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COVID-19 results in increased expression of inflammatory cytokines, but inflammation-targeting clinical trials have yielded poor to mixed results. Our studies of other disorders with an inflammatory component, including Alzheimer's disease, chemobrain, Down syndrome, normal aging, and West Nile Virus infection, showed that treatment with the 'pro-inflammatory' cytokine granulocyte-macrophage colony stimulating factor (GM-CSF) in humans or mouse models alleviated clinical, behavioral, and pathological features. We proposed that human recombinant GM-CSF (sargramostim) be repurposed to promote both the innate and adaptive immune responses in COVID-19 to reduce viral load and mortality1. Here, we report the results of a placebo-controlled study of GM-CSF in human ACE2 transgenic mice inoculated intranasally with SARS-CoV2 virus, a model of COVID-19. Infection resulted in high viral titers in lungs and brains and over 85% mortality. GM-CSF treatment beginning one day after infection increased anti-viral antibody titers, lowered mean lung viral titers proportionately (p=0.0020) and increased the odds of long-term survival by up to 5.8-fold (p=0.0358), compared to placebo. These findings suggest that, as an activator of both the innate and adaptive immune systems, GM-CSF/sargramostim may be an effective COVID-19 therapy with the potential to protect from re-infection more effectively than treatment with antiviral drugs or monoclonal antibodies.

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Over a million people in Peru may be exposed to lead (Pb) due to past or present mining-related activities; however, neither soil Pb nor blood Pb are routinely monitored throughout the country. Because little is known about Pb contamination in smaller mining-impacted towns, soil Pb was mapped in four such towns with a portable X-ray fluorescence analyzer in 2015. The roadside mapping delineated hotspots of highly contaminated soil (1,000-6,000 mg/kg Pb) in two of the towns. The local health department, provided with a LeadCare II analyzer, then measured blood-Pb levels >5 in 65% and >10 µg/dL in 15% of children (n = 200) up to 6 years of age in these same four communities. There were no clear relations between child blood-Pb levels and Pb levels in soil samples collected inside (n = 50) or outside the home (n = 50). Increased child blood Pb was associated with decreased level of cleanliness of parent clothing (n = 136) and shoes (n = 138), linking a possible behavioral factor for transferring contaminated soil and dust to children. In order to explore individual exposure and variations in soil Pb, 10 parents of children with blood Pb >10 µg/dL and 10 parents of children with blood Pb <5 µg/dL were invited to collect soil samples in areas where their children play and screen it for Pb using a color-based field procedure. Importantly, parents identified a new hotspot of Pb contamination that had been missed by the previous portable X-ray fluorescence soil mapping. The findings highlight the feasibility and value of involving families impacted by environmental contamination to identify and reduce environmental health risk.

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BACKGROUND: Meningoencephalomyelitis of unknown origin (MUO) is a common and life-threatening neuroinflammatory disease in dogs. Features of the disease are suggestive of an underlying immune-mediated process, but the association of this disease with a pathogen is still unknown. HYPOTHESIS/OBJECTIVES: To search for candidate etiologic agent associated with cases if MUO using next generation metagenomic sequencing. ANIMALS: Twenty-two dogs diagnosed with either MUO (11/22; 10 CSF and 3 brain), or noninflammatory CNS diseases inconsistent with MUO (11/22; 11 CSF and 2 brain) that served as negative controls. METHODS: A case control study was performed by identifying MUO and non-MUO cases. Samples were blindly processed and then unblinded for comparative analyses. Inclusion criteria for MUO cases included consistent MRI lesions and inflammatory CSF with a negative PCR panel for infectious agents or histopathologic diagnosis. Dogs with glucocorticoid therapy within 2 weeks of sample collection were excluded. Fresh-frozen cerebrospinal fluid (CSF; 21) and brain (5) samples were collected and RNA and DNA were extracted separately for shotgun metagenomic sequencing. Known positive samples were used as controls to validate our sequencing and analysis pipelines and to establish limits of detection. Sequencing results were analyzed at a nucleotide and protein level for broad comparison to known infectious organisms. RESULTS: No candidate etiologic agents were identified in dogs with MUO. CONCLUSIONS AND CLINICAL IMPORTANCE: These results support but do not prove the hypothesis that MUO is not associated with infectious agents and might be an autoimmune disease.

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Listeriosis is a serious foodborne disease caused by Listeria monocytogenes, a pathogen often found in food processing plants. Poultry meat and its derivatives may harbor L. monocytogenes even if good manufacturing practices are implanted in abattoirs. Little information exists in Brazil on the frequency of L. monocytogenes contamination, even though the country is considered the top poultry meat exporter in the world. This study attempted to compare 2 exporters poultry facilities following same the standards but differing only in manual (plant M) or automatic (plant A) evisceration. Eight hundred fifty-one samples from food, food contact and non-food contact surfaces, water, and workers' hands were collected from cage to finished products over a 1-yr period. In plant A, 20.1% of the samples were positive for L. monocytogenes, whereas in plant M, 16.4% was found. The greatest incidence of contamination with the pathogen in plant A was found in non-food contact surfaces (27.3%), while in plant M, it was found in products (19.4%). The most prevalent serovars were 1/2a or 3a (plant M) and 4b, 4d, or 4e (plant A). Despite having proper hygiene and good manufacturing practices, controlling the entry and persistence of L. monocytogenes in processing facilities remains a formidable task.

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OBJECTIVE: We performed a review of current data to determine the effect that operation has on pulmonary function, aerobic capacity, and stroke volume in patients with pectus excavatum. STUDY DESIGN: Two reviewers independently assessed clinical trials and collected data on interventions and outcomes. To qualify for inclusion, a study had to include preoperative and postoperative assessment, provide outcomes in either a published percentile or qualified matched control form to control for interval growth, and include only original patient groups. RESULTS: Postoperative total lung capacity for patients who had Ravitch repair was significantly lower (SMD, 0.71 [CI -1.06, -0.36]; I(2) = 19.6%) than preoperative. Based on 2 studies after removal of the Nuss bar, FEV(1) was significantly increased from preoperative values (SMD, 0.39 [CI, 0.03, 0.74]; I(2) = 0%). Stroke volume increased after surgery (SMD, 0.40 [CI, 0.10, 0.70]; I(2) = 0%) after Ravitch repair. There was a trend toward improved exercise tolerance, but it was not statistically significant. CONCLUSIONS: Total lung capacity was decreased after Ravitch repair, and FEV(1) was increased after Nuss bar removal. Stroke volume may be increased after Ravitch repair. Exercise tolerance was not improved after either type of surgical repair.

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OBJECTIVES: To investigate the extent to which the abnormalities in cerebral white matter in adolescents and adults with phenylketonuria (PKU) are reversible. METHOD: Magnetic resonance imaging (MRI) of the brain was repeated in 41 patients with PKU (age range, 14 to 49 years) after an interval (median, 9 months; range, 3 to 12 months) of dietary intervention. Scans were scored according to the extent of the white matter involvement. After an initial MRI, five patients returned to a strict low-phenylalanine diet with amino acid supplement; 21 patients started a low-protein diet (1 gm/kg) with amino acids supplement; and 15 patients made no dietary alteration. RESULTS: Scans improved in all five patients who returned to a strict low-phenylalanine diet, in 5 of the 21 patients on the low-protein diet plus amino acid supplement, and in 4 of the 15 patients who made no dietary change. There was a significant association between change in the MRI findings and in the blood phenylalanine concentration (Pearson correlation: r = 0.55; p < 0.0002) and between change in the MRI and in the phenylalanine level at the time of the second scan (r = 0.58; p < 0.0001). Improvement was seen primarily in those in whom phenylalanine levels were reduced to less than 900 mumol/L. There was no obvious change in MRI score after 3 weeks of strict phenylalanine restriction for the two adults who underwent serial scanning. CONCLUSION: The MRI changes in PKU are at least partially reversible by lowering the blood phenylalanine concentration.

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