Isotope Dilution Research Articles

A comparative study on indicators of vitamin A status and risk factors for sensitivity and specificity of the methods to detect vitamin A deficiency

BackgroundSerum retinol (SR) and retinol-binding protein (RBP) are commonly used indicators, but they are affected by infections and inflammation. This study aimed to assess the sensitivity and specificity of VA indicators to detect vitamin A deficiency (VAD) in 36–59-month-old children living in a rural area in Burkina Faso.MethodsIn a community-based study, two cross-sectional surveys were carried out from November 2016 to September 2017 in the health district of Dandé in Burkina Faso. The surveys included 115 children 36–59 months old. Indicators of VA and inflammation assessed in all children included SR, RBP and total liver VA reserves (TLR) estimated by retinol isotope dilution, and inflammation markers (C-reactive protein (CRP) and alpha 1-acid glycoprotein (AGP)). We calculated the sensitivity, specificity, positive and negative predictive values. In addition, the effects of inflammation, helminth infection, and season on sensitivity and specificity were assessed.ResultsThe prevalence of VAD assessed by SR (< 0.7 µmol/L), RBP (< 0.7 µmol/L), and TLR (< 0.1 µmol/g liver) were, respectively, 30.9%, 33.3%, and 0%. Compared to TLR, the specificity, positive predictive value, and negative predictive value of SR were 71.1%, 0%, and 100%, and of RBP, were 68.9%, 0%, and 100%, respectively. The sensitivity was indeterminable for SR and RBP. The specificity of SR and RBP was lower during the dry season. Elevated CRP (> 5.0 mg/L) and AGP (> 1.0 g/L) were detected in 1.9% and 28.6% of children, respectively. The adjustment of VA indicators for inflammation improved SR’s specificity to 75.9% and decreased RBP’s specificity to 67.8%.ConclusionNo cases of VAD were identified by TLR. However, (inflammation-adjusted) SR and RBP had varying accuracy in the estimation of VAD.Trial registrationThe study was registered, retrospectively, on 22 March 2018 as a clinical trial with the Pan African Clinical Trials Registry under the number Cochrane South Africa; PACTR201803002999356.

Initial Validation of a Soil-Based Mass-Balance Approach for Empirical Monitoring of Enhanced Rock Weathering Rates.

Enhanced rock weathering (ERW) is a promising scalable and cost-effective carbon dioxide removal (CDR) strategy with significant environmental and agronomic co-benefits. A major barrier to large-scale implementation of ERW is a robust monitoring, reporting, and verification (MRV) framework. To successfully quantify the amount of carbon dioxide removed by ERW, MRV must be accurate, precise, and cost-effective. Here, we outline a mass-balance-based method in which analysis of the chemical composition of soil samples is used to track in situ silicate rock weathering. We show that signal-to-noise issues of in situ soil analysis can be mitigated by using isotope-dilution mass spectrometry to reduce analytical error. We implement a proof-of-concept experiment demonstrating the method in controlled mesocosms. In our experiment, a basalt rock feedstock is added to soil columns containing the cereal crop Sorghum bicolor at a rate equivalent to 50 t ha-1. Using our approach, we calculate rock weathering corresponding to an average initial CDR value of 1.44 ± 0.27 tCO2eq ha-1 from our experiments after 235 days, within error of an independent estimate calculated using conventional elemental budgeting of reaction products. Our method provides a robust time-integrated estimate of initial CDR, to feed into models that track and validate large-scale carbon removal through ERW.

Microbe-derived uremic solutes enhance thrombosis potential in the host.

Alterations in gut microbial composition and function have been linked to numerous diseases. Identifying microbial pathways responsible for producing molecules that adversely impact the host is an important first step in the development of therapeutic interventions. Here, we first use large-scale clinical observations to link blood levels of defined microbial products to cardiovascular disease risks. Notably, the previously identified uremic toxins p-cresol sulfate and indoxyl sulfate were shown to predict 5-year mortality risks. After identifying the microbes and microbial enzymes involved in the generation of these uremic toxins, we used bioengineering technologies coupled with colonization of germ-free mice to show that the gut microbial genes that generate p-cresol and indole are sufficient to confer p-cresol sulfate and indoxyl sulfate formation, and a pro-thrombotic phenotype in vivo. The findings and tools developed serve as a critical step in both the study and targeting of these gut microbial pathways in vivo.

Simultaneous determination of ergothioneine, selenoneine, and their methylated metabolites in human blood using ID-LC-MS/MS.

Ergothioneine and selenoneine are structurally related dietary antioxidants and cytoprotectants that may help prevent several chronic diseases associated with inflammation and aging. Both compounds share pharmacokinetic characteristics such as cellular uptake through the ergothioneine transporter, accumulation in red blood cells, and biotransformation to methylated metabolites. A rapid, sensitive, specific, precise, and cost-effective analytical method is required to further investigate the potential health benefits of these compounds, individually or combined, in large epidemiological studies. We developed and validated an isotope-dilution liquid chromatography tandem mass spectrometry (ID-LC-MS/MS) method for the simultaneous specific quantification of these analytes in human blood following a simple sample preparation consisting of dilution in aqueous dithiothreitol followed by centrifugal filtration. Chromatographic separation of the analytes is achieved using a reversed-phase chromatography within an 8-min run. Analyte detection is performed using triple quadrupole mass spectrometry in multiple reaction monitoring mode. Each analyte is quantified against its corresponding isotopically labeled internal standard either commercially available or synthesized in-house (77Se-labeled selenoneine compounds). The validated method demonstrates excellent linearity and very good precision (all CV < 10%). Matrix effects are minimal, suggesting that this method could easily be adapted to other matrices. Freeze/thaw cycles have little effect on methylated metabolites but significantly reduced concentrations of the parent compounds. The method was successfully applied to a small set of volunteer blood samples containing low levels of the analytes. The developed ID-LC-MS/MS method opens new avenues for exploring the roles of these bioactive compounds and their metabolites in human health and disease.

High-resolution chronostratigraphy of late Mesozoic sequences in northern North China: Implications for the linkages among intracontinental orogeny, volcanism, Jehol Biota, and Pacific plate subduction

Abstract Subduction of the paleo-Pacific plate during the late Mesozoic is thought to have been responsible for the destruction of the North China craton, manifested by intense volcanism, lithospheric deformation, and dramatic changes in surface morphology and terrestrial ecosystems. However, the timing and correlations of these consequential events remain obscure. This issue was addressed here by carrying out a high-resolution geochronologic study on the Upper Jurassic–Lower Cretaceous sequences of the Luanping basin, northern Hebei Province, China. Secondary ion mass spectrometry (SIMS) and chemical abrasion–isotope dilution–isotope ratio mass spectrometry (CA-ID-IRMS) zircon U-Pb ages from samples near the boundaries of the stratigraphic units help to redefine the chronostratigraphic framework of this basin and more importantly reveal that the second phase of the Yanshanian orogeny, representing a tectonic transition from flat to steep subduction of the paleo-Pacific plate, occurred within 0.87 ± 0.10 m.y. between 134.162 ± 0.091 Ma and 133.295 ± 0.043 Ma. Crustal extension then followed and resulted in development of rift basins and vigorous volcanism. The Jehol Biota came into being in Lower Cretaceous successions formed after ca. 130 Ma. The late Mesozoic Luanping basin therefore records how the subduction of the paleo-Pacific plate drove intracontinental orogeny, volcanism, basin development, and ecosystem evolution.

Distribution and transition of aroma-active compounds in dark chocolate model systems under conching conditions

Understanding mechanisms inside the conche is inevitable for targeted conching. Therefore, distribution and transition of aroma-active volatiles (acetic acid, benzaldehyde, (R,S)-(±)-linalool, 2,3,5,6-tetramethylpyrazine, 2-phenylethanol, and 2-phenylethyl acetate) between the different components of dark chocolate (cocoa butter, cocoa particles, sugar particles) were studied. Different model systems were designed and aroma-analytically analyzed by stable isotope dilution analysis. Diffusion mechanisms of selected aroma-active compounds within the chocolate mass depended on their physico-chemical properties and the mass composition, such as fat content and crystallization state of the sugar particles. The compound accumulation in the fat phase increased with decreasing compound polarity and increasing fat content. In the presence of cocoa particles, a 1.5-fold fat content resulted in a 1.6-fold higher proportional acetic acid concentration in the fat phase. Further, total acetic acid concentrations raised in all model systems containing crystalline sugar or cocoa particles (by 13.8–56.9 %), indicating the formation of free acetic acid.

Development and Validation of a Stable Isotope Dilution Headspace–SPME–GC/MS Method for the Determination of Vanillin in Fragrant Vegetable Oils

It has been reported that vanillin has been intentionally added to enhance the taste and flavor of low-quality vegetable oils. Therefore, it is crucial to investigate the accurate concentrations of vanillin in three types of fragrant vegetable oils commonly consumed in China. In this study, a method has been developed for the quantification of vanillin in commercial fragrant vegetable oils using the stable isotope dilution assay (SIDA) and headspace–solid-phase microextraction (HS–SPME) coupled with gas chromatography/mass spectrometry (GC/MS). The limit of detection (LOD) and limit of quantification (LOQ) of the analyte were determined to be 20 µg kg−1 and 50 µg kg−1, respectively. The validation study demonstrated that the recoveries ranged from 89% to 101%, with intra-day and inter-day precision being less than 7.46%. A survey of 80 commercially available fragrant vegetable oils was performed using the present method. Vanillin was found to be widely present in fragrant vegetable oils, with sesame oils showing the highest average content (842.6 µg kg−1), followed by rapeseed oils (262.1 µg kg−1) and peanut oils (115.0 µg kg−1). The results indicate that the proposed method is a simple, accurate, and eco-friendly approach for determining the presences of vanillin in fragrant vegetable oils.

DBS are suitable for 1,5-anhydroglucitol monitoring in GSD1b and G6PC3-deficient patients taking SGLT2 inhibitors to treat neutropenia

Glycogen storage disease type Ib (GSD1b) and G6PC3-deficiency are rare autosomal recessive diseases caused by inactivating mutations in SLC37A4 (coding for G6PT) and G6PC3, respectively. Both diseases are characterized by neutropenia and neutrophil dysfunction due to the intracellular accumulation of 1,5-anhydroglucitol-6-phosphate (1,5-AG6P), a potent inhibitor of hexokinases. We recently showed that the use of SGLT2 inhibitor therapy to reduce tubular reabsorption of its precursor, 1,5-anhydroglucitol (1,5-AG), a glucose analog present in blood, successfully restored the neutropenia and neutrophil function in G6PC3-deficient and GSD1b patients. The intra-individual variability of response to the treatment and the need to adjust the dose during treatment, especially in pediatric populations, can only be efficiently optimized if the concentration of 1,5-AG in blood is monitored during treatment, together with the patients' clinical signs and symptoms. Monitoring the 1,5-AG levels would be greatly simplified if it could be performed on dry blood spots (DBS) which are easy to collect, store and transport. The challenge is to know if a suitable method can be developed to perform accurate and reproducible assays for 1,5-AG using DBS. Here, we describe and validate an assay that quantifies 1,5-AG in DBS using isotopic dilution quantitation by LC-MS/MS that should greatly facilitate patients' follow-up. 1,5-AG levels measured in plasma and DBS give comparable values. This assay was used to monitor the levels of 1,5-AG in DBS from 3 G6PC3-deficient and 6 GSD1b patients during treatment with SGLT2 inhibitors. We recommend this approach to verify the adequate therapeutical response and compliance to the treatment in G6PC3-deficient and GSD1b patients treated with SGLT2 inhibitors.

Oxidative/nitrosative stress increased the risk of recurrent pregnancy loss–Taiwan Recurrent Pregnancy Loss and Environmental Study (TREPLES)

ObjectiveOxidative stress biomarkers (OSBs) may be strongly associated with disease progression and recurrent pregnancy loss (RPL). However, the research on associations of most OSBs (e.g., 8-nitroguanine [8-NO2Gua] and 4-hydroxy-2-nonenal-mercapturic acid [HNE-MA]) with RPL is limited. Therefore, we aimed to investigate the effect of OSBs exposure on RPL risk by performing a case-control study. Material and methodsWe use our established dataset, Taiwan Recurrent Pregnancy Loss and Environmental Study (TREPLES), which included 514 Taiwanese reproductive age women (aged 20–50 years; 397 cases and 117 controls) from National Cheng Kung University Hospital. RPL is clinically defined by a history of two or more consecutive miscarriages, where a miscarriage is defined as the termination of pregnancy before 20 weeks of gestation. The urinary levels of several OSBs (e.g., 8-hydroxy-2′-deoxyguanosine [8-OHdG], 8-NO2Gua, 8-isoprostaglandin F2α [8-isoPGF2α], and HNE-MA) and malondialdehyde (MDA) were measured using isotope dilution liquid chromatography-tandem mass spectrometry and thiobarbituric acid reactive substances, respectively. ResultsThe median levels of 8-NO2Gua (6.15 vs. 3.76 ng/mL) and HNE-MA (30.12 and 21.54 ng/mL) were significantly higher in the RPL group than in the control group. By categorizing the OSBs data into tertiles, after we adjusted for age and urine creatinine levels discovered that the RPL risk associated with 8-NO2Gua and HNE-MA levels in the third tertile were approximately 2 times higher than those in the first tertile (8-NO2Gua, adjusted OR = 3.27, 95 % CI = 1.66–6.43; HNE-MA, adjusted OR = 1.96, 95 % CI = 1.05–3.64; p < 0.05). These findings suggest that the oxidative stress biomarkers of 8-NO2Gua and HNE-MA are risk factors for RPL. ConclusionOur findings indicate that specific OSBs are associated with an increased RPL risk, suggesting that reducing OSB levels can improve RPL risk. Nevertheless, more studies on preventive medicine are required to understand the exposure sources and adverse outcome pathways of OSBs associated with RPL.

Identification of ethyl vanillin in strawberry (Fragaria × ananassa) using a targeted metabolomics strategy: From artificial to natural

Improving flavor can be an important goal of strawberry through breeding that is enhanced through the accurate identification and quantification of flavor compounds. Herein, a targeted metabolomics strategy was developed using liquid–liquid extraction, an in-house standard database, and GC–MS/MS analysis. The database consisted of key food odorants (KFOs), artificial flavor compounds (AFCs) and volatiles. A total of 131 flavor compounds were accurately identified in Medallion® ‘FL 16.30-128′ strawberry. Importantly, ethyl vanillin was identified for the first time in natural food. Multiple techniques, including GC–MS, GC–MS/MS and UPLC-MS/MS were applied to ensure the identification. The ethyl vanillin in the Medallion® samples were determined in a range of concentrations from 0.070 ± 0.0006 µg/kg to 0.1372 ± 0.0014 µg/kg by using stable isotope dilution analysis. The identification of ethyl vanillin in strawberry implys the future commercial use a natural flavor compound and the potential to identify genes and proteins associated with its biosynthesis.

U–Pb age constraints on the Carboniferous–Permian transition in continental basins of eastern equatorial Pangaea (France): implications for the depositional history and correlations across the late Variscan Belt

Intramontane late Carboniferous–Permian basins of western Europe developed during the latest orogenic stages of the Variscan Mountain Belt in eastern Pangaea, at equatorial palaeolatitudes. Their stratigraphic framework is mainly based on continental subdivisions (e.g. Stephanian and Autunian continental stages), which can be contentious owing to biostratigraphic biases, resulting in long-distance diachronous subdivisions. To provide precise inter-basinal and global correlations to the internationally recognized chronostratigraphic marine stages, this study reports new U–Pb geochronology from the Aumance and Decize–La Machine basins, located in the northern French Massif Central. Zircon grains extracted from three volcanic ash-fall layers give weighted mean 206 Pb/ 238 U ages of 299.11 ± 0.35, 298.73 ± 0.36 and 298.59 ± 0.35 Ma (2 σ total propagated uncertainty) by the chemical abrasion isotope dilution thermal ionization mass spectrometry method, coinciding with the Carboniferous–Permian transition (Gzhelian and Asselian stages). These ages imply that the northern Massif Central basins developed synchronously in relatively short periods of time (&lt;10 myr), reflecting substantial sedimentation rates. Finally, the new chronology of infilling of these basins confirms that they were connected during the late Carboniferous and early Permian periods, improving the knowledge on the late orogenic Variscan geodynamic setting in this area. Supplementary material: Operating conditions and complete analytical results are available at https://doi.org/10.6084/m9.figshare.c.6805228

Contribution of Key Odorants from Skins, Seeds, and Stems to the Aroma of Chardonnay Marc: A Valuable Coproduct of the Wine Industry.

Chardonnay marc, a co-product of the wine making industry, has recently garnered attention due to its health-promoting properties and is growing in popularity as a potential healthy and flavorful food ingredient. While previous studies have characterized the odorants in marc skins and identified the key odorants in marc seeds, the key odorants in the skins and stems and the contribution of each component to the whole marc aroma remains unknown. In this study, 27 odorants were identified in marc stems using solvent-assisted flavor evaporation and aroma extract dilution analysis. Four odorants were quantitated employing stable isotope dilution assays, and odor activity values (OAVs) were calculated. An odor simulation model prepared using odorants with OAVs > 1 sensorially matched the aroma of the marc stems. Omission studies showed that 3-methylnonane-2,4-dione, ethyl octanoate, oct-1-en-3-one, (2E,4E)-deca-2,4-dienal, (2E,4E)-nona-2,4-dienal, β-ionone, linalool, hexanal, HDMF, and 3-(methylsulfonyl)propanal were the key odorants in marc skins, while hexanal and 3-methylnonane-2,4-dione were the key odorants in marc stems. Mass balance studies suggested that the skins were the main contributor to the hay, floral, and fruity attributes of the whole marc, the seeds contributed mostly to the fatty attribute, and the stems had a minor contribution.

Relationship of body mass index to percent body fat determined by deuterium isotopic dilution and impedancemetry among Tunisian schoolchildren.

This study aims to evaluate the relation of body mass index (BMI) to fat mass among children by two techniques impedancemetry and deuterium oxide dilution (D2O). This study was carried out in 156 schoolchildren aged between 8 and 11 years. The children received interrogation specifying lifestyle and food habits. Body composition was determined using the impedancemetry and D2O technique. The results showed a difference between the percentage of obese and overweight children according to BMIZ classification (30.1%), bioelectrical impedance method (14.7%) and D2O technique (42.9%). Despite the difference between the last two classifications, we found a significant correlation between body fat percentages determined by impedancemetry and D2O technique (r = 0.695, p<0.01). Bioelectrical impedance analysis underestimated %BF by 78.02% in overall children, by 70.05% in boys and by 84.73% in girls compared to D2O technique. This study has demonstrated that the percentage of overweight and obesity varied according the methods used. Further development of body composition methods is needed in children for the real determination of the obesity prevalence and therefore a better monitoring of this public health problem.

A shifty Toba magma reservoir: Improved eruption chronology and petrochronological evidence for lateral growth of a giant magma body

Polycyclic caldera complexes hold clues to understanding why some magmatic systems develop into supersized magma bodies and how they can recover to produce several caldera-forming eruptions. However, the geologic records of the transitions between successive caldera events are very often inaccessible due to limited preservation of eruptive products of inter-caldera activity, prompting the search for alternative archives of magma evolution such as accessory minerals. Here we applied multiple geochemical tools to study one of the most active caldera centres of the Quaternary, the Toba caldera complex in Sumatra (Indonesia), which produced at least four caldera-forming eruptions in the last 1.6 My, including the iconic Youngest Toba Tuff at 74 ka. We combined feldspar 40Ar/39Ar and zircon U–Pb geochronology of proximal pyroclastic deposits with glass and mineral chemistry of both the tuffs and distal marine tephra to revise the eruption chronology of Toba, obtaining new eruption ages of 1417 -31/+14 ka (zircon) or 1339 ± 39/39 ka (plagioclase, internal/full external 2σ uncertainty) for the Haranggaol Dacite Tuff, 783.81 ± 0.85/1.32 ka (sanidine) for Oldest Toba Tuff, and 503.61 ± 1.36/1.50 ka (sanidine) for Middle Toba Tuff. Isotope dilution thermal ionisation mass spectrometry (ID-TIMS) U–Pb crystallisation ages, trace element contents and Hf isotopic ratios of zircons illuminate changes in the shallow magma reservoir which saw near-continuous zircon crystallisation over 1.6 My. Prolonged build-ups to each eruption with highly scattered zircon trace element compositions reflect a complex, heterogeneous character of the shallow reservoir, without a clear temporal trend or indications of the eruption trigger. In contrast, hafnium isotopes in zircon display a pronounced shift towards unradiogenic values immediately after the OTT caldera collapse, followed by a gradual recovery to a baseline value of εHf = -7 at the time of YTT eruption, interpreted as a reflection of the shift in magma reservoir position corresponding to change in the character of assimilated crust. We can show in unprecedented detail how a large caldera collapse affects magma geochemistry; however, identification of patterns in the behaviour of the Toba system and making geochemistry-based predictions about its future development remain a challenge.

Measurement of Magnesium, Zinc, and Copper in Human Serum by Using Isotope Dilution Inductively Coupled Plasma Mass Spectrometry (ID ICP-MS).

In order to evaluate the reliability of the ID ICP-MS method for the measurement of magnesium, zinc, and copper in human serum, we investigated the traceability, precision, trueness, and uncertainty of the method. This method traces the contents of magnesium, zinc, and copper in human serum to the standard materials NIST SRM3131a, SRM3168a, and SRM3114 respectively, thus completing the traceability to SI unit. The repeatability of this method for measuring magnesium, zinc, and copper in the human serum reference material GBW09152 was found to be 0.2%, 0.7%, and 0.6% (n = 9), respectively. The measurement, when employed to measure the magnesium, zinc, and copper in standard materials, had caused a maximum deviation of less than 0.88%, 1.35%, and 1.15%, respectively. The measurement results are within the stated uncertainty range of standard materials. The expanded uncertainties were 0.2 mg·kg-1, 0.04 mg·kg-1, and 0.08 mg·kg-1 (K = 2) for magnesium, zinc, and copper, respectively. Therefore, this method has high trueness, good reproducibility, and simple operation and is suitable for tracing the values of magnesium, zinc, and copper in human serum.

U–Pb zircon ages from tuffaceous beds in the Terreneuvian to Cambrian Series 2 sections of Avalonian southern New Brunswick, Canada: new constraints on chronostratigraphic correlations and the Cambrian time scale

Abstract Avalonian sections in the Saint John area, southern New Brunswick, have long contributed to global understanding of Cambrian chronostratigraphy. A tuffaceous bed in the Ratcliffe Brook Formation (RBF) in the Somerset Street section dated at c. 531 Ma has traditionally been considered to post-date small shelly fossils attributed to the Watsonella crosbyi Zone in the Hanford Brook section. A fine-grained tuffaceous bed approximately 8 m stratigraphically lower in the Somerset Street section yields a chemical abrasion isotope dilution–thermal ionization mass spectrometry zircon age of 532.3 ± 0.3 Ma; a tuffaceous carbonate unit in the lower RBF in Hanford Brook gives an age of 531.5 ± 0.3 Ma. Crystal and crystal-lithic tuff beds near the top of the RBF yield ages of 520.3 ± 0.3 Ma (in Hanford Brook) and 519.1 ± 0.3 Ma (in Ratcliffe Brook). The new ages confirm the correlation between the Somerset Street and Hanford Brook sections based on acritarchs and make the association of small shelly fossils in the Hanford Brook section younger than 531 Ma. This result is relevant to ongoing discussions on the age of the base of undefined Cambrian Stage 2. The radiometric ages also support a young age for the upper part of the RBF, perhaps extending into Epoch 2.

U–Pb zircon ages from tuffaceous beds in the Terreneuvian to Cambrian Series 2 sections of Avalonian southern New Brunswick, Canada: new constraints on chronostratigraphic correlations and the Cambrian time scale

Abstract Avalonian sections in the Saint John area, southern New Brunswick, have long contributed to global understanding of Cambrian chronostratigraphy. A tuffaceous bed in the Ratcliffe Brook Formation (RBF) in the Somerset Street section dated at c. 531 Ma has traditionally been considered to post-date small shelly fossils attributed to the Watsonella crosbyi Zone in the Hanford Brook section. A fine-grained tuffaceous bed approximately 8 m stratigraphically lower in the Somerset Street section yields a chemical abrasion isotope dilution–thermal ionization mass spectrometry zircon age of 532.3 ± 0.3 Ma; a tuffaceous carbonate unit in the lower RBF in Hanford Brook gives an age of 531.5 ± 0.3 Ma. Crystal and crystal-lithic tuff beds near the top of the RBF yield ages of 520.3 ± 0.3 Ma (in Hanford Brook) and 519.1 ± 0.3 Ma (in Ratcliffe Brook). The new ages confirm the correlation between the Somerset Street and Hanford Brook sections based on acritarchs and make the association of small shelly fossils in the Hanford Brook section younger than 531 Ma. This result is relevant to ongoing discussions on the age of the base of undefined Cambrian Stage 2. The radiometric ages also support a young age for the upper part of the RBF, perhaps extending into Epoch 2.

Urinary Glyphosate, 2,4-D and DEET Biomarkers in Relation to Neurobehavioral Performance in Ecuadorian Adolescents in the ESPINA Cohort.

Herbicides are the most used class of pesticides worldwide, and insect repellents are widely used globally. Yet, there is a dearth of studies characterizing the associations between these chemical groups and human neurobehavior. Experimental studies suggest that glyphosate and 2,4-dichlorophenoxyacetic acid (2,4-D) herbicides can affect neurobehavior and the cholinergic and glutamatergic pathways in the brain. We aim to assess whether herbicides and insect repellents are associated with neurobehavioral performance in adolescents. We assessed 519 participants (11-17 years of age) living in agricultural communities in Ecuador. We quantified urinary concentrations of glyphosate, 2,4-D, and two N,N-diethyl-meta-toluamide (DEET) insect repellent metabolites [3-(diethylcarbamoyl)benzoic acid (DCBA) and 3-(ethylcarbamoyl)benzoic acid (ECBA)] using isotope-dilution mass spectrometry. We assessed neurobehavioral performance using 9 subtests across 5 domains (attention/inhibitory control, memory/learning, language, visuospatial processing, and social perception). We characterized the associations using generalized estimating equations and multiple imputation for metabolites below detection limits. Models were adjusted for demographic and anthropometric characteristics, urinary creatinine, and sexual maturation. Mediation by salivary cortisol, dehydroepiandrosterone, , and testosterone was assessed using structural equation modeling. The mean of each neurobehavioral domain score was between 7.0 and 8.7 [standard deviation (SD) range: 2.0-2.3]. Glyphosate was detected in 98.3% of participants, 2,4-D in 66.2%, DCBA in 63.3%, and ECBA in 33.4%. 2,4-D was negatively associated with all neurobehavioral domains, but statistically significant associations were observed with attention/inhibition [score difference per 50% higher metabolite concentration 95% confidence interval (CI): , ], language [ (95% CI: , )], and memory/learning [ (95% CI: , 0.01)]. Glyphosate had a statistically significant negative association only with social perception [ (95% CI: , )]. DEET metabolites were not associated with neurobehavioral performance. Mediation by gender and adrenal hormones was not observed. This study describes worse neurobehavioral performance associated with herbicide exposures in adolescents, particularly with 2,4-D. Replication of these findings among other pediatric and adult populations is needed. https://doi.org/10.1289/EHP11383.

Impact of classical home cooking processes on chlordecone and chlordecol concentrations in animal products originated from French West Indies

Behaviors of chlordecone (CLD) and chlordecol (CLDOH) during three home classical cooking processes (pan, oven, and microwave cooking) were assessed on a large variety of animal products (spiny lobster, crayfish, chicken, egg, pork and fish). Concentrations were measured by liquid chromatography coupled with mass spectrometer using isotopic dilution before and after home cooking process. Inter-species and intra-individual variability during microwave cooking, as well as the impact of cooking time and sample weight on CLD and CLDOH processing factors (PFs) were evaluated. In general, oven cooking (62% < PFs CLD <100%) and microwave cooking (16% < PFs CLD <102%) decreased CLD concentrations compared to the pre-cooked state. Matrix composition, as well as cooking time and sample weight, could be key parameters of cooking efficiencies. Moreover, low to moderate concentrations of CLDOH were occasionally quantified in cooked matrices. These data will be useful for risk assessment in this specific context.

Traceable value of immunoglobulin G against receptor-binding domain of SARS-CoV-2 confirmation and application to point-of-care testing system development.

A highly purified and bioactive immunoglobulin G monoclonal antibody against receptor-binding domain of SARS-CoV-2 (RBD-IgG-MAb) has been accurately quantified by amino acid determination using isotope dilution liquid chromatography-mass spectrometry. Absolute quantification of RBD-IgG-MAb was achieved by averaging 4 amino acid certified reference materials, which allows the quantitative value (66.1 ± 5.8 μg/L) to be traced to SI unit (mol). Afterwards, the RBD-IgG-MAb was employed as control and calibrationcompound for the development of a point-of-care testing (POCT) system based on colloidal gold lateral flow immunoassay, which aimed to rapidly and accurately detect the level of protective RBD-IgG after vaccination. Under the detection parameters, a sigmoidal curve has been plotted between signal intensity and the logarithmic concentration for quantitative detection with the limit of detection of about 0.39μg/mL. The relative standard deviations of intra-assay and inter-assay were lower than 2.3% and 14%, and the recoveries ranged from 87 to 100%, respectively. Fingertip blood samples from 37 volunteers after vaccination were analyzed by the POCT system; results showed that levels of RBD-IgG in 33 out of 37 samples ranged from 0.45 to 2.46μg/mL with the average level of 0.91μg/mL. The developed POCT system has been successfully established with the quantity-traceability RBD-IgG-MAb as control and calibration compound, and the scientific contribution of this work can be promoted to other areas.