{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T21:59:04Z","timestamp":1791410344356,"version":"4.3.3"},"reference-count":29,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,6,15]],"date-time":"2020-06-15T00:00:00Z","timestamp":1592179200000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI001086\u201008"],"award-info":[{"award-number":["AI001086\u201008"]}],"id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2020,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The detection of prion seeding activity in CSF and olfactory mucosal brushings using real\u2010time quaking\u2010induced conversion assays allows highly accurate clinical diagnosis of sporadic Creutzfeldt\u2013Jakob disease. To gauge transmission risks associated with these biospecimens and their testing, we have bioassayed prion infectivity levels in patients\u2019 brain tissue, nasal brushings, and CSF, and assessed the pathogenicity of amplified products of real\u2010time quaking\u2010induced conversion assays seeded with Creutzfeldt\u2013Jakob disease prions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We obtained olfactory mucosal brushings and CSF from patients with a final diagnosis of sporadic Creutzfeldt\u2013Jakob disease subtype MM1 (n\u00a0=\u00a03). Samples were inoculated intracerebrally into Tg66 transgenic mice that overexpress the homologous human 129M prion protein. The mice were evaluated for clinical, neuropathological, and biochemical evidence of prion infection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Patients\u2019 brain tissue at 10\n                      <jats:sup>2<\/jats:sup>\n                      to 10\n                      <jats:sup>5<\/jats:sup>\n                      fold dilutions affected 47\/48 Tg66 mice. In contrast, maximum acutely tolerable doses of insoluble pellets from their olfactory mucosa brushings caused evidence of prion disease in only 4\/28 inoculated mice, and no effects were seen with\u00a010\u2010fold dilutions. No clinical prion disease was observed in mice inoculated with\n                      <jats:italic>antemortem<\/jats:italic>\n                      CSF samples or prion\u2010seeded real\u2010time quaking\u2010induced conversion assay products.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Pellets from patients\u2019 olfactory mucosa brushings had\u00a0\u226510,000\u2010fold lower infectivity per unit volume than brain tissue, while CSF lacked detectable infectivity. Nonetheless, the results suggest that appropriate precautions may be warranted in surgical interventions involving the olfactory areas. The lack of pathogenic infectivity in the real\u2010time quaking\u2010induced conversion assay products provides evidence that the assay does not replicate biohazardous prions in vitro.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/acn3.51057","type":"journal-article","created":{"date-parts":[[2020,6,15]],"date-time":"2020-06-15T05:46:04Z","timestamp":1592199964000},"page":"932-944","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Transmission of CJD from nasal brushings but not spinal fluid or RT\u2010QuIC product"],"prefix":"10.1002","volume":"7","author":[{"given":"Gregory J.","family":"Raymond","sequence":"first","affiliation":[{"name":"Laboratory of Persistent Viral Diseases Rocky Mountain Laboratories National Institute for Allergy and Infectious Diseases National Institutes of Health Hamilton 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