4 per cent were corrected to 6/12 or better at near. CONCLUSION: The majority of the participants who were examined did not have the spectacles that they needed. Over one-third of those participants who presented without spectacles had distance vision better than 6/12 and could be improved to good near vision with ready-made near-only spectacles.