Temporal Transcriptome Profiling of Pinus densiflora Infected with Pine Wood Nematode Reveals Genetically Programmed Changes upon Pine Wilt Disease.

Pine, an evergreen conifer, is widely distributed worldwide. It is economically, scientifically, and ecologically important. However, pine wilt disease (PWD) induced by the pine wood nematode (PWN) adversely affects pine trees. Many studies have been conducted on the PWN and its beetle vectors to prevent the spread of PWD. However, studies providing a comprehensive understanding of the pine tree transcriptome in response to PWN infection are lacking. Here, we performed temporal profiling of the pine tree transcriptome using PWD-infected red pine trees, Pinus densiflora, inoculated with the PWN by RNA sequencing. Our analysis revealed that defense-responsive genes involved in cell wall modification, jasmonic acid signaling, and phenylpropanoid-related processes were significantly enriched 2 weeks after PWD infection. Furthermore, some WRKY-type and MYB-type transcription factors were upregulated 2 weeks after PWD infection, suggesting that these transcription factors might be responsible for the genome-wide reprogramming of defense-responsive genes in the early PWD stage. Our comprehensive transcriptome analysis will assist in developing PWD-resistant pine trees and identifying genes to diagnose PWD at the early stage of infection, during which large-scale phenotypic changes are absent in PWD-infected pine trees.

Increased Risk of Alzheimer's Disease in Patients with Head and Neck Cancer.

Patients with head and neck cancer (HNC) often experience cognitive impairment. However, the relationship between cancer and Alzheimer's disease (AD) remains unclear. We aimed to elucidate the relationship between patients with HNC and their subsequent AD development. This retrospective study used data from a nationwide representative cohort sample, the Korean National Health Insurance Service Cohort. The cancer group was defined based on the presence of diagnostic codes for HNC (C00-C14 and C30-C32). After matching the independent variables with a propensity score of 4:1, a total of 2304 people without HNC and 576 with HNC were enrolled in this study. Hazard ratios (HRs) of AD incidence (per 1000 person-years) and 95% confidence intervals (CIs) in HNC patients were calculated. The incidence of AD was 14.92 in HNC patients and 9.77 in non-cancer patients. Additionally, the HNC group was found to have a higher risk of developing AD compared with the non-cancer group. Female and middle-aged HNC patients had a higher risk of developing AD events compared with other subgroups. Surprisingly, during the observation period, the risk of developing AD was relatively high within the first year after HNC diagnosis. In conclusion, our study suggests that HNC and AD are positively correlated.

Effect of Chronic Rhinosinusitis on the Risk of Development of Rheumatoid Arthritis.

PURPOSE: Several studies have reported a possible link between chronic rhinosinusitis (CRS) and rheumatoid arthritis (RA). However, it remains unclear whether CRS could influence the risk of developing RA. Therefore, in this study, we focused on examining the association between CRS and RA. METHODS: A total of 14,867 individuals with CRS and 14,867 without CRS were enrolled after 1:1 propensity score match from a nationwide longitudinal cohort database in South Korea. RA incidence was assessed using person-years at risk, and the hazard ratio (HR) was examined using the Cox proportional hazards model. RESULTS: The incidence of RA (per 1,000 person-years) was 6.51 for those with CRS, 6.55 for those with CRS without nasal polyps (CRSsNP), and 5.96 for those with CRS with nasal polyps (CRSwNP). We found that CRS individuals had a significantly increased risk of subsequent RA development with an adjusted HR of 1.41, regardless of the phenotype (adjusted HR was 1.42 in CRSsNP and 1.37 in CRSwNP patients). Moreover, the risk of developing RA over time was relatively higher within the first 4 years after the diagnosis of CRS. CONCLUSIONS: Our nationwide population-based cohort study suggests that CRS may be associated with a subsequent increase in RA events, regardless of the phenotype. Therefore, physicians should consider RA risk when diagnosing and treating CRS patients.

KAAACI Allergic Rhinitis Guidelines: Part 2. Update in Non-pharmacological Management.

Allergic rhinitis is the most common chronic disease worldwide. Various upper airway symptoms lower quality of life, and due to the recurrent symptoms, multiple treatments are usually attempted rather than one definitive treatment. There are alternatives to medical (medication-based) and non-medical treatments. A guideline is needed to understand allergic rhinitis and develop an appropriate treatment plan. We have developed guidelines for medical treatment based on previous reports. The current guidelines herein are associated with the "KAAACI Evidence-Based Guidelines for Allergic Rhinitis in Korea, Part 1: Update in pharmacotherapy" in which we aimed to provide evidence-based recommendations for the medical treatment of allergic rhinitis. Part 2 focuses on non-pharmacological management, including allergen-specific immunotherapy, subcutaneous or sublingual immunotherapy, nasal saline irrigation, environmental management strategies, companion animal management, and nasal turbinate surgery. The evidence to support the treatment efficacy, safety, and selection has been systematically reviewed. However, larger controlled studies are needed to elevate the level of evidence to select rational non-medical therapeutic options for patients with allergic rhinitis.

KAAACI Allergic Rhinitis Guidelines: Part 1. Update in Pharmacotherapy.

The prevalence of allergic rhinitis (AR) and the socioeconomic burden associated with the medical cost and quality of life (QOL) of AR have progressively increased. Therefore, practical guidelines for the appropriate management of AR need to be developed based on scientific evidence while considering the real-world environment, values, and preferences of patients and physicians. The Korean Academy of Asthma, Allergy and Clinical Immunology revised clinical guidelines of AR to address key clinical questions of the management of AR. Part 1 of the revised guideline covers the pharmacological management of patients with AR in Korea. Through a meta-analysis and systematic review, we made 4 recommendations for AR pharmacotherapy, including intranasal corticosteroid (INCS)/intranasal antihistamine (INAH) combination therapy, oral antihistamine/INCS combination therapy, leukotriene receptor antagonist treatment in AR patients with asthma, and prophylactic treatment for patients with pollen-induced AR. However, all recommendations are conditional because of the low or very low evidence of certainty. Well-designed and strictly executed randomized controlled trials are needed to measure and report appropriate outcomes.

Unusual Causes of Nasal Septal Abscess Including a COVID-19 Swab Test After Nasal Surgery.

A nasal septal abscess is a rare lesion that usually results from a nasal septal hematoma after nasal trauma or surgery, although it can occur unexpectedly. Nasal septal abscesses should be prevented and treated immediately. The authors describe 2 unusual cases: 1 caused by sudden loosening of the quilting suture of the nasal septum and the other by a nasopharyngeal swab test for coronavirus disease-2019. The authors also provide an intraoperative video and a literature review.

Anatomical Variations Associated With Maxillary Sinus Fungal Ball.

OBJECTIVE: We investigated the anatomical and dental factors associated with unilateral maxillary sinus fungal ball (MSFB). Also, we evaluated the effect of combinations of those factors on the incidence of MSFB. METHODS: Three hundred patients were divided into MSFB, normal, and chronic rhinosinusitis (CRS) groups. We reviewed paranasal computed tomography scans for the presence of deviated nasal septum, concha bullosa (CB), Haller cells, and various dental factors. Also, we measured the ethmoid infundibulum, maxillary natural ostium, and CB. RESULTS: Maxillary sinus fungal ball showed a more significant association with CB compared to the other 2 groups (37%, P < .05). The MSFB group had a lower rate of Haller cells than the normal group (10% vs 22%, respectively; P < .05). Also, the MSFB group had a wider maxillary sinus ostium than the normal group (7.07 ± 1.8 vs 5.48 ± 1.3 mm; P < .01). Moreover, the combination of CB and Haller cells was significantly associated with a decreased rate of the fungal ball (P = .047, odds ratio = 0.694). The dental factors were more prevalent in the MSFB and CRS groups (73% and 75%, respectively) than in the normal group (32%, P < .001). CONCLUSIONS: Maxillary sinus fungal ball is significantly associated with CB, Haller cells, an increased maxillary sinus ostium size, and dental factors.

Endoscopic Endonasal Optic Nerve Decompression in a Patient With Invasive Fungal Sinusitis Invasion Into the Orbital Apex: Intraoperative Video and Literature Review.

Invasive fungal sinusitis (IFS) is rare but potentially fatal in immunocompromised patients. Orbital extension of IFS can cause visual loss or ophthalmoplegia, and the rate of recovery of visual acuity can be low even after treatment with antifungal agents and sinus surgery. In this case, optic nerve decompression with the endoscopic endonasal approach was successful for the treatment of visual loss in a patient with IFS with orbital apex extension. The authors describe the recovery of visual acuity after optic nerve decompression in a patient with IFS who had exhibited visual loss caused by invasion into the orbital apex. The authors also provide an intraoperative video and literature review.

Immunomodulatory Effects of Primed Tonsil-Derived Mesenchymal Stem Cells on Atopic Dermatitis via B Cell Regulation.

Mesenchymal stem cells (MSCs) ameliorate T-and B cell-mediated immune responses. In particular, tonsil-MSCs (T-MSCs) are attractive candidates for practical and clinical applications because of their ease of acquisition and relatively low immunogenicity compared with other MSC sources. The use of MSCs as a therapeutic tool in atopic dermatitis (AD) has been investigated, but that of T-MSCs remains to be explored. Therefore, we investigated the immunomodulatory effects of primed T-MSCs in AD pathogenesis. In our animal study, primed T-MSCs showed greater immunological suppressive effects than naïve T-MSCs. Additionally, in vitro, the proliferation of B cells was downregulated by the addition of primed T-MSCs compared with naïve T-MSCs. The activation of B cells to differentiate into antibody-secreting cells and produce IgE was also reduced when primed T-MSCs were added. Moreover, under CD40-knockdown conditions, we found that CD40 in primed T-MSCs played a critical role as a regulator of B cell activation and was mediated by the non-canonical NF-κB pathway. Therefore, our findings suggest a promising role for primed T-MSCs in the treatment of AD by regulating B cell-mediated inflammatory responses, which are dependent on CD40 expression on primed T-MSCs mediated through the non-canonical NF-κB pathway.

Could Chronic Rhinosinusitis Increase the Risk of Ulcerative Colitis? A Nationwide Cohort Study.

Chronic rhinosinusitis (CRS) is a common chronic inflammatory disease of the sinonasal mucosa with an inflammatory or infectious etiology. Inflammatory bowel disease (IBD) causes chronic intestinal inflammation. Thus, both diseases share innate immune and epithelial barrier dysfunctions of the mucosa. However, the association between sinusitis and IBD is not well-known. We aimed to determine the association between CRS and the risk for IBDs, such as Crohn's disease (CD) and ulcerative colitis (UC). In this long-term retrospective cohort study, 15,175 patients with CRS and 30,350 patients without CRS (comparison group) were enrolled after 1:2 propensity score matching. The incidence rates of CD and UC were 0.22 and 0.51 (1000 person-years), respectively. The adjusted hazard ratio (HR) for developing CD and UC in CRS patients was 1.01 (95% confidence interval (CI), 0.66-1.54) and 1.72 (95% CI, 1.26-2.36), respectively. Additionally, in the subgroup analysis using the CRS phenotype, the adjusted HRs of UC were significantly increased in patients with CRS without nasal polyps (adjusted HR = 1.71; 95% CI, 1.24-2.35), but not in those with CRS with nasal polyps. CRS without nasal polyps is associated with an increased incidence of UC but not CD. Therefore, clinicians should pay attention to the early detection of UC when treating patients with CRS without nasal polyps.

Surgical and Radiological Differences in Intersphenoid Sinus Septation and the Prevalence of Onodi Cells with the Endoscopic Endonasal Transsphenoidal Approach.

Background and Objectives: Understanding the anatomical variation in the sphenoid sinus is important to fully expose the sellar floor and clivus. Materials and Methods: The Onodi cell and intersphenoid sinus septation based on preoperative paranasal sinus computed tomography (PNS CT) and the surgical records of 877 patients who underwent the endoscopic endonasal transsphenoidal approach (EETSA) were retrospectively reviewed. Results: An intersphenoid sinus septum (ISS) blocking the clivus was defined as a pseudoclivus. Complete and incomplete pseudoclivuses were found in 2.97% and 10.5% of patients, respectively. Intraoperative and PNS CT ISS findings differed in 17.1% of patients. Misconceptions regarding a ridge or vertical ISS and confusion between an incomplete pseudoclivus and a vertical ISS were common. Conclusions: Because intraoperative and PNS CT findings may differ, anatomical variation in the paraclival area should be evaluated carefully. A pseudoclivus mimicking the clivus is important to attain a fully exposed EETSA surgical view.

Human Palatine Tonsils Are Linked to Alzheimer's Disease through Function of Reservoir of Amyloid Beta Protein Associated with Bacterial Infection.

Amyloid-ß (Aß)-peptide production or deposition in the neuropathology of Alzheimer's disease (AD) was shown to be caused by chronic inflammation that may be induced by infection, but the role of pathogenic-bacteria-related AD-associated Aß is not yet clearly understood. In this study, we validated the hypothesis that there is a correlation between the Aß-protein load and bacterial infection and that there are effects of bacteria, Staphylococcus aureus (S. aureus), on the Aß load in the inflammatory environment of human tonsils. Here, we detected Aß-peptide deposits in human tonsil tissue as well as tissue similar to tonsilloliths found in the olfactory cleft. Interestingly, we demonstrated for the first time the presence of Staphylococcus aureus (S. aureus) clustered around or embedded in the Aß deposits. Notably, we showed that treatment with S. aureus upregulated the Aß-protein load in cultures of human tonsil organoids and brain organoids, showing the new role of S. aureus in Aß-protein aggregation. These findings suggest that a reservoir of Aß and pathogenic bacteria may be a possible therapeutic target in human tonsils, supporting the treatment of antibiotics to prevent the deposition of Aß peptides via the removal of pathogens in the intervention of AD pathogenesis.

Effect of Sleep Disturbance on Cognitive Function in Elderly Individuals: A Prospective Cohort Study.

Many epidemiologic and clinical studies have shown significant links between the degree of sleep disturbance and severity of impairment of selective cognitive functions, including the risk of neurodegenerative diseases. However, the sleep parameters that affect cognitive function in old age are unclear. Therefore, we investigated the association between sleep parameters and cognitive function in older patients. Patients aged above 65 years who complained of sleep-disordered breathing were enrolled consecutively. The Mini-Mental-State Examination tool was used to evaluate cognitive function. Eighty patients (normal cognitive function, n = 32 and cognitive impairment, n = 42) were included in this study. Multiple linear regression and binary logistic regression analyses were performed to explain the relationship between sleep parameters and cognitive function. We found that the body mass index (BMI) was significantly lower in the cognitive impairment group than in the normal cognitive function group. Additionally, the cognitive impairment group showed significantly decreased sleep efficiency and an increased apnea index compared with normal subjects. Moreover, lower BMI, reduced sleep efficiency, and high frequency of apnea events during sleep were associated with an increased risk of cognitive impairment.

The optimized core peptide derived from CABIN1 efficiently inhibits calcineurin-mediated T-cell activation.

The C-terminal fragment of CABIN1 interacts with calcineurin and represses the transcriptional activity of the nuclear factor of activated T cells (NFAT). However, the specific sequences and mechanisms through which it binds to calcineurin are unclear. This study determined that decameric peptide (CABIN1 residues 2146-2155) is minimally required for binding to calcineurin. This peptide contains a unique "PPTP" C-terminal sequence and a "PxIxIT" N-terminal motif. Furthermore, p38MAPK phosphorylated the threonine residue of the "PPTP" sequence under physiological conditions, dramatically enhancing the peptide's binding affinity to calcineurin. Therefore, the CABIN1 peptide inhibited the calcineurin-NFAT pathway and the activation of T cells more efficiently than the VIVIT peptide without affecting calcineurin's phosphatase activity. The CABIN1 peptide could thus be a more potent calcineurin inhibitor and provide therapeutic opportunities for various diseases caused by the calcineurin-NFAT pathway.

Risk of Burning Mouth Syndrome in Patients with Migraine: A Nationwide Cohort Study.

Migraine is a common neurological disease that causes a variety of symptoms, most notably throbbing, which is described as a pulsing headache on one side of the head. Burning mouth syndrome (BMS) is defined as an intra-oral burning sensation. Currently, no medical or dental cause has been identified for BMS. Interestingly, neuropathic pain is a characteristic feature of BMS; however, it remains unclear whether migraine can cause BMS. We aimed to identify the association of migraine with the risk of developing BMS. We used a representative nationwide cohort sample of approximately 1 million patients from 2002 to 2013 to investigate the prospective association between migraine and BMS. A total of 4157 migraine patients (migraine group) and 16,628 patients without migraine (comparison group) were enrolled after 1:4 propensity score matching. The overall incidence of BMS was significantly higher in the migraine group (0.15 per 1000 person-years) than in the comparison group (0.05 per 1000 person-years). The adjusted HR for patients with migraine who reported BMS events during the 10-year follow-up period was 2.96 (95% confidence interval, 1.02-8.56), after adjusting for other covariates. However, in the subgroup analysis, the adjusted HR for BMS events did not show a significant difference between the migraine and comparison group according to sex, age, and comorbidities. This study suggests that migraine is associated with an increased incidence of BMS. Therefore, clinicians should be attentive to detect BMS at an early stage when treating patients with migraine.

Changes in symptoms of Eustachian tube dysfunction after nasal surgery.

PURPOSE: To investigate the effects of nasal surgery including endoscopic sinus surgery (ESS) and/or septoplasty on Eustachian tube dysfunction (ETD) symptoms using the Eustachian Tube Dysfunction Questionnaire 7 (ETDQ-7). METHODS: Patients who underwent ESS and/or septoplasty between April 2020 and October 2021 were retrospective reviewed. The patients were divided into 3 groups according to the type of surgery: group A, septoplasty alone (76 patients); group B, ESS alone (209 patients); and group C, septoplasty + ESS (74 patients). Responses to the ETDQ-7, SNOT-22, and NOSE questionnaires were collected preoperatively and at 3 months after surgery and compared between groups. RESULTS: A total of 359 patients were included in the study. The prevalence of ETD was 28.9% (22 patients) in group A, 27.3% (57 patients) in group B, and 31.1% (23 patients) in group C. The ETDQ-7 score decreased significantly after surgery: total patient population, 12.47 ± 7.0 to 8.2 ± 2.48 (p < 0.001); group A, 12.76 ± 6.62 to 8.47 ± 2.66 (p < 0.001); group B, 12.05 ± 6.89 to 8.35 ± 2.73 (p < 0.001); and group C, 13.24 ± 7.72 to 7.55 ± 1.25 (p < 0.001). Both SNOT-22 and NOSE scores also decreased significantly after surgery in the total patient population and in all three groups. There was a strong correlation between ETDQ-7 and SNOT-22 scores (r = 0.56, p < 0.001) and a moderate correlation between ETDQ-7 and NOSE scores (r = 0.33, p < 0.001). CONCLUSION: Patients with CRS and/or NSD suffered from ETD, and showed significant improvement after surgery. In addition, ETD symptoms were shown to be affected by nasal obstruction as well as CRS symptoms.

Effects of Dental Factors on Fungal Sinusitis.

OBJECTIVES: This study aimed to investigate the associations between dental treatments and fungal maxillary sinusitis (FMS). METHODS: We retrospectively reviewed medical charts between July 2014 and March 2019. In total, 100 cases of FMS were included in this study. We also recruited 200 patients as a control group in the same period. Therefore, each of the FMS, chronic rhinosinusitis (CRS), and normal sinus groups consisted of 100 patients. We recorded all endodontic treatments (EDTs), tooth extractions, dental implantations, and apical lesions (ALs). RESULTS: The FMS group had higher incidences of tooth extraction (49% vs. 11%, respectively) and EDT (29% vs. 16%, respectively) compared to the normal sinus group and fewer ALs compared to the CRS group (6% vs. 24%, respectively). There were significant differences between the CRS and normal sinus groups in the extraction rate (53% vs. 11%, respectively) and frequency of ALs (24% vs. 4%, respectively). The dental implantation prevalence rates were similar across all 3 groups. CONCLUSION: The rates of tooth extraction were significantly higher in the FMS and CRS groups compared to the normal sinus group. In addition, of the 3 conditions, FMS was related to EDT, and CRS was related to ALs.

Long-term efficacy and safety of 3D printed implant in patients with nasal septal deformities.

PURPOSE: To investigate the long-term safety and efficacy of a 3D-printed bioresorbable polycaprolactone (PCL) nasal implant for nasal septal deformity reconstruction. METHODS: Fourteen patients who had undergone nasal septum reconstruction surgery using 3D-printed PCL nasal septal implants were enrolled. The primary outcome was the change in total Nasal Obstruction Symptom Evaluation (NOSE) scale scores between postoperative 3 months and current status (3.59 ± 0.51 years). The secondary outcomes were changes in the minimum cross-sectional area (MCA) and volume of both nasal cavities based on acoustic rhinometry, the cross-sectional area of the ostiomeatal unit, and the nasal septum angle of the paranasal sinus (PNS) in computed tomography (CT) images, and a visual analog scale (VAS) of the patients' subjective satisfaction. RESULTS: The results showed no significant changes in the MCAs (Cohen's d:0.09; p = 0.711) or nasal volume (Cohen's d:0.26; p = 0.356), the area of the ostiomeatal unit (Cohen's d:0.49; p = 0.064), septum angles (Cohen's d:0.18; p = 0.831), the NOSE scale (Cohen's d:0.14; p = 0.621), or patients' subjective satisfaction (Cohen's d:0.52; p = 0.076) during the follow-up period. CONCLUSIONS: This homogeneous composite microporous PCL nasal septal implant demonstrated long-term clinical efficacy and safety in human tissues that required maintenance of mechanical strength. Therefore, the indications for this implant could extend to various other craniofacial reconstructions in the future.

Phosphorylation of OGFOD1 by Cell Cycle-Dependent Kinase 7/9 Enhances the Transcriptional Activity of RNA Polymerase II in Breast Cancer Cells.

2-oxoglutarate and iron-dependent oxygenase domain-containing protein 1 (OGFOD1) expression is upregulated in a variety of cancers and has been related to poor prognosis. However, despite this significance to cancer progression, the precise oncogenic mechanism of OGFOD1 is not understood. We demonstrated that OGFOD1 plays a role in enhancing the transcriptional activity of RNA polymerase II in breast cancer cells. OGFOD1 directly binds to the C-terminal domain of RNA polymerase II to alter phosphorylation status. The elimination of OGFOD1 resulted in decreased tumor development. Additionally, cell cycle-dependent kinase 7 and cell cycle-dependent kinase 9, critical enzymes for activating RNA polymerase II, phosphorylated serine 256 of OGFOD1, whereas a non-phosphorylated mutant OGFOD1 failed to enhance transcriptional activation and tumor growth. Consequently, OGFOD1 helps promote tumor growth by enhancing RNA polymerase II, whereas simultaneous phosphorylation of OGFOD1 by CDK enzymes is essential in stimulating RNA polymerase II-mediated transcription both in vitro and in vivo, and expression of target genes.