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Background: Fever of unknown origin (FUO) is a well-known pediatric presentation. The primary studies determining the causes of prolonged fever in children were performed 4 decades ago, before major advances in laboratory and diagnostic testing. Given that the distribution of diagnosed causes of adult FUO has changed in recent decades, we hypothesized that the etiology of FUO in children has concordantly changed and also may be impacted by a definition that includes a shorter required duration of fever., Methods: A single-center, retrospective review of patients 6 months to 18 years of age admitted to the North Carolina Children's Hospital from January 1, 2002, to December 21, 2012, with an International Classification of Diseases, Ninth Revision diagnosis of fever, a documented fever duration >7 days before admission, and a previous physician evaluation of each patient's illness., Results: A total of 1164 patients were identified, and of these, 102 met our inclusion criteria for FUO. Etiologic categories included "infectious" (42 out of 102 patients), "autoimmune" (28 out of 102 patients), "oncologic" (18 out of 102 patients), and "other" or "unknown" (14 out of 102 patients). Several clinical factors were statistically and significantly different between etiologic categories, including fever length, laboratory values, imaging performed, length of stay, and hospital costs., Conclusions: Unlike adult studies, the categorical distribution of diagnoses for pediatric FUO has marginally shifted compared to previously reported pediatric studies. Patients hospitalized with FUO undergo prolonged hospital stays and have high hospital costs. Additional study is needed to improve the recognition, treatment, and expense of diagnosis of prolonged fever in children., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2018 by the American Academy of Pediatrics.)

Eukaryotic aminopeptidase P1 (APP1), also known as X-prolyl aminopeptidase (XPNPEP1) in human tissues, is a cytosolic exopeptidase that preferentially removes amino acids from the N-terminus of peptides possessing a penultimate N-terminal proline residue. The enzyme has an important role in the catabolism of proline containing peptides since peptide bonds adjacent to the imino acid proline are resistant to cleavage by most peptidases. We show that recombinant and catalytically active Caenorhabditis elegans APP-1 is a dimer that uses dinuclear zinc at the active site and, for the first time, we provide structural information for a eukaryotic APP-1 in complex with the inhibitor, apstatin. Our analysis reveals that C. elegans APP-1 shares similar mode of substrate binding and a common catalytic mechanism with other known X-prolyl aminopeptidases.