Consideration of Hyoid Variability in the Diagnostic Workup of Fishbone Foreign Body Aspiration.

Fishbone foreign body (FFB) can lodge in the upper respiratory or gastrointestinal tracts and frequently cause discomfort. While FFBs are common, variations in the hyoid may present radiographically similarly. The authors present a case in which a 32-year-old woman presented with pain in the right neck with a globus sensation after eating fish. Examination, including flexible fiberoptic laryngoscopy, did not reveal a foreign body. Given the patients' persistent symptoms, a noncontrast computed tomography was performed, demonstrating a radiopaque body superior to the right lateral hyoid bone, consistent with FFB. Direct examination under anesthesia was performed, and no FFB was noted. A reassessment of the imaging suggested a likely aberrant hyoid bone. The authors report this case to remind clinicians that while rare, aberrant hyoid variants may mimic FFB. The authors also review the imaging findings of aberrant hyoid variants in this report, as recognition of hyoid variability can mitigate unnecessary intervention.

Postoperative analgesic options after spine surgery: finding the optimal treatment strategies.

INTRODUCTION: Spine surgery is one of the most common types of surgeries performed in the United States; however, managing postoperative pain following spine surgery has proven to be challenging. Patients with spine pathologies have higher incidences of chronic pain and resultant opioid use and potential for tolerance. Implementing a multimodal plan for postoperative analgesia after spine surgery can lead to enhanced recovery and outcomes. AREAS COVERED: This review presents several options for analgesia following spine surgery with an emphasis on multimodal techniques to best aid this specific patient population. In addition to traditional therapeutics, such as acetaminophen, non-steroidal anti-inflammatory medications, and opioids, we discuss intrathecal morphine administration and emerging regional anesthesia techniques. EXPERT OPINION: Several adjuncts to improve analgesia following spine surgery are efficacious in the postoperative period. Intrathecal morphine provides sustained analgesia and can be instilled intraoperatively by the surgical team under direct visualization. Local anesthetics deposited under ultrasound guidance by an anesthesiologist trained in regional techniques also provide the opportunity for single injections or continuous analgesia via an indwelling catheter.

Assembly and regulation of the mammalian mRNA processing body.

Messenger RNA processing bodies (P-bodies) are cytoplasmic membrane-free organelles that contain proteins involved in mRNA silencing, storage and decay. The mechanism by which P-body components interact and the factors that regulate the stability of these structures are incompletely understood. In this study, we used a fluorescence-based, two-hybrid assay to investigate interactions between P-body components that occur inside the cell. LSm14a, PATL1, XRN1, and NBDY were found to interact with the N-terminal, WD40-domain-containing portion of EDC4. The N-terminus of full-length PATL1 was required to mediate the interaction between EDC4 and DDX6. The C-terminal, alpha helix-domain- containing portion of EDC4 was sufficient to mediate interaction with DCP1a and CCHCR1. In the absence of endogenous P-bodies, caused by depletion of LSm14a or DDX6, expression of the portion of EDC4 that lacked the N-terminus retained the ability to form cytoplasmic dots that were indistinguishable from P-bodies at the level of UV light microscopy. Despite the absence of endogenous P-bodies, this portion of EDC4 was able to recruit DCP1a, CCHCR1 and EDC3 to cytoplasmic dots. The results of this study permit the development of a new model of P-body formation and suggest that the N-terminus of EDC4 regulates the stability of these structures.

UBA6 and NDFIP1 regulate the degradation of ferroportin.

Hepcidin regulates iron homeostasis by controlling the level of ferroportin, the only membrane channel that facilitates export of iron from within cells. Binding of hepcidin to ferroportin induces the ubiquitination of ferroportin at multiple lysine residues and subsequently causes the internalization and degradation of the ligand-channel complex within lysosomes. The objective of this study was to identify components of the ubiquitin system that are involved in ferroportin degradation. A HepG2 cell line, which inducibly expresses ferroportingreen fluorescent protein (FPN-GFP), was established to test the ability of small interfering (siRNA) directed against components of the ubiquitin system to prevent BMP6- and exogenous hepcidin-induced ferroportin degradation. Of the 88 siRNA directed against components of the ubiquitin pathway that were tested, siRNA-mediated depletion of the alternative E1 enzyme UBA6 as well as the adaptor protein NDFIP1 prevented BMP6- and hepcidin-induced degradation of ferroportin in vitro. A third component of the ubiquitin pathway, ARIH1, indirectly inhibited ferroportin degradation by impairing BMP6-mediated induction of hepcidin. In mice, the AAV-mediated silencing of Ndfip1 in the murine liver increased the level of hepatic ferroportin and increased circulating iron. The results suggest that the E1 enzyme UBA6 and the adaptor protein NDFIP1 are involved in iron homeostasis by regulating the degradation of ferroportin. These specific components of the ubiquitin system may be promising targets for the treatment of iron-related diseases, including iron overload and anemia of inflammation.

The Role of Unobtrusive Home-Based Continuous Sensing in the Management of Postacute Sequelae of SARS CoV-2.

Amid the COVID-19 pandemic, it has been reported that greater than 35% of patients with confirmed or suspected COVID-19 develop postacute sequelae of SARS CoV-2 (PASC). PASC is still a disease for which preliminary medical data are being collected-mostly measurements collected during hospital or clinical visits-and pathophysiological understanding is yet in its infancy. The disease is notable for its prevalence and its variable symptom presentation, and as such, management plans could be more holistically made if health care providers had access to unobtrusive home-based wearable and contactless continuous physiologic and physical sensor data. Such between-hospital or between-clinic data can quantitatively elucidate a majority of the temporal evolution of PASC symptoms. Although not universally of comparable accuracy to gold standard medical devices, home-deployed sensors offer great insights into the development and progression of PASC. Suitable sensors include those providing vital signs and activity measurements that correlate directly or by proxy to documented PASC symptoms. Such continuous, home-based data can give care providers contextualized information from which symptom exacerbation or relieving factors may be classified. Such data can also improve the collective academic understanding of PASC by providing temporally and activity-associated symptom cataloging. In this viewpoint, we make a case for the utilization of home-based continuous sensing that can serve as a foundation from which medical professionals and engineers may develop and pursue long-term mitigation strategies for PASC.

Sulfide catabolism ameliorates hypoxic brain injury.

The mammalian brain is highly vulnerable to oxygen deprivation, yet the mechanism underlying the brain's sensitivity to hypoxia is incompletely understood. Hypoxia induces accumulation of hydrogen sulfide, a gas that inhibits mitochondrial respiration. Here, we show that, in mice, rats, and naturally hypoxia-tolerant ground squirrels, the sensitivity of the brain to hypoxia is inversely related to the levels of sulfide:quinone oxidoreductase (SQOR) and the capacity to catabolize sulfide. Silencing SQOR increased the sensitivity of the brain to hypoxia, whereas neuron-specific SQOR expression prevented hypoxia-induced sulfide accumulation, bioenergetic failure, and ischemic brain injury. Excluding SQOR from mitochondria increased sensitivity to hypoxia not only in the brain but also in heart and liver. Pharmacological scavenging of sulfide maintained mitochondrial respiration in hypoxic neurons and made mice resistant to hypoxia. These results illuminate the critical role of sulfide catabolism in energy homeostasis during hypoxia and identify a therapeutic target for ischemic brain injury.

Hepcidin Deficiency Protects Against Atherosclerosis.

Objective- Inflammatory stimuli enhance the progression of atherosclerotic disease. Inflammation also increases the expression of hepcidin, a hormonal regulator of iron homeostasis, which decreases intestinal iron absorption, reduces serum iron levels and traps iron within macrophages. The role of macrophage iron in the development of atherosclerosis remains incompletely understood. The objective of this study was to investigate the effects of hepcidin deficiency and decreased macrophage iron on the development of atherosclerosis. Approach and Results- Hepcidin- and LDL (low-density lipoprotein) receptor-deficient ( Hamp-/-/ Ldlr-/-) mice and Hamp+/+/ Ldlr-/- control mice were fed a high-fat diet for 21 weeks. Compared with control mice, Hamp-/-/ Ldlr-/- mice had decreased aortic macrophage activity and atherosclerosis. Because hepcidin deficiency is associated with both increased serum iron and decreased macrophage iron, the possibility that increased serum iron was responsible for decreased atherosclerosis in Hamp-/-/ Ldlr-/- mice was considered. Hamp+/+/ Ldlr-/- mice were treated with iron dextran so as to produce a 2-fold increase in serum iron. Increased serum iron did not decrease atherosclerosis in Hamp+/+/ Ldlr-/- mice. Aortic macrophages from Hamp-/-/ Ldlr-/- mice had less labile free iron and exhibited a reduced proinflammatory (M1) phenotype compared with macrophages from Hamp+/+/ Ldlr-/- mice. THP1 human macrophages treated with an iron chelator were used to model hepcidin deficiency in vitro. Treatment with an iron chelator reduced LPS (lipopolysaccharide)-induced M1 phenotypic expression and decreased uptake of oxidized LDL. Conclusions- In summary, in a hyperlipidemic mouse model, hepcidin deficiency was associated with decreased macrophage iron, a reduced aortic macrophage inflammatory phenotype and protection from atherosclerosis. The results indicate that decreasing hepcidin activity, with the resulting decrease in macrophage iron, may prove to be a novel strategy for the treatment of atherosclerosis.