Multi-institutional Protocol Guidance for Pediatric Photon-counting CT.

Performing CT in children comes with unique challenges such as greater degrees of patient motion, smaller and densely packed anatomy, and potential risks of radiation exposure. The technical advancements of photon-counting detector (PCD) CT enable decreased radiation dose and noise, as well as increased spatial and contrast resolution across all ages, compared with conventional energy-integrating detector CT. It is therefore valuable to review the relevant technical aspects and principles specific to protocol development on the new PCD CT platform to realize the potential benefits for this population. The purpose of this article, based on multi-institutional clinical and research experience from pediatric radiologists and medical physicists, is to provide protocol guidance for use of PCD CT in the imaging of pediatric patients.

Pediatric Applications of Photon-Counting Detector CT.

Photon-counting detector (PCD) CT represents the most recent generational advance in CT technology. PCD CT has the potential to reduce image noise, improve spatial resolution and contrast resolution, and provide multispectral capability, all of which may be achieved with an overall decrease in the radiation dose. These effects may be used to reduce the iodinated contrast media dose and potentially obtain multiphase images through a single-acquisition technique. The benefits of PCD CT have previously been shown primarily in phantoms and adult patients. This article describes the application of PCD CT in children, as illustrated by clinical examples from a commercially available PCD CT system.

Hepatic manifestations of systemic disease: an imaging-based review.

The liver is responsible for many processes that maintain human metabolic homeostasis and can be affected by several pediatric systemic diseases. In this manuscript, we explore key pathological findings and imaging features across multiple modalities of a spectrum of congenital, metabolic and autoimmune disorders. Strengthening the radiologists' knowledge regarding potential hepatic manifestations of these systemic diseases will ultimately lead to improved care for pediatric patients.

Awareness of relative CT utilization among peers is not associated with changes in imaging requests among emergency department providers in a large county hospital.

PURPOSE: The purpose of this quality improvement initiative was to study the effect of providing scorecards to emergency department providers to assess its effect on changes in utilization. METHODS: CT of the abdomen and pelvis, CT angiogram of the chest for pulmonary embolism, and CT of the head were targeted due to ordering variability, cost, and radiation exposure. The utilization rate for each provider was assessed for emergency department providers. Following this, providers were given scorecards regarding their utilization as well as their relative utilization compared with each other. Utilization was then monitored following the intervention to assess the effect of the scorecard on ordering practices. RESULTS: No significant effect on the utilization of these 3 exams was found after the scorecard intervention. CONCLUSION: Providing scorecards to make emergency department providers aware of their relative utilization does not significantly alter ordering behavior. Incentive-based systems may be required in order to lessen overutilization of these 3 commonly ordered radiology procedures in the emergency department.

SUMO in Drosophila Development.

The ubiquitin -like protein SUMO is conjugated covalently to hundreds of target proteins in organisms throughout the eukaryotic domain. Genetic and biochemical studies using the model organism Drosophila melanogaster are beginning to reveal many essential functions for SUMO in cell biology and development. For example, SUMO regulates multiple signaling pathways such as the Ras/MAPK, Dpp, and JNK pathways. In addition, SUMO regulates transcription through conjugation to many transcriptional regulatory proteins, including Bicoid, Spalt , Scm, and Groucho. In some cases, conjugation of SUMO to a target protein inhibits its normal activity, while in other cases SUMO conjugation stimulates target protein activity. SUMO often modulates a biological process by altering the subcellular localization of a target protein. The ability of SUMO and other ubiquitin-like proteins to diversify protein function may be critical to the evolution of developmental complexity.

A second hotspot for pathogenic exon-skipping variants in CDC45.

Biallelic pathogenic variants in CDC45 are associated with Meier-Gorlin syndrome with craniosynostosis (MGORS type 7), which also includes short stature and absent/hypoplastic patellae. Identified variants act through a hypomorphic loss of function mechanism, to reduce CDC45 activity and impact DNA replication initiation. In addition to missense and premature termination variants, several pathogenic synonymous variants have been identified, most of which cause increased exon skipping of exon 4, which encodes an essential part of the RecJ-orthologue's DHH domain. Here we have identified a second cohort of families segregating CDC45 variants, where patients have craniosynostosis and a reduction in height, alongside common facial dysmorphisms, including thin eyebrows, consistent with MGORS7. Skipping of exon 15 is a consequence of two different variants, including a shared synonymous variant that is enriched in individuals of East Asian ancestry, while other variants in trans are predicted to alter key intramolecular interactions in α/ß domain II, or cause retention of an intron within the 3'UTR. Our cohort and functional data confirm exon skipping is a relatively common pathogenic mechanism in CDC45, and highlights the need for alternative splicing events, such as exon skipping, to be especially considered for variants initially predicted to be less likely to cause the phenotype, particularly synonymous variants.

An Elite Privilege: Top-Ranked Medical Schools Provide Fewer Comparative Performance Data on Their Students.

PURPOSE: The objective of this study was to determine differences in the reporting of performance data on medical student performance evaluations (MSPEs) by medical school ranking. METHODS: MSPEs from all US allopathic and osteopathic medical schools received by a single diagnostic radiology residency program during the 2021-2022 application cycle were retrospectively reviewed. Preclinical class and core clerkship grades were categorized as pass/fail or multitiered. Comparative summative assessments provided in the MSPEs were recorded. Medical schools were grouped by their US News & World Report rankings, and the proportion of reported performance metrics for each group was compared. RESULTS: Information from 95% of US allopathic medical schools (148 of 155) and 73% of osteopathic medical schools (27 of 37) was collected, on the basis of 1,046 applications received. For preclinical classes, multitiered grading was reported by no schools ranked in the top 10, 17% of schools ranked 11th to 50th, 52% of schools ranked 51st to 100th, and 59% of unranked schools (P < .001). For core clinical clerkships, multitiered grades were reported by 70% of the top 10 ranked schools, 90% of schools ranked 11th to 50th, 94% of those ranked 51st to 100th, and 94% of unranked schools (P = .0463). Comparative summative assessments were reported by none of the top 10 ranked schools, 56% of schools ranked 11th to 50th, 80% of those ranked 51th to 100th, and 81% of unranked schools (P < .001). CONCLUSIONS: Higher ranked medical schools are less likely to provide comparative assessment data on their MSPEs, which may disadvantage students from lower ranked medical schools.

Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin.

Parkinson's disease is the second most common neurodegenerative disorder and is characterized by the degeneration of dopaminergic neurons in the substantia nigra. Mitochondrial dysfunction has been implicated as an important trigger for Parkinson's disease-like pathogenesis because exposure to environmental mitochondrial toxins leads to Parkinson's disease-like pathology. Recently, multiple genes mediating familial forms of Parkinson's disease have been identified, including PTEN-induced kinase 1 (PINK1; PARK6) and parkin (PARK2), which are also associated with sporadic forms of Parkinson's disease. PINK1 encodes a putative serine/threonine kinase with a mitochondrial targeting sequence. So far, no in vivo studies have been reported for pink1 in any model system. Here we show that removal of Drosophila PINK1 homologue (CG4523; hereafter called pink1) function results in male sterility, apoptotic muscle degeneration, defects in mitochondrial morphology and increased sensitivity to multiple stresses including oxidative stress. Pink1 localizes to mitochondria, and mitochondrial cristae are fragmented in pink1 mutants. Expression of human PINK1 in the Drosophila testes restores male fertility and normal mitochondrial morphology in a portion of pink1 mutants, demonstrating functional conservation between human and Drosophila Pink1. Loss of Drosophila parkin shows phenotypes similar to loss of pink1 function. Notably, overexpression of parkin rescues the male sterility and mitochondrial morphology defects of pink1 mutants, whereas double mutants removing both pink1 and parkin function show muscle phenotypes identical to those observed in either mutant alone. These observations suggest that pink1 and parkin function, at least in part, in the same pathway, with pink1 functioning upstream of parkin. The role of the pink1-parkin pathway in regulating mitochondrial function underscores the importance of mitochondrial dysfunction as a central mechanism of Parkinson's disease pathogenesis.

Loss-of-function analysis suggests that Omi/HtrA2 is not an essential component of the PINK1/PARKIN pathway in vivo.

Recently, a mutation in the mitochondrial protease Omi/HtrA2, G399S, was found in sporadic Parkinson's disease (PD) patients, leading to the designation of Omi/HtrA2 as PD locus 13 (PARK13). G399S reportedly results in reduced Omi protease activity. In vitro studies have suggested that Omi/HtrA2 acts downstream of PINK1, mutations in which mediate recessive forms of PD. We, as well as other, have previously shown that the Drosophila homologs of the familial PD genes, PINK1 (PARK6) and PARKIN (PARK2), function in a common genetic pathway to regulate mitochondrial integrity and dynamics. Whether Omi/HtrA2 regulates mitochondrial integrity and whether it acts downstream of PINK1 in vivo remain to be explored. Here, we show that Omi/HtrA2 null mutants in Drosophila, in contrast to pink1 or parkin null mutants, do not show mitochondrial morphological defects. Extensive genetic interaction studies do not provide support for models in which Omi/HtrA2 functions in the same genetic pathway as pink1, or carries out partially redundant functions with pink1, at least with respect to regulation of mitochondrial integrity and dynamics. Furthermore, Omi/HtrA2 G399S retains significant, if not full, function of Omi/HtrA2, compared with expression of protease-compromised versions of the protein. In light of recent findings showing that G399S can be found at comparable frequencies in PD patients and healthy controls, we do not favor a hypothesis in which Omi/HtrA2 plays an essential role in PD pathogenesis, at least with respect to regulation of mitochondrial integrity in the pink1/parkin pathway.

MRI findings of metronidazole neurotoxicity in a pediatric patient with chronic diarrhea.

Neurotoxicity is a rare side effect of metronidazole therapy. Shown here are findings of metronidazole toxicity in a patient, who received chronic metronidazole as prophylaxis for pseudomembranous colitis following bowel resection as an infant. Findings depicted include increased T2 signal in the dentate nuclei and brainstem. Discontinuing the medication resulted in reversal of the findings.