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Innate immunity responds to pathogens by producing alarm signals and activating pathways that make host cells inhospitable for pathogen replication. The intracellular bacterium Burkholderia thailandensis invades the cytosol, hijacks host actin, and induces cell fusion to spread to adjacent cells, forming multinucleated giant cells (MNGCs) which promote bacterial replication. We show that type I interferon (IFN) restricts macrophage MNGC formation during B. thailandensis infection. Guanylate-binding proteins (GBPs) expressed downstream of type I IFN were required to restrict MNGC formation through inhibition of bacterial Arp2/3-dependent actin motility during infection. GTPase activity and the CAAX prenylation domain were required for GBP2 recruitment to B. thailandensis, which restricted bacterial actin polymerization required for MNGC formation. Consistent with the effects in in vitro macrophages, Gbp2-/-, Gbp5-/-, GbpChr3-KO mice were more susceptible to intranasal infection with B. thailandensis than wildtype mice. Our findings reveal that IFN and GBPs play a critical role in restricting cell-cell fusion and bacteria-induced pathology during infection.

An 82-year-old man with type 2 diabetes and recent glucocorticoid use presented with a 2-week history of headache and spontaneous bruising around his eye. Black eschars were observed in the nasal cavity (shown in a video).

Background Intranasal drug delivery offers a non-invasive and convenient dosing option for patients and physicians, especially for conditions requiring chronic/repeated-treatment administration. However, in some cases such delivery may be harmful to nasal and olfactory epithelia. Objective The aim of this study was to assess the potential impact of long-term intermittent treatment with esketamine nasal spray, taken in conjunction with an oral antidepressant (AD), on olfactory function and nasal tolerability in patients with treatment-resistant depression (TRD). Methods A total of 1142 patients with TRD participated from four multicenter, randomized, double-blind, phase III studies: three short-term studies (two in patients aged 18–64 years, one in patients ≥65 years), and one long-term maintenance study of esketamine nasal spray + AD versus placebo nasal spray + AD. Across the four studies, assessments were performed at 208 sites in 21 countries. Olfactory function was measured using the 40-item University of Pennsylvania Smell Identification Test (UPSIT ® ) and the single-staircase Snap & Sniff ® Odor Detection Threshold Test (S&S-T). Nasal tolerability, including nasal examinations and a quantitative, self-administered nasal symptom questionnaire (NSQ), was also assessed. Data were analyzed using analyses of covariance. Results Of 1142 participants, 734 were women (64.3%). The mean age of all participants ranged from 45.7 to 70.0 years across the studies. Overall, 855 patients received esketamine nasal spray + AD and 432 received placebo nasal spray + AD. Objective evaluation of nasal function showed no evidence of an adverse impact following esketamine administration. Based on the UPSIT ® and S&S-T results, intranasal administration of esketamine had no effect on the odor identification or threshold test scores compared with placebo nasal spray + oral AD. Similarly, repeated administration with esketamine nasal spray had no meaningful impact on assessments of nasal function. No dose–response relationship was observed between esketamine doses and the olfactory test scores. Esketamine nasal spray was well tolerated, as indicated by responses on the NSQ and negative nasal examination findings. Conclusion Findings from this analysis indicate that there was no evidence of adverse effect on either olfactory or nasal health measures with repeated intermittent administration of esketamine nasal spray at any dose over the course of short-term (4 weeks) or long-term (16–100 weeks) studies. Clinical trial registration TRANSFORM-1: NCT02417064, date of registration: 15/04/2015; TRANSFORM-2: NCT02418585, date of registration: 16/04/2015; TRANSFORM-3: NCT02422186, date of registration: 21/04/2015; SUSTAIN-1: NCT02493868, date of registration: 10/07/2015.

Enhancer of zeste homolog 2 (EZH2), a protein encoded by the EZH2 gene, is a crucial subunit in polycomb repressive complex 2. EZH2 controls the transcription of genes critical for cell proliferation, differentiation, amplification, and function through both methylated and unmethylated functions. EZH2 is considered to be a transcriptional suppressor protein when it controls histone methylation. Its dysregulation is related to a variety of cancers, with significant evidence showing its role in prostate cancer and breast cancer. EZH2 is also thought to be involved in the differentiation and function of immune cells. Ongoing research on EZH2 has revealed the correlation between inflammatory nasal diseases, the occurrence and development of nasal sinus tumors, and EZH2. This article aimed to review the research progress on the role of EZH2 in nasal diseases and explore the possibility of future EZH2-targeted therapies for nasal diseases.

Convolutional neural networks are a subclass of deep learning or artificial intelligence that are predominantly used for image analysis and classification. This proof-of-concept study attempts to train a convolutional neural network algorithm that can reliably determine if the middle turbinate is pneumatised (concha bullosa) on coronal sinus computed tomography images. Consecutive high-resolution computed tomography scans of the paranasal sinuses were retrospectively collected between January 2016 and December 2018 at a tertiary rhinology hospital in Australia. The classification layer of Inception-V3 was retrained in Python using a transfer learning method to interpret the computed tomography images. Segmentation analysis was also performed in an attempt to increase diagnostic accuracy. The trained convolutional neural network was found to have diagnostic accuracy of 81 per cent (95 per cent confidence interval: 73.0-89.0 per cent) with an area under the curve of 0.93. A trained convolutional neural network algorithm appears to successfully identify pneumatisation of the middle turbinate with high accuracy. Further studies can be pursued to test its ability in other clinically important anatomical variants in otolaryngology and rhinology.

Air pollution, an emerging global environmental issue, alongside extreme meteorological conditions exacerbated by climate change, threaten the sustainability of modern society and contribute to the onset and progression of various ear and nose diseases. Nonetheless, the impact of these environmental factors on ear and nose diseases and related dysfunctions remain inadequately explored. The present review involved a comprehensive search of PubMed, Web of Science, the Cochrane Library and Embase for relevant epidemiological and experimental data. How environmental factors contribute to olfactory and auditory system dysfunctions as well as the potential underlying mechanisms from the perspectives of immunity and inflammation were examined in the present review. It was found that air pollution and meteorological factors significantly influence the prevalence of major ear and nose diseases, including allergic rhinitis, otitis media and sudden sensorineural hearing loss. Of note, the present review also provides an examination of the interaction between severe acute respiratory syndrome coronavirus 2 and environmental factors in ear and nose diseases, highlighting how environmental stressors may worsen disease progression. In conclusion, the present review underscores the burden of multimorbidity caused by air pollution and extreme weather and emphasizes the need for more targeted prevention and management strategies for ear and nose diseases.

Hereditary nasal parakeratosis (HNPK) is an inherited disorder described in Labrador Retrievers and Greyhounds. It has been associated with breed-specific variants in the SUV39H2 gene encoding a histone 3 methyltransferase involved in epigenetic silencing. Formalin-fixed biopsies of the nasal planum of Labrador Retrievers were screened by immunofluorescence microscopy for the presence and distribution of epidermal proliferation and differentiation markers. Gene expression of these markers was further analysed using RNA sequencing (RNA-seq) and ultrastructural epidermal differences were investigated by electron microscopy. Differentiation of the nasal planum in the basal and suprabasal epidermal layers of HNPK-affected dogs (n = 6) was similar compared to control dogs (n = 6). In the upper epidermal layers, clear modifications were noticed. Loricrin protein was absent in HNPK-affected nasal planum sections in contrast to sections of the same location of control dogs. However, loricrin was present in the epidermis of paw pads and abdominal skin from HNPK dogs and healthy control dogs. The patterns of keratins K1, K10 and K14, were not markedly altered in the nasal planum of HNPK-affected dogs while the expression of the terminal differentiation marker involucrin appeared less regular. Based on RNA-seq, LOR and IVL expression levels were significantly decreased, while KRT1, KRT10 and KRT14 levels were up-regulated (log2fold-changes of 2.67, 3.19 and 1.71, respectively) in HNPK-affected nasal planum (n = 3) compared to control dogs (n = 3). Electron microscopical analysis revealed structural alterations in keratinocytes and stratum corneum, and disrupted keratinocyte adhesions and distended intercellular spaces in lesional samples (n = 3) compared to a sample of a healthy control dog (n = 1). Our findings demonstrate aberrant keratinocyte terminal differentiation of the nasal planum of HNPK-affected Labrador Retrievers and provide insights into biological consequences of this inactive SUV39H2 gene variant.

BackgroundThe thick-skinned nose is still one of the most challenging aspects of rhinoplasty. The possible effects of oral isotretinoin on cosmetic results of rhinoplasty in patients with thick nasal skin have been considered during recent years.MethodsIn this double-blind placebo-controlled clinical trial, 48 cases were divided into two groups randomly. Oral isotretinoin (0.5-mg/kg) was started on the 31st day after surgery and given every other day for 1 month and after that daily for two additional months in the first group. The second group received a placebo in the same form, sequence and interval as the first group. The cosmetic results based on patient satisfaction and ranking by an expert surgeon were compared between the two groups at 3 months, 6 months and 1 year after surgery.ResultsPatient satisfaction and ranking by an expert surgeon in the isotretinoin group at 3 months and 6 months after surgery were significantly better than in the placebo group (p value < 0.05); however, at 12 months after surgery there was no statistically significant difference between the two groups (p value > 0.05).ConclusionThough postoperative use of oral isotretinoin in patients with thick nasal skin accelerates improvement in cosmetic results during the early months after surgery, it does not significantly affect the final cosmetic result 1 year after surgery.Level of Evidence IIThis journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Intranasal (i.n.) infections preferentially generate Th17 cells. We explored the basis for this anatomic preference by tracking polyclonal CD4⁺ T cells specific for an MHC class II-bound peptide from the mucosal pathogenStreptococcus pyogenes. S. pyogenesMHC class II-bound peptide-specific CD4⁺ T cells were first activated in the cervical lymph nodes following i.n. inoculation and then differentiated into Th17 cells.S. pyogenes-induced Th17 formation depended on TGF-β1 from dendritic cells and IL-6 from a CD301b⁺ dendritic cell subset located in the cervical lymph nodes but not the spleen. Thus, the tendency of i.n. infection to induce Th17 cells is related to cytokine production by specialized dendritic cells that drain this site.

Introduction Encephaloceles are considered by most to be a type of neural tube defect characterized by a herniation of the brain and meninges through structural weaknesses in the bony structures of the skull. Discussion Many different types of encephaloceles have been classified according to the location of the bony defect. Basal and frontoethmoidal encephaloceles constitute a nasal subclass of encephaloceles, which are herniations from the skull base and ethmoid bone, respectively. Basal encephaloceles are usually occult and can herniate into nasal structures causing obstruction. Frontoethmoidal encephaloceles usually present as a protrusion that is visible at birth and enlarges during crying. Both of these entities are rare with an incidence ranging from 1 in 5,000 to 1 in 40,000 live births around the world with the majority of cases localized in Southeast Asia. Conclusion Although cases have been recorded since the sixteenth century, there is still a scarcity of knowledge on the exact causes and factors associated with the development of the disease. Many studies have determined these to be caused by a combination of genetic and environmental factors. Most cases are nonlife threatening and the preferred method of treatment is surgical removal after diagnosis is confirmed with computerized tomography or magnetic resonance imaging. Prognosis is generally positive, especially in the subset of patients with frontoethmoidal encephaloceles.