Streptococcus mutans is the causative agent of dental caries, a significant concern for human health, and therefore an attractive target for therapeutics development. Previous work in our laboratory has identified a homodimeric, manganese-dependent repressor protein, SloR, as an important regulator of cariogenesis and has used site-directed mutagenesis to map functions to specific regions of the protein. Here we extend those studies to better understand the structural interaction between SloR and its operator and its effector metal ions. The results of DNase I assays indicate that SloR protects a 42-bp region of DNA that overlaps the sloABC promoter on the S. mutans UA159 chromosome, while electrophoretic mobility shift and solution binding assays indicate that each of two SloR dimers binds to this region. Real-time semiquantitative reverse transcriptase PCR (real-time semiqRT-PCR) experiments were used to determine the individual base pairs that contribute to SloR-DNA binding specificity. Solution studies indicate that Mn 2؉ is better than Zn 2؉ at specifically activating SloR to bind DNA, and yet the 2.8-Å resolved crystal structure of SloR bound to Zn 2؉ provides insight into the means by which selective activation by Mn 2؉ may be achieved and into how SloR may form specific interactions with its operator. Taken together, these experimental observations are significant because they can inform rational drug design aimed at alleviating and/or preventing S. mutans-induced caries formation. IMPORTANCE This report focuses on investigating the SloR protein as a regulator of essential metal ion transport and virulence gene expression in the oral pathogen Streptococcus mutans and on revealing the details of SloR binding to its metal ion effectors and binding to DNA that together facilitate this expression. We used molecular and biochemical approaches to characterize the interaction of SloR with Mn2؉ and with its SloR recognition element to gain a clearer picture of the regulatory networks that optimize SloRmediated metal ion homeostasis and virulence gene expression in S. mutans. These experiments can have a significant impact on caries treatment and/or prevention by revealing the S. mutans SloR-DNA binding interface as an appropriate target for the development of novel therapeutic interventions. Cariogenesis is a disease that derives from interactions involving the human dentition, an acidogenic microflora, including Streptococcus mutans, and dietary factors. Specifically, S. mutans, which is among the most cariogenic of the oral microbes, assumes an obligate biofilm lifestyle upon colonizing the tooth surface during the first year of life, shortly after tooth eruption. Commonly found in the human oral cavity as the most abundant species in the dental plaque biofilm, S. mutans metabolizes exogenous dietary carbohydrates to generate energy for itself via fermentation and releases acid as a metabolic byproduct. The buffering capacity of saliva combined with appropriate oral hygiene practices can maintain the p...

Sickle cell disease, a complex disorder with known pulmonary complications, has the potential to confound the diagnosis of pulmonary embolism. We hypothesized that when the choice of imaging is guided by chest radiographic results, CT pulmonary angiography (CTPA) and ventilation-perfusion (V/Q) scintigraphy have comparable diagnostic performance in sickle cell disease. A retrospective cohort of adults with sickle cell disease who were imaged for suspected pulmonary embolism with either CTPA or V/Q, from 2000 to 2016 at our institution, was established. To reduce radiation exposure, our practice recommends V/Q for stable patients with normal chest radiographs. Results of index pulmonary embolism imaging, 90-d follow-up, and results of chest radiography were recorded. Two hundred forty-five adults with sickle cell disease comprised the cohort. The mean age (±SD) was 33 ± 10.5 y, and 58% (141) were men. Index imaging was V/Q in 62.9% ( = 154) and CTPA in 37.1% ( = 91). Chest radiographs, performed in 96.3% ( = 236), were normal in 72.9% ( = 172). Imaging results for pulmonary embolism were negative in 88.2% ( = 216), positive in 4.1% ( = 10), and indeterminate in 7.8% ( = 19) with no difference between V/Q and CTPA ( = 0.63). Reimaging within 90 d occurred in 9.8% ( = 24), 14.7% (20/136) after initial V/Q, and 5% (4/109) after initial CTPA ( = 0.08). Reimaging revealed a pulmonary embolism diagnosis after negative/indeterminate results in 0.7% (1/149) of V/Qs and 1.2% of (1/86) CTPAs ( = 0.69). Over the 17-y study period, 47% (114/245) underwent repeated imaging, and 11% (27/245) were diagnosed with pulmonary embolism at least once. In sickle cell disease patients with suspected pulmonary embolism, positive imaging rates were low for any given clinical presentation, but 11% of the cohort was diagnosed with pulmonary embolism over the 17-y study period. CTPA and V/Q performed comparably for pulmonary embolism diagnosis when the choice of imaging was guided by results of chest radiography. Hence, V/Q is a reasonable first choice for sickle cell disease patients with normal chest radiographs.

Purpose: To determine whether diagnostic quality thoracic computed tomography angiography (CTA) studies can be obtained without general anesthesia (GA) in infants and young children using dual-source computed tomography (DSCT) with turbo flash spiral mode (TFSM) and free-breathing technique.Materials and Methods: All consecutive infants and young children (≤ 6 years old) who underwent thoracic CTA studies from January 2018 to October 2020 for suspected congenital thoracic disorders were categorized into two groups: with GA (Group 1) and without GA (Group 2). All thoracic CTA studies were performed on a DSCT scanner using TFSM and free-breathing technique. Two pediatric thoracic radiologists independently evaluated motion artifact in three lung zones (upper, mid, and lower). Degree of motion artifact was graded 0-3 (0, none; 1, mild; 2, moderate; and 3, severe). Logistic models adjusted for age and gender were used to compare the degree of motion artifact between lung zones. Interobserver agreement between reviewers was evaluated with kappa statistics.Results: There were a total of 73 pediatric patients (43 males (59%) and 30 females (41%); mean age, 1.4 years; range, 0-5.9 years). Among these 73 patients, 42 patients (58%) underwent thoracic CTA studies with GA (Group 1) and the remaining 31 patients (42%) underwent thoracic CTA studies without GA (Group 2). Overall, the degree of motion artifact was higher for Group 2 (without GA). However, only a very small minority (1/31, 3%) of Group 2 (without GA) thoracic CTA studies had severe motion artifact. There was no significant difference between the two groups with respect to the presence of severe motion artifact (odds ratio [OR] = 6, p = .222).When two groups were compared with respect to the presence of motion artifact for individual lung zones, motion artifact was significantly higher in the upper lung zone for Group 2 (without GA) (OR = 20, p = .043). Interobserver agreement for motion artifact was high, the average Kappa being 0.81 for Group 1 and 0.95 for Group 2. Conclusion:Although the degree of motion artifact was higher in the group without GA, only a small minority (3%) of thoracic CTA studies performed without GA had severe motion artifact, rendering the study nondiagnostic. Therefore, the results of this study support the use of thoracic CTA without GA using DSCT with TFSM and free-breathing in infants and young children. In addition, given that motion artifact was significantly higher in the upper lung zone without GA, increased stabilization in the upper chest and extremities should be considered. K E Y W O R D S chest, children, computed tomography angiography (CTA), dual-source computed tomography (DSCT), infants, motion, motion artifact, sedation, turbo flash spiral mode (TFSM), young children How to cite this article: Tivnan P, Winant AJ, Johnston PR, et al. Thoracic CTA in infants and young children: Image quality of dual-source CT (DSCT) with high-pitch spiral scan mode (turbo flash spiral mode) with or without general anesthesia with freebr...

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