Objective: Patients with coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), exhibit not only respiratory symptoms but also symptoms of chemo‐sensitive disorders. Cellular entry of SARS‐CoV‐2 depends on the binding of its spike protein to a cellular receptor named angiotensin‐converting enzyme 2 (ACE2), and the subsequent spike protein‐priming by host cell proteases, including transmembrane protease serine 2 (TMPRSS2). Thus, high expression of ACE2 and TMPRSS2 is considered to enhance the invading capacity of SARS‐CoV‐2.Methods: To elucidate the underlying histological mechanisms of the aerodigestive disorders caused by SARS‐CoV‐2, we investigated the expression of ACE2 and TMPRSS2 proteins using immunohistochemistry, in the aerodigestive tracts of the tongue, hard palate with partial nasal tissue, larynx with hypopharynx, trachea, esophagus, and lung of rats.Results: Co‐expression of ACE2 and TMPRSS2 proteins was observed in the taste buds of the tongue, nasal epithelium, trachea, bronchioles, and alveoli with varying degrees of expression. Remarkably, TMPRSS2 expression was more distinct in the peripheral alveoli than in the central alveoli. These results coincide with the reported clinical symptoms of COVID‐19, such as the loss of taste, loss of olfaction, and respiratory dysfunction.Conclusions: A wide range of organs have been speculated to be affected by SARS‐CoV‐2 depending on the expression levels of ACE2 and TMPRSS2. Differential distribution of TMPRSS2 in the lung indicated the COVID‐19 symptoms to possibly be exacerbated by TMPRSS2 expression. This study might provide potential clues for further investigation of the pathogenesis of COVID‐19.Level of Evidence: NA Laryngoscope, 131:E932–E939, 2021

Objective: We examined the influence of liquid thickness levels on the frequency of liquid penetration‐aspiration in patients with dysphagia and evaluated the clinical risk factors for penetration‐aspiration and aspiration pneumonia development.Study Design: A case series.Setting: Single‐institution academic center.Methods: We reviewed medical charts from 2018 to 2019. First, we evaluated whether liquid thickness levels influence the frequency of liquid penetration‐aspiration in patients with dysphagia. Penetration‐aspiration occurrence in a videofluoroscopic swallowing study was defined as Penetration‐Aspiration Scale (PAS) scores ≥3. Second, the association between liquid thickness level and penetration‐aspiration was analyzed, and clinical risk factors were identified. Moreover, clinical risk factors for aspiration pneumonia development within 6 months were investigated.Results: Of 483 patients, 159 showed penetration‐aspiration. The thickening of liquids significantly decreased the incidence of penetration‐aspiration (P <. 001). Clinical risk factors for penetration‐aspiration were vocal fold paralysis (odds ratio [OR], 1.99), impaired laryngeal sensation (OR, 5.01), and a history of pneumonia (OR, 2.90). Twenty‐three patients developed aspiration pneumonia while undertaking advised dietary changes, including liquid thickening. Significant risk factors for aspiration pneumonia development were poor performance status (OR, 1.85), PAS score ≥3 (OR, 4.03), and a history of aspiration pneumonia (OR, 7.00).Conclusion: Thickening of liquids can reduce the incidence of penetration‐aspiration. Vocal fold paralysis, impaired laryngeal sensation, and history of aspiration pneumonia are significant risk factors of penetration‐aspiration. Poor performance status, PAS score ≥3, and history of aspiration pneumonia are significantly associated with aspiration pneumonia development following recommendations on thickening liquids.Level of Evidence: 3.

The structural and magnetic properties of the single-molecule magnet $\left[{\mathrm{Mn}}_{11}\mathrm{Cr}{\mathrm{O}}_{12}{\left({\mathrm{O}}_2\mathrm{C}\mathrm{C}{\mathrm{H}}_3\right)}_{16}{\left({\mathrm{H}}_2\mathrm{O}\right)}_4\right]\bullet 2\mathrm{C}{\mathrm{H}}_3\mathrm{C}\mathrm{O}\mathrm{O}\mathrm{H}\bullet 4{\mathrm{H}}_2\mathrm{O}$ $\left({\mathrm{Mn}}_{11}\mathrm{Cr}\right)$ are studied through the analysis of a ${\mathrm{Mn}}_{11}\mathrm{Cr}∕{\mathrm{Mn}}_{12}$ $(\approx 1:1)$ mixed crystal, where ${\mathrm{Mn}}_{12}$ is $\left[{\mathrm{Mn}}_{12}{\mathrm{O}}_{12}{\left({\mathrm{O}}_2{\mathrm{C}\mathrm{C}\mathrm{H}}_3\right)}_{16}{\left({\mathrm{H}}_2\mathrm{O}\right)}_4\right]\bullet 2\mathrm{C}{\mathrm{H}}_3\mathrm{C}\mathrm{O}\mathrm{O}\mathrm{H}\bullet 4{\mathrm{H}}_2\mathrm{O}$. X-ray absorption spectra reveal that the Cr ion in ${\mathrm{Mn}}_{11}\mathrm{Cr}$ is in the $+3$ valence state and occupies a specific ${\mathrm{Mn}}^{3+}$ site in the ${\mathrm{Mn}}_{12}$ skeleton. High-frequency electron paramagnetic resonance (EPR) spectra are well explained by assuming that ${\mathrm{Mn}}_{11}\mathrm{Cr}$ is in a ground spin-state of $S=19∕2$ with nearly the same EPR parameter set as for ${\mathrm{Mn}}_{12}$. The lower spin quantum number results in lower barrier height $\left(56.8\mathrm{K}\right)$ compared to ${\mathrm{Mn}}_{12}$. The magnetization curves indicate a coercive field of $0.95\mathrm{T}$ for ${\mathrm{Mn}}_{11}\mathrm{Cr}$ at $1.8\mathrm{K}$, nearly half that for ${\mathrm{Mn}}_{12}$. Quantum tunneling of magnetization (QTM) in ${\mathrm{Mn}}_{11}\mathrm{Cr}$ is observed below the blocking temperature $T_B$, with the same field interval as for ${\mathrm{Mn}}_{12}$. The magnetization of ${\mathrm{Mn}}_{11}\mathrm{Cr}$ and ${\mathrm{Mn}}_{12}$ in the mixed crystal can be independently manipulated by utilizing the difference between their coercive fields. The resonance fields of QTM in ${\mathrm{Mn}}_{11}\mathrm{Cr}$ are significantly affected by the magnetization direction of ${\mathrm{Mn}}_{12}$, suggesting the effect of dipolar-biased tunneling.

Background: Research on regenerative medicine using basic fibroblast growth factor (bFGF) has recently advanced in the field of laryngology. We previously reported that local administration of bFGF 1 month after recurrent laryngeal nerve (RLN) paralysis compensated for atrophy of the thyroarytenoid muscle. The objective of this study was to elucidate the effects of early bFGF administration on the thyroarytenoid muscle after RLN transection and to investigate the underlying mechanisms. Methods: A rat model of RLN paralysis was established in this study. One day after RLN transection, low- (200 ng) or high-dose (2000 ng) bFGF or saline (control) was administered to the thyroarytenoid muscle. The larynges were excised for histological and immunohistochemical examinations at 1, 7, 14, 28, and 56 days after administration. Results: The cross-sectional thyroarytenoid muscle area was significantly larger in the high-dose group than in the saline and low-dose groups on days 28 and 56. Immunohistochemistry indicated that bFGF significantly increased the number of satellite cells in the thyroarytenoid muscle up to day 14 and that of neuromuscular junctions on days 28 and 56. Conclusions: A single, early local administration of high-dose bFGF prevented atrophic changes in the thyroarytenoid muscles by activating satellite cell proliferation and reforming neuromuscular junctions. As increased neuromuscular junctions are expected to maintain myofiber volume, bFGF administration may prevent thyroarytenoid muscle atrophy in the mid to long term. Graphical

To review the various basic research and treatments available to regenerate the vocal folds and to discuss the direction for future treatments. A comprehensive review was performed in PubMed database and Google Scholar utilizing search terms including combinations and variations of the following concepts: vocal fold anatomy, vocal fold disorders, and regenerative therapies. No particular inclusion or exclusion criteria were set due to the nature of this narrative review article. The regenerative treatments available for each vocal fold layer are the following: 1) epidermal growth factor and transforming growth factor-β1 for the epithelial layer, 2) autologous fibroblasts, autologous bone-marrow derived mesenchymal stem cells (MSCs), autologous adipose tissue-derived stromal vascular fraction (ADSVF), basic fibroblast growth factor (bFGF), collagen-hyaluronic acid nanofiber, pirfenidone, hepatocyte growth factor (HGF), pulsed dye laser (PDL), diode laser, and platelet-rich plasma (PRP) for the lamina propria, 3) bFGF and controlled-release bFGF with autologous fascia, HGF, c-Met agonistic antibody, and PRP for the muscular layer, 4) and bFGF and PRP-loaded nerve guidance conduit for the nerve. Treatments deemed clinically safe with sustained efficacy assessed up to 6 months are HGF and PDL, while bFGF, autologous fibroblasts, autologous bone marrow-derived MSCs, ADSVF, and PRP have been studied up to 12 months. An ideal regenerative treatment is one that restores the injured or lost components of the vocal fold. The layered structure of the vocal fold allows for several mechanisms of action for these regenerative therapies. Further experimental and clinical studies are warranted, and these would dictate the impact of vocal fold regenerative therapies. Regenerative medicine may soon be at the forefront for treating vocal fold disorders. Clinicians should be open to advancements in treatment and consider the potential of novel therapies to treat specific pathologies.