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Long-distance RNA transport enables local protein synthesis at metabolicallyactive sites distant from the nucleus. This process ensures an appropriate spatial organization of proteins, vital to polarized cells such as neurons. Here, we present a mechanism for RNA transport in which RNA granules “hitchhike” on moving lysosomes. In vitro biophysical modeling, live-cell microscopy, and unbiased proximity labeling proteomics reveal that annexin A11 (ANXA11), an RNA granule-associated phosphoinositide-binding protein, acts as a molecular tether between RNA granules and lysosomes. ANXA11 possesses an N-terminal low complexity domain, facilitating its phase separation into membraneless RNA granules, and a C-terminal membrane binding domain, enabling interactions with lysosomes. RNA granule transport requires ANXA11, and amyotrophic lateral sclerosis (ALS) mutations impair RNA granule transport in neurons by disrupting their interactions with lysosomes. Thus, ANXA11 mediates neuronal RNA transport by tethering RNA granules to actively-transported lysosomes, performing a critical cellular function that is disrupted in ALS.

Choledochal cysts are rare but serious bile duct abnormalities are found in young children, usually during the first year of life.1 They require urgent surgical intervention due to the risk of developing cholangiocarcinoma.2 Clinicians should consider this diagnosis and perform a point-of-care ultrasound (POCUS) when a child presents to the emergency department (ED) with findings of jaundice, abdominal pain, and the presence of an abdominal mass. We present the case of a six-year-old child presenting only with abdominal pain upon arrival to our ED and was ultimately diagnosed by POCUS to have a choledochal cyst.

This retrospective study was conducted to identify hemodynamic alterations associated with the administration of an ionic iodinated contrast media in dogs. Case records of 49 dogs that were anesthetized for computed tomography scanning were reviewed. Values for heart rate (HR) and direct arterial pressure were obtained. Overall, 37% of dogs had a ≥20% change in either HR or systolic arterial pressure from baseline values. Four dogs (8%) became tachycardic and two dogs (4%) became bradycardic. Eight dogs (16%) became hypertensive and two dogs (4%) became hypotensive. A significant proportion of dogs experienced changes in HR and blood pressure following IV administration of an ionic iodinated contrast media under general anesthesia.

We present a case of successful resuscitation from cardiac arrest after 25 minutes of ventricular fibrillation (VF) secondary to peripartum cardiomyopathy. This case highlights a rare disease, but also, more importantly, the successful use of the five links of survival: early access to 9-1-1, early cardiopulmonary resuscitation (CPR), early defibrillation, early advanced life support, and postresuscitative care. We also demonstrate the importance of high-quality resuscitation practices in order to achieve a successful outcome. Manual compressions can be performed at a guidelines-compliant rate. With training, users are able to achieve high compression fractions. Pre/post shock delays can be minimized to further increase compression fraction. Nationally, CPR interruptions are often long. We recommend closer attention to uninterrupted 2-minute cycles of CPR, minimizing delays in CPR through training, and a focus on a closely choreographed approach. User review of transthoracic impedance feedback data should play a vital role in a cardiac arrest quality-improvement program.

Background: The standard evaluation of patients with right upper quadrant (RUQ) abdominal pain consists of a history and physical examination, laboratory analysis, and radiological investigation. Given the increasing availability of bedside ultrasound in the Emergency Department (ED), a growing proportion of Emergency Physicians are now performing their own ultrasound examinations in patients with RUQ abdominal pain to circumvent diagnostic delays and improve patient care. Objective: To determine the economic “opportunity” costs of additional radiographic testing after identification of acute cholecystitis by focused ED ultrasound performed by registered diagnostic medical sonographer (RDMS)-certified personnel. Methods: A retrospective analysis of a consecutive sample of patients with “positive” focused ED ultrasounds of the RUQ that were significant for cholecystitis, who presented from June 1, 2005 through February 30, 2006. Cost analysis was performed using standard Medicare compensation indices for radiological examinations of the abdomen/hepatobiliary system. Results: There were 37 patients enrolled; 32 patients exhibited RUQ pain with a focused ED ultrasound significant for cholecystitis. Eight (25%) patients received no further radiographic tests and exhibited positive pathology. Twenty-four (75%) patients had additional diagnostic examinations; 22 (92%) showed positive pathology. Based upon Medicare compensation indices, an opportunity cost of $6885.34 was incurred at our institution over 9 months due to additional examinations. Using nationally comparable indices, this was extrapolated to an opportunity cost of $63 million (95% confidence interval $48.3–$78.9 million) per year across the nation, assuming that 50% of patients with cholecystitis present to the ED and receive an ultrasound examination by an RDMS-certified Emergency Physician. Conclusions: In this small sample, additional radiological testing after ED ultrasounds significant for acute cholecystitis led to sizable economic costs on a local and national level. Formal cost-benefit analyses are needed to evaluate the full economic and patient care implications of ED ultrasound use in this setting.

Purpose: This study determined the effects of a single session of heavy-resistance exercise on myosin heavy-chain (MHC) mRNA expression, along with the expression of the transcription factors Myo-D, myogenin, and Id-1. Methods: Four male subjects participated in a control group (CON) and seven in a resistance-exercise group (REX). REX performed one resistance-exercise session employing three sets of 8-10 repetitions at 75-80% one-repetition maximum on the squat, leg press, and leg extension. Vastus lateralis biopsies were obtained pre, post, and at 6 h postexercise. Results: In regard to CON. no significant differences were located for any criterion variable (P > 0.05). For REX, elevations of 38.19%, 45.61%, and 74.24% (P < 0.05), respectively, occurred at 6 h-post for Type I, IIa, and IIx MHC mRNA. Myo-D and myogenin mRNA were elevated 27.28% and 23.58% postexercise (P < 0.05), respectively, but no change was observed in Id-1 mRNA. Elevations at 6 h-post of 46.85% and 46.41% (P < 0.05), respectively, occurred for Myo-D and myogenin mRNA with no change in Id-1. Myo-D and myogenin protein increased 57.91% and 52.30%, respectively, postexercise and 317.56% and 254.08 at 6 h-post (P < 0.05), whereas no change was noted for Id-1. Myofibrillar protein was elevated 84.52% at 6 h-post (P < 0.05). Type I and IIa MHC mRNA at 6 h-post were correlated with myogenin mRNA and protein postexercise and 6 h-post, whereas Type IIx at 6 h-post was correlated with Myo-D mRNA and protein postexercise and 6 h-post (P < 0.05). Conclusions: These results indicate that the mRNA expression of all three MHC isoforms is up-regulated after a single session of heavy-resistance exercise and that Myo-D and myogenin seem to play a role in MHC isoform gene expression.

Willoughby DS, Priest JW, Nelson M. Expression of the stress proteins, ubiquitin, heat shock protein 72, and myofibrillar protein content after 12 weeks of leg cycling in persons with spinal cord injury. Arch Phys Med Rehabil 2002;83:649-54. Objective: To determine the effects of leg cycling exercise on ubiquitin (UBI), heat shock protein 72 (HSP-72) mRNA, protein expression, and myofibrillar protein content in individuals with spinal cord injury (SCI). Design: Case series. Setting: Motor behavior laboratory. Participants: Seven subjects with motor-complete SCI (4 men, 3 women). Intervention: A 12-week exercise program involving an electromagnetically braked recumbent bicycle ergometer, which allowed for passive exercise of the legs. Training occurred 2 days a week at approximately 75% of each subject's maximum heart rate. Main Outcome Measures: Total body mass (TBM) and muscle biopsies were obtained pre- and posttraining. The mRNA and protein expression of UBI, HSP-72, and myofibrillar protein content were determined. Results: Nonsignificant increases ( P >.05) of 2.45% were observed for TBM. There were significant increases ( P P P Conclusion: Leg cycling exercise in SCI increases myofibrillar protein content, possibly because of up-regulation in the expression of HSP-72 with concomitant down-regulation in the expression of UBI. © 2002 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation