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Although circular RNAs (circRNAs) are enriched in the brain, their relevance for brain function and psychiatric disorders is poorly understood. Here, we show that circHomer1 is inversely associated with relative HOMER1B mRNA isoform levels in both the orbitofrontal cortex (OFC) and stem-cell-derived neuronal cultures of subjects with psychiatric disorders. We further demonstrate that in vivo circHomer1 knockdown (KD) within the OFC can inhibit the synaptic expression of Homer1b mRNA. Furthermore, we show that circHomer1 directly binds to Homer1b mRNA and that Homer1b-specific KD increases synaptic circHomer1 levels and improves OFC-mediated behavioral flexibility. Importantly, double circHomer1 and Homer1b in vivo co-KD results in a complete rescue in circHomer1-associated alterations in both chance reversal learning and synaptic gene expression. Lastly, we uncover an RNA-binding protein that can directly bind to circHomer1 and promote its biogenesis. Taken together, our data provide mechanistic insights into the importance of circRNAs in brain function and disease.

Although circular RNAs (circRNAs) are abundantly expressed in the mammalian brain and preferentially-derived from synaptic genes, their relevance for brain function and psychiatric disorders and their interactions with neuronal protein-coding gene expression still remain poorly understood. Here we show that alterations in the levels of circHomer1, a neuronal-enriched circRNA altered in psychiatric disease that has been shown to influence OFC-mediated cognitive flexibility, are inversely associated with the relative expression of the long linear HOMER1B mRNA isoform in both the orbitofrontal cortex (OFC) and stem cell-derived neuronal cultures of subjects with psychiatric disorders. Using in vivo mature circHomer1-specific knockdown (KD) in adult mouse OFC, we further demonstrate that downregulation of circHomer1 results in increased synaptic expression of Homer1b mRNA. Furthermore, we utilize circRNA antisense purification to show that circHomer1 directly binds to Homer1b mRNA. We then demonstrate that in vivo Homer1b-specific KD increases synaptic circHomer1 levels within the OFC and improves OFC-mediated behavioral flexibility. Importantly, we show that double circHomer1 and Homer1b in vivo co-KD results in a complete rescue in circHomer1-associated alterations in both chance reversal learning and synaptic gene expression. Lastly, we demonstrate that circHomer1 is an experience-dependent circRNA that is significantly altered during chance reversal learning and that variability in its baseline expression within the OFC is significantly inversely correlated to behavioral performance during chance reversal learning. Taken together our data provide novel mechanistic insights into the importance of circRNAs in brain function and disease.

Background Pressure cookers are common kitchen appliances with a good safety record and only rare associated explosions. Case Report Here we present a case of unintentional pressure cooker explosion leading to polytrauma with injuries including pneumothorax, intracranial hemorrhage, open skull fracture, and multiple facial fractures. Why Should an Emergency Physician Be Aware of This? Extreme forces and temperatures are involved in pressure cooking. Given the infrequent but real risk of mechanical failure and the increasing use of such devices to create intentional explosions, emergency physicians should be aware of the potentially significant blast injuries that can be associated with them.

Background In pharmacologic management of fetal supraventricular tachycardia (SVT), antiarrhythmic agents are administered to the pregnant patient serving as a vehicle of transplacental delivery to the fetus. Given that antiarrhythmic therapy can have profound maternal adverse effects, administration of initial loading and dose adjustments should involve deliberate attention to pharmacologic principles with close maternal monitoring for adverse effects. We reviewed current monitoring practices and maternal complications of transplacental antiarrhythmic therapy for fetal SVT. Methods A query of the Embase database for search terms ”Fetal” or ”Foetal” and ”Supraventricular Tachycardia” or ”SVT” yielded 93 titles, of which 19 articles detailing the modalities of therapy for Fetal SVT were reviewed. Results The 19 articles represented 565 cases of fetal SVT, 111 of which had developed hydrops fetalis. Of these cases, 184 received a course of digoxin alone and 33, 56, and 5 cases received a combination therapy of digoxin with flecainide, sotalol, or amiodarone. Flecainide, Sotalol, and amiodarone were given as monotherapy in 89, 77, and 6 cases, respectively. Maternal monitoring information was available in 15 studies. Investigators performed electrocardiograms (EKGs) at baseline and during follow-up in 12 studies, and monitored electrolytes in five. Two studies reported a mandatory cardiologist consultation for all mothers and two studies considered performing echocardiography in select mothers. Digoxin and flecainide levels were measured in eight and four studies, respectively. Toxicity was reported in 5 patients: two on digoxin monotherapy, two on flecainide monotherapy, and one on combination of digoxin and flecainide. Conclusion Pharmacologic management of fetal SVT is generally safe for mothers with normal baseline cardiac assessments and close monitoring of symptoms, EKG, electrolytes, and/or drug levels. Future prospective studies on the treatment of fetal SVT should also include a systematic monitoring strategy for mothers, with consistent reporting of adverse reactions.