Effect of Glycocalyx-targeted Therapy on Vascular Function in Older Adults: A Randomized Controlled Trial.

Advancing age increases cardiovascular disease risk, in part, because of impaired glycocalyx thickness and endothelial dysfunction. Glycocalyx-targeted therapies, such as Endocalyx Pro{trade mark, serif}, could improve both glycocalyx thickness and endothelial function in older adults, however, this has yet to be tested. We hypothesized that Endocalyx Pro{trade mark, serif} supplementation would increase glycocalyx thickness and endothelial function in older adults. Twenty-three older adults aged 66±7 years (52% female) were enrolled in a randomized, double-blind, placebo-controlled, parallel-arms study to investigate the effect of 12-week Endocalyx Pro{trade mark, serif} supplementation (3,712 mg/day) on glycocalyx thickness and endothelial function. Glycocalyx thickness was assessed using the GlycoCheck and endothelial function was determined via brachial artery flow-mediated dilation (FMD). Between-group comparisons revealed Endocalyx Pro{trade mark, serif} did not increase glycocalyx thickness in microvessels 4-25µm (P=0.33), 4-7µm (P=0.07), or 10-25µm (P=0.47) in diameter when compared with placebo. Additionally, Endocalyx Pro did not significantly improve FMD [mean ratio (95% CI) for between-group comparisons, 1.16 (0.77-1.74); P=0.48]. However, Endocalyx Pro{trade mark, serif} improved FMD normalized to shear rate area under the curve [mean ratio (95% CI) for between-group comparisons, 2.41 (1.14,4.13); P=0.001]. Moreover, Endocalyx Pro{trade mark, serif} increased capillary glycocalyx thickness more than placebo in individuals not taking anti-hypertensive medication [mean difference (95% CI) for between-group comparison, -0.08 (-0.15,-0.01); P=0.02]. Our pilot study suggests that Endocalyx Pro{trade mark, serif} supplementation is feasible in older adults but had no measurable effect on overall glycocalyx thickness and FMD. However, Endocalyx Pro{trade mark, serif} may have select effects on capillary glycocalyx thickness and FMD normalized to shear rate among older adults, but further investigation is warranted.

Food security status and cardiometabolic health by sex/gender and race/ethnicity among adults in the United States.

BACKGROUND: Minoritized racial/ethnic groups and women in the United States (US) are disproportionately burdened by food insecurity, which likely contributes to disparities in cardiovascular health (CVH). Disparities are projected to widen due to the worsening climate crisis that is straining the agricultural system including food supplies. Nonetheless, studies have not investigated the relationship between food security status and 'ideal' CVH in a large, nationally-representative and racially/ethnically diverse US sample. METHODS AND RESULTS: We investigated household food security status in relation to 'ideal' CVH among US adults (N = 157,001) using 2014-2018/2020 National Health Interview Survey data. Food security status was defined as very low, low, marginal, or high. A summed score of 4 health behaviors and 3 clinical factors totaling 7 different measures was dichotomized (yes/no) to assess modified 'ideal' CVH (mICVH). Using Poisson regression with robust variance, we estimated prevalence ratios (PRs) and 95% CIs of mICVH by household food security status. We stratified models by sex/gender and race/ethnicity. Very low food security prevalence was higher among non-Hispanic (NH)-Black (8.0%) compared to Hispanic/Latinx (5.1%), NH-White (3.1%) and NH-Asian (1.7%) adults. The association between very low versus high food security and mICVH was stronger among women (PR = 0.23 [95% CI: 0.17-0.31]) than men (PR = 0.48 [95% CI: 0.35-0.66]). Compared to NH-White adults with high food security, racially/ethnically minoritized groups with very low to high food security were generally less likely (range: [PRvery low = 0.25[95% CI: 0.14-0.44] - [PRhigh = 0.88 [95% CI: 0.79-0.97]) to meet mICVH criteria. CONCLUSIONS: Food insecurity was associated with lower mICVH prevalence and racially/ethnically minoritized groups were disproportionately burdened.

High-resolution freshwater dissolved calcium and pH data layers for Canada and the United States.

Freshwater ecosystems are biologically important habitats that provide many ecosystem services. Calcium concentration and pH are two key variables that are linked to multiple chemical processes in these environments, influence the biology of organisms from diverse taxa, and can be important factors affecting the distribution of native and non-native species. However, it can be challenging to obtain high-resolution data for these variables at regional and national scales. To address this data gap, water quality data for lakes and rivers in Canada and the continental USA were compiled and used to generate high-resolution (10 × 10 km) interpolated raster layers, after comparing multiple spatial interpolation approaches. This is the first time that such data have been made available at this scale and resolution, providing a valuable resource for research, including projects evaluating risks from environmental change, pollution, and invasive species. This will aid the development of conservation and management strategies for these vital habitats.

Features of the Physical and Social Neighborhood Environment and Neighborhood-Level Alzheimer's Disease and Related Dementia in South Carolina.

BACKGROUND: Studies are increasingly examining the relationship between the neighborhood environment and cognitive decline; yet, few have investigated associations between multiple neighborhood features and Alzheimer's disease and related dementias (ADRD). OBJECTIVE: We investigated the relationship between neighborhood features and ADRD cumulative incidence from 2010 to 2014 in the South Carolina Alzheimer's Disease Registry (SCADR). METHODS: Diagnosed ADRD cases ≥50 years of age were ascertained from the SCADR by ZIP code and census tract. Neighborhood features from multiple secondary sources included poverty, air pollution [particulate matter with a diameter of 2.5 micrometers or less (PM2.5)], and rurality at the census-tract level and access to healthy food, recreation facilities, and diabetes screening at the county level. In addition to using Poisson generalized linear regression to estimate ADRD incident rate ratios (IRR) with 95% confidence intervals (CIs), we applied integrated nested Laplace approximations and stochastic partial differential equations (INLA-SPDE) to address disparate spatial scales. We estimated associations between neighborhood features and ADRD cumulative incidence. RESULTS: The average annual ADRD cumulative incidence was 690 per 100,000 people per census tract (95% CI: 660, 710). The analysis was limited to 98% of census tracts with a population ≥50 years old (i.e., 1,081 of 1,103). The average percent of families living below the federal poverty line per census tract was 18.8%, and ∼20% of census tracts were considered rural. The average percent of households with limited access to healthy food was 6.4%. In adjusted models, every 5µg/m3) increase of PM2.5 was associated with 65% higher ADRD cumulative incidence (IRR=1.65; 95% CI: 1.30, 2.09), where PM2.5 at or below 12 µg/m3 is considered healthy. Compared to large urban census tracts, rural and small urban tracts had 10% (IRR=1.10; 95% CI: 1.00, 1.23) and 5% (IRR=1.05; 95% CI: 0.96, 1.16) higher ADRD, respectively. For every percent increase of the county population with limited access to healthy food, ADRD was 2% higher (IRR=1.02; 95% CI: 1.01, 1.04). CONCLUSIONS: Neighborhood environment features, such as higher air pollution levels, were associated with higher neighborhood ADRD incidence. The INLA-SPDE method could have broad applicability to data collected across disparate spatial scales. https://doi.org/10.1289/EHP13183.

Serum macrophage migration inhibitory factor levels predict brain atrophy in people with primary progressive multiple sclerosis.

BACKGROUND: Macrophage migration inhibitory factor (MIF) is a cytokine linked to multiple sclerosis (MS) progression that is thought to be inhibited by ibudilast. SPRINT-MS was a phase 2 placebo-controlled trial of ibudilast in progressive multiple sclerosis (PMS). OBJECTIVE: To determine whether baseline MIF levels predict imaging outcomes and assess the effects of ibudilast on serum and cerebrospinal fluid (CSF) MIF levels in people with PMS treated with ibudilast. METHODS: Participants in the SPRINT-MS trial were treated with either ibudilast or placebo and underwent brain magnetic resonance imaging (MRI) every 24 weeks over a duration of 96 weeks. MIF was measured in serum and CSF. RESULTS: MIF levels were compared with imaging outcomes in 223 participants from the SPRINT-MS study. In the primary progressive multiple sclerosis (PPMS) cohort, males had higher serum (p < 0.001) and CSF (p = 0.01) MIF levels, as compared with females. Higher baseline serum MIF levels in PPMS were associated with faster brain atrophy (beta = -0.113%, 95% confidence interval (CI): -0.204% to -0.021%; p = 0.016). These findings were not observed in secondary progressive multiple sclerosis (SPMS). Ibudilast did not affect either serum or CSF MIF levels. CONCLUSIONS: Serum MIF levels were associated with male sex and predicted brain atrophy in PPMS, but not SPMS. Ibudilast did not demonstrate an effect on MIF levels, as compared with placebo, although we cannot exclude a functional effect.

Effect of acute heparin administration on glycocalyx thickness and endothelial function in healthy younger adults.

The endothelial glycocalyx is a dynamic, gel-like layer that is critical to normal vascular endothelial function. Heparin impairs the endothelial glycocalyx and reduces vascular endothelial function in a murine model; however, this has yet to be tested in healthy humans. We hypothesized that a single bolus dose of heparin would increase circulating glycocalyx components and decrease endothelial glycocalyx thickness resulting in blunted brachial artery vasodilation in healthy younger adults. Healthy adults (n = 19, aged 18-39 yr, 53% female) underwent measurements of the endothelial glycocalyx and vascular endothelial function at baseline and after a single bolus 5,000 U dose of heparin. The glycocalyx components syndecan-1 and heparan sulfate were measured from plasma samples using enzyme-linked immunosorbent assays. Glycocalyx thickness was determined as perfused boundary region (PBR) in sublingual microvessels using the GlycoCheck. Endothelial function was measured via ultrasonography and quantified as brachial artery flow-mediated dilation (FMD). Following acute heparin administration, there was no increase in syndecan-1 or heparan sulfate (P = 0.90 and P = 0.49, respectively). In addition, there was no change in PBR 4-7 µm (P = 0.55), PBR 10-25 µm (P = 0.63), or 4-25 µm (P = 0.49) after heparin treatment. Furthermore, we did not observe a change in FMDmm (P = 0.23), FMD% (P = 0.35), or plasma nitrite concentrations (P = 0.10) in response to heparin. Finally, time to peak dilation and peak FMD normalized to shear stress were unchanged following heparin (P = 0.59 and P = 0.21, respectively). Our pilot study suggests that a single bolus intravenous dose of heparin does not result in endothelial glycocalyx degradation or vascular endothelial dysfunction in healthy younger adults.NEW & NOTEWORTHY The endothelial glycocalyx's role in modulating vascular endothelial dysfunction with aging and disease is becoming increasingly recognized. This study presents novel findings that acute heparin administration is not a feasible method to experimentally degrade the endothelial glycocalyx and measure concurrent changes in vascular endothelial function in healthy humans. Alternative approaches will be needed to translate findings from preclinical studies and test the effects of acute endothelial glycocalyx degradation on vascular endothelial function in humans.

Prediction of Aqueous Reduction Potentials of X•, ChH•, and XO• Radicals with X = Halogen and Ch = Chalcogen.

The aqueous electron affinity and aqueous reduction potentials for F•, Cl•, Br•, I•, OH•, SH•, SeH•, TeH•, ClO•, BrO•, and IO• were calculated using electronic structure methods for explicit cluster models coupled with a self-consistent reaction field (SMD) to treat the aqueous solvent. Calculations were conducted using MP2 and correlated molecular orbital theory up to the CCSD(T)-F12b level for water tetramer clusters and MP2 for octamer cluster. Inclusion of explicit waters was found to be important for accurately predicting the redox potentials in a number of cases. The calculated reduction potentials for X• and ChH• were predicted to within ∼0.1 V of the reported literature values. Fluorine is anomalous due to abstraction of a hydrogen from one of the surrounding water molecules to form a hydroxyl radical and hydrogen fluoride, so its redox potential was calculated using only an implicit model. Larger deviations from experiment were predicted for ClO• and BrO•. These deviations are due to the free energy of solvation of the anion being too negative, as found in the pKa calculations, and that for the neutral being too positive with the current approach.

NHC Carbene-Metal Complex Ligand Binding Energies.

The ligand binding energies (LBEs) of N-heterocyclic carbenes (NHCs) and CH2 and CF2 adducts with group 1, 2, 10, and 11 metals and complexes with metals from these groups are predicted at the coupled cluster CCSD(T) level of theory by using density functional theory optimized geometries. The differences in LBEs as a function of the metal and the types of bonding interactions as well as the type of carbene are described. The bonding between the alkali cations and alkaline earth dications is predominantly ionic with a linear correlation between the LBEs and the cation hardness. In contrast, the bonding behaviors of the group 10 and 11 metals and metal complexes have only a weak, indirect correlation between the LBEs and the metal hardness. The difference in bonding behavior between the groups of metals arises due to the accessibility of electron donation between the ligand and the metal in the transition metal complexes, which results in more covalent-like bonding behavior. The presence of the methyl groups on the NHC nitrogen results in only slightly more delocalized charge from the metal onto the ring, but there is significant redistribution of the charge on the ring. Saturation of the NHC ring had a much smaller effect on how the charge was distributed on the ring. The analysis of the bonding behavior of NHCs with various metal groups enables improved understanding of carbene-metal interactions to inform rational design of NHC-based systems.

QuantumScents: Quantum-Mechanical Properties for 3.5k Olfactory Molecules.

Quantitative structure-odor relationships are critically important for studies related to the function of olfaction. Current literature data sets contain expert-labeled molecules but lack feature data. This paper introduces QuantumScents, a quantum mechanics augmented derivative of the Leffingwell data set. QuantumScents contains 3.5k structurally and chemically diverse molecules ranging from 2 to 30 heavy atoms (CNOS) and their corresponding 3D coordinates, total PBE0 energy, molecular dipole moment, and per-atom Hirshfeld charges, dipoles, and ratios. The authors demonstrate that Hirshfeld charges and ratios contain sufficient information to perform molecular classification by training a Message Passing Neural Network with chemprop (Heid, E.; et al. ChemRxiv, 2023, DOI: 10.26434/chemrxiv-2023-3zcfl) to predict scent labels. The QuantumScents data set is freely available on Zenodo along with the authors' code, example models, and data set generation workflow (https://zenodo.org/doi/10.5281/zenodo.8239853).

Residential proximity to metal emitting industries and toenail metal concentration in the US Gulf States.

Objective: The US Gulf region is heavily reliant on metal-emitting petrochemical and manufacturing industries. We characterized the effect of residential proximity to metal-emitting sites and metal body burden in Gulf states residents with particular attention to potential differential exposure burden by race. Methods: We measured toenail concentrations of arsenic, chromium, lead, manganese, mercury, and selenium using inductively coupled plasma mass spectrometry in 413 non-smoking men from the Gulf Long-term Follow-Up Study. Point sources of industrial metal emissions were identified using the US EPA's National Emissions Inventory (NEI) database and geocoded to participant residential addresses. For each metal, we assessed associations of toenail metal concentrations with the inverse-distance weighted number of emissions sites and volume of air-metal emissions within 30 km radial buffers of participant residences using multivariable linear regression. Results were stratified by race. Results: Compared to self-identified Non-Hispanic (NH) White participants, NH Black participants lived closer to NEI sites but had 23-70% lower toenail metal concentrations adjusting for other personal/behavioral factors. Residential proximity to lead-emitting NEI sites was positively associated with toenail Pb concentration while proximity to mercury-emitting NEI sites was inversely associated with toenail Hg concentration. Findings for lead were significantly attenuated after adjustment for neighborhood-level socioeconomic factors. Conclusion: Residential proximity to lead-emitting NEI sites in the US Gulf region is associated with a higher body burden of lead. However, this relationship may be driven in part by non-NEI factors related to residence in industry-adjacent neighborhoods.

Cannabis use and sleep disturbances among White, Black, and Latino adults in the United States: A cross-sectional study of National Comorbidity Survey-Replication (2001-2003) data.

OBJECTIVE: Research investigating cannabis use and sleep health is limited, and results are mixed. Few studies were nationally representative with racially-ethnically diverse samples or assessed potential modifiers. Our objective was to investigate cross-sectional associations between reported cannabis use and sleep disturbances by potential modifiers among non-Hispanic White, non-Hispanic Black, and Hispanic/Latino men and women in the United States. METHODS: We used nationally representative National Comorbidity Survey-Replication data collected from 2001 to 2003 among 3929 adults. Poisson regression with robust variance estimated prevalence ratios (PR) and 95% confidence intervals of patterns of sleep disturbances identified through latent class analysis. Models adjusted for sociodemographic, health behavior, and clinical characteristics were stratified by race-ethnicity and by race-ethnicity along with sex/gender, and age, separately. RESULTS: Over half of adults reported cannabis use (52%-ever/lifetime vs 48%-never). We identified two latent classes: multiple sleep disturbances with daytime sleepiness and no sleep disturbances with some daytime sleepiness. Prevalence of multiple sleep disturbances with daytime sleepiness was higher among participants reporting lifetime cannabis use (23% vs 20%). Associations did not vary by race-ethnicity or sex/gender. Lifetime vs never cannabis use was marginally associated with a higher prevalence of multiple sleep disturbances with daytime sleepiness only among adults aged 25-29years (PR=1.09 [95% confidence interval: 1.00-1.18]; eg, PRage 40+ years=1.00 [0.97-1.03], pinteraction=0.03). CONCLUSIONS: Associations between cannabis use and sleep may vary by age. Replication with more recent data and prospective studies that investigate intersectional identities among diverse populations with objective assessments are warranted.

Neighborhood Social Cohesion and Obesity in the United States.

Low neighborhood social cohesion (nSC) has been associated with obesity. Still, few studies have assessed the nSC-obesity relationship among a large, nationally representative, and racially/ethnically diverse sample of the United States population. To address this literature gap, we examined cross-sectional associations among 154,480 adult participants of the National Health Interview Survey (NHIS) from 2013-2018. We also determined if associations varied by race/ethnicity, sex/gender, age, annual household income, and food security status. Based on a 4-item scale from the Project on Human Development in Chicago Neighborhoods Community Survey, we categorized nSC as low, medium, and high. Based on body mass index (BMI) recommendations, we categorized obesity as ≥30 kg/m2. We used Poisson regression with robust variance to directly estimate prevalence ratios (PRs) and 95% confidence intervals (CIs) while adjusting for sociodemographic characteristics, such as annual household income, educational attainment, and marital status, along with other confounders. Study participants' mean age ± standard error was 47.1±0.1 years; most (69.2%) self-identified as Non-Hispanic (NH)-White, and 51.0% were women. NH-Black and Hispanic/Latinx adults comprised more of the population in neighborhoods with low nSC (14.0% NH-Black, 19.1% Hispanic/Latinx, and 61.8% NH-White) versus high nSC (7.7% NH-Black, 10.4% Hispanic/Latinx and 77.0% NH-White). Low vs. high nSC was associated with a 15% higher prevalence of obesity (PR=1.15 [95% CI: 1.12-1.18]), and the magnitude of the association was more substantial among NH-White (PR=1.21 [95% CI: 1.17-1.25]) compared to associations among Hispanic/Latinx (PR=1.04 [95% CI: 0.97-1.11]) and NH-Black (PR=1.01 [95% CI: 0.95-1.07]) adults. Low vs. high nSC was associated with a 20% higher prevalence of obesity in women (PR=1.20 [95% CI: 1.16-1.24]) compared to a 10% higher prevalence in men (PR=1.10 [95% CI: 1.06-1.14]). Low vs. high nSC was associated with a 19% higher prevalence of obesity among adults ≥50 years old (PR=1.19 [95% CI: 1.15-1.23]) compared to a 7% higher prevalence of obesity among adults <50 years old (PR=1.07 [95% CI: 1.03-1.11]). Efforts to address nSC may improve health and address health disparities.

Association between spill-related exposure to fine particulate matter and peripheral motor and sensory nerve function among oil spill response and cleanup workers following the Deepwater Horizon oil spill.

BACKGROUND: Burning/flaring of oil/gas during the Deepwater Horizon oil spill response and cleanup (OSRC) generated high concentrations of fine particulate matter (PM2.5). Personnel working on the water during these activities may have inhaled combustion products. Neurologic effects of PM2.5 have been reported previously but few studies have examined lasting effects following disaster exposures. The association of brief, high exposures and adverse effects on sensory and motor nerve function in the years following exposure have not been examined for OSRC workers. OBJECTIVES: We assessed the relationship between exposure to burning/flaring-related PM2.5 and measures of sensory and motor nerve function among OSRC workers. METHODS: PM2.5 concentrations were estimated from Gaussian plume dispersion models and linked to self-reported work histories. Quantitative measures of sensory and motor nerve function were obtained 4-6 years after the disaster during a clinical exam restricted to those living close to two clinics in Mobile, AL or New Orleans, LA (n = 3401). We obtained covariate data from a baseline enrollment survey and a home visit, both in 2011-2013. The analytic sample included 1186 participants. RESULTS: We did not find strong evidence of associations between exposure to PM2.5 and sensory or motor nerve function, although there was a suggestion of impairment based on single leg stance among individuals with high exposure to PM2.5. Results were generally consistent whether we examined average or cumulative maximum exposures or removed individuals with the highest crude oil exposures to account for co-pollutant confounding. There was no evidence of exposure-response trends. IMPACT STATEMENT: Remediating environmental disasters is essential for long-term human and environmental health. During the Deepwater Horizon oil spill disaster, burning and flaring of oil and gas were used to remove these pollutants from the environment, but led to potentially high fine particulate matter exposures for spill response workers working on the water. We investigate the potential adverse effects of these exposures on peripheral nerve function; understanding the potential health harm of remediation tactics is necessary to inform future clean up approaches and protect human health.

Assigning harvested waterfowl to geographic origin using feather δ2H isoscapes: What is the best analytical approach?

Establishing links between breeding, stopover, and wintering sites for migratory species is important for their effective conservation and management. Isotopic assignment methods used to create these connections rely on the use of predictable, established relationships between the isotopic composition of environmental hydrogen and that of the non-exchangeable hydrogen in animal tissues, often in the form of a calibration equation relating feather (δ2Hf) values derived from known-origin individuals and amount-weighted long-term precipitation (δ2Hp) data. The efficacy of assigning waterfowl to moult origin using stable isotopes depends on the accuracy of these relationships and their statistical uncertainty. Most current calibrations for terrestrial species in North America are done using amount-weighted mean growing-season δ2Hp values, but the calibration relationship is less clear for aquatic and semi-aquatic species. Our objective was to critically evaluate current methods used to calibrate δ2Hp isoscapes to predicted δ2Hf values for waterfowl. Specifically, we evaluated the strength of the relationships between δ2Hp values from three commonly used isoscapes and known-origin δ2Hf values three published datasets and one collected as part of this study, also grouping these data into foraging guilds (dabbling vs diving ducks). We then evaluated the performance of assignments using these calibrations by applying a cross-validation procedure. It remains unclear if any of the tested δ2Hp isoscapes better predict surface water inputs into food webs for foraging waterfowl. We found only marginal differences in the performance of the tested known-origin datasets, where the combined foraging-guild-specific datasets showed lower assignment precision and model fit compared to data for individual species. We recommend the use of the more conservative combined foraging-guild-specific datasets to assign geographic origin for all dabbling duck species. Refining these relationships is important for improved waterfowl management and contributes to a better understanding of the limitations of assignment methods when using the isotope approach.

Reliability of low mass toenail samples as biomarkers of chronic metal exposure.

BACKGROUND: Toenails are a promising matrix for chronic metal exposure assessment, but there are currently no standard methods for collection and analysis. Questions remain about sample mass requirements and the extent to which metals measured in this matrix are representative of chronic body burden. OBJECTIVE: This study proposes a method to maximize sample conservation for toenail metals analysis using inductively coupled plasma mass spectrometry (ICP-MS). We demonstrate the reliability of an ~25 mg toenail sample (typically 1-2 clippings) for metals analysis and evaluate the intra-individual variability of multiple metals in this matrix over time in men from the Gulf Long-term Follow-up (GuLF) Study. METHODS: Toenail samples from 123 GuLF Study participants were collected at two visits 3 years apart and analyzed for 18 elements using ICP-MS. Participants with samples exceeding 200 mg at the first visit (n = 29) were selected for triplicate sub-sample analysis. Kendall's coefficient of concordance (W) was used to assess sub-sample reliability and Spearman's correlation coefficients (ρ) were used to evaluate fluctuations in elemental concentrations over time. RESULTS: Results were not reported for Cd, Co, Mo, Sb, and V (detected in <60% of the samples). There was strong agreement among triplicate samples (Kendall's W: 0.72 (Cu)-0.90 (Cu)) across all elements evaluated, moderate correlations of elemental concentrations (Spearman's ρ: 0.21-0.42) over 3 years for As, Ca, Cr, Fe, Pb, Mn, and Zn, and strong correlations (>0.50) for Se, Cu, and Hg. IMPACT STATEMENT: This toenail reliability study found that a low-mass (~25 mg) toenail sample (1-2 clippings) is suitable for the determination of most elements using ICP-MS and helps to increase the analytical capacity of limited toenail biospecimens collected in cohort studies. The results highlight differences in the suitability of toenails for chronic metal exposure assessment by element and underscore the need to consider intra-person variability, especially when comparing results across studies. We also provide recommendations for analytical standardization and the partitioning of the total collected toenail sample into multiple analytic sub-samples for future studies using toenail biospecimen for multiple assays.

The Effects of NLY01, a Novel Glucagon-Like Peptide-1 Receptor Agonist, on Cuprizone-Induced Demyelination and Remyelination: Challenges and Future Perspectives.

Recent evidence suggests that the glucagon-like peptide-1 receptor (GLP-1R) agonists have neuroprotective activities in the CNS in animal models of Parkinson's disease, Alzheimer's disease, and multiple sclerosis (MS). This study aimed to investigate whether a novel long-acting GLP-1R agonist, NLY01, could limit demyelination or improve remyelination as occurs in MS using the cuprizone (CPZ) mouse model. Herein, we assessed the expression of GLP-1R on oligodendrocytes in vitro and found that mature oligodendrocytes (Olig2+PDGFRa-) express GLP-1R. We further confirmed this observation in the brain by immunohistochemistry and found that Olig2+CC1+ cells express GLP-1R. We next administered NLY01 twice per week to C57B6 mice while on CPZ chow diet and found that NLY01 significantly reduced demyelination with greater weight loss than vehicle-treated controls. Because GLP-1R agonists are known to have anorexigenic effect, we then administered CPZ by oral gavage and treated the mice with NLY01 or vehicle to ensure the dose consistency of CPZ ingestion among mice. Using this modified approach, NLY01 was no longer effective in reducing demyelination of the corpus callosum (CC). We next sought to examine the effects of NLY01 treatment on remyelination after CPZ intoxication and during the recovery period using an adoptive transfer-CPZ (AT-CPZ) model. We found no significant differences between the NLY01 and vehicle groups in the amount of myelin or the number of mature oligodendrocytes in the CC. In summary, despite the promising anti-inflammatory and neuroprotective effects of GLP-1R agonists that have been previously described, our experiments provided no evidence to support a beneficial effect of NLY01 on limiting demyelination or enhancing remyelination. This information may be useful in selecting proper outcome measures in clinical trials of this promising class of drugs in MS.

Suicidal ideation and psychological dating violence victimization-A short report.

As the second leading cause of death among Americans aged 10 to 34, suicide is a serious public health concern. One potential predictor of suicidality is dating violence (DV) victimization, such as any physical, psychological, or sexual abuse by a current or former intimate partner. However, little longitudinal data exists on the relationship between suicidal ideation and DV. To address this gap in knowledge, we leverage data from two years of our longitudinal study Dating It Safe. Specifically, we examine whether physical and psychological DV victimization is associated with subsequent suicidal ideation in our ethnically diverse sample of young adults (n = 678; mean age = 25 at Wave 9; 63.6% female). While physical DV victimization was not linked to suicidal ideation over time, psychological DV victimization was (χ2 = 7.28, p = 0.007 for females; χ2 = 4.87, p = 0.027 for males). That psychological abuse was potentially as or more impactful than physical violence is consistent with the broader literature on the deleterious impacts of psychological violence, as well as the limited longitudinal literature looking at DV and suicidality specifically. These findings reinforce the notion that psychological abuse is as consequential as physical violence in the long-term, has unique impacts on mental health, and points to the need for both suicide and violence intervention programs to address this form of dating violence victimization.

Negating coordinative cysteine and methionine residues during metathesis of unprotected peptides.

Ru-Alkylidene catalysed olefin metathesis generates metabolically stable cystine bridge peptidomimetics with defined geometry. Deleterious coordinative bonding to the catalyst by sulfur-containing functionality found in cysteine and methionine residues can be negated by in situ and reversible oxidation of thiol and thioether functionality, as disulfides and S-oxides respectively, to facilitate high yielding ring-closing and cross metathesis of bioorthogonally protected peptides.

Efficient 3-D Finite Element Modeling of Periodic XBAR Resonators.

An efficient technique is presented for 3-D finite element modeling of large-scale periodic excited bulk acoustic resonator (XBAR) resonators in the time-harmonic domain. In this technique, a domain decomposition scheme is used to decompose the computational domain into many small subdomains whose FE subsystems can be factorized with a direct sparse solver at a low cost. Transmission conditions (TCs) are enforced to interconnect adjacent subdomains, and a global interface system is formulated and solved iteratively. To accelerate the convergence, a second-order TC (SOTC) is designed to make the subdomain interfaces transparent for propagating and evanescent waves. An effective forward-backward preconditioner is constructed that when combined with the SOTC significantly reduce the number of iterations at no additional cost. Numerical results are given to demonstrate the accuracy, efficiency, and capability of the proposed algorithm.

Volatile Hydrocarbon Exposures and Incident Coronary Heart Disease Events: Up to Ten Years of Follow-up among Deepwater Horizon Oil Spill Workers.

BACKGROUND: During the 2010 Deepwater Horizon (DWH) disaster, response and cleanup workers were potentially exposed to toxic volatile components of crude oil. However, to our knowledge, no study has examined exposure to individual oil spill-related chemicals in relation to cardiovascular outcomes among oil spill workers. OBJECTIVES: Our aim was to investigate the association of several spill-related chemicals [benzene, toluene, ethylbenzene, xylene, n-hexane (BTEX-H)] and total hydrocarbons (THC) with incident coronary heart disease (CHD) events among workers enrolled in a prospective cohort. METHODS: Cumulative exposures to THC and BTEX-H across the cleanup period were estimated via a job-exposure matrix that linked air measurement data with self-reported DWH spill work histories. We ascertained CHD events following each worker's last day of cleanup work as the first self-reported physician-diagnosed myocardial infarction (MI) or a fatal CHD event. We estimated hazard ratios (HR) and 95% confidence intervals for the associations of exposure quintiles (Q) with risk of CHD. We applied inverse probability weights to account for bias due to confounding and loss to follow-up. We used quantile g-computation to assess the joint effect of the BTEX-H mixture. RESULTS: Among 22,655 workers with no previous MI diagnoses, 509 experienced an incident CHD event through December 2019. Workers in higher quintiles of each exposure agent had increased CHD risks in comparison with the referent group (Q1) of that agent, with the strongest associations observed in Q5 (range of HR=1.14-1.44). However, most associations were nonsignificant, and there was no evidence of exposure-response trends. We observed stronger associations among ever smokers, workers with ≤high school education, and workers with body mass index <30 kg/m2. No apparent positive association was observed for the BTEX-H mixture. CONCLUSIONS: Higher exposures to volatile components of crude oil were associated with modest increases in risk of CHD among oil spill workers, although we did not observe exposure-response trends. https://doi.org/10.1289/EHP11859.