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  1. McGuire JR, Bester SM, Guelta MA, Cheung J, Langley C, Winemiller MD, et al.
    Chem Res Toxicol, 2021 03 15;34(3):804-816.
    PMID: 33538594 DOI: 10.1021/acs.chemrestox.0c00406
    The recent use of organophosphate nerve agents in Syria, Malaysia, Russia, and the United Kingdom has reinforced the potential threat of their intentional release. These agents act through their ability to inhibit human acetylcholinesterase (hAChE; E.C. 3.1.1.7), an enzyme vital for survival. The toxicity of hAChE inhibition via G-series nerve agents has been demonstrated to vary widely depending on the G-agent used. To gain insight into this issue, the structures of hAChE inhibited by tabun, sarin, cyclosarin, soman, and GP were obtained along with the inhibition kinetics for these agents. Through this information, the role of hAChE active site plasticity in agent selectivity is revealed. With reports indicating that the efficacy of reactivators can vary based on the nerve agent inhibiting hAChE, human recombinatorially expressed hAChE was utilized to define these variations for HI-6 among various G-agents. To identify the structural underpinnings of this phenomenon, the structures of tabun, sarin, and soman-inhibited hAChE in complex with HI-6 were determined. This revealed how the presence of G-agent adducts impacts reactivator access and placement within the active site. These insights will contribute toward a path of next-generation reactivators and an improved understanding of the innate issues with the current reactivators.
  2. Khoo CS, Kim SE, Lee BI, Shin KJ, Ha SY, Park J, et al.
    Eur Neurol, 2020;83(1):56-64.
    PMID: 32320976 DOI: 10.1159/000506591
    INTRODUCTION: Seizures as acute stroke mimics are a diagnostic challenge.

    OBJECTIVE: The aim of the study was to characterize the perfusion patterns on perfusion computed tomography (PCT) in patients with seizures masquerading as acute stroke.

    METHODS: We conducted a study on patients with acute seizures as stroke mimics. The inclusion criteria for this study were patients (1) initially presenting with stroke-like symptoms but finally diagnosed to have seizures and (2) with PCT performed within 72 h of seizures. The PCT of seizure patients (n = 27) was compared with that of revascularized stroke patients (n = 20) as the control group.

    RESULTS: Among the 27 patients with seizures as stroke mimics, 70.4% (n = 19) showed characteristic PCT findings compared with the revascularized stroke patients, which were as follows: (1) multi-territorial cortical hyperperfusion {(73.7% [14/19] vs. 0% [0/20], p = 0.002), sensitivity of 73.7%, negative predictive value (NPV) of 80%}, (2) involvement of the ipsilateral thalamus {(57.9% [11/19] vs. 0% [0/20], p = 0.007), sensitivity of 57.9%, NPV of 71.4%}, and (3) reduced perfusion time {(84.2% [16/19] vs. 0% [0/20], p = 0.001), sensitivity of 84.2%, NPV of 87%}. These 3 findings had 100% specificity and positive predictive value in predicting patients with acute seizures in comparison with reperfused stroke patients. Older age was strongly associated with abnormal perfusion changes (p = 0.038), with a mean age of 66.8 ± 14.5 years versus 49.2 ± 27.4 years (in seizure patients with normal perfusion scan).

    CONCLUSIONS: PCT is a reliable tool to differentiate acute seizures from acute stroke in the emergency setting.

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