Adeno-Associated Virus-Encapsulated Alginate Microspheres Loaded in Collagen Gel Carriers for Localized Gene Transfer.

This work reports localized in vivo gene transfer by biodegradation of the adeno-associated virus-encapsulating alginate microspheres (AAV-AMs) loaded in collagen gel carriers. AAV-AMs are centrifugally synthesized by ejecting a mixed pre-gel solution of alginate and AAV to CaCl2 solution to form an ionically cross-linked hydrogel microsphere immediately. The AAV-AMs are able to preserve the AAV without diffusing out even after spreading them on the cells, and the AAV is released and transfected by the degradation of the alginate microsphere. In addition, AAV-AMs can be stored by cryopreservation until use. By implanting this highly convenient AAV-encapsulated hydrogel, AAV-AMs can be loaded into collagen gel carriers to fix the position of the implanted AAV-AMs and achieve localized gene transfer in vivo. In vivo experiments show that the AAV-AMs loaded in collagen gel carriers are demonstrated to release the encapsulated AAV for gene transfer in the buttocks muscles of mice. While conventional injections caused gene transfer to the entire surrounding tissue, the biodegradation of AAV-AMs shows that gene transfer is achieved locally to the muscles. This means that the proposed AAV-loaded system is shown to be a superior method for selective gene transfer.

Epigenetic Regulation as a New Therapeutic Target for Middle Ear Cholesteatoma.

HYPOTHESIS: To evaluate the effectiveness of the menin-MLL inhibitor, MI503, as a conservative treatment of middle ear cholesteatoma (cholesteatoma) in a mouse model and to confirm its safety profile regarding auditory function in vivo. BACKGROUND: Cholesteatoma is a mass formed by the keratinizing squamous epithelium in the tympanic cavity and/or mastoid and subepithelial connective tissue and by the progressive accumulation of keratin debris with/without a surrounding inflammatory reaction. Although the main treatment is surgical therapy, the techniques to prevent recurrence remain a critical area of research. Recently, the use of MI503 in experiments resulted in the inhibition of the growth of cholesteatoma in vivo under histone modification. METHODS: After cholesteatoma was induced in ICR mice (n = 7) by keratinocyte growth factor expression vector transfection, MI503 (50 µM) or phosphate-buffered saline was topically injected for 14 days. The effects of MI503 against cholesteatoma were analyzed by micro-computed tomography images. For the in vivo ototoxicity study, a single intratympanic injection of MI503 (50 or 500 µM) or phosphate-buffered saline (n = 4 each) was done in the ICR mice. An auditory brainstem response was performed at days 0, 1, and 14. For morphological analysis, immunostaining for Phalloidin/F-actin and Myo7a was performed. RESULTS: MI503 reduced keratinocyte growth factor-induced cholesteatoma in vivo (4 of 4 [100%]). No difference was found in the mean variation of the average of the auditory brainstem response thresholds between the three groups in the in vivo ototoxicity study, thus confirming its safety profile regarding auditory function. MI503 does not demonstrate any deleterious effects on murine hair cells when assessed by immunostaining. CONCLUSION: These findings demonstrate an encouraging safety profile for the use of menin-MLL inhibitor for the conservative treatment of cholesteatoma.

Squamous and Respiratory Metaplasia After Olfactory Mucosal Resection.

Resection of the olfactory mucosa (OM) is sometimes unavoidable during surgery; however, it is not known whether the OM can completely recover thereafter. The aim of this study was to uncover whether the OM fully recovers after mucosal resection and describe the process of OM regeneration. 8-week-old male Sprague-Dawley rats (n = 18) were subjected to OM resection at the nasal septum; six rats were euthanized for histological examination 0, 30, and 90 days after surgery. Immunohistochemistry was performed to identify olfactory receptor neuron (ORN) lineage cells [mature and immature ORNs and ORN progenitors, and olfactory ensheathing cells (OECs)], as well as dividing and apoptotic cells. Squamous and respiratory metaplasia and inflammatory cell infiltration were also assessed. On day 30 after resection, the mucosa had regenerated, and mainly contained thin nerve bundles, basal cells, and immature ORNs, with a few mature ORNs and OECs. On day 90, the repaired nasal mucosa had degenerated into stratified squamous or ciliated pseudostratified columnar epithelia, with reducing ORNs. The lamina propria contained numerous macrophages. Partial regeneration was observed within 1 month after OM resection, whereas subsequent degeneration into squamous and respiratory epithelia occurred within 3 months. Given the poor persistence of ORNs and OECs, OM resection is likely to result in olfactory impairment. Overall, surgeons should be cautious not to injure the OM during surgery.

Global study of variability in olfactory sensitivity.

Variability in human olfactory sensitivity has been attributed to individual-level factors such as genetics, age, sex, medical history of infections and trauma, neurogenerative diseases, and emotional disorders. Scarce evidence exists on the cross-cultural variation in olfactory sensitivity. Hence, we performed 2 studies to estimate the variability in olfactory threshold as a function of location and environment. Study 1 involved 11 laboratories from 4 continents (N = 802). In each location, in a designated laboratory, approximately 80 subjects underwent olfactory sensitivity testing with custom-made tests with eucalyptol and phenylethanol (PEA) odors. Tests were based on the Threshold subtest of the Sniffin' Sticks battery. In Study 2, we compared olfactory sensitivity and suprathreshold perception of PEA and eucalyptol in 2 Chinese (N = 160) and 2 Indian (N = 92) populations-one based in their native country and the other in Germany. Both studies present large-scale evidence that olfactory sensitivity varies as a function of geographical location and suggest that environmental factors play an important role in shaping olfactory sensitivity and suprathreshold olfactory perception. We delineate further steps necessary to identify specific factors underlying uncovered variability and the relationship between olfactory sensitivity and suprathreshold odor perception. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Metastasis of Papillary Thyroid Carcinoma to the Maxillary Sinus: Case Report and Review of the Literature.

Metastasis of the thyroid carcinoma to the paranasal sinuses is rarely reported. Among these sinuses, metastasis to the maxillary sinus alone has been reported only in a few cases. This is the first reported case in a 76-year-old woman with papillary thyroid carcinoma metastasizing to the maxillary sinus alone and resected through endoscopic sinonasal surgery. When patients have sinus lesions and a history of malignancy, metastasis should be included in the differential diagnosis. If they have an isolated metastatic lesion to the paranasal sinus, ESS, either palliative or radical, can be a useful treatment option.