Exercise capacity and incidence of myocardial perfusion defects after Kawasaki disease in children and adolescents

Objectives.This study evaluated exercise performance and myocardial perfusion during exercise in patients with Kawasaki disease who had a broad spectrum of residual coronary abnormalities.Background.Reports of exercise performance after Kawasaki disease have generally included a small number of patients evaluated by various protocols, frequently with incomplete data. Myocardial perfusion studies have usually been limited to those using pharmacologically induced coronary vasodilation. Therefore, to our knowledge there has not been a large study directly correlating exercise performance, electrocardiographic (ECG) changes and myocardial perfusion imaging.Methods.Forty-six patients were classified into three groups on the basis of coronary artery status: group 1 (n = 27) had no objective evidence of coronary artery lesions; group 2 (n = 11) had resolved aneurysms; group 3 (n = 8) had persistent coronary aneurysms. All patients underwent exercise testing with monitor ing of ECG changes and oxygen consumption. Single-photon emission computed tomographic imaging was performed at rest and during peak exercise using technetium-99m sestamibi.Results.Maximal oxygen consumption was within normal limits and was similar for all three groups. Five patients had mild ST segment changes at peak exercise. Two of these patients had stress-induced perfusion defects. Myocardial perfusion defects were present in 37% of patients in group 1, 63% in group 2 and 100% in group 3. Perfusion defects corresponded to the coronary artery lesion site in all but three patients.Conclusions.Maximal oxygen consumption is normal after Kawasaki disease regardless of coronary artery status. Stressinduced perfusion defects are frequent even in the absence of coronary abnormalities and are common in the absence of ST segment changes suggestive of ischemia

Revising evidence of hurricane strikes on Abaco Island (the Bahamas) over the last 700 years

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Winkler, T. S., van Hengstum, P. J., Donnelly, J. P., Wallace, E. J., Sullivan, R. M., MacDonald, D., & Albury, N. A. Revising evidence of hurricane strikes on Abaco Island (the Bahamas) over the last 700 years. Scientific Reports, 10(1), (2020): 16556, doi:10.1038/s41598-020-73132-x.The northern Bahamas have experienced more frequent intense-hurricane impacts than almost anywhere else in the Atlantic since 1850 CE. In 2019, category 5 (Saffir-Simpson scale) Hurricane Dorian demonstrated the destructive potential of these natural hazards. Problematically, determining whether high hurricane activity levels remained constant through time is difficult given the short observational record (< 170 years). We present a 700-year long, near-annually resolved stratigraphic record of hurricane passage near Thatchpoint Blue Hole (TPBH) on Abaco Island, The Bahamas. Using longer sediment cores (888 cm) and more reliable age-control, this study revises and temporally expands a previous study from TPBH that underestimated the sedimentation rate. TPBH records at least 13 ≥ category 2 hurricanes per century between 1500 to 1670 CE, which exceeds the 9 ≥ category 2 hurricanes per century within 50 km of TPBH since 1850 CE. The eastern United States also experienced frequent hurricanes from 1500 to 1670 CE, but frequency was depressed elsewhere in the Atlantic Ocean. This suggests that spatial heterogeneity in Atlantic hurricane activity since 1850 CE could have persisted throughout the last millennium. This heterogeneity is impacted by climatic and stochastic forcing, but additional high-resolution paleo-hurricane reconstructions are required to assess the mechanisms that impact regional variability.Field support was provided by Jody Albury and the staff of Friends of the Environment in Marsh Harbour, The Bahamas, and technical support was provided was provided by M. Horgan and S. Molodtsov. Funding for this project was provided by NSF Awards OCE-1356509, OCE-1356708, OCE-1854917, OCE-1903616, and ICER-1854980. The open access publishing fees for this article have been covered by the Texas A&M University Open Access to Knowledge Fund (OAKFund), supported by the University Libraries

Prospectus, April 1, 1987

https://spark.parkland.edu/prospectus_1987/1010/thumbnail.jp

Immune Protection of Nonhuman Primates against Ebola Virus with Single Low-Dose Adenovirus Vectors Encoding Modified GPs

BACKGROUND: Ebola virus causes a hemorrhagic fever syndrome that is associated with high mortality in humans. In the absence of effective therapies for Ebola virus infection, the development of a vaccine becomes an important strategy to contain outbreaks. Immunization with DNA and/or replication-defective adenoviral vectors (rAd) encoding the Ebola glycoprotein (GP) and nucleoprotein (NP) has been previously shown to confer specific protective immunity in nonhuman primates. GP can exert cytopathic effects on transfected cells in vitro, and multiple GP forms have been identified in nature, raising the question of which would be optimal for a human vaccine. METHODS AND FINDINGS: To address this question, we have explored the efficacy of mutant GPs from multiple Ebola virus strains with reduced in vitro cytopathicity and analyzed their protective effects in the primate challenge model, with or without NP. Deletion of the GP transmembrane domain eliminated in vitro cytopathicity but reduced its protective efficacy by at least one order of magnitude. In contrast, a point mutation was identified that abolished this cytopathicity but retained immunogenicity and conferred immune protection in the absence of NP. The minimal effective rAd dose was established at 10(10) particles, two logs lower than that used previously. CONCLUSIONS: Expression of specific GPs alone vectored by rAd are sufficient to confer protection against lethal challenge in a relevant nonhuman primate model. Elimination of NP from the vaccine and dose reductions to 10(10) rAd particles do not diminish protection and simplify the vaccine, providing the basis for selection of a human vaccine candidate

Antibody-mediated neutralization of Ebola virus can occur by two distinct mechanisms

AbstractHuman Ebola virus causes severe hemorrhagic fever disease with high mortality and there is no vaccine or treatment. Antibodies in survivors occur early, are sustained, and can delay infection when transferred into nonhuman primates. Monoclonal antibodies (mAbs) from survivors exhibit potent neutralizing activity in vitro and are protective in rodents. To better understand targets and mechanisms of neutralization, we investigated a panel of mAbs shown previously to react with the envelope glycoprotein (GP). While one non-neutralizing mAb recognized a GP epitope in the nonessential mucin-like domain, the rest were specific for GP1, were neutralizing, and could be further distinguished by reactivity with secreted GP. We show that survivor antibodies, human KZ52 and monkey JP3K11, were specific for conformation-dependent epitopes comprising residues in GP1 and GP2 and that neutralization occurred by two distinct mechanisms; KZ52 inhibited cathepsin cleavage of GP whereas JP3K11 recognized the cleaved, fusion-active form of GP

Neutralizing Antibody Fails to Impact the Course of Ebola Virus Infection in Monkeys

Prophylaxis with high doses of neutralizing antibody typically offers protection against challenge with viruses producing acute infections. In this study, we have investigated the ability of the neutralizing human monoclonal antibody, KZ52, to protect against Ebola virus in rhesus macaques. This antibody was previously shown to fully protect guinea pigs from infection. Four rhesus macaques were given 50 mg/kg of neutralizing human monoclonal antibody KZ52 intravenously 1 d before challenge with 1,000 plaque-forming units of Ebola virus, followed by a second dose of 50 mg/kg antibody 4 d after challenge. A control animal was exposed to virus in the absence of antibody treatment. Passive transfer of the neutralizing human monoclonal antibody not only failed to protect macaques against challenge with Ebola virus but also had a minimal effect on the explosive viral replication following infection. We show that the inability of antibody to impact infection was not due to neutralization escape. It appears that Ebola virus has a mechanism of infection propagation in vivo in macaques that is uniquely insensitive even to high concentrations of neutralizing antibody

The prevalence of mild cognitive impairment in Gulf War veterans: a follow-up study

IntroductionGulf War Illness (GWI), also called Chronic Multisymptom Illness (CMI), is a multi-faceted condition that plagues an estimated 250,000 Gulf War (GW) veterans. Symptoms of GWI/CMI include fatigue, pain, and cognitive dysfunction. We previously reported that 12% of a convenience sample of middle aged (median age 52 years) GW veterans met criteria for mild cognitive impairment (MCI), a clinical syndrome most prevalent in older adults (e.g., ≥70 years). The current study sought to replicate and extend this finding.MethodsWe used the actuarial neuropsychological criteria and the Montreal Cognitive Assessment (MoCA) to assess the cognitive status of 952 GW veterans. We also examined regional brain volumes in a subset of GW veterans (n = 368) who had three Tesla magnetic resonance images (MRIs).ResultsWe replicated our previous finding of a greater than 10% rate of MCI in four additional cohorts of GW veterans. In the combined sample of 952 GW veterans (median age 51 years at time of cognitive testing), 17% met criteria for MCI. Veterans classified as MCI were more likely to have CMI, history of depression, and prolonged (≥31 days) deployment-related exposures to smoke from oil well fires and chemical nerve agents compared to veterans with unimpaired and intermediate cognitive status. We also replicated our previous finding of hippocampal atrophy in veterans with MCI, and found significant group differences in lateral ventricle volumes.DiscussionBecause MCI increases the risk for late-life dementia and impacts quality of life, it may be prudent to counsel GW veterans with cognitive dysfunction, CMI, history of depression, and high levels of exposures to deployment-related toxicants to adopt lifestyle habits that have been associated with lowering dementia risk. With the Food and Drug Administration’s recent approval of and the VA’s decision to cover the cost for anti-amyloid β (Aβ) therapies, a logical next step for this research is to determine if GW veterans with MCI have elevated Aβ in their brains