SARS-CoV-2 (Severe Acute Respiratory Syndrome Corona Virus-2), cause of COVID-19 (Coronavirus Disease of 2019), represents a significant risk to people living with pre-existing conditions associated with exacerbated inflammatory responses and consequent dysfunctional immunity. In this paper, we have evaluated the influence of obesity, a condition associated with chronic systemic inflammation, on the secretion of SARS-CoV-2-specific IgG antibodies in the blood of COVID-19 patients. Our hypothesis is that obesity is associated with reduced amounts of specific IgG antibodies. Results have confirmed our hypothesis and have shown that SARS-CoV-2 IgG antibodies are negatively associated with Body Mass Index (BMI) in COVID-19 obese patients, as expected based on the known influence of obesity on humoral immunity. Antibodies in COVID-19 obese patients are also negatively associated with serum levels of pro-inflammatory and metabolic markers of inflammaging and pulmonary inflammation, such as SAA (serum amyloid A protein), CRP (C-reactive protein), and ferritin, but positively associated with NEFA (nonesterified fatty acids). These results altogether could help to identify an inflammatory signature with strong predictive value for immune dysfunction. Inflammatory markers identified may subsequently be targeted to improve humoral immunity in individuals with obesity and in individuals with other chronic inflammatory conditions.

Background/objectives Obesity decreases the secretion of SARS-CoV-2-specific IgG antibodies in the blood of COVID-19 patients. How obesity impacts the quality of the antibodies secreted, however, is not understood. Therefore, the objective of this study is to evaluate the presence of neutralizing versus autoimmune antibodies in COVID-19 patients with obesity. Subjects/methods Thirty serum samples from individuals who tested positive for SARS-CoV-2 infection by RT-PCR were collected from inpatient and outpatient settings. Of these, 15 were lean (BMI < 25) and 15 were obese (BMI ≥ 30). Control serum samples were from 30 uninfected individuals, age-, gender-, and BMI-matched, recruited before the current pandemic. Neutralizing and autoimmune antibodies were measured by ELISA. IgG autoimmune antibodies were specific for malondialdehyde (MDA), a marker of oxidative stress and lipid peroxidation, and for adipocyte-derived protein antigens (AD), markers of virus-induced cell death in the obese adipose tissue. Results SARS-CoV-2 infection induces neutralizing antibodies in all lean but only in few obese COVID-19 patients. SARS-CoV-2 infection also induces anti-MDA and anti-AD autoimmune antibodies more in lean than in obese patients as compared to uninfected controls. Serum levels of these autoimmune antibodies, however, are always higher in obese versus lean COVID-19 patients. Moreover, because the autoimmune antibodies found in serum samples of COVID-19 patients have been correlated with serum levels of C-reactive protein (CRP), a general marker of inflammation, we also evaluated the association of anti-MDA and anti-AD antibodies with serum CRP and found a positive association between CRP and autoimmune antibodies. Conclusions Our results highlight the importance of evaluating the quality of the antibody response in COVID-19 patients with obesity, particularly the presence of autoimmune antibodies, and identify biomarkers of self-tolerance breakdown. This is crucial to protect this vulnerable population at higher risk of responding poorly to infection with SARS-CoV-2 than lean controls.

Forty‐three fatalities involving the potent synthetic cannabinoid, 5‐Fluoro‐ADB, are summarized. For each case, a description of the terminal event, autopsy findings, cause of death, qualitative identification of 5‐Fluoro‐ADB and its ester hydrolysis metabolite, 5‐Fluoro‐ADB metabolite 7, in urine, and the quantitative values obtained in the blood specimens are outlined. Central blood concentrations ranged from 0.010 to 2.2 ng/mL for 5‐Fluoro‐ADB and 2.0 to 166 ng/mL for 5‐Fluoro‐ADB metabolite 7. Peripheral blood concentrations ranged from 0.010 to 0.77 ng/mL and 2.0 to 110 ng/mL for 5‐Fluoro‐ADB and 5‐Fluoro‐ADB metabolite 7, respectively. The majority of cases resulted in central to peripheral blood concentration ratios greater than 1 for 5‐Fluoro‐ADB (58%) and 5‐Fluoro‐ADB metabolite 7 (71%) suggesting that postmortem redistribution occurs to some extent. Combining the increased cardiac weight and/or gastric volume and toxicology data identifying 5‐Fluoro‐ADB, it is hypothesized that abuse of this substance may precipitate a dysrhythmia and cause sudden death.

No abstract

Recently, it has been documented that there has been a rise in synthetic opioid abuse. Synthetic opioids are compounds that were created to act as agonists for the opioid receptors. Like synthetic cannabinoids, most of these compounds were created by research groups or pharmaceutical companies in an attempt to find compounds that have medicinal use. Synthetic opioids have severe health implications when abused that can include hospitalization and death. Due to the high potency and the low dose required to produce the desired effects for these compounds, it was hypothesized that they may not be detectable in human performance case samples. However, this report documents a male driver who was involved in a single-vehicle incident. First responders treated the subject with naloxone as opioid drug impairment was suspected and he was transported to the local emergency room. The subject consented to a blood draw for a driving under the influence (DUI) investigation. Initial routine testing identified alprazolam at 55 ng/mL and fentanyl at less than 0.5 ng/mL. Further testing using a validated liquid chromatography-tandem mass spectrometry (LC-MS-MS) assay, confirmed the presence of carfentanil, furanyl fentanyl, para-fluoroisobutyryl fentanyl, U-47700 and its metabolite. To the author's knowledge, this is the first report of a DUI cases where carfentanil, U-47700 and other synthetic opioids were confirmed and described in a human performance blood sample. This case demonstrates the need to supplement routine toxicological analyses with a sensitive methodology that can detect synthetic opioids in human performance cases where opioid use may be implicated.

Paints have a dual role in society, to protect materials from environmental agents such as ultraviolet light, moisture and oxygen, and to make painted materials look more attractive. Variability in paint samples is often due to binder and pigment type within the sample. The most common resin used in decorative paints is drying oil alkyd resin, which incorporates soybean oil and vinyl acrylic based latexes. Traditional analytical methods used by forensic scientists may be able to say whether two paint samples are indistinguishable but cannot conclusively say that they both originate from the same source. To find out if isotopic composition can provide an added dimension of information, 28 different white architectural paints were analysed for (13)C abundance using isotope ratio mass spectrometry. In addition, variations in application, drying time and thickness were also investigated to assess the discriminatory power of (13)C data from white paints with an unknown history. Preliminary results indicate that this method could aid screening of paint samples.

Toxicology laboratories commonly employ immunoassay methodologies to perform an initial drug screen on urine specimens to direct confirmatory testing. Due to limitations of immunoassay testing and the need to screen for a broader range of drugs with lower limits of detection at a lower cost, mass spectrometry screening techniques have gained favor in the toxicology field. A liquid chromatography–tandem mass spectrometry (LC-MS-MS) urine screening panel was developed and validated for 52 drugs and metabolites. A simple dilute-and-shoot with enzymatic hydrolysis technique was utilized to prepare the urine specimens for analysis. Limit of detection, interference, ionization suppression/enhancement, carryover and stability of processed specimens were assessed during validation. To evaluate the toxicological results obtained from utilizing the LC-MS-MS in comparison with the laboratory’s current enzyme-linked immunosorbent assay (ELISA) panel, 100 authentic urine specimens from suspected driving under the influence and drug-facilitated crime cases were analyzed using both methodologies and the results were compared. In addition, the cost of each methodology was evaluated and compared. The validated LC-MS-MS method had limits of detection that were equal to or lower than the concentrations validated for ELISA cutoffs, had fewer exogenous interferences, and the cost of screening per specimen was reduced by ~70% when compared to ELISA. Comparing the toxicology results of forensic urine specimens demonstrated that by only using ELISA, the laboratory was unable to detect benzoylecgonine in 26%, lorazepam in 33% and oxymorphone in 60% of the positive specimens. Additional analytes detected using the LC-MS-MS method were zolpidem and/or metabolite, gabapentin, tramadol and metabolite, methadone and metabolite, meprobamate and phentermine. The results of the validation, the toxicological result comparison and the cost comparison showed that the LC-MS-MS screening method is a simple, sensitive and cost-effective alternative to ELISA screening methods for urine specimens.

In 1993, Zolpidem (Ambien), a non-benzodiazepine hypnotic agent, was approved for use in the United States for the short-term treatment of insomnia. Zolpidem has a rapid onset of action and short elimination half-life, rendering it ideal as a sleep aid. The objective of this study was to evaluate, and retrospectively compare, the use of the Immunalysis ELISA kit and gas chromatograpy-mass spectrometry (GC-MS) to screen blood/urine specimens for zolpidem. In addition, results for the incidence of zolpidem in suspected DUI drivers in 2007 are compared to previous years' data. The ELISA kit was evaluated for cross-reactivity with zaleplon and zopiclone and zolpidem metabolite I. Urine samples (n = 100) and blood samples (n = 100) were selected from specimens received into the DUI laboratory in 2007 and were screened via the Immunalysis Zolpidem ELISA kit and on GC-MS in full EI scan mode following an alkaline liquid-liquid extraction. Results show 5% of the urine and blood samples screened positive for zolpidem using the ELISA kits, and all 5% confirmed positive for zolpidem using GC-MS. The ELISA kit demonstrated no cross-reactivity to zaleplon or zopiclone at a spiked urine concentration of 1000 ng/mL. Ten cases of suspected DUI drivers in 2007 confirmed positive for zolpidem by ELISA and GC-MS in blood/urine, a higher incidence rate than in the previous years. Because of the low percentage elimination of the parent compound in urine, a screening method for the detection of the main metabolite of zolpidem may be needed for better detection of drug impairment driving due to zolpidem.