Showing papers by "Walter Goessler published in 2022"

Comparison of two LC-MS/MS methods for the quantification of 24,25-dihydroxyvitamin D3 in patients and external quality assurance samples.

Abstract: OBJECTIVES In-house developed liquid-chromatography mass spectrometry (LC-MS/MS) methods are used more and more frequently for the simultaneous quantification of vitamin D metabolites. Among these, 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) is of clinical interest. This study assessed the agreement of this metabolite in two validated in-house LC-MS/MS methods. METHODS 24,25(OH)2D3 was measured in 20 samples from the vitamin D external quality assurance (DEQAS) program and in a mixed cohort of hospital patients samples (n=195) with the LC-MS/MS method at the Medical University of Graz (LC-MS/MS 1) and at the University of Liege (LC-MS/MS 2). RESULTS In DEQAS samples, 24,25(OH)2D3 results with LC-MS/MS 1 had a proportional bias of 1.0% and a negative systemic difference of -0.05%. LC-MS/MS 2 also showed a proportional bias of 1.0% and the negative systemic bias was -0.22%. Comparing the EQA samples with both methods, no systemic bias was found (0.0%) and the slope was 1%. The mean difference of 195 serum sample measurements between the two LC-MS/MS methods was minimal (-0.2%). Both LC-MS/MS methods showed a constant bias of 0.31 nmol/L and a positive proportional bias of 0.90%, respectively. CONCLUSIONS This study is the first to assess the comparability of 24,25(OH)2D3 concentrations in a mixed cohort of hospitalized patients with two fully validated in-house LC-MS/MS methods. Despite different sample preparation, chromatographic separation and ionization, both methods showed high precision measurements of 24,25(OH)2D3. Furthermore, we demonstrate the improvement of accuracy and precision measurements of 24,25(OH)2D3 in serum samples and in the DEQAS program.

Arsenic Exposure, Blood DNA Methylation, and Cardiovascular Disease

Abstract: Background: Epigenetic dysregulation has been proposed as a key mechanism for arsenic-related cardiovascular disease (CVD). We evaluated differentially methylated positions (DMPs) as potential mediators on the association between arsenic and CVD. Methods: Blood DNA methylation was measured in 2321 participants (mean age 56.2, 58.6% women) of the Strong Heart Study, a prospective cohort of American Indians. Urinary arsenic species were measured using high-performance liquid chromatography coupled to inductively coupled plasma mass spectrometry. We identified DMPs that are potential mediators between arsenic and CVD. In a cross-species analysis, we compared those DMPs with differential liver DNA methylation following early-life arsenic exposure in the apoE knockout (apoE−/−) mouse model of atherosclerosis. Results: A total of 20 and 13 DMPs were potential mediators for CVD incidence and mortality, respectively, several of them annotated to genes related to diabetes. Eleven of these DMPs were similarly associated with incident CVD in 3 diverse prospective cohorts (Framingham Heart Study, Women’s Health Initiative, and Multi-Ethnic Study of Atherosclerosis). In the mouse model, differentially methylated regions in 20 of those genes and DMPs in 10 genes were associated with arsenic. Conclusions: Differential DNA methylation might be part of the biological link between arsenic and CVD. The gene functions suggest that diabetes might represent a relevant mechanism for arsenic-related cardiovascular risk in populations with a high burden of diabetes.

Urinary Zinc and Incident Type 2 Diabetes: Prospective Evidence From the Strong Heart Study.

Abstract: OBJECTIVE Hyperglycemia can increase urinary zinc excretion. We evaluated the association of higher urinary zinc level with new diagnosis of incident type 2 diabetes mellitus (T2DM) in adult populations with a high burden of T2DM from AZ, OK, and ND and SD. We also assessed the cross-sectional association of urinary zinc levels with prevalent prediabetes. RESEARCH DESIGN AND METHODS We included 1,339 adults free of T2DM at baseline (1989-1991) followed through 1998-1999 in the Strong Heart Study (SHS) and 1,905 family members of SHS participants followed as part of the Strong Heart Family Study (SHFS) through 2006-2009. RESULTS T2DM incidence was 14.7% (mean follow-up 6.6 years) in the SHS and 13.5% (mean follow-up 5.6 years) in the SHFS. After adjustment for sex, site, education, smoking status, BMI, and estimated glomerular filtration rate, the hazard ratio of T2DM in comparing 75th vs. 25th percentiles of urinary zinc distribution was 1.21 (95% CI 1.08, 1.36) in the SHS and 1.12 (0.96, 1.31) in the SHFS. These associations were attenuated but significant in the SHS after adjustment for HOMA of insulin resistance (HOMA-IR) score. With exclusion of participants with prediabetes at baseline, urinary zinc remained significantly associated with T2DM in the SHS. In cross-sectional analyses, prediabetes was associated with higher urinary zinc levels. CONCLUSIONS Urinary zinc levels were associated with T2DM incidence and prediabetes prevalence even after adjustment for HOMA-IR in populations with a high burden of T2DM. These results highlight the importance of zinc metabolism in diabetes development.

Elution with 1,2-Hexanediol Enables Coupling of ICPMS with Reversed-Pase Liquid Chromatography under Standard Conditions

Abstract: The inductively coupled plasma mass spectrometry (ICPMS) has been attracting increasing attention for many applications as an element-selective chromatographic detector. A major and fundamental limitation in coupling ICPMS with liquid chromatography is the limited compatibility with organic solvents, which has so far been addressed via a tedious approach, collectively referred to as the “organic ICPMS mode”, that can decrease detection sensitivity by up to 100-fold. Herein, we report 1,2-hexanediol as a new eluent in high-performance liquid chromatography–ICPMS which enables avoiding the current limitations. Unlike commonly used eluents, 1,2-hexanediol was remarkably compatible with ICPMS detection at high flow rates of 1.5 mL min–1 and concentrations of at least 30% v/v, respectively, under the standard conditions and instrumental setup normally used with 100% aqueous media. Sensitivity for all tested elements (P, S, Cl, Br, Se, and As) was enhanced with 10% v/v 1,2-hexanediol relative to that of 100% aqueous media by 1.5–7-fold depending on the element. Concentrations of 1,2-hexanediol at ≤30% v/v were superior in elution strength to concentrations at >90% v/v of the common organic phases, which greatly decreases the amount of carbon required to elute highly hydrophobic compounds such as lipids and steroids, enabling detection at ultra-trace levels. The proposed approach was applied to detect arsenic-containing fatty acids in spiked human urine, and detection limits of <0.01 μg As L–1 were achieved, which is >100-fold lower than those previously reported using the organic ICPMS mode. Nontargeted speciation analysis in Allium sativum revealed the presence of a large number of hydrophobic sulfur-containing metabolomic features at trace levels.

Development of a two-dimensional liquid chromatography-tandem mass-spectrometry method for the determination of vitamin D2 in mushrooms

Abstract: Abstract Different foods, especially mushrooms, are a valuable source of vitamin D2. However, published concentrations in mushrooms show large variabilities. One reason for this is certainly the high biological variability caused by growth conditions, and another could also be found in the analytical methodology. Therefore, this study aimed to develop a sensitive and highly selective two-dimensional liquid chromatography mass spectrometry (LC–MS/MS) method for vitamin D2 analysis in mushrooms. After validation, the method was applied to four different mushroom species. The developed method with a one-step extraction procedure showed a limit of detection of 0.01 µg vitamin D2/g dry mass (DM), a limit of quantification of 0.05 µg vitamin D2/g DM, and recovery rates between 87.6 and 94.8%. The total run time including the re-equilibration of the columns for the next injection was 7.5 min. After adding increased concentrations of pure substance to Pleurotus ostreatus , Lentinula edodes , and brown and white button mushrooms the standard addition plot showed excellent correlation coefficients ( R 2 ) of > 0.9994. Mean vitamin D2 concentrations were observed at 0.122 ± 0.007, 0.074 ± 0.005, 0.099 ± 0.007, and 0.073 ± 0.005 µg/g DM. The coefficient of variation (CV) was between 5.1 and 7.6%. This well-optimized, sensitive LC–MS/MS method, with a fast and simple sample preparation and a short run time, can be applied to future studies especially in different mushroom species with variable growing conditions. This will improve our knowledge about the vitamin D2 content in mushrooms. Graphical abstract

High level of selenium exposure in the Strong Heart Study: a cause for incident cardiovascular disease?

Abstract: Increasing evidence suggests that high selenium (Se) exposure is associated with adverse health effects. However, limited evidence exists on the association of Se exposure with cardiovascular disease (CVD), especially in communities affected by high naturally occurring Se in environmental media. We evaluated the prospective association between urinary Se levels and CVD incidence and mortality for 2,727 American Indian adults who participated in the Strong Heart Study, with urinary Se levels measured at baseline (1989-1991) and CVD outcomes ascertained through 2017. The median (interquartile range) of urinary Se was 49.0 (36.7, 67.4) µg/g creatinine. The multivariable adjusted hazard ratios (95%CI) of incident CVD, coronary heart disease, and stroke comparing the 75th vs. 25th percentile of urinary Se distributions were 1.11 (1.01, 1.22), 1.05 (0.94, 1.17), and 1.08 (0.88, 1.33), respectively. In flexible dose-response models, increased risk for CVD incidence was only observed when urinary Se level exceeded 60 µg/g creatinine. For CVD mortality, a non-statistically significant U-shaped relationship was found across urinary Se levels. There was no evidence of effect modification by other urinary metal/metalloid levels. Our observation leads to the hypothesis that elevated Se exposure is a risk factor for CVD, especially in Se-replete populations.

Lipid Metabolites and Arsenic Methylation in the Strong Heart Family Study: An Untargeted Metabolomics Approach

Abstract: Background and Aim. There are no safe levels of arsenic (As) exposure. Inorganic As (iAs) is methylated into mono-methyl (MMA) and dimethyl (DMA) arsenicals; methylation to DMA facilitates urinary As elimination and potentially reduces As-related toxicity. Our goal is to identify metabolites associated with As methylation patterns, as measured by the As species (iAs%, MMA%, and DMA%), and As methylation indices (primary methylation index (PMI:MMA/iAs) and secondary methylation index (SMI:DMA/MMA) which are less influenced by As exposure levels. Methods. This study leveraged urinary As and untargeted lipid metabolite data from 1,838 participants in the Strong Heart Family Study, which recruited adult participants from 12 American Indian communities in Arizona, Oklahoma, and North/South Dakota in 2001–2003. Metabolite data was performed on plasma samples using a quadrupole time-of-flight mass spectrometer. We used linear regression models to evaluate the cross-sectional associations between lipid metabolites and As methylation patterns and Mummichog for metabolic pathways analysis. Results. 1543 (543 identified, 1000 unidentified) lipid metabolic features were included. From 1,088 lipid metabolites that were significantly associated (pFDR&#x3c;0.05) with at least one As species in linear regression models, 531 were associated with all three species, and 541 overlapped with MMA%, DMA% and SMI. Pathway enrichment analyses of associated metabolites (p&#x3c;0.1) with &#x2265;3 significant lipid metabolites in the pathway showed effects in 12 pathways that were associated with As methylation markers. Although there were only 3 pathways that were associated with PMI, (lineolate, fatty acid activation, and carnitine shuttle metabolism), these same pathways were associated with all 5 measures of As methylation. Conclusions. We found that associations between As methylation indices and lipid metabolites predominantly affect the secondary methylation of As, from MMA to DMA along fatty acid metabolism pathways. Future work will investigate if these metabolites are also associated with adverse health outcomes. Keywords: Arsenic methylation, metabolomics

Corrosion of Passive Aluminum Anodes in a Chloroaluminate Deep Eutectic Solvent for Secondary Batteries: The Bad, the Good, and the Ugly

Abstract: The passivity of aluminum is detrimental to its performance as an anode in batteries. Soaking of native oxide-covered aluminum in a chloroaluminate deep eutectic solvent gradually activates the electrode surface, which is reflected in a continuously decreasing open circuit potential. The underlying processes were studied by analyzing the 3 to 7 nm thick layer of native oxide after increasing periods of soaking with secondary neutral mass spectrometry, X-ray photoelectron spectroscopy, and energy-dispersive spectroscopy in a transmission electron microscope. They consistently show permeation of electrolyte species into the layer associated with gradual swelling. After extended periods of soaking at open circuit potentials, local deposits of a range of foreign metals have been found in scanning electron microscopy images of the electrode surface. The pitting corrosion is caused by trace metal ion impurities present in the electrolyte and results in highly nonuniform current density distribution during discharge/charge cycling of battery cells as shown by local deposits of aluminum. The processes during soaking at open circuit potentials have been monitored by electrochemical impedance spectroscopy and could be analyzed by fitting an equivalent circuit model for pitting corrosion.

Urinary Zinc and Incident Diabetes: Prospective Evidence from the Strong Heart Study

Abstract: Background and aim: Diabetes, a chronic metabolic condition, is a major risk factor for cardiovascular disease. Hyperglycaemia can increase zinc excretion due to its insulin-mimetic function. We aimed to assess the association between urinary zinc and incident diabetes in two populations with a high burden of diabetes from Arizona, Oklahoma, North Dakota and South Dakota. Methods: Baseline urinary zinc was measured using Inductively Coupled Plasma Mass Spectrometry (ICP-MS) in 1,339 adults free of diabetes at baseline (1989-1991) and followed through 1998-1999 in the Strong Heart Study (SHS) and in 1,905 family members of SHS participants free of diabetes at baseline (1998-1999) followed as part of the Strong Heart Family Study (SHFS) through 2006-2009. Results: In the SHS, diabetes incidence was 14.7% (mean follow-up 6.6 years). Median urinary zinc was 0.46 mg/g and 0.50 mg/g for participants without and with diabetes, respectively. After adjustment for sex, site, education, smoking status, and BMI, the hazard ratio (HR) (95%CI) of diabetes comparing IQR percentiles of urinary zinc distribution was 1.21 (1.08, 1.36). In the SHFS, diabetes incidence was 13.5% (mean follow-up 5.6 years). Median urinary zinc was 0.59 and 0.65 for participants without and with diabetes, respectively. The HR(95%CI) in the SHFS was 1.12 (0.96, 1.31). These associations were attenuated in the SHS after adjustment for insulin levels, fasting glucose levels and HOMA-IR score. Excluding participants with prediabetes at baseline, the association of urinary zinc with incident diabetes remained significant in the SHS and suggestive for the SHFS. Conclusions: Baseline urinary zinc concentrations were associated with diabetes incidence even after adjustment for fasting plasma insulin and plasma glucose levels in adult populations with a high burden of diabetes. These results highlight the need for greater understanding of zinc metabolism in diabetes pathology and identify possible treatment approaches for diabetes prevention.

Changes in cellular ferritin distribution of human brain tissue during autolysis revealed using analytical electron microscopy

Abstract: Iron in the human brain is stored in the cores of ferritin proteins. Excess iron has been implicated in neurological disorders, so a careful balance of the iron concentration is thought to be essential for human health. Though it is known that oligodendrocytes contain most of the brain ferritin, followed by other glial cells and neurons, little is known about changes in the cellular ferritin distribution when total iron load changes. Moreover, changes in the number of filled ferritins or in their cellular distribution during autolysis have not been revealed yet. To reveal these changes, we examined brain samples taken from six deceased humans at different post mortem times. To compare samples with different ferritin content, the samples included the frontal gray and frontal white matter, which store a low amount of iron, and the putamen and globus pallidus, which store a high amount of iron. We quantified the number of loaded ferritin cores from iron L - elemental maps obtained with energy filtered transmission electron microscopy and compared this number to the iron concentrations determined using inductively coupled plasma mass spectrometry and quantitative magnetic resonance imaging. The more loaded ferritin cores we found in the tissues, the higher the proportion of ferritins found in neurons instead of glial cells, indicating that total ferritin load scales with the proportion of ferritin that is located in neurons. Second, we found a statistically significant correlation between the post mortem interval and the amount / concentration of loaded ferritins and found that this concentration is highly dependent on the post mortem interval (PMI): the longer the PMI, the lower the ferritin concentration found in a sample. Third, the longer the post mortem interval, the higher the proportion of ferritins found in neurons instead of glial cells, indicating that ferritin loss during autolysis affects neurons and glial cells at different rates.

Cohort profile: The Pregnancy, Arsenic, and Immune Response (PAIR) Study, a longitudinal pregnancy and birth cohort in rural northern Bangladesh

Abstract: Purpose: Arsenic exposure and micronutrient deficiencies may alter immune reactivity to influenza vaccination in pregnant women, transplacental transfer of maternal antibodies to the fetus, and maternal and infant acute morbidity. The Pregnancy, Arsenic, and Immune Response (PAIR) Study is a longitudinal pregnancy and birth cohort designed to assess whether arsenic exposure and micronutrient deficiencies alter maternal or newborn immunity and acute morbidity following maternal seasonal influenza vaccination during pregnancy. Participants: We enrolled 784 pregnant women in rural Gaibandha District in northern Bangladesh between October 2018 and March 2019. Women received a quadrivalent seasonal inactivated influenza vaccine at enrollment in the late first or early second trimester between 11 and 17 weeks of gestational age. Follow-up included up to 13 visits between enrollment and three months postpartum as well as weekly telephone surveillance to ascertain influenza-like illness and other acute morbidity symptoms in women and infants. Tube well drinking water and urine specimens were collected to assess arsenic exposure. Of 784 women who enrolled, 736 (93.9%) delivered live births and 551 (70.3%) completed follow-up visit to three months postpartum. Findings to Date: Arsenic was [≥]0.02 g/L in 97.9% of water specimens collected from participants at enrollment. The medians (interquartile ranges) of water and urinary arsenic were 5.1 (0.5-25.1) g/L and 33.1 (19.6-56.5) g/L, respectively. Water and urinary arsenic were strongly correlated (Spearman's {rho}=0.72) among women with water arsenic [≥] median but weakly correlated ({rho}=0.18) among women with water arsenic < median. Future Plans: The PAIR Study is well positioned to examine the effects of low-moderate arsenic exposure and micronutrient deficiencies on immune outcomes in women and infants. Registration: NCT03930017

Differential uranium exposure and its association with hypertension and elevated blood pressure in American Indian communities in the Strong Heart Family Study

Abstract: Background: Urinary uranium (U) is present at higher concentrations in American Indian (AI) participants in the Strong Heart Study compared to the general US population. Cardiovascular disease is the leading cause of death among American Indians, of which hypertension is an important risk factor. We evaluated the association between U exposure and incident hypertension and increased blood pressure (BP) among Strong Heart Family Study (SHFS) participants. Methods: We included 1453 SHFS participants with baseline visits in 1998-1999 or 2001–2003, and follow-up visits in 2001-2003 and/or 2006–2009. We estimated the association of urinary U exposure with changes in systolic BP and diastolic BP levels using linear regressions, and hypertension incidence using Poisson regression with robust variance, accounting for family clustering. Results: Median (IQR) urinary uranium levels were 0.029 (0.013, 0.059) &#x3bc;g/g creatinine. At follow-up, 17.4% of participants developed hypertension. After adjustment for sociodemographic variables, eGFR, pre-diabetes status, and BMI, comparing the highest to lowest urinary uranium quartiles, the RR (95% CI) of incident hypertension was 1.38 (1.00, 1.91) and the mean difference (95% CI) in systolic BP levels between baseline and follow-up was -2.00 (-3.83, -0.16) mmHg. After adjustment for urinary cadmium and arsenic, the corresponding RR (95% CI) was 1.44 (1.04, 1.99) and the mean difference (95% CI) for systolic BP between baseline and follow-up was -1.48 (-3.32, 0.37) mmHg. The association between uranium and blood pressure levels at follow-up was non-linear, with an increased risk at higher urinary uranium levels. Conclusions: These findings suggest moderate increased risk for hypertension at urinary uranium levels greater than 0.06 &#x3bc;g/g, typical of the Southwest and Great Plains, furthermore a potential association with higher systolic BP levels and higher uranium exposure levels. Further work is needed to assess the cardiovascular effects of chronic uranium exposure in US populations. Keywords: Uranium, hypertension, blood pressure