Exploiting Trans-Sulfinylation for the Synthesis of Diverse N-Alkyl Sulfinamides via Decarboxylative Sulfinamidation.

Combining simple amines with the bench-stable sulfinylamine Tr-NSO allows in situ preparation of reactive alkyl sulfinylamines, which when combined with alkyl radicals generated by photocatalytic decarboxylation, provides N-alkyl sulfinamides. The reactions are broad in scope and tolerate a wide variety of functional groups on both the acid and amine components. The sulfinamide products are used to prepare a selection of challenging S(VI) products. The method provides a convenient way to use reactive and unstable alkyl sulfinylamines.

Photocatalytic Carboxylate to Sulfinamide Switching Delivers a Divergent Synthesis of Sulfonamides and Sulfonimidamides.

sulfinamides, sulfonamides, and sulfonimidamides are in-demand motifs in medicinal chemistry, yet methods for the synthesis of alkyl variants that start from simple, readily available feedstocks are scarce. In addition, bespoke syntheses of each class of molecules are usually needed. In this report, we detail the synthesis of these three distinct sulfur functional groups, using readily available and structurally diverse alkyl carboxylic acids as the starting materials. The method harnesses alkyl radical generation from carboxylic acids using acridine photocatalysts and 400 nm light with subsequent radical addition to sulfinylamine reagents, delivering sulfinamide products. Using the N-alkoxy sulfinylamine reagent t-BuO-NSO as the radical trap provides common N-alkoxy sulfinamide intermediates, which can be converted in a divergent manner to either sulfonamides or sulfonimidamides, by treatment with sodium hydroxide, or an amine, respectively. The reactions are scalable, tolerate a broad range of functional groups, and can be used for the diversification of complex biologically active compounds.

The Inflammation Biomarker GlycA Reflects Plasma N-Glycan Branching.

BACKGROUND: GlycA is a nuclear magnetic resonance (NMR) signal in plasma that correlates with inflammation and cardiovascular outcomes in large data sets. The signal is thought to originate from N-acetylglucosamine (GlcNAc) residues of branched plasma N-glycans, though direct experimental evidence is limited. Trace element concentrations affect plasma glycosylation patterns and may thereby also influence GlycA. METHODS: NMR GlycA signal was measured in plasma samples from 87 individuals and correlated with MALDI-MS N-glycomics and trace element analysis. We further evaluated the genetic association with GlycA at rs13107325, a single nucleotide polymorphism resulting in a missense variant within SLC39A8, a manganese transporter that influences N-glycan branching, both in our samples and existing genome-wide association studies data from 22 835 participants in the Women's Health Study (WHS). RESULTS: GlycA signal was correlated with both N-glycan branching (r2 ranging from 0.125-0.265; all P < 0.001) and copper concentration (r2 = 0.348, P < 0.0001). In addition, GlycA levels were associated with rs13107325 genotype in the WHS (ß [standard error of the mean] = -4.66 [1.2674], P = 0.0002). CONCLUSIONS: These results provide the first direct experimental evidence linking the GlycA NMR signal to N-glycan branching commonly associated with acute phase reactive proteins involved in inflammation.

Airborne levels of cadmium are correlated with urinary cadmium concentrations among young children living in the New York state city of Syracuse, USA.

Air pollution is a serious public health issue with early childhood exposure being of high concern because of the greater risk that children might experience negative health outcomes. Industrial sources in and near communities are one potential path of exposure that children might face with greater levels of air pollution correlating with higher levels of toxicants detected in children. We compare estimated ambient air concentrations of Cadmium (Cd) to a cohort (n = 281) of 9 to 11-year old children during their early childhood years (0-5 years of age) in a mid-size city in Upstate New York. Levels of Cd air pollution are compared to children's urine-Cd levels. Urine has been shown to be a superior biomarker to blood for Cd exposure particularly for longer-term exposures. We find that participants who reside in households that faced greater Cd air pollution during the child's early years have higher urine-Cd levels. This association is stable and stronger than previously presented associations for blood-Cd. Findings support expanded use of air modelling data for risk screening to reduce the potential health burden that industrial pollution can have.

Perfluoroalkyl substances (PFAS) and lead (Pb) as "cardiovascular disruptors" in 9-11-year-old children living in Syracuse, New York, United States.

OBJECTIVE: Per- and polyfluoro-alkyl substances (PFAS) and lead (Pb) are ubiquitous environmental toxicants with apparent impact on cardiovascular disease (CVD) risk. As one possible mechanism for this increased risk, we have previously demonstrated an association between Pb exposure and heightened cardiovascular reactivity to acute psychological stress, a CVD risk factor. The present study expands this approach and considers both PFAS and Pb exposures (and the possible interaction). METHODS: We assessed 14 serum PFAS and whole blood Pb concentrations in a sample of 9-11 year-old children (N = 291; 43.2% White, 56.8% Black; 53.5% female). We measured cardiovascular functioning at rest and during psychological stress as well as multiple indicators of subclinical CVD including resting blood pressure (BP), carotid-femoral pulse wave velocity (cfPWV), carotid intima-media thickness (cIMT), and left ventricular mass (LVM). Data analysis included general linear modeling as well as a non-parametric approach to study metal mixtures, specifically Bayesian Kernel Machine Regression (BKMR). RESULTS: Significant interactions between different PFAS and with Pb suggest the importance of considering toxicant mixtures when assessing potential disruption of the cardiovascular system. The pattern of findings suggests that greater "vascular reactivity" (elevated BP and vascular resistance during acute psychological stress) was associated with higher concentrations of perfluorononanoic acid (PFNA), perfluorohexane sulfonate (PFHxS), and Pb, but only when perfluorooctanoic acid (PFOA) was concurrently elevated. With respect to subclinical outcomes, increasing perfluorodecanoic acid (PFDA) was associated with greater cIMT (ß = 0.21, p = 0.010). CONCLUSION: To our knowledge this is the first study to consider how PFAS exposures might affect cardiovascular functioning and subclinical disease. Although a complex pattern of associations emerged, it does appear that PFAS and Pb can be classified as "cardiovascular disruptors" in children. Further research is needed to replicate these novel findings and determine whether these disruptions produce future cardiovascular disease.

Progression from remodeling to hibernation of ribosomes in zinc-starved mycobacteria.

Zinc starvation in mycobacteria leads to remodeling of ribosomes, in which multiple ribosomal (r-) proteins containing the zinc-binding CXXC motif are replaced by their motif-free paralogues, collectively called C- r-proteins. We previously reported that the 70S C- ribosome is exclusively targeted for hibernation by mycobacterial-specific protein Y (Mpy), which binds to the decoding center and stabilizes the ribosome in an inactive and drug-resistant state. In this study, we delineate the conditions for ribosome remodeling and hibernation and provide further insight into how zinc depletion induces Mpy recruitment to C- ribosomes. Specifically, we show that ribosome hibernation in a batch culture is induced at an approximately two-fold lower cellular zinc concentration than remodeling. We further identify a growth phase in which the C- ribosome remains active, while its hibernation is inhibited by the caseinolytic protease (Clp) system in a zinc-dependent manner. The Clp protease system destabilizes a zinc-bound form of Mpy recruitment factor (Mrf), which is stabilized upon further depletion of zinc, presumably in a zinc-free form. Stabilized Mrf binds to the 30S subunit and recruits Mpy to the ribosome. Replenishment of zinc to cells harboring hibernating ribosomes restores Mrf instability and dissociates Mpy from the ribosome. Finally, we demonstrate zinc-responsive binding of Mpy to ribosomes in Mycobacterium tuberculosis (Mtb) and show Mpy-dependent antibiotic tolerance of Mtb in mouse lungs. Together, we propose that ribosome hibernation is a specific and conserved response to zinc depletion in both environmental and pathogenic mycobacteria.

Body mass and growth rates in captive chimpanzees (Pan troglodytes) cared for in African wildlife sanctuaries, zoological institutions, and research facilities.

Captive chimpanzees (Pan troglodytes) mature earlier in body mass and have a greater growth rate compared to wild individuals. However, relatively little is known about how growth parameters compare between chimpanzees living in different captive environments. To investigate, body mass was measured in 298 African sanctuary chimpanzees and was acquired from 1030 zoological and 442 research chimpanzees, using data repositories. An analysis of covariance, adjusting for age, was performed to assess same-sex body mass differences between adult sanctuary, zoological, and research populations. Piecewise linear regression was performed to estimate sex-specific growth rates and the age at maturation, which were compared between sexes and across populations using extra-sum-of-squares F tests. Adult body mass was greater in the zoological and resarch populations compared to the sanctuary chimpanzees, in both sexes. Male and female sanctuary chimpanzees were estimated to have a slower rate of growth compared with their zoological and research counterparts. Additionally, male sanctuary chimpanzees were estimated to have an older age at maturation for body mass compared with zoological and research males, whereas the age at maturation was similar across female populations. For both the zoological and research populations, the estimated growth rate was greater in males compared to females. Together, these data contribute to current understanding of growth and maturation in this species and suggest marked differences between the growth patterns of chimpanzees living in different captive environments.

Low Tidal Volume Ventilation for Emergency Department Patients: A Systematic Review and Meta-Analysis on Practice Patterns and Clinical Impact.

OBJECTIVES: Data suggest that low tidal volume ventilation (LTVV) initiated in the emergency department (ED) has a positive impact on outcome. This systematic review and meta-analysis quantify the impact of ED-based LTVV on outcomes and ventilator settings in the ED and ICU. DATA SOURCES: We systematically reviewed MEDLINE, EMBASE, Scopus, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, references, conferences, and ClinicalTrials.gov. STUDY SELECTION: Randomized and nonrandomized studies of mechanically ventilated ED adults were eligible. DATA EXTRACTION: Two reviewers independently screened abstracts. The primary outcome was mortality. Secondary outcomes included ventilation duration, lengths of stay, and occurrence rate of acute respiratory distress syndrome (ARDS). We assessed impact of ED LTVV interventions on ED and ICU tidal volumes. DATA SYNTHESIS: The search identified 1,023 studies. Eleven studies (n = 12,912) provided outcome data and were meta-analyzed; 10 additional studies (n = 1,863) provided descriptive ED tidal volume data. Overall quality of evidence was low. Random effect meta-analytic models revealed that ED LTVV was associated with lower mortality (26.5%) versus non-LTVV (31.1%) (odds ratio, 0.80 [0.72-0.88]). ED LTVV was associated with shorter ICU (mean difference, -1.0; 95% CI, -1.7 to -0.3) and hospital (mean difference, -1.2; 95% CI, -2.3 to -0.1) lengths of stay, more ventilator-free days (mean difference, 1.4; 95% CI, 0.4-2.4), and lower occurrence rate (4.5% vs 8.3%) of ARDS (odds ratio, 0.57 [0.44-0.75]). ED LTVV interventions were associated with reductions in ED (-1.5-mL/kg predicted body weight [PBW] [-1.9 to -1.0]; p < 0.001) and ICU (-1.0-mL/kg PBW [-1.8 to -0.2]; p = 0.01) tidal volume. CONCLUSIONS: The use of LTVV in the ED is associated with improved clinical outcomes and increased use of lung protection, recognizing low quality of evidence in this domain. Interventions aimed at implementing and sustaining LTVV in the ED should be explored.

Emergency Medicine Telehealth: A Pandemic Becomes a Gateway for Virtual Care in Missouri.

Telehealth provides a novel bridge between patient needs and available resources. On-demand telehealth visits provide urgent medical services in a virtual setting. Telehealth can be used to provide care for patients despite geographical distance. Emergency Medicine quickly adapted in response to the COVID-19 pandemic through utilization of telehealth to solve various problems. Tele-triage was used to coordinate COVID-19 testing and treatment. Greater utilization of all current and emerging telehealth modalities could increase access and quality of care for all Missourians.

Measurement harmonization and traceability for trace element analyses across the Children's Health Exposure Analysis Resource laboratory network.

Harmonization and traceability are related metrological principles that are indispensable to assuring measurement comparability across different biomonitoring studies. The Children's Health Exposure Analysis Resource (CHEAR) was established in 2015 with six laboratories providing environmental exposure measurements on biospecimens. To ensure harmonization across studies for trace elements, CHEAR used a multi-faceted approach that included: 1) an initial interlaboratory validation exercise based on the analysis of certified blood and urine reference materials; 2) frequent participation in an established interlaboratory proficiency program for trace elements; and 3) analysis of a common pool of well-characterized biological reference materials with each analytical batch. Method accuracy and precision were established for each laboratory via analysis of NIST SRM 955c Toxic Elements in Caprine Blood, SRM 2668 Toxic Elements in Frozen Human Urine and SRM 3668 Mercury, Perchlorate, and Iodide in Frozen Human Urine. The differences among the six laboratories for As, Cd, Hg, and Mn in urine and Cd, Hg, and Pb in whole blood were judged to be fit-for-purpose. Interlaboratory performance over a 5-year period demonstrated an improvement in performance, such that for 2018-2019, >99% of challenges for urine As, Cd, Hg, and Mn, and 95% for whole blood Cd, Hg, Pb, and Mn, were found to be satisfactory. The CHEAR common reference materials were analyzed by at least 5 laboratories for 22 elements in urine and 13-14 elements in whole blood, thus providing a rich source of data to assess intra- and inter-run performance. The suite of trace elements with assigned values in both blood and urine matrices are more comprehensive than similar reference materials from other sources, and is reflective of the concentrations necessary to support biomonitoring studies. While some areas for future improvement were identified, significant progress was made to improve harmonization of trace element measurements in biological matrices among the CHEAR network labs.

Co-exposure to manganese and lead and pediatric neurocognition in East Liverpool, Ohio.

Exposure to metal mixtures may lead to health impacts greater than the effects associated with singular exposures. Two common childhood environmental exposures, manganese (Mn) and lead (Pb), are associated with similar adverse neurodevelopmental effects; however, the effects surrounding concurrent exposure to both metals remain unclear. We study the impact of joint exposure to Mn and Pb on cognitive performance in school-aged children participating in the Communities Actively Researching Exposure Study (CARES) based in East Liverpool, Ohio. Blood Pb levels were measured for each child (geometric mean (GM) = 1.13 µg/dL, range 0.30 µg/dL - 6.64 µg/dL). Mn was measured in participant blood, hair, and toenails with GMs of 10.1 µg/L, 360 ng/g, 0.974 µg/g, respectively. Trained team members administered the Wechsler Intelligence Scale for Children-IV (WISC-IV) to assess intelligence quotient (IQ). The WISC-IV provides scores for Full Scale IQ, Perceptual Reasoning, Processing Speed, Working Memory, and Verbal Comprehension. Interactions between blood Pb and all Mn biomarkers were tested in linear models adjusted for child sex, household income, and serum cotinine. Separate regression models were run for each of the Mn biomarkers. The cohort was comprised of 106 children with a mean age of 8.4 years. Interactions between blood Pb and hair Mn were significant (p < 0.05) for four out of the five IQ domains. The effect of blood Pb on IQ was more pronounced at higher levels of hair and toenail Mn. No significant associations were observed when characterizing the main effect of Mn using blood. Uncovering the health impacts associated with exposure mixtures is critical to understanding the impact of real-life conditions. Our findings suggest that joint exposure to Mn and Pb may produce heightened neurocognitive impacts even at blood Pb levels below the CDC reference concentration of 5 µg/dL.

Linking metal (Pb, Hg, Cd) industrial air pollution risk to blood metal levels and cardiovascular functioning and structure among children in Syracuse, NY.

BACKGROUND: Exposure to air pollution has been linked to individual health effects in occupational environments and communities proximate to air pollution sources. Use of estimated chemical concentrations from the Risk Screening Environmental Indicators (RSEI) model, derived from the Toxics Release Inventory, can help approximate some contributions to individual lifetime exposure to risk from air pollution and holds potential for linkages with specific health outcome data. OBJECTIVES: Our objectives were: (1) use regression modeling to test for associations between observed blood metal concentrations in children and RSEI total air concentrations of the same metals released from proximate manufacturing facilities; (2) determine the relative contribution of RSEI air pollution to blood metal concentrations; and (3) examine associations between chronic metal exposure and cardiovascular functioning and structure in study participants. METHODS: Using data synthesis methods and regression modeling we linked individual blood-based levels of lead, mercury, and cadmium(Pb, Hg, Cd) and cardiovascular functioning and structure to proximate industrial releases of the same metals captured by the Environmental Protection Agency's (EPA) RSEI geographic microdata. RESULTS: We found that RSEI-derived ground-level ambient air concentrations of Hg and Cd were a significant predictor of blood metal levels, when controlling for covariates and other exposure variables. In addition to associations with blood metal findings, RSEI concentrations also predicted cardiovascular dysfunction and risk including changes in left-ventricular mass, blood pressure, and heart rate. DISCUSSION: Right-to-know data, such as EPA's RSEI, can be linked to objective health outcomes, rather than simply serving as a non-specific risk estimate. These data can serve as a proxy for hazard exposure and should be used more widely to understand the dynamics of environmental exposure. Furthermore, since these data are both a product of and contribute to regulatory decision making, they could serve as an important link between disease risk and translation-orientated national environmental health policy.

Dietary contributions to increased background lead, mercury, and cadmium in 9-11 Year old children: Accounting for racial differences.

BACKGROUND: Initial interest in the adverse consequences of exposure to lead (Pb), mercury (Hg), and cadmium (Cd) focused on relatively high exposures through environmental or occupational sources; however, recent evidence suggests even low-level background exposure to non-essential metals might be detrimental, particularly for children's health and development. One potentially important source of increased background levels of non-essential toxic metals is diet. OBJECTIVES: We considered whether differences in diet are associated with levels of non-essential metals in blood and whether racial differences in metals are mediated by dietary differences. METHODS: We assessed blood levels of Pb, Hg, and Cd in a sample of 9-11 year-old children (N = 295) comprised of 42% European Americans (EAs), 58% African American (AAs), and 47% female. Diet was assessed using 24-h dietary recalls during phone interviews administered to parents on two consecutive days (Friday and Saturday). The Healthy Eating Index-2105 (HEI-2015) was calculated to assess diet quality. RESULTS: The current study identified significant dietary sources of non-essential metal exposure - namely total fruit for Pb, total protein for Hg, and greens and beans for Cd. Moreover, AAs were found to have significantly higher blood levels of Pb and Hg than EAs and these racial differences were significantly mediated by these dietary differences. DISCUSSION: This study is one of very few to consider total diet in children and exposure to the non-essential metals Pb, Hg, and Cd, and the first to demonstrate that racial differences in increased background blood levels of non-essential toxic metals can be accounted for by racial differences in diet. Given regional differences in food consumption patterns and specific farm and store sources for the foods, the generalizability of the current findings has yet to be determined; however, commonly consumed foods appear to be a significant source of low-level non-essential metals.

Variability in the spatial density of vacant properties contributes to background lead (Pb) exposure in children.

BACKGROUND: Heightened blood lead levels (BLL) are associated with cognitive deficiencies and adverse behavioral outcomes. Lead-contaminated house dust is the primary source of exposure in U.S. children, and evidence suggests that even background (low-level) exposure has negative consequences. Identifying sources of background exposure is of great public health significance because of the larger number of children that can be affected. METHODS: Blood lead was assessed in a bi-racial sample of children from Syracuse, NY, aged 9-11, using established biomonitoring methods. The spatial density of vacant properties was modelled from publicly available georeferenced datasets. Further, regression models were used to measure the impact of this spatial density variable on children's BLL. RESULTS: In a sample of 221 children, with a mean BLL of 1.06 µg/dL (SD = 0.68), results showed increases in spatial density of vacant properties predict increases in median blood-PB levels, b = 0.14 (0.06-0.21), p < .001. This association held true even after accounting for demographic covariates, and age of individual housing. Further analysis showed spatial autocorrelation of the residuals changed from a clustered pattern to a random pattern once the spatial density variable was introduced to the model. DISCUSSION: This study is the first to identify a background-lead exposure source using spatial density modelling. As vacant properties deteriorate, lead-contaminated dust likely disperses into the surrounding environment. High-density areas have an accumulation of lead hazards in environmental media, namely soil and dust, putting more children at risk of exposure.

Biomonitoring of populations in Western New York at risk for exposure to Great Lakes contaminants.

The New York State Department of Health conducted the Healthy Fishing Communities Program in collaboration with the Agency for Toxic Substances and Disease Registry to assess human exposure to contaminants common to Lake Ontario, Lake Erie and surrounding rivers and waterways among populations in western New York State who eat locally caught fish. The program enrolled licensed anglers and Burmese refugees and immigrants, living near four designated Great Lakes Areas of Concern: Buffalo River, Niagara River, Eighteenmile Creek, and the Rochester Embayment. These target populations were sampled and enrolled independently into the program between February and October of 2013. A core set of contaminants were measured in blood and urine of 409 licensed anglers and 206 Burmese refugees and immigrants which included lead, cadmium, mercury, PCBs, PBDEs, organochlorine pesticides (hexachlorobenzene, mirex, DDT, DDE, and chlordane and its metabolites oxychlordane and trans-Nonachlor), and PFOS and PFOA. Biomonitoring results showed that both groups had higher geometric means for blood lead, total blood mercury, and serum PFOS compared to the 2013-2014 NHANES reference levels. The Burmese refugee group also showed higher geometric means for creatinine-adjusted urine mercury and lipid-adjusted serum DDE compared to national levels. Licensed angler participants reported eating a median of 16 locally caught fish meals in the past year. Burmese participants consumed local fish throughout the year, and most frequently in the summer (median 39 fish meals or 3 times a week). The study results provide valuable information on populations at high risk of exposure to contaminants in the Great Lakes Basin of western New York. The results provide the foundation for developing and implementing public health actions to reduce potential exposures to Great Lakes pollutants.

Coal smoke, gestational cadmium exposure, and fetal growth.

BACKGROUND: Gestational cadmium exposure may impair fetal growth. Coal smoke has largely been unexplored as a source of cadmium exposure. We investigated the relationship between gestational cadmium exposure and fetal growth, and assessed coal smoke as a potential source of airborne cadmium, among non-smoking pregnant women in Ulaanbaatar, Mongolia, where coal combustion in home heating stoves is a major source of outdoor and indoor air pollution. METHODS: This observational study was nested within the Ulaanbaatar Gestation and Air Pollution Research (UGAAR) study, a randomized controlled trial of portable high efficiency particulate air (HEPA) filter air cleaner use during pregnancy, fetal growth, and early childhood development. We measured third trimester blood cadmium concentrations in 374 out of 465 participants who had a live birth. We used multiple linear and logistic regression to assess the relationships between log2-transformed maternal blood cadmium concentrations and birth weight, length, head circumference, ponderal index, low birth weight, small for gestational age, and preterm birth in crude and adjusted models. We also evaluated the relationships between log2-transformed blood cadmium concentrations and the density of coal-burning stoves within 5000 m of each participant's apartment as a proxy of coal smoke emissions from home heating stoves. RESULTS: The median (25th,75th percentile) blood cadmium concentration was 0.20 (0.15, 0.29) µg/L. A doubling of blood cadmium was associated with a 95 g (95% CI: 34, 155 g) reduction in birth weight in adjusted models. An interquartile range increase in coal stove density (from 3.4 to 4.9 gers/hectare) surrounding participants' apartments was associated with a 12.2% (95% CI: 0.3, 25.6%) increase in blood cadmium concentrations. CONCLUSIONS: Gestational cadmium exposure was associated with reduced birth weight. In settings where coal is a widely used fuel, cadmium may play a role in the putative association between air pollution and impaired fetal growth.

Determination of lipid bilayer affinities and solvation characteristics by electrokinetic chromatography using polymer-bound lipid bilayer nanodiscs.

Styrene-maleic acid polymer-bound lipid bilayer nanodiscs have been investigated and characterized by electrokinetic chromatography. Linear solvation energy relationship analysis was employed to characterize the changes in solvation environment of nanodiscs of varied belt to lipid ratio, belt polymer chemistry and molecular weight, and lipid composition. Increases in the lipid to belt polymer ratio resulted in smaller, more cohesive nanodiscs with greater electrophoretic mobility. Nanodisc structures with belt polymers of different chemistry and molecular weight were compared and showed only minor changes in solvent characteristics and selectivity consistent with changes in structure of the lipid bilayer. Seven phospholipid and sphingomyelin nanodiscs of different lipid composition were characterized. Changes in lipid head group structure had a significant effect on bilayer-solute interactions. In most cases, changes in alkyl tail structure had no discernible effect on solvation environment aside from those explained by changes in the gel-liquid transition temperature. Comparison to vesicles of similar lipid composition show only minor differences in solvation environment, likely due to differences in lipid composition and bilayer curvature. Together these results provide evidence that the dominant solute-nanodisc interactions are with the lipid bilayer and that head group chemistry has a greater impact on bilayer-solute interactions than alkyl tail or belt polymer structure. Nanodisc electrokinetic chromatography is demonstrated to allow characterization of solute interactions with lipid bilayers of varied composition.

Tracking Declines in Mercury Exposure in the New York City Adult Population, 2004-2014.

Mercury is a toxic metal that can be measured in human blood and urine. Population-based biomonitoring from 2004 guided New York City (NYC) Department of Health and Mental Hygiene (DOHMH) efforts to reduce exposures by educating the public about risks and benefits of fish consumption-a predominant source of exposure in the general population-and removing mercury-containing skin-lightening creams and other consumer products from the marketplace. We describe changes in exposures over the past decade in relation to these local public health actions and in the context of national changes by comparing mercury concentrations measured in blood (1201 specimens) and urine (1408 specimens) from the NYC Health and Nutrition Examination Survey (NYC HANES) 2013-2014 with measurements from NYC HANES 2004 and National Health and Nutrition Examination Surveys (NHANES) 2003-2004 and 2013-2014. We found that NYC adult blood and urine geometric mean mercury concentrations decreased 46% and 45%, respectively. Adult New Yorkers with blood mercury concentration ≥ 5 µg/L (the New York State reportable level) declined from 24.8% (95% CL = 22.2%, 27.7%) to 12.0% (95% CL = 10.1%, 14.3%). The decline in blood mercury in NYC was greater than the national decline, while the decline in urine mercury was similar. As in 2004, Asian New Yorkers had higher blood mercury concentrations than other racial/ethnic groups. Foreign-born adults of East or Southeast Asian origin had the highest prevalence of reportable levels (29.7%; 95% CL = 21.0%, 40.1%) across sociodemographic groups, and Asians generally were the most frequent fish consumers, eating on average 11 fish meals in the past month compared with 7 among other groups (p < 0.001). Fish consumption patterns were similar over time, and fish continues to be consumed more frequently in NYC than nationwide (24.7% of NYC adults ate fish ten or more times in the past 30 days vs. 14.7% nationally, p < 0.001). The findings are consistent with the hypothesis that blood mercury levels have declined in part because of local and national efforts to promote consumption of lower mercury fish. Local NYC efforts may have accelerated the reduction in exposure. Having "silver-colored fillings" on five or more teeth was associated with the highest 95th percentile for urine mercury (4.06 µg/L; 95% CL = 3.1, 5.9). An estimated 5.5% of the adult population (95% CL = 4.3%, 7.0%) reported using a skin-lightening cream in the past 30 days, but there was little evidence that use was associated with elevated urine mercury in 2013-14.

Declines in adult blood lead levels in New York City compared with the United States, 2004-2014.

OBJECTIVES: To assess changes in lead exposure in the New York City (NYC) adult population over a 10-year period and to contrast changes with national estimates, overall, and by socio-demographics and smoking status. METHODS: We used measurements of blood lead levels (BLLs) from NYC resident adults who participated in the NYC Health and Nutrition Examination Surveys (HANES) in 2004 and 2013-2014. We compared estimates of geometric means (GM), 95th percentiles, and prevalence of BLL ≥ 5 µg/dL overall and by subgroups over time, with adults who participated in the National HANES (NHANES) 2001-2004 and 2011-2014. RESULTS: The GM BLLs among NYC adults declined from 1.79 µg/dL in 2004 to 1.13 µg/dL in 2013-2014 (P < .0001). The declines over this period ranged from 30.1% to 43.2% across socio-demographic groups and smoking status (P < .0001 for all comparisons), and were slightly greater than declines observed nationally. The drop in prevalence of elevated BLLs (≥ 5 µg/dL) was also greater in NYC (4.8-0.5%), compared with NHANES (3.8-2.0%). By 2013-2014, NYC adults with lower annual family income (< $20,000) no longer had higher GM BLLs relative to those with higher incomes (≥ $75,000), a disparity improvement not observed nationally. Likewise, GM BLLs and 95th percentiles for non-Hispanic black adults in NYC were lower than GM BLLs for non-Hispanic white adults. Non-Hispanic Asian adults had the highest GM BLLs compared with other racial/ethnic groups, both in NYC in 2013-14 and nationally in 2011-2014 (1.37 µg/dL, P = .1048 and 1.22 µg/dL, P = .0004, respectively). CONCLUSION: The lessening of disparity in lead exposure across income groups and decreasing exposure at the high end of the distribution among non-Hispanic black and Asian adults in NYC suggest that regulatory and outreach efforts have effectively targeted these higher exposure risk groups. However, Asian adults still had the highest average BLL, suggesting a need for enhanced outreach to this group. Local surveillance remains an important tool to monitor BLLs of local populations and to inform initiatives to reduce exposures in those at highest risk.

A Quasi-Experimental, Before-After Trial Examining the Impact of an Emergency Department Mechanical Ventilator Protocol on Clinical Outcomes and Lung-Protective Ventilation in Acute Respiratory Distress Syndrome.

OBJECTIVES: To evaluate the impact of an emergency department mechanical ventilation protocol on clinical outcomes and adherence to lung-protective ventilation in patients with acute respiratory distress syndrome. DESIGN: Quasi-experimental, before-after trial. SETTING: Emergency department and ICUs of an academic center. PATIENTS: Mechanically ventilated emergency department patients experiencing acute respiratory distress syndrome while in the emergency department or after admission to the ICU. INTERVENTIONS: An emergency department ventilator protocol which targeted variables in need of quality improvement, as identified by prior work: 1) lung-protective tidal volume, 2) appropriate setting of positive end-expiratory pressure, 3) oxygen weaning, and 4) head-of-bed elevation. MEASUREMENTS AND MAIN RESULTS: A total of 229 patients (186 preintervention group, 43 intervention group) were studied. In the emergency department, the intervention was associated with significant changes (p < 0.01 for all) in tidal volume, positive end-expiratory pressure, respiratory rate, oxygen administration, and head-of-bed elevation. There was a reduction in emergency department tidal volume from 8.1 mL/kg predicted body weight (7.0-9.1) to 6.4 mL/kg predicted body weight (6.1-6.7) and an increase in lung-protective ventilation from 11.1% to 61.5%, p value of less than 0.01. The intervention was associated with a reduction in mortality from 54.8% to 39.5% (odds ratio, 0.38; 95% CI, 0.17-0.83; p = 0.02) and a 3.9 day increase in ventilator-free days, p value equals to 0.01. CONCLUSIONS: This before-after study of mechanically ventilated patients with acute respiratory distress syndrome demonstrates that implementing a mechanical ventilator protocol in the emergency department is feasible and associated with improved clinical outcomes.