Variability in Occult Injury Screening Among Siblings/Household Contacts of Physical Abuse Victims.

OBJECTIVE: The objective of this study is to examine radiologic occult injury screening performance/yield among contacts presenting for precautionary medical assessments and assess factors associated with deferred screening. METHODS: Data were collected retrospectively from charts of contacts younger than 8 years presenting for precautionary evaluation to a level 1 pediatric emergency department January 1, 2018 to March 31, 2023. Demographics, radiologic performance/yield, physical examination, social work-based psychosocial assessment, reasons for deferred imaging, and diagnostic codes were abstracted. Descriptive statistics and χ 2 analysis are reported. RESULTS: Three hundred ninety contacts were identified; 364 (93.3%) were biological siblings. Most (276, 70.8%) were 2 to 8 years old. Statistically significant relationships were identified with age, insurance, and hospital social work assessment and screening. Thirty-four infants (54%) underwent neuroimaging; no studies were abnormal. Of 114 contacts, <2 years old, 97 (85%) underwent skeletal survey (SS); 9 (9%) SS were abnormal. Twenty-seven (24%) returned for follow-up SS; 4 (14.8%) were abnormal. For 2 contacts, an abnormal initial SS was refuted by follow-up imaging. Physical examinations were abnormal for 11% of contacts. Reasons for deferred imaging included contact well appearance, caregiver concerns, and clinician disagreement with indications. Encounter International Classification of Diseases codes varied, commonly reflecting nonspecific screening assessments. CONCLUSIONS: Despite national clinical practice guidelines, studies of abusive injury prevalence and radiologic yield among at-risk contacts exposed to unsafe environments are few. Screening evaluations inclusive of physical examination and radiologic studies identify abuse concerns among at-risk contacts. Further study of factors impacting radiologic screening decisions is needed. Considerations to advance epidemiologic research include standardized diagnostic coding and prospective assessment of radiologic yield.

Manipulation of a cation-π sandwich reveals conformational flexibility in phenylalanine hydroxylase.

Phenylalanine hydroxylase (PAH) is an allosteric enzyme that maintains phenylalanine (Phe) below neurotoxic levels; its failure results in phenylketonuria, an inborn error of amino acid metabolism. Wild type (WT) PAH equilibrates among resting-state (RS-PAH) and activated (A-PAH) conformations, whose equilibrium position depends upon allosteric Phe binding. The RS-PAH conformation of WT rat PAH (rPAH) contains a cation-π sandwich involving Phe80 that cannot exist in the A-PAH conformation. Phe80 variants F80A, F80D, F80L, and F80R were prepared and evaluated using native PAGE, size exclusion chromatography, ion exchange behavior, intrinsic protein fluorescence, enzyme kinetics, and limited proteolysis, each as a function of [Phe]. Like WT rPAH, F80A and F80D show allosteric activation by Phe while F80L and F80R are constitutively active. Maximal activity of all variants suggests relief of a rate-determining conformational change. Limited proteolysis of WT rPAH (minus Phe) reveals facile cleavage within a 4-helix bundle that is buried in the RS-PAH tetramer interface, reflecting dynamic dissociation of that tetramer. This cleavage is not seen for the Phe80 variants, which all show proteolytic hypersensitivity in a linker that repositions during the RS-PAH to A-PAH interchange. Hypersensitivity is corrected by addition of Phe such that all variants become like WT rPAH and achieve the A-PAH conformation. Thus, manipulation of Phe80 perturbs the conformational space sampled by PAH, increasing sampling of on-pathway intermediates in the RS-PAH and A-PAH interchange. The behavior of the Phe80 variants mimics that of disease-associated R68S and suggests a molecular basis for proteolytic susceptibility in PKU-associated human PAH variants.