Zicam-Induced Damage to Mouse and Human Nasal Tissue

Intranasal medications are used to treat various nasal disorders. However, their effects on olfaction remain unknown. Zicam (zinc gluconate; Matrixx Initiatives, Inc), a homeopathic substance marketed to alleviate cold symptoms, has been implicated in olfactory dysfunction. Here, we investigated Zicam and several common intranasal agents for their effects on olfactory function. Zicam was the only substance that showed significant cytotoxicity in both mouse and human nasal tissue. Specifically, Zicam-treated mice had disrupted sensitivity of olfactory sensory neurons to odorant stimulation and were unable to detect novel odorants in behavioral testing. These findings were long-term as no recovery of function was observed after two months. Finally, human nasal explants treated with Zicam displayed significantly elevated extracellular lactate dehydrogenase levels compared to saline-treated controls, suggesting severe necrosis that was confirmed on histology. Our results demonstrate that Zicam use could irreversibly damage mouse and human nasal tissue and may lead to significant smell dysfunction

Generation of ribosome imprinted polymers for sensitive detection of translational responses

Whilst the profiling of the transcriptome and proteome even of single-cells becomes feasible, the analysis of the translatome, which refers to all messenger RNAs (mRNAs) engaged with ribosomes for protein synthesis, is still an elaborate procedure requiring millions of cells. Herein, we report the generation and use of “smart materials”, namely molecularly imprinted polymers (MIPs) to facilitate the isolation of ribosomes and translated mRNAs from merely 1,000 cells. In particular, we show that a hydrogel-based ribosome imprinted polymer could recover ribosomes and associated mRNAs from human, simian and mice cellular extracts, but did not selectively enrich yeast ribosomes, thereby demonstrating selectivity. Furthermore, ribosome imprinted polymers enabled the sensitive measurement of an mRNA translational regulatory event, requiring 1,000-fold less cells than current methodologies. These results provide first evidence for the suitability of MIPs to selectively recover ribonucleoprotein complexes such as ribosomes, founding a novel means for sensitive detection of gene regulation

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

Autonomic nervous system Activity Measured Directly and QT-Interval Variability in Normal and Pacing-Induced Tachycardia Heart Failure Dogs.

BACKGROUND- The QT variability index (QTVI), a noninvasive marker of temporal cardiac repolarization dispersion, is among the risk factors for sudden death during congestive heart failure (CHF). Among factors influencing the duration and temporal dispersion of cardiac repolarization are the myocardial damage and the autonomic nervous system activity typical of dilated cardiomyopathy. In this study, to find out more about relationship between sympathetic and vagal nerve activity and the cardiac repolarization, we measured QTVI in a canine model of pacing-induced tachycardia CHF. METHODS and RESULTS- Using the data previous recorded in 6 ambulatory dogs before and after pacing-induced tachycardia CHF, we assessed autonomic nervous system activity recorded from an implanted data transmitter that monitored integrated left stellate-ganglion nervous activity (iSGNA), integrate vagus nerve activity (iVNA), and electrocardiogram (ECG). We selected for analysis 36 segments recorded at baseline and 36 after induced CHF. We then arbitrarily identified recording segments as containing low or high sympathetic activity values according to whether they contained more than or less than or equal to the 50th percentile of sympathetic activity, and we compared corrected QT intervals and the QTVI under a given sympathetic activity condition at baseline and after inducing CHF. In the high sympathetic activity subgroup, both QT variables increased significantly from baseline to CHF (corrected QTs, p<0.01; QTVI, p<0.05) whereas in the low sympathetic activity group they remained unchanged. The baseline QTVI correlated inversely with iVNA (r2: 0.16; b: -0.47; p<0.05) whereas, during CHF, the QTVI correlated directly with iSGNA (r2: 0.32; b: 0.27, p<0.01). CONCLUSIONS- In a canine model of pacing-induced tachycardia CHF, sympathetic activation is associated with an increase in the QT interval and QTVI. Because these changes vary over time, they could result from myocardial structural damage and sympathetic activation combined. Conversely, under normal conditions, when myocardial damage is missing, no relationship exists between sympathetic activation and the QT interval or QTVI