Directly measuring octanol-air partition ratios using a gas chromatography retention time (GC-RT) method.

The octanol-air partition ratio (K) is a fundamental property used for screening chemicals for concern, depending on their potential to bioaccumulate and harm living systems. With millions of chemicals used in commerce, unfortunately, less than 800 compounds currently have experimentally measured K values due to limitations in traditional measurement techniques. We aimed to develop a direct gas chromatography retention time (GC-RT) method using a custom-packed column, with octanol as the stationary phase, for rapidly measuring K.

Fetal Hemodynamics, Early Survival, and Neurodevelopment in Patients With Cyanotic Congenital Heart Disease.

Background: Fetuses with cyanotic congenital heart disease (CHD) exhibit profound fetal circulatory disturbances that may affect early outcomes.

Objectives: This study sought to investigate the relationship between fetal hemodynamics and early survival and neurodevelopmental (ND) outcomes in patients with cyanotic CHD.

Methods: In this longitudinal observational study, fetuses with cyanotic CHD underwent late gestational fetal cardiovascular magnetic resonance (CMR) to measure vessel blood flow and oxygen content.

A method for measuring the bioaccessibility of polycyclic aromatic hydrocarbons in cell culture media.

Airborne polycyclic aromatic hydrocarbons (PAHs) and their derivatives are of particular concern for population health due to their abundance and toxicity via inhalation. Lung toxicity testing includes exposing lung epithelial cell lines to PAHs in a culture medium containing inorganic species, lipids, proteins, and other biochemicals where the cell response is influenced among others by the toxic chemical accessibility in the medium. While inhalation bioaccessibility of PAHs and other toxicants was previously studied in surrogate lung fluids, studies measuring bioaccessibility in cell culture media are rare.

Characterizing the Movement of Per- and Polyfluoroalkyl Substances in an Avian Aquatic-Terrestrial Food Web.

The movement of per- and polyfluoroalkyl substances (PFAS) through linked aquatic-terrestrial food webs is not well understood. Tree swallows () in such systems may be exposed to PFAS from multiple abiotic and/or biotic compartments. We show from fatty acid signatures and carbon stable isotopes that tree swallow nestlings in southwestern Ontario fed on both terrestrial and aquatic macroinvertebrates.

Trace Metals in Global Air: First Results from the GAPS and GAPS Megacities Networks.

Trace metals, as constituents of ambient air, can have impacts on human and environmental health. The Global Atmospheric Passive Sampling (GAPS) and GAPS Megacities (GAPS-MC) networks investigated trace metals in the air at 51 global locations by deploying polyurethane foam disk passive air samplers (PUF-PAS) for periods of 3-12 months. Aluminum and iron exhibited the highest concentrations in air ( = 3400 and 4630 ng/m, respectively), with notably elevated values at a rural site in Argentina thought to be impacted by resuspended soil.

Emissions and fate of organophosphate esters in outdoor urban environments.

Cities are drivers of the global economy, containing products and industries that emit many chemicals. Here, we use the Multimedia Urban Model (MUM) to estimate atmospheric emissions and fate of organophosphate esters (OPEs) from 19 global mega or major cities, finding that they collectively emitted ~81,000 kg yr of ∑OPEs in 2018. Typically, polar "mobile" compounds tend to partition to and be advected by water, while non-polar "bioaccumulative" chemicals do not.

Per- and polyfluoroalkyl substances and volatile methyl siloxanes in global air: Spatial and temporal trends.

The study reports on the atmospheric concentrations of per- and polyfluoroalkyl substances (PFAS) and volatile methyl siloxanes (VMS) measured using sorbent-impregnated polyurethane foam disks (SIPs) passive air samplers. New results are reported for samples collected in 2017, which extends temporal trend information to the period 2009-2017, for 21 sites where SIPs have been deployed since 2009. Among neutral PFAS, fluorotelomer alcohols (FTOHs) had higher concentrations than perfluoroalkane sulfonamides (FOSAs) and perfluoroalkane sulfonamido ethanols (FOSEs) with levels of ND‒228, ND‒15.

Genomic landscape of the DHA1 family in Candida auris and mapping substrate repertoire of CauMdr1.

The last decade has witnessed the rise of an extremely threatening healthcare-associated multidrug-resistant non-albicans Candida (NAC) species, Candida auris. Since besides target alterations, efflux mechanisms contribute maximally to antifungal resistance, it is imperative to investigate their contributions in this pathogen. Of note, within the major facilitator superfamily (MFS) of efflux pumps, drug/H antiporter family 1 (DHA1) has been established as a predominant contributor towards xenobiotic efflux.

Air monitoring of tire-derived chemicals in global megacities using passive samplers.

Pollution from vehicle tires has received world-wide research attention due to its ubiquity and toxicity. In this study, we measured various tire-derived contaminants semi-quantitatively in archived extracts of passive air samplers deployed in 18 major cities that comprise the Global Atmospheric Passive Sampling (GAPS) Network (GAPS-Megacities). Analysis was done on archived samples, which represent one-time weighted passive air samples from each of the 18 monitoring sites.

Medium- and long-chain chlorinated paraffins in air: A review of levels, physicochemical properties, and analytical considerations.

Chlorinated paraffins (CPs) are synthetic chemicals that are produced at high volumes and have a global presence. CPs are generally divided into three groups based on their carbon chain lengths: short-chain CPs (SCCPs, C), medium-chain CPs (MCCPs, C), and long-chain CPs (LCCPs, C). SCCPs have been formally recognized as persistent organic pollutants (POPs) and have been listed under the Stockholm Convention on POPs.

High-flow nasal cannula and noninvasive ventilation: effects on alveolar recruitment and overdistension.

https://bit.ly/3jFCSG9.

Cholic-Acid-Derived Amphiphiles Can Prevent and Degrade Fungal Biofilms.

Infections caused by fungal species via their existence as biofilms on medical devices can cause organ damage via candidiasis and candidemia. Different species like can pose a serious threat by resisting host's immune system and by developing drug resistance against existing antimycotic agents. Therefore, targeting of fungal membranes can be used as an alternative strategy to combat the fungal infections.

Cytotoxic and Transcriptomic Effects in Avian Hepatocytes Exposed to a Complex Mixture from Air Samples, and Their Relation to the Organic Flame Retardant Signature.

Assessing complex environmental mixtures and their effects is challenging. In this study, we evaluate the utility of an avian in vitro screening approach to determine the effects of passive air sampler extracts collected from different global megacities on cytotoxicity and gene expression. Concentrations of a suite of organic flame retardants (OFRs) were quantified in extracts from a total of 19 megacities/major cities in an earlier study, and levels were highly variable across sites.

Uncovering global-scale risks from commercial chemicals in air.

Commercial chemicals are used extensively across urban centres worldwide, posing a potential exposure risk to 4.2 billion people. Harmful chemicals are often assessed on the basis of their environmental persistence, accumulation in biological organisms and toxic properties, under international and national initiatives such as the Stockholm Convention.

Fugacity-Based Trophic Magnification Factors Characterize Bioaccumulation of Cyclic Methyl Siloxanes within an Urban Terrestrial Avian Food Web: Importance of Organism Body Temperature and Composition.

Trophic magnification of cyclic volatile methyl siloxanes (cVMS) in a terrestrial food web was investigated by measuring concentrations of octamethylcyclotetrasiloxane (D4), decamethylcyclopentasiloxane (D5), and dodecamethylcyclohexasiloxane (D6) and two reference chemicals within air and biota samples from an avian food web located in a mixed urban-agricultural landscape. Terrestrial trophic magnification factors derived from lipid normalized concentrations (TMFs) for D5 and D6 were 0.94 (0.

Guidance on the Application of Polyurethane Foam Disk Passive Air Samplers for Measuring Nonane and Short-Chain Chlorinated Paraffins in Air: Results from a Screening Study in Urban Air.

This study provides guidance on using polyurethane foam-based passive air samplers (PUF-PASs) for atmospheric nonane chlorinated paraffins (C-CPs) and short-chain CPs (SCCPs) and reports SCCP concentrations in air in the Greater Toronto Area (GTA), Canada. We estimated the partition coefficients between PUF and air () and between octanol and air () for C-CP and SCCP congeners using the COSMO-RS method, so that PUF disk uptake profiles for each formula group could be calculated. We then measured SCCP concentrations in PUF disk samples collected from distinct source sectors in urban air across the GTA.

Metabolic Enzyme DLST Promotes Tumor Aggression and Reveals a Vulnerability to OXPHOS Inhibition in High-Risk Neuroblastoma.

High-risk neuroblastoma remains therapeutically challenging to treat, and the mechanisms promoting disease aggression are poorly understood. Here, we show that elevated expression of dihydrolipoamide S-succinyltransferase (DLST) predicts poor treatment outcome and aggressive disease in patients with neuroblastoma. DLST is an E2 component of the α-ketoglutarate (αKG) dehydrogenase complex, which governs the entry of glutamine into the tricarboxylic acid cycle (TCA) for oxidative decarboxylation.

Characterization of Opalescence in low Volume Monoclonal Antibody Solutions Enabled by Microscale Nephelometry.

Monoclonal antibody (mAb)-based drugs are often prone to unfavorable solution behaviors including high viscosity, opalescence, phase separation, and aggregation at the high concentrations needed to enable patient-centric subcutaneous dosage forms. Given that these can have a detrimental impact on manufacturability, stability, and delivery, approaches to identifying, monitoring, and controlling these behaviors during drug development are critical. Opalescence presents a significant challenge due to its relationship to liquid-liquid phase separation.

A single molecular descriptor to predict solution behavior of therapeutic antibodies.

Despite the therapeutic success of monoclonal antibodies (mAbs), early identification of developable mAb drug candidates with optimal manufacturability, stability, and delivery attributes remains elusive. Poor solution behavior, which manifests as high solution viscosity or opalescence, profoundly affects the developability of mAb drugs. Using a diverse dataset of 59 mAbs, including 43 approved products, and an array of molecular descriptors spanning colloidal, conformational, charge-based, hydrodynamic, and hydrophobic properties, we show that poor solution behavior is prevalent (>30%) in mAbs and is singularly predicted (>90%) by the diffusion interaction parameter ( ), a dilute-solution measure of colloidal self-interaction.

GAPS-megacities: A new global platform for investigating persistent organic pollutants and chemicals of emerging concern in urban air.

A pilot study was initiated in 2018 under the Global Atmospheric Passive Sampling (GAPS) Network named GAPS-Megacities. This study included 20 megacities/major cities across the globe with the goal of better understanding and comparing ambient air levels of persistent organic pollutants and other chemicals of emerging concern, to which humans residing in large cities are exposed. The first results from the initial period of sampling are reported for 19 cities for several classes of flame retardants (FRs) including organophosphate esters (OPEs), polybrominated diphenyl ethers (PBDEs), and halogenated flame retardants (HFRs) including new flame retardants (NFRs), tetrabromobisphenol A (TBBPA) and hexabromocyclododecane (HBCDD).

Decreased Brain Volumes and Infants With Congenital Heart Disease Undergoing Venoarterial Extracorporeal Membrane Oxygenation.

Objectives: The aims of this study were to: i) determine the spectrum of brain injury and ii) compare brain volumes between pre- and postoperative brain MRI in the infants receiving extracorporeal membrane oxygenation compared with those who did not require extracorporeal membrane oxygenation.

Design: Cohort study of infants with D-transposition of the great arteries or single ventricle physiology. Brain volume (cm) was measured using a segmentation of a volumetric T1-weighted gradient echo sequence.

Experimental Study of OH-Initiated Heterogeneous Oxidation of Organophosphate Flame Retardants: Kinetics, Mechanism, and Toxicity.

The environmental risks and health impacts associated with particulate organophosphate flame retardants (OPFRs), which are ubiquitous in the global atmosphere, have not been adequately assessed due to the lack of data on the reaction kinetics, products, and toxicity associated with their atmospheric transformations. Here, the importance of such transformations for OPFRs are explored by investigating the reaction kinetics, degradation chemical mechanisms, and toxicological evolution of two OPFRs (2-ethylhexyl diphenyl phosphate (EHDP) and diphenyl phosphate (DPhP)) coated on (NH)SO particles upon heterogeneous OH oxidation. The derived reaction rate constants for the heterogeneous loss of EHDP and DPhP are (1.

Direct measurements of polyurethane foam (PUF) ‒ air partitioning coefficients for chemicals of emerging concern capable of equilibrating in PUF disk samplers.

Organophosphate esters (OPEs), novel flame retardants (NFRs) and organochlorine pesticides (OCPs) are volatile to semi-volatile chemicals and therefore susceptible to approach equilibrium during typical deployments of polyurethane foam (PUF) disk passive air samplers. A generator column approach was used to measure the PUF-air partitioning coefficient (K) for these targeted chemicals. K values are required for these chemicals to estimate sampled equivalent air volumes, which vary substantially with temperature.