Identification of CD8 T-cell dysfunction associated with symptoms in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Long COVID and treatment with a nebulized antioxidant/anti-pathogen agent in a retrospective case series.

Background: Patients with post-acute sequelae of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection (PASC, i.e., Long COVID) have a symptom complex highly analogous to many features of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), suggesting they may share some aspects of pathogenesis in these similar disorders. ME/CFS is a complex disease affecting numerous organ systems and biological processes and is often preceded by an infection-like episode. It is postulated that the chronic manifestations of illness may result from an altered host response to infection or inability to resolve inflammation, as is being reported in Long COVID. The immunopathogenesis of both disorders is still poorly understood. Here, we show data that suggest Long COVID and ME/CFS may be due to an aberrant response to an immunological trigger-like infection, resulting in a dysregulated immune system with CD8 T-cell dysfunction reminiscent of some aspects of T-cell clonal exhaustion, a phenomenon associated with oxidative stress. As there is an urgent need for diagnostic tools and treatment strategies for these two related disabling disorders, here, in a retrospective case series, we have also identified a potential nebulized antioxidant/anti-pathogen treatment that has evidence of a good safety profile. This nebulized agent is comprised of five ingredients previously reported individually to relieve oxidative stress, attenuate NF-κB signaling, and/or to act directly to inhibit pathogens, including viruses. Administration of this treatment by nebulizer results in rapid access of small doses of well-studied antioxidants and agents with anti-pathogen potential to the lungs; components of this nebulized agent are also likely to be distributed systemically, with potential to enter the central nervous system. Methods: and Findings: We conducted an analysis of CD8 T-cell function and severity of symptoms by self-report questionnaires in ME/CFS, Long COVID and healthy controls. We developed a CD8 T-cell functional assay, assessing CD8 T-cell dysfunction by intracellular cytokine staining (ICS) in a group of ME/CFS (n = 12) and Long COVID patients (n = 8), comparing to healthy controls (HC) with similar age and sex (n = 10). Magnet-enriched fresh CD8 T-cells in both patient groups had a significantly diminished capacity to produce both cytokines, IFNγ or TNFα, after PMA stimulation when compared to HC. The symptom severity questionnaire showed similar symptom profiles for the two disorders. Fortuitously, through a retrospective case series, we were able to examine the ICS and questionnaire data of 4 ME/CFS and 4 Long COVID patients in conjunction with their treatment (3-15 months). In parallel with the treatment pursued electively by participants in this retrospective case series, there was an increase in CD8 T-cell IFNγ and TNFα production and a decrease in overall self-reported symptom severity score by 54%. No serious treatment-associated side effects or laboratory anomalies were noted in these patients. Conclusions: Here, in this small study, we present two observations that appear potentially fundamental to the pathogenesis and treatment of Long COVID and ME/CFS. The first is that both disorders appear to be characterized by dysfunctional CD8 T-cells with severe deficiencies in their abilities to produce IFNγ and TNFα. The second is that in a small retrospective Long COVID and ME/CFS case series, this immune dysfunction and patient health improved in parallel with treatment with an immunomodulatory, antioxidant pharmacological treatment with anticipated anti-pathogen activity. This work provides evidence of the potential utility of a biomarker, CD8 T-cell dysfunction, and suggests the potential for benefit from a new nebulized antioxidant/anti-pathogen treatment. These immune biomarker data may help build capacity for improved diagnosis and tracking of treatment outcomes during clinical trials for both Long COVID and ME/CFS while providing clues to new treatment avenues that suggest potential efficacy for both conditions.

Effects of visible and UV light on the characteristics and properties of crude oil-in-water (O/W) emulsions.

The effects of visible and UV light on the characteristics and properties of Prudhoe Bay (PB) and South Louisiana (SL) emulsions were investigated to better understand the role of sunlight on the fate of spilled crude oils that form emulsions with a dispersant in the aquatic environment. Before irradiation, crude oil emulsions showed the presence of dispersed crude oil micelles in a continuous water phase and crude oil components floating on the surface. The crude oil micelles decreased in size with irradiation, but emulsions retained their high degree of polydispersity. UV irradiation reduced the stability of emulsions more effectively than visible light. The reduction of micelles size caused the viscosity of emulsions to increase and melting point to decrease. Further, irradiation increased acid concentrations and induced ion formation which lowered the pH and increased the conductivity of emulsions, respectively. Ni and Fe in PB emulsions were extracted from crude oil with UV irradiation, which may provide an efficient process for metal removal. The emulsions were stable toward freeze/thaw cycles and their melting temperatures generally decreased with irradiation. Evidence of ˙OH production existed when emulsions were exposed to UV but not to visible light. The presence of H(2)O(2) enhanced the photodegradation of crude oil. Overall, the changes in emulsion properties were attributed to direct photodegradation and photooxidation of crude oil components.

Biosynthesis of iron and silver nanoparticles at room temperature using aqueous sorghum bran extracts.

Iron and silver nanoparticles were synthesized using a rapid, single step, and completely green biosynthetic method employing aqueous sorghum extracts as both the reducing and capping agent. Silver ions were rapidly reduced by the aqueous sorghum bran extracts, leading to the formation of highly crystalline silver nanoparticles with an average diameter of 10 nm. The diffraction peaks were indexed to the face-centered cubic (fcc) phase of silver. The absorption spectra of colloidal silver nanoparticles showed a surface plasmon resonance (SPR) peak centered at a wavelength of 390 nm. Amorphous iron nanoparticles with an average diameter of 50 nm were formed instantaneously under ambient conditions. The reactivity of iron nanoparticles was tested by the H(2)O(2)-catalyzed degradation of bromothymol blue as a model organic contaminant.

Degradation of volatile organic compounds with thermally activated persulfate oxidation.

This study investigated the extent and treatability of the degradation of 59 volatile organic compounds (VOCs) listed in the EPA SW-846 Method 8260B with thermally activated persulfate oxidation. Data on the degradation of the 59 VOCs (in mixture) reacted with sodium persulfate in concentrations of 1 g l(-1) and 5 g l(-1) and at temperatures of 20 degrees C, 30 degrees C, and 40 degrees C were obtained. The results indicate that persulfate oxidation mechanisms are effective in degrading many VOCs including chlorinated ethenes (CEs), BTEXs and trichloroethanes that are frequently detected in the subsurface at contaminated sites. Most of the targeted VOCs were rapidly degraded under the experimental conditions while some showed persistence to the persulfate oxidation. Compounds with "CC" bonds or with benzene rings bonded to reactive functional groups were readily degraded. Saturated hydrocarbons and halogenated alkanes were much more stable and difficult to degrade. For those highly persulfate-degradable VOCs, degradation was well fitted with a pseudo first-order decay model. Activation energies of reactions of CEs and BTEXs with persulfate were determined. The degradation rates increased with increasing reaction temperature and oxidant concentration. Nevertheless, to achieve complete degradation of persulfate-degradable compounds, the systems required sufficient amounts of persulfate to sustain the degradation reaction.

Kinetics of heat-assisted persulfate oxidation of methyl tert-butyl ether (MTBE).

The kinetics of heat-assisted persulfate oxidation of methyl tert-butyl ether (MTBE) in aqueous solutions at various pH, temperature, oxidant concentration and ionic strength levels was studied. The MTBE degradation was found to follow a pseudo-first-order decay model. The pseudo-first-order rate constants of MTBE degradation by persulfate (31.5 mM) at pH 7.0 and ionic strength 0.11 M are approximately 0.13 x 10(-4), 0.48 x 10(-4), 2.4 x 10(-4) and 5.8 x 10(-4) S(-1) at 20, 30, 40 and 50 degrees C, respectively. Under the above reaction conditions, the reaction has an activation energy of 24.5 +/- 1.6 kcal/ mol and is influenced by temperature, oxidant concentration, pH and ionic strength. Raising the reaction temperature and persulfate concentration may significantly accelerate the MTBE degradation. However, increasing both pH (over the range of 2.5-11) and ionic strength (over the range of 0.11-0.53 M) will decrease the reaction rate. Reaction intermediates including tert-butyl formate, tert-butyl alcohol, acetone and methyl acetate were observed. These intermediate compounds were also degraded by persulfate under the experimental conditions. Additionally, MTBE degradation by persulfate in a groundwater was much slower than in phosphate-buffer solutions, most likely due to the presence of bicarbonate ions (radical scavengers) in the groundwater.

Atmospheric mercury monitoring survey in Beijing, China.

With the aid of one industrial, two urban, two suburban, and two rural sampling locations, diurnal patterns of total gaseous mercury (TGM) were monitored in January, February and September of 1998 in Beijing, China. Monitoring was conducted in six (two urban, two suburban, one rural and the industrial sites) of the seven sampling sites during January and February (winter) and in four (two urban, one rural, and the industrial sites) of the sampling locations during September (summer) of 1998. In the three suburban sampling stations, mean TGM concentrations during the winter sampling period were 8.6, 10.7, and 6.2 ng/m3, respectively. In the two urban sampling locations mean TGM concentrations during winter and summer sampling periods were 24.7, 8.3, 10, and 12.7 ng/m3, respectively. In the suburban-industrial and the two rural sampling locations, mean mercury concentrations ranged from 3.1-5.3 ng/m3 in winter to 4.1-7.7 ng/m3 in summer sampling periods. In the Tiananmen Square (urban), and Shijingshan (suburban) sampling locations the mean TGM concentrations during the summer sampling period were higher than winter concentrations, which may have been caused by evaporation of soil-bound mercury in warm periods. Continuous meteorological data were available at one of the suburban sites, which allowed the observation of mercury concentration variations associated with some weather parameters. It was found that there was a moderate negative correlation between the wind speed and the TGM concentration at this suburban sampling location. It was also found that during the sampling period at the same site, the quantity of TGM transported to or from the sampling site was mainly influenced by the duration and frequency of wind occurrence from certain directions.

Kinetics and mechanism of oxidation of tetrachloroethylene with permanganate.

The kinetics, reaction pathways and product distribution of oxidation of tetrachloroethylene (PCE) by potassium permanganate (KMnO4) were studied in phosphate-buffered solutions under constant pH, isothermal, completely mixed and zero headspace conditions. Experimental results indicate that the reaction is first-order with respect to both PCE and KMnO4 and has an activation energy of 9.3+/-0.9 kcal/mol. The second-order rate constant at 20 degrees C is 0.035+/-0.004 M(-1) s(-1), and is independent of pH and ionic strength (I) over a range of pH 3-10 and I approximately 0-0.2 M, respectively. The PCE-KMnO4 reaction may proceed through further oxidation and/or hydrolysis reaction pathways, greatly influenced by the acidity of the solution, to yield CO2(g), oxalic acid, formic acid and glycolic acid. Under acidic conditions (e.g., pH 3), the further oxidation pathway will dominate and PCE tends to be directly mineralized into CO2 and chloride. Under neutral (e.g., pH 7) and alkaline conditions (e.g., pH 10), the hydroxylation pathway dominates the reaction and PCE is primarily transformed into oxalic acid prior to complete PCE mineralization. Moreover, all chlorine atoms in PCE are rapidly liberated during the reaction and the rate of chloride production is very close to the rate of PCE degradation.