Antibody Levels from High-Throughput Variant-Specific SARS-CoV-2 Anti-Spike IgG and ACE2 Neutralization Assays Correlate with COVID Infection Risk in a Large Population.

Background: SARS-CoV-2 antibody levels have been proposed as a correlate of protection (CoP) from infection. Yet, large-scale prospective studies of cost-effective scalable antibody measures as predictors of infection under real-world conditions are limited. We examined whether antibody levels measured using high-throughput variant-specific SARS-CoV-2 anti-spike immunoglobulin G (IgG) and ACE2-neutralization assays correlate with cell-based neutralizing antibody (NAb) measurements, and whether they can serve as a reasonable CoP from SARS-CoV-2 infection.

Longitudinal assessment of the impact of COVID-19 infection on mask-wearing behaviors.

Background: Wearing a mask was a crucial component in slowing the COVID-19 pandemic. However, little is known about the intersectionality between mask usage, risk perception, and infection. The purpose of this study was to investigate whether risk perceptions and masking behaviors are associated with contracting SARS-CoV-2 and how contracting SARS-CoV-2 subsequently changes masking behaviors in specific situations.

Humoral immune response to SARS-CoV-2 in pregnant and nonpregnant women following infection.

Background: Immune changes that occur during pregnancy may place pregnant women at an increased risk for severe disease following viral infections like SARS-CoV-2. Whether these immunologic changes modify the immune response to SARS-CoV-2 infection during pregnancy is not well understood.

Objective: This study aimed to compare the humoral immune response to SARS-CoV-2 infection in pregnant and nonpregnant women.

Implementation of Practical Surface SARS-CoV-2 Surveillance in School Settings.

Surface sampling for SARS-CoV-2 RNA detection has shown considerable promise to detect exposure of built environments to infected individuals shedding virus who would not otherwise be detected. Here, we compare two popular sampling media (VTM and SDS) and two popular workflows (Thermo and PerkinElmer) for implementation of a surface sampling program suitable for environmental monitoring in public schools. We find that the SDS/Thermo pipeline shows superior sensitivity and specificity, but that the VTM/PerkinElmer pipeline is still sufficient to support surface surveillance in any indoor setting with stable cohorts of occupants (e.

Emergence and rapid transmission of SARS-CoV-2 B.1.1.7 in the United States.

The highly transmissible B.1.1.

Genomic epidemiology identifies emergence and rapid transmission of SARS-CoV-2 B.1.1.7 in the United States.

As of January of 2021, the highly transmissible B.1.1.

Pyrrole adducts in globin and plasma of workers exposed to hexane.

Objectives: Urinary excretion of 2,5-hexanedione is currently used to estimate the exposure levels of hexane occurring to an individual during the previous work shift. However, because hexane exposures and urinary 2,5-hexanedione levels can vary considerably from day to day, and subchronic to chronic exposures to hexane are required to produce neuropathy, this biomarker may not accurately reflect the risk of an individual for developing hexane neuropathy. This investigation examines the potential of hexane-derived pyrrole adducts produced on globin and plasma proteins as markers for integrating cumulative exposures.

Peripheral nerve and brain differ in their capacity to resolve N,N-diethyldithiocarbamate-mediated elevations in copper and oxidative injury.

Previous studies have demonstrated that N,N-diethyldithiocarbamate (DEDC) elevates copper and promotes oxidative stress within the nervous system. However, whether these effects resolve following cessation of exposure or have the potential to persist and result in cumulative injury has not been determined. In this study, an established model for DEDC myelin injury in the rat was used to determine whether copper levels, oxidative stress, and neuromuscular deficits resolve following the cessation of DEDC exposure.

Multiexponential T2, magnetization transfer, and quantitative histology in white matter tracts of rat spinal cord.

Quantitative MRI measures of multiexponential T(2) relaxation and magnetization transfer were acquired from six samples of excised and fixed rat spinal cord and compared with quantitative histology. MRI and histology data were analyzed from six white matter tracts, each of which possessed unique microanatomic characteristics (axon diameter and myelin thickness, in particular) but a relatively constant volume fraction of myelin. The results indicated that multiexponential T(2) relaxation characteristics varied substantially with variation of microanatomy, while the magnetization transfer characteristics remained close to constant.

N,N-diethyldithiocarbamate promotes oxidative stress prior to myelin structural changes and increases myelin copper content.

Dithiocarbamates are a commercially important class of compounds that can produce peripheral neuropathy in humans and experimental animals. Previous studies have supported a requirement for copper accumulation and enhanced lipid peroxidation in dithiocarbamate-mediated myelinopathy. The study presented here extends previous investigations in two areas.

Nitrogen substituent polarity influences dithiocarbamate-mediated lipid oxidation, nerve copper accumulation, and myelin injury.

Dithiocarbamates have a wide spectrum of applications in industry, agriculture, and medicine, with new applications being investigated. Past studies have suggested that the neurotoxicity of some dithiocarbamates may result from copper accumulation, protein oxidative damage, and lipid oxidation. The polarity of a dithiocarbamate's nitrogen substituents influences the lipophilicity of the copper complexes that it generates and thus potentially determines its ability to promote copper accumulation within nerve and induce myelin injury.

A specific HPLC-UV method for the determination of cysteine and related aminothiols in biological samples.

We present a highly selective and sensitive method for the determination of cysteine (Cys) and related aminothiols that play important roles in health and disease. The key step in the analysis is treatment with 1,1'-thiocarbonyldiimidazole (TCDI) that rapidly and quantitatively reacts with both the amino and thiol groups to form stable cyclic dithiocarbamates with intense UV absorption. Cys, homocysteine (hCys), and cysteinylglycine in plasma (75 microl), urine (100 microl), or cerebrospinal fluid (100-500 microl) were determined by separating and measuring their cyclic derivatives by a high performance liquid chromatograph (HPLC) connected to a UV detector.

Copper accumulation and lipid oxidation precede inflammation and myelin lesions in N,N-diethyldithiocarbamate peripheral myelinopathy.

Dithiocarbamates have a wide spectrum of applications in industry, agriculture and medicine with new applications being actively investigated. One adverse effect of dithiocarbamates is the neurotoxicity observed in humans and experimental animals. Results from previous studies have suggested that dithiocarbamates elevate copper and promote lipid oxidation within myelin membranes.

Globin s-propyl cysteine and urinary N-acetyl-S-propylcysteine as internal biomarkers of 1-bromopropane exposure.

1-Bromopropane (1-BP), an alternative to ozone-depleting solvents, is a neuro and reproductive toxicant in animals and humans. In this study, the dose responses for urinary AcPrCys and S-propylcysteine (PrCys) adducts on globin and neurofilaments were determined as a function of 1-BP exposure level and duration in the rat; and globin PrCys adducts and urinary AcPrCys were quantified in samples obtained from workers in a 1-BP production facility. Rats were exposed to 1-BP by inhalation for 2 weeks at 0, 50, 200, or 800 ppm and to 1-BP at 0 or 50 ppm for 4 weeks.

Multicomponent T2 analysis of dithiocarbamate-mediated peripheral nerve demyelination.

Standard light microscope histological evaluation of peripheral nerve lesions has been used routinely to assess peripheral nerve demyelination; however, the development of magnetic resonance (MR) methodology for assessing peripheral nerve may provide complementary information, with less expense and in less time than nerve histology methods. In this study, the utility of multicomponent NMR T(2) relaxation analysis for assessing myelin injury in toxicology studies was examined using two dithiocarbamates, N,N-diethyldithiocarbamate (DEDC) and pyrrolidine dithiocarbamate (PDTC), known to produce myelin injury and elevate copper in the nervous system. T(2) analysis was used in conjunction with standard histological methods to assess myelin injury and determine if dithiocarbamate-mediated copper accumulation in peripheral nerve was associated with more severe myelin lesions.

Peripheral nerve protein expression and carbonyl content in N,N-diethlydithiocarbamate myelinopathy.

Human exposure to dithiocarbamates results from their uses as pesticides, in manufacturing, and as pharmaceutical agents. Neurotoxicity is an established hazard of dithiocarbamate exposure and has been observed in both humans and experimental animals. Previous studies have shown that the neurotoxicity of certain dithiocarbamates, including N,N-diethyldithiocarbamate (DEDC), disulfiram, and pyrrolidine dithiocarbamate, can manifest as a primary myelinopathy of peripheral nerves.

Dietary copper enhances the peripheral myelinopathy produced by oral pyrrolidine dithiocarbamate.

The neurotoxic hazard of a dithiocarbamate is influenced by route of exposure and acid stability of the dithiocarbamate. As an example, oral administration of the acid labile dithiocarbamate N,N-diethyldithiocarbamate (DEDC) causes a central-peripheral axonopathy thought to result from acid-promoted decomposition to CS2 in the stomach. In contrast, parenteral administration of DEDC, which bypasses the acidic environment of the stomach, causes a primary demyelination that is thought to be mediated through the intact parent dithiocarbamate.

Brainstem axonal degeneration in mice with deletion of selenoprotein p.

Selenoprotein P is an abundant extracellular protein that is expressed in liver, brain, and other tissues. Studies in mice with the selenoprotein P gene deleted (Sepp-/- mice) have implicated the protein in maintaining brain selenium. Sepp-/- mice fed a normal or low selenium diet develop severe motor impairment and die, but Sepp-/- mice fed a high selenium diet remain clinically unimpaired.

N,N-diethyldithiocarbamate produces copper accumulation, lipid peroxidation, and myelin injury in rat peripheral nerve.

Previous studies have demonstrated the ability of the dithiocarbamate, disulfiram, to produce a peripheral neuropathy in humans and experimental animals and have also provided evidence that N,N-diethyldithiocarbamate (DEDC) is a proximate toxic species of disulfiram. The ability of DEDC to elevate copper levels in the brain suggests that it may also elevate levels of copper in peripheral nerve, possibly leading to oxidative stress and lipid peroxidation from redox cycling of copper. The study presented here investigates the potential of DEDC to promote copper accumulation and lipid peroxidation in peripheral nerve.

Characterization of S-(N,N-Dialkylaminocarbonyl)cysteine Adducts and Enzyme Inhibition Produced by Thiocarbamate Herbicides in the Rat.

Thiocarbamates are a major class of herbicides used extensively in the agricultural industry. It has been shown that thiocarbamates can form reactive sulfoxide and sulfone intermediates, which may be involved in the toxicity of thiocarbamates through covalent modification of cysteine and serine active sites of enzymes. Molinate has been shown to generate an S-hexahydro-1H-azepine-1-carbonyl adduct on the Cys-125 residue of the beta2- and beta3-chains of rat globin analogous to that reported for disulfiram and to inhibit aldehyde dehydrogenase and nonspecific esterase activity.

Parenteral N,N-diethyldithiocarbamate produces segmental demyelination in the rat that is not dependent on cysteine carbamylation.

Disulfiram, a dithiocarbamate drug used in alcohol aversion therapy, produces a peripheral neuropathy characterized in rats as segmental demyelination accompanied by generation of S-(diethylaminocarbonyl)cysteine (DETC-Cys) adducts. N,N-Diethyldithiocarbamate (DEDC) is a major metabolite of disulfiram that can undergo methylation and oxidation to S-methyl-N,N-diethylthiocarbamate (MeDETC) sulfoxide and sulfone, thought to be responsible for carbamylation of sulfhydryl functions by disulfiram. To assess the role of cysteine carbamylation in disulfiram toxicity, DEDC and MeDETC were administered parenterally to male Sprague-Dawley rats for 4 and 8 weeks.

Cytotoxic mechanisms of hydrosulfide anion and cyanide anion in primary rat hepatocyte cultures.

Hydrogen sulfide and hydrogen cyanide are known to compromise mitochondrial respiration through inhibition of cytochrome c oxidase and this is generally considered to be their primary mechanism of toxicity. Experimental studies and the efficiency of current treatment protocols suggest that H(2)S may exert adverse physiological effects through additional mechanisms. To evaluate the role of alternative mechanisms in H(2)S toxicity, the relative contributions of electron transport inhibition, uncoupling of mitochondrial respiration, and opening of the mitochondrial permeability transition pore (MPTP) to hydrosulfide and cyanide anion cytotoxicity in primary hepatocyte cultures were examined.