Relationship Between Snoring Intensity and Severity of Obstructive Sleep Apnea

ObjectivesThe aim of this study was to determine the relationship between the intensity of snoring and severity of sleep apnea using Watch-PAT (peripheral arterial tone) 100.MethodsA total of 404 patients (338 males and 66 females) who underwent home-based portable sleep study using Watch-PAT 100 for obstructive sleep apnea (OSA) from January 2009 through December 2011 were included in this study. Subjects were divided into 4 groups; no OSA (PAT apnea hypopnea index [pAHI]<5/hour), mild OSA (5≤pAHI<15/hour), moderate OSA (15≤pAHI<30/hour), or severe OSA groups (pAHI≥30/hour). Mean snoring intensity and percent sleep time with snoring intensity greater than 40, 50, and 60 dB were measured by Watch-PAT 100. Correlations of these parameters with apnea hypopnea index (AHI), respiratory disturbance index (RDI), and oxygen desaturation index were assessed.ResultsThe mean age and body mass index were 46.5±14.8 years and 24.7±3.4 kg/m2, respectively. Mean AHI and RDI were 16.5±15.3/hour and 20.8±14.3/hour, respectively. The mean snoring intensity in the no, mild, moderate, and severe OSA groups was 44.0±2.7, 45.4±6.0, 47.7±5.0, and 50.5±5.6 dB, respectively (P<0.001). There was a positive correlation between snoring intensity and pAHI or PAT RDI (pRDI) (r=0.391 and r=0.385, respectively, both P<0.001). There was also a positive correlation between percent sleep time with the snoring intensity greater than 50 dB and pAHI or pRDI (r=0.423 and r=0.411, respectively, both P<0.001).ConclusionThis study revealed that the intensity of snoring increased with the severity of sleep apnea, which suggests that the loudness of snoring might be an indicator of the severity of OSA

Epithelial-Mesenchymal Transition in Chronic Rhinosinusitis

Chronic rhinosinusitis (CRS) is characterized by prolonged inflammation of the nasal and paranasal sinus mucosa lasting over 12 weeks. CRS is divided into two main types based on the presence of nasal polyps: CRS without nasal polyps and CRS with nasal polyps. The condition is further classified into endotypes based on type 1, type 2, and type 3 inflammatory signatures, with differences in terms of disease severity, prognosis, and treatment response. Recent studies have emphasized the importance of the epithelial-mesenchymal transition (EMT) in CRS progression. In CRS, the EMT can be triggered by infections, allergens, hypoxia, and environmental pollutants. Specifically, EMT induction proceeds through the following mechanisms: viral and bacterial infections disrupt the epithelial barrier, house dust mites and other allergens activate the TGF-β and EGFR signaling pathways, hypoxia increases HIF-1α and other mesenchymal markers, and diesel exhaust particles and particulate matter cause oxidative stress. Maintaining the integrity of the epithelial barrier is essential for nasal mucosa homeostasis. In CRS, barrier damage activates repair processes that trigger the EMT, resulting in barrier dysfunction and tissue remodeling. Epithelial barrier dysfunction allows antigens and pathogens to penetrate, perpetuating inflammation and promoting the EMT. This disruption is a hallmark of CRS, emphasizing the importance of barrier integrity in the development of the disease. Key signaling pathways regulating the EMT in CRS include TGF-β, Wnt, HMGB1, AGE/ERK, TNF-α, and various miRNAs. These signaling pathways connect to various downstream pathways, such as the Smad2/3, GSK-3β/β-catenin, RAGE, and NF-κB pathways. This review focuses on the complex mechanisms of the EMT in CRS, emphasizing the role of epithelial barrier dysfunction and subsequent EMT processes in driving the disease’s development and progression. A deeper understanding of these EMT-driven mechanisms will help identify the potential therapeutic targets aimed at restoring epithelial integrity and reversing the EMT

Tricho-dento-osseous Syndrome Mutant Dlx3 Shows Lower Transactivation Potential but Has Longer Half-life than Wild-type Dlx3

Dlx3 is a homeodomain protein and is known to play a role in development and differentiation of many tissues. Deletion of four base pairs in DLX3 (NT3198) is causally related to tricho-dento-osseous (TDO) syndrome (OMIM #190320), a genetic disorder manifested by taurodontism, hair abnormalities, and increased bone density in the cranium. The molecular mechanisms that explain the phenotypic characteristics of TDO syndrome have not been clearly determined. In this study, we examined phenotypic characteristics of wild type DLX3 (wtDlx3) and 4-BP DEL DLX3 (TDO mtDlx3) in C2C12 cells. To investigate how wtDlx3 and TDO mtDlx3 differentially regulate osteoblastic differentiation, reporter assays were performed by using luciferase reporters containing the promoters of alkaline phosphatase, bone sialoprotein or osteocalcin. Both wtDlx3 and TDO mtDlx3 enhanced significantly all the reporter activities but the effect of mtDlx3 was much weaker than that of wtDlx3. In spite of these differences in reporter activity, electrophoretic mobility shift assay showed that both wtDlx3 and TDO mtDlx3 formed similar amounts of DNA binding complexes with Dlx3 binding consensus sequence or with ALP promoter oligonucleotide bearing the Dlx3 binding core sequence. TDO mtDlx3 exhibits a longer half-life than wtDlx3 and it corresponds to PESTfind analysis result showing that potential PEST sequence was missed in carboxy terminal of TDO mtDlx3. In addition, co-immunoprecipitation demonstrated that TDO mtDlx3 binds to Msx2 more strongly than wtDlx3. Taken together, though TDO mtDlx3 acted as a weaker transcriptional activator than wtDlx3 in osteoblastic cells, there is possibility that during in vivo osteoblast differentiation TDO mtDlx3 may antagonize transcriptional repressor activity of Msx2 more effectively and for longer period than wtDlx3, resulting in enhancement of osteoblast differentiation

The Association of the GABRP

Gamma-aminobutyric acid receptor subunit pi (GABRP) is involved in inhibitory synaptic transmission in the central nervous system. This gene encodes multisubunit chloride channels and is also expressed in numerous nonneuronal tissues such as the uterus and the ovaries. This study was aimed to validate whether the polymorphisms in the GABRP gene are associated with the susceptibility to systematic lupus erythematosus (SLE). The genotype frequencies of the rs929763, rs732157, and rs3805455 of the GABRP gene in SLE patients were significantly different from those of the control group (P<0.0001, P=0.05 and 0.002, resp.). Additional analysis showed that the genotype of the rs929763 and rs3805455 of the GABRP gene were also significantly associated with female SLE patients (P<0.0001, P=0.005, resp.). Two haplotype frequencies including a major haplotype of GABRP SNPs were more significantly different between the SLE patients and the healthy controls (P=0.038 and 4.2E-24, resp.). These results suggest that the polymorphisms in the GABRP gene might be associated with the susceptibility to SLE and the haplotype of GABRP SNPs is useful genetic marker for SLE

Biologics for Chronic Rhinosinusitis With Nasal Polyps: Current Status and Clinical Considerations in Korea

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a prevalent condition that significantly impacts quality of life and places a burden on healthcare systems. The advent of biologics targeting type 2 immune pathways offers new therapeutic options for severe and/or uncontrolled CRSwNP. Initially, biologic use was guided by the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) 2020 and the European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) guidelines, despite limited data on clinical indications, response measures, and treatment duration. Since then, numerous studies and the EPOS/EUFOREA 2023 update have refined these guidelines. The update defines clinical indications for biologics based on type 2 inflammation markers by lowering the blood eosinophil threshold from 250 to 150 cells/μL. The response to biologics is now more simply categorized into three levels based on reductions in nasal polyp size, improvements in quality of life, and enhancement of smell. Treatment evaluation is recommended at 6 months with annual follow-up. Longer administration intervals, such as every four weeks, have also proven effective in well-controlled patients. Although specific guidelines for discontinuation or switching biologics remain lacking, clinical judgment is essential in determining when treatment should be stopped or adjusted. Additionally, regulatory updates support the use of biologics for CRSwNP, and novel agents such as tezepelumab (an anti-thymic stromal lymphopoietin monoclonal antibody) continue to show promise. Finally, in Korea, biologics for CRSwNP are not covered by national health insurance, leading to extended dosing intervals due to high costs. Despite this limitation, studies have shown that adjusted dosing can maintain subjective quality of life. Recent studies by Korean authors have also explored practical considerations such as dosing intervals and comparisons to surgery. Further research is needed to optimize treatment strategies, particularly regarding cost-effectiveness and prospective studies tailored to the Korean healthcare system

IL-25 Could Be Involved in the Development of Allergic Rhinitis Sensitized to House Dust Mite

Background and Purpose. When house dust mite (HDM), a common allergen, comes into the mucosal membrane, it may stimulate innate immunity. However, the precise role of interleukin- (IL-) 25 in the development of HDM-induced nasal allergic inflammation is still unclear. Therefore, we investigated the role of IL-25 in allergic rhinitis (AR) patients sensitized to HDM. Methods. To confirm the production of IL-25 in human nasal epithelial cells (HNECs), we stimulated HNECs. IL-25 expression in the nasal mucosa from control, non-AR (NAR) patients, and HDM-sensitized AR patients was assessed using immunohistochemistry, and quantitative reverse transcription PCR. Correlations between IL-25 and other inflammatory markers were explored. Results. An in vitro study showed significantly elevated concentrations of IL-25 in the HNEC samples with highest doses of HDM. Nasal tissues from AR patients sensitized to HDM showed significantly higher IL-25 expression, compared to those from the control or NAR patients. Moreover, the expression of IL-25 in nasal tissues from AR patients sensitized to HDM was positively associated with Th2 markers, such as ECP and GATA3. Conclusions. IL-25 expression increased with high-dose HDM stimulation and was related to Th2 markers. Therefore, IL-25 neutralization might offer a new strategy for treating patients with HDM-sensitized AR

Transplantation of Neural Stem Cells in Anosmic Mice

ObjectivesTreating olfactory dysfunction is a challenge for physicians. One of the therapeutic options could be transplantation of stem cells. In this study, neural stem cells were transplanted into anosmic mice.MethodsNeural stem cells were generated from the olfactory bulb of green fluorescent protein (GFP)-transgenic C57BL6 mice. Anosmia were induced by injection of intraperitoneal 3-methylindole. The neural stem cells were transplanted transnasally on the next day. The olfactory function was evaluated by a food-finding test once a week. The olfactory neuroepithelium was harvested for histologic examination and protein analysis at 4 weeks.ResultsTwenty-five percent (6/24) of the control mice that were not transplanted with neural stem cells survived at 4 weeks while 67% (8/12) of the transplanted mice survived (P=0.029). The food finding test showed that the transplanted mice resumed finding food at 3 weeks while the control mice resumed finding food at 4 weeks. GFP-positive cells were observed in the olfactory neuroepithelium of the transplanted mice. Western blotting revealed that the olfactory marker protein expression was significantly lower in the control mice than that in the transplanted mice.ConclusionThis study demonstrated that improvement of mouse survival was achieved and recovery of olfactory function was promoted by transnasal transplantation of neural stem cells in the anosmic mouse model. These results indicate that stem cells might be one of the future modalities for treating olfactory impairment

Early Compliance and Efficacy of Sublingual Immunotherapy in Patients with Allergic Rhinitis for House Dust Mites

Objectives. Sublingual immunotherapy (SLIT) has recently received much attention around the world as a treatment for allergic rhinitis. This study aimed to investigate the efficacy and adverse effects of SLIT in Korean patients with allergic rhinitis caused by house dust mites. The treatment compliance and the patient satisfaction with SLIT were also assessed. Methods. The patients who were sensitized to Dermatophagoides pteronyssinus and Dermatophagoides farinae and who started SLIT between November 2007 and July 2008 were included in this study. The symptom questionnaires, which included items on rhinorrhea, sneezing, nasal obstruction, itchy nose, olfactory disturbance, eye discomfort and sleep disturbance, were obtained before and 6 months after SLIT. The patient satisfaction and the adverse effects were also investigated. Results. One hundred forty-two patients started SLIT and 98 of them continued SLIT for 6 months or more. Ninety-two of the 98 patients completed the questionnaires. The duration of receiving SLIT was 9.8 months on average (range, 6 to 13 months). All the symptoms of allergic rhinitis were improved with SLIT. Forty-five percent of the patients were satisfied for SLIT, while 12% were unsatisfied. The incidence of adverse effects was 12% during maintenance therapy, although it was 48% during the up-dosing phase. The drop-out rate of SLIT was 31.0%. Conclusion. The subjective symptoms were improved with SLIT in Korean patients with allergic rhinitis for house dust mites. Yet the drop out rate was high despite of the symptomatic improvement.Roder E, 2008, CLIN EXP ALLERGY, V38, P1659, DOI 10.1111/j.1365-2222.2008.03060.xEsch RE, 2008, CURR OPIN OTOLARYNGO, V16, P260Frew AJ, 2008, NEW ENGL J MED, V358, P2259BOUSQUET J, 2008, ALLERGY S, V86, P8Eifan AO, 2007, ALLERGY, V62, P567, DOI 10.1111/j.1398-9995.2006.01301.xDunsky EH, 2006, ALLERGY, V61, P1235, DOI 10.1111/j.1398-9995.2006.01137.xAntico A, 2006, ALLERGY, V61, P1236, DOI 10.1111/j.1398-9995.2006.01155.xDahl R, 2006, J ALLERGY CLIN IMMUN, V118, P434, DOI 10.1016/j.jaci.2006.05.003Durham SR, 2006, J ALLERGY CLIN IMMUN, V117, P802, DOI 10.1016/j.jaci.2005.12.1358Passlacqua G, 2006, J ALLERGY CLIN IMMUN, V117, P946, DOI 10.1016/j.jaci.2005.12.1312Canonica GW, 2006, ALLERGY, V61, P20PASSALACQUA G, 2006, INFLAMM ALLERGY DRUG, V5, P43RIENZO VD, 2005, CLIN EXP ALLERGY, V35, P560KIM DY, 2004, KOREAN J OTOLARYNGOL, V47, P132WILSON DR, 2003, COCHRANE DB SYST REV, P2893NUHOGLU Y, 2003, J INVESTIG ALLERGOL, V17, P375Lombardi C, 2001, ALLERGY, V56, P989Guez S, 2000, ALLERGY, V55, P369, DOI 10.1034/j.1398-9995.2000.00413.xPurello-D`Ambrosio F, 1999, ALLERGY, V54, P968Pradalier A, 1999, ALLERGY, V54, P819Durham SR, 1996, J ALLERGY CLIN IMMUN, V97, P1356CASANOVAS M, 1994, J INVEST ALLERG CLIN, V4, P305

Ternary full adder using multi-threshold voltage graphene barristors

Ternary logic circuit has been studied for several decades because it can provide simpler circuits and subsequently lower power consumption via succinct interconnects. We demonstrated a ternary full adder exhibiting a low power-delay-product of ~10-16 J, which is comparable with the binary equivalent circuit. The ternary full adder was modeled using device parameters extracted from the experimentally demonstrated multi-Vth ternary graphene barristors