Vesicular monoamine transporters (VMATs) mediate the transport of dopamine (DA), serotonin (5HT), and other monoamines into secretory vesicles. The regulation of mammalian VMAT and the related vesicular acetylcholine transporter (VAChT) has been proposed to involve membrane trafficking, but the mechanisms remain unclear. To facilitate a genetic analysis of vesicular transporter function and regulation, we have cloned the Drosophila homolog of the vesicular monoamine transporter (dVMAT). We identify two mRNA splice variants (DVMAT-A and B) that differ at their C-terminus, the domain responsible for endocytosis of mammalian VMAT and VAChT. DVMAT-A contains trafficking motifs conserved in mammals but not C. elegans, and internalization assays indicate that the DVMAT-A C-terminus is involved in endocytosis. DVMAT-B contains a divergent C-terminal domain and is less efficiently internalized from the cell surface. Using in vitro transport assays, we show that DVMAT-A recognizes DA, 5HT, octopamine, tyramine, and histamine as substrates, and similar to mammalian VMAT homologs, is inhibited by the drug reserpine and the environmental toxins 2,2,4,5,6-pentachlorobiphenyl and heptachlor. We have developed a specific antiserum to DVMAT-A, and find that it localizes to dopaminergic and serotonergic neurons as well as octopaminergic, type II terminals at the neuromuscular junction. Surprisingly, DVMAT-A is co-expressed at type II terminals with the Drosophila vesicular glutamate transporter. Our data suggest that DVMAT-A functions as a vesicular transporter for DA, 5HT, and octopamine in vivo, and will provide a powerful invertebrate model for the study of transporter trafficking and regulation.

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The causes of many sporadic diseases are unexplained; the contribution of recessive loci with reduced penetrance is one possibility that has been difficult to explore. We describe an approach to this problem by first searching for diseases with higher prevalence in populations with high rates of consanguinity, then determining whether disease cases are more commonly the product of consanguinous union than controls in such populations, followed by analysis of genetic linkage in consanguinous cases. We demonstrate the utility of this approach by investigation of congenital heart disease in Iran. We found that patent ductus arteriosus (PDA), a common congenital heart disease, accounts for a higher fraction of congenital heart disease in Iran (15%) than in the United States

Treating patients undergoing chemotherapy who display findings of liver toxicity, requires a solid understanding of these medications. It is important for any clinician to have an index of suspicion for liver toxicity and be able to recognize it, even on imaging. Cancer chemotherapy has evolved, and newer medications that target cell biology have a different pattern of liver toxicity and may differ from the more traditional cytotoxic agents. There are several hepatic conditions that can result and keen clinical as well as radiographic recognition are paramount. Conditions such as sinusoidal obstructive syndrome, steatosis, and pseudocirrhosis are more commonly associated with chemotherapy. These conditions can display clinical signs of acute hepatitis, liver cirrhosis, and even liver failure. It is important to anticipate and recognize these adverse reactions and thus appropriate clinical action can be taken. Often times, patients with these liver manifestations can be managed with supportive therapies, and liver toxicity may resolve after discontinuation of chemotherapy.

Appendicitis, intussusception, and hypertrophic pyloric stenosis (HPS) are three of the most common reasons for emergent abdominal imaging in pediatric patients. Although the use of computed tomography has risen dramatically over the past 2 decades, children are particularly at risk for the adverse effects of ionizing radiation, and even low-dose radiation is associated with a small but significant increase in lifetime risk of fatal cancer. In most emergency departments, the use of magnetic resonance (MR) imaging as a primary modality for the evaluation of a child with abdominal pain remains impractical due to its high cost, its limited availability, and the frequent need for sedation. Ultrasonography (US) does not involve ionizing radiation and, unlike MR imaging, is relatively inexpensive, is widely available, and does not require sedation. Another major advantage of US in abdominal imaging is that it allows dynamic assessment of bowel peristalsis and compressibility. Delayed diagnosis of any of the aforementioned disease processes can lead to serious morbidity and, in some cases, death. The ability to diagnose or exclude disease with US should be part of a core radiology skill set for any practice that includes a pediatric population.

Doppler ultrasonography of the hepatic vasculature is an integral part of evaluating precirrhotic and cirrhotic patients. While the reversal of the portal venous flow is a well-recognized phenomenon, other flow patterns, although not as easily understood, may play an important role in assessing the disease status. This article discusses the different characteristic flow patterns observed from the portal vein, hepatic artery, and hepatic vein in patients with liver cirrhosis or related complications and procedures. Knowledge of these different flow patterns provides additional information that may reinforce the diagnosis of cirrhosis, help in staging, and offer prognostic information for determining the direction of therapy. Doppler ultrasonography is invaluable when liver transplantation is being considered and aids in the diagnosis of cirrhosis and portal hypertension.

Purpose The coronavirus disease 2019 (COVID-19) pandemic has led to significant disruptions in the healthcare system including surges of infected patients exceeding local capacity, closures of primary care offices, and delays of non-emergent medical care. Government-initiated measures to decrease healthcare utilization (i.e., "flattening the curve") have included shelterin-place mandates and social distancing, which have taken effect across most of the USA. We evaluate the immediate impact of the Public Health Messaging and shelter-in-place mandates on Emergency Department (ED) demand for radiology services. Methods We analyzed ED radiology volumes from the five University of California health systems during a 2-week time period following the shelter-in-place mandate and compared those volumes with March 2019 and early April 2019 volumes. Results ED radiology volumes declined from the 2019 baseline by 32 to 40% (p < 0.001) across the five health systems with a total decrease in volumes across all 5 systems by 35% (p < 0.001). Stratifying by subspecialty, the smallest declines were seen in non-trauma thoracic imaging, which decreased 18% (p value < 0.001), while all other non-trauma studies decreased by 48% (p < 0.001). Conclusion Total ED radiology demand may be a marker for public adherence to shelter-in-place mandates, though ED chest radiology demand may increase with an increase in COVID-19 cases.

Prostate carcinoma is one of the most prevalent cancers worldwide. Multiparametric magnetic resonance imaging (mpMRI) is a non-invasive tool that can improve prostate lesion detection, classification, and volume quantification. Machine learning (ML), a branch of artificial intelligence, can rapidly and accurately analyze mpMRI images. ML could provide better standardization and consistency in identifying prostate lesions and enhance prostate carcinoma management. This review summarizes ML applications to prostate mpMRI and focuses on prostate organ segmentation, lesion detection and segmentation, and lesion characterization. A literature search was conducted to find studies that have applied ML methods to prostate mpMRI. To date, prostate organ segmentation and volume approximation have been well executed using various ML techniques. Prostate lesion detection and segmentation are much more challenging tasks for ML and were attempted in several studies. They largely remain unsolved problems due to data scarcity and the limitations of current ML algorithms. By contrast, prostate lesion characterization has been successfully completed in several studies because of better data availability. Overall, ML is well situated to become a tool that enhances radiologists’ accuracy and speed.