COVID-19 Induces Neuroinflammation and Suppresses Peroxisomes in the Brain.

OBJECTIVE: Peroxisome injury occurs in the central nervous system (CNS) during multiple virus infections that result in neurological disabilities. We investigated host neuroimmune responses and peroxisome biogenesis factors during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection using a multiplatform strategy. METHODS: Brain tissues from coronavirus disease 2019 (COVID-19) (n = 12) and other disease control (ODC) (n = 12) patients, as well as primary human neural cells and Syrian hamsters, infected with a clinical variant of SARS-CoV-2, were investigated by droplet digital polymerase chain reaction (ddPCR), quantitative reverse transcriptase PCR (RT-qPCR), and immunodetection methods. RESULTS: SARS-CoV-2 RNA was detected in the CNS of 4 patients with COVID-19 with viral protein (NSP3 and spike) immunodetection in the brainstem. Olfactory bulb, brainstem, and cerebrum from patients with COVID-19 showed induction of pro-inflammatory transcripts (IL8, IL18, CXCL10, NOD2) and cytokines (GM-CSF and IL-18) compared to CNS tissues from ODC patients (p < 0.05). Peroxisome biogenesis factor transcripts (PEX3, PEX5L, PEX11ß, and PEX14) and proteins (PEX3, PEX14, PMP70) were suppressed in the CNS of COVID-19 compared to ODC patients (p < 0.05). SARS-CoV-2 infection of hamsters revealed viral RNA detection in the olfactory bulb at days 4 and 7 post-infection while inflammatory gene expression was upregulated in the cerebrum of infected animals by day 14 post-infection (p < 0.05). Pex3 transcript levels together with catalase and PMP70 immunoreactivity were suppressed in the cerebrum of SARS-CoV-2 infected animals (p < 0.05). INTERPRETATION: COVID-19 induced sustained neuroinflammatory responses with peroxisome biogenesis factor suppression despite limited brainstem SARS-CoV-2 neurotropism in humans. These observations offer insights into developing biomarkers and therapies, while also implicating persistent peroxisome dysfunction as a contributor to the neurological post-acute sequelae of COVID-19. ANN NEUROL 2023;94:531-546.

Evaluating the Effect of Imidacloprid Administered in Artificial Diet on Feeding Behavior of Diaphorina citri (Hemiptera: Liviidae) Using Electropenetrography.

The Asian citrus psyllid, Diaphorina citri Kuwayama (Hemiptera: Liviidae) is the vector of Candidatus Liberibacter asiaticus (CLas), the presumed cause of Huanglongbing (HLB) in citrus. Management strategies were developed in Florida that used soil-applied neonicotinoids to protect young trees. Despite the implementation of intense management programs, infection spread among the most intensively managed groves. We used electopenetrography to test five imidacloprid doses (0.55, 5.5, 55, 550, and 5,500 ppm) administered in artificial diet to approximate the dosage required to reduce feeding activity and prevent salivation/ingestion activity. We failed to detect a significant effect of 0.55 ppm imidacloprid on probing behavior, pathway, or salivation/ingestion activity when compared with the untreated control. We observed a significant reduction in the number of probes and the number of pathway with both 5.5 and 55 ppm imidacloprid. We detected a significant reduction in the number of salivation/ingestion events at both 5.5 ppm and 55 ppm imidacloprid (57 and 54 percent, respectively) compared with the untreated control, and a reduction in number of sustained (>600 s) salivation/ingestion at 55 ppm. While reductions in feeding activity were apparent at dosages of at least 5.5 ppm, we were unable to prevent salivation/ingestion with dosages as high as 5,500 ppm, which is greater than what is known to occur following application in the field. While soil-applied imidacloprid may slow the spread of CLas, our findings suggest that prevention of CLas inoculation in the field is unlikely. Management strategies must be refined to prevent the spread of HLB in Florida.

Influence of Tree Size and Application Rate on Expression of Thiamethoxam in Citrus and Its Efficacy Against Diaphorina citri (Hemiptera: Liviidae).

Neonicotinoids are a key group of insecticides used to manage Diaphorina citri Kuwayama (Hemiptera: Liviidae), in Florida citrus. Diaphorina citri is the vector of Candidatus Liberibacter asiaticus, the presumed causal agent of huanglongbing, a worldwide disease of citrus. A two-season field study was conducted to evaluate the effect of tree size and application rate on the expression of thiamethoxam in young citrus following application to the soil. D. citri adult and nymph abundance was also correlated with thiamethoxam titer in leaves. Tree size and application rate each significantly affected thiamethoxam titer in leaf tissue. The highest mean thiamethoxam titer observed (33.39 ppm) in small trees (mean canopy volume = 0.08 m3) occurred after application of the high rate (0.74 g Platinum 75SG per tree) tested. There was a negative correlation between both nymph and adult abundance with increasing thiamethoxam titer in leaves. A concentration of 64.63 ppm thiamethoxam was required to reach a 1% probability of encountering a flush shoot with at least one adult D. citri, while 19.05 ppm was required for the same probability of encountering nymphs. The LC90 for the field population was 7.62 ppm thiamethoxam when administered through ingestion. Exposure to dosages as low as 7.62 ppm would likely result in sublethal exposure of some proportion of the population, which could exacerbate resistance development. Based on our results, subsequent work should investigate the use of neonicotinoids by foliar rather than soil application to maintain the chemical class in future insecticide management programs in Florida citrus.

Field dissipation of 4-nonylphenol, 4-t-octylphenol, triclosan and bisphenol A following land application of biosolids.

The persistence of contaminants entering the environment through land application of biosolids needs to be understood to assess the potential risks associated. This study used two biosolids treatments to examine the dissipation of four organic compounds: 4-nonylphenol, 4-t-octylphenol, bisphenol A and triclosan, under field conditions in South Australia. The pattern of dissipation was assessed to determine if a first-order or a biphasic model better described the data. The field dissipation data was compared to previously obtained laboratory degradation data. The concentrations of 4-nonylphenol, 4-t-octylphenol and bisphenol A decreased during the field study, whereas the concentration of triclosan showed no marked decrease. The time taken for 50% of the initial concentration of the compounds in the two biosolids to dissipate (DT50), based on a first-order model, was 257 and 248 d for 4-nonylphenol, 231 and 75 d for 4-t-octylphenol and 289 and 43 d for bisphenol A. These field DT50 values were 10- to 20-times longer for 4-nonylphenol and 4-t-octylphenol and 2.5-times longer for bisphenol A than DT50 values determined in the laboratory. A DT50 value could not be determined for triclosan as this compound showed no marked decrease in concentration. The biphasic model provided a significantly improved fit to the 4-t-octylphenol data in both biosolids treatments, however, for 4-nonylphenol and bisphenol A it only improved the fit for one treatment. This study shows that the use of laboratory experiments to predict field persistence of compounds in biosolids amended soils may greatly overestimate degradation rates and inaccurately predict patterns of dissipation.

Degradation of 4-nonylphenol, 4-t-octylphenol, bisphenol A and triclosan following biosolids addition to soil under laboratory conditions.

Land application of biosolids is common practice in many countries, however, there are some potential risks associated with the presence of contaminants within the biosolids. This laboratory study examined the degradation of four commonly found organic compounds, 4-nonylphenol, 4-t-octylphenol, bisphenol A, and triclosan, in soil following the addition of two biosolids over 32 weeks. The pattern of degradation was assessed to determine if it followed a standard first-order decay model or if a biphasic model with a degrading and a recalcitrant fraction better described the data. The time taken for the initial concentrations to decrease by 50% (DT50), based on a first-order model, was 12-25 d for 4-nonylphenol, 10-14 d for 4-t-octylphenol, 18-102 d for bisphenol A, and 73-301 d for triclosan. For 4-nonylphenol, bisphenol A and triclosan, the biphasic model fitted the degradation data better than the first-order model, indicating the presence of a degrading fraction and a non-degrading recalcitrant fraction. The recalcitrant fraction for these three compounds at the completion of the 32 week experiment was 17-21%, 24-42%, and 30-51% of the initial concentrations, respectively. For 4-t-octylphenol, the first-order model was sufficient in explaining the degradation data, indicating that no recalcitrant fraction was present. This study showed that biphasic degradation occurred for some organic compounds in biosolids amended soil and that the use of standard first-order degradation models may underestimate the persistence of some organic compounds following land application of biosolids.

Long-term exposure to high fat diet is bad for your brain: exacerbation of focal ischemic brain injury.

A diet consisting of high levels of saturated fat has been linked to a dramatic rise in obesity, type II diabetes, and metabolic syndrome. The effect of these co-morbidities on stroke outcome has not been examined in detail in human or animal studies. In this study we hypothesized that maintaining animals on a high fat, "Western diet" (WD), for an extended period would have a detrimental effect on ischemic outcome. Forty-eight male Sprague-Dawley rats were exposed to 1 month of either WD or control diets initiated at 6 weeks of age (Experiment 1) or 3 months of either WD or control diets initiated at 4 weeks of age (Experiment 2) prior to endothelin-1-induced ischemia. Following ischemia, animals were assessed in the staircase reaching and beam-traversing tests at 2 and 4 weeks post-ischemia and infarct volumes were calculated at 4 weeks post-ischemia. Analysis revealed no difference between animals exposed to either WD or control diets for 1 month in behavioral or histological assessments. In contrast, 3 months of WD diet exposure significantly increased functional impairments in both the staircase and beam-traversing tests as well as increasing the volume of infarction, primarily in the cortex. The results of this study demonstrate that long-term exposure to WD diets are detrimental to ischemic outcome. Consequently, it is important to incorporate disease co-morbidities and/or risk factors in pre-clinical evaluation of neuroprotective or restorative interventions if therapies are to be translated into the clinic.

Aquatic hazard assessment for pharmaceuticals, personal care products, and endocrine-disrupting compounds from biosolids-amended land.

Reuse of biosolids on agricultural land is a common practice. Following the application of biosolids to land, contaminants in the biosolids have the potential to migrate offsite via surface runoff and/or leaching and pose a hazard to aquatic ecosystems. The aim of this screening-level assessment study was to determine the relative hazard posed to aquatic ecosystems by pharmaceuticals, personal care products, and endocrine-disrupting compounds (EDCs) that have been detected and quantified in biosolids. This involved estimating maximum possible runoff water concentrations of compounds, using an equilibrium partitioning approach and then comparing these with the lowest available aquatic toxicity data, using the hazard quotient (HQ) approach. A total of 45 pharmaceuticals, personal care products, and EDCs have been detected in biosolids. Ten of these compounds (tonalide, galaxolide, 17ß-estradiol, 17α-ethinylestradiol, ciprofloxacin, doxycycline, norfloxacin, ofloxacin, triclosan, and triclocarban) posed a high (HQ >1.0) hazard to aquatic ecosystems relative to the other compounds. This hazard assessment indicated that further research into potential offsite migration and deleterious effects on aquatic ecosystems is warranted for the 10 organic contaminants identified, and possibly for chemicals with similar physicochemical and toxicological properties, in biosolids-amended soils. Because many antibiotic compounds (e.g., ciprofloxacin, norfloxacin, and ofloxacin) have ionic properties, the methods used may have overestimated their predicted aqueous concentrations and hazard. Further research that includes site-specific variables, e.g., dilution factors in waterways, rain intensity, slope of land, degradation, and the use of management strategies such as buffer zones, is likely to decrease the hazard posed by these high hazard compounds.

Distribution, Hosts, and Morphological Characteristics of Tylenchulus palustris in Florida and Bermuda.

Studies on the geographical distribution and hosts of Tylenchulus palustris were conducted over a 3-year period in Florida and Bermuda. Tylenchulus palustris was found on Aster elliottii and Liquidambar styraciflua roots in swamps of northern and central Florida. It was detected also on Borrichia arborescens and B. frutescens roots in tidal marshes of northern Florida and coastal rocklands of southern Florida and Bermuda. Posterior bodies of T. palustris swollen females from Bermuda did not differ from those of the paratypes; however, second-stage juvenile bodies and male tails from Bermuda were longer than those of the paratypes. Greenhouse host tests indicated that Mikania scandens is a host of T. palustris but not of T. semipenetrans.