Functional Outcomes Associated With Blood Pressure Decrease After Endovascular Thrombectomy.

Importance: The associations between blood pressure (BP) decreases induced by medication and functional outcomes in patients with successful endovascular thrombectomy remain uncertain. Objective: To evaluate whether BP reductions induced by intravenous BP medications are associated with poor functional outcomes at 3 months. Design, Setting, and Participants: This cohort study was a post hoc analysis of the Outcome in Patients Treated With Intra-Arterial Thrombectomy-Optimal Blood Pressure Control trial, a comparison of intensive and conventional BP management during the 24 hours after successful recanalization from June 18, 2020, to November 28, 2022. This study included 302 patients who underwent endovascular thrombectomy, achieved successful recanalization, and exhibited elevated BP within 2 hours of successful recanalization at 19 stroke centers in South Korea. Exposure: A BP decrease was defined as at least 1 event of systolic BP less than 100 mm Hg. Patients were divided into medication-induced BP decrease (MIBD), spontaneous BP decrease (SpBD), and no BP decrease (NoBD) groups. Main Outcomes and Measures: The primary outcome was a modified Rankin scale score of 0 to 2 at 3 months, indicating functional independence. Primary safety outcomes were symptomatic intracerebral hemorrhage within 36 hours and mortality due to index stroke within 3 months. Results: Of the 302 patients (median [IQR] age, 75 [66-82] years; 180 [59.6%] men), 47 (15.6%)were in the MIBD group, 39 (12.9%) were in the SpBD group, and 216 (71.5%) were in the NoBD group. After adjustment for confounders, the MIBD group exhibited a significantly smaller proportion of patients with functional independence at 3 months compared with the NoBD group (adjusted odds ratio [AOR], 0.45; 95% CI, 0.20-0.98). There was no significant difference in functional independence between the SpBD and NoBD groups (AOR, 1.41; 95% CI, 0.58-3.49). Compared with the NoBD group, the MIBD group demonstrated higher odds of mortality within 3 months (AOR, 5.15; 95% CI, 1.42-19.4). The incidence of symptomatic intracerebral hemorrhage was not significantly different among the groups (MIBD vs NoBD: AOR, 1.89; 95% CI, 0.54-5.88; SpBD vs NoBD: AOR, 2.75; 95% CI, 0.76-9.46). Conclusions and Relevance: In this cohort study of patients with successful endovascular thrombectomy after stroke, MIBD within 24 hours after successful recanalization was associated with poor outcomes at 3 months. These findings suggested lowering systolic BP to below 100 mm Hg using BP medication might be harmful.

Polarization-Dependent Memory and Erasure in Quantum Dots/Graphene Synaptic Devices.

We demonstrate excitatory and inhibitory properties in a single heterostructure consisting of two quantum dots/graphene synaptic elements using linearly polarized monochromatic light. Perovskite quantum dots and PbS quantum dots were used to increase and decrease photocurrent weights, respectively. The polarization-dependent photocurrent was realized by adding a polarizer in the middle of the PbS quantum dots/graphene and perovskite quantum dots/graphene elements. When linearly polarized light passed through the polarizer, both the lower excitatory and upper inhibitory devices were activated, with the lower device with the stronger response dominating to increase the current weight. In contrast, the polarized light was blocked by the polarizer, and the above device was only operated, reducing the current weight. Furthermore, two orthogonal polarizations of light were used to perform the sequential processes of potentiation and habituation. By adjustment of the polarization angle of light, not only the direction of the current weight but also its level was altered.

Association between substantia nigra degeneration and functional outcome in patients with basal ganglia infarction.

BACKGROUND AND PURPOSE: Cerebral infarction in the basal ganglia may cause secondary and delayed neuronal degeneration in the substantia nigra (SN). However, the clinical significance of SN degeneration remains poorly understood. METHODS: This retrospective observational study included patients with acute ischemic stroke in the basal ganglia on initial diffusion-weighted imaging who underwent follow-up diffusion-weighted imaging between 4 and 30 days after symptom onset. SN degeneration was defined as a hyperintensity lesion in the SN observed on diffusion-weighted imaging. We compared functional outcomes at 3 months between patients with and without SN degeneration. A poor outcome was defined as a score of 3-6 (functional dependence or death) on the modified Rankin Scale. RESULTS: Of 350 patients with basal ganglia infarction (median age = 74.0 years, 53.7% male), 125 (35.7%) had SN degeneration. The proportion of functional dependence or death was 79.2% (99/125 patients) in patients with SN degeneration, which was significantly higher than that in those without SN degeneration (56.4%, 127/225 patients, p < 0.001). SN degeneration was more frequent in patients with functional dependence or death (99/226 patients, 43.8%) than in those with functional independence (26/124 patients, 21.0%, p < 0.001). Multivariable logistic regression analysis showed a significant association between SN degeneration and functional dependence or death (odds ratio = 2.91, 95% confidence interval = 1.17-7.21, p = 0.021). CONCLUSIONS: The study showed that patients with degeneration of SN were associated with functional dependence or death at 3 months, suggesting that secondary degeneration is a predictor of poor stroke outcomes and a potential therapeutic target.

Listeria monocytogenes requires DHNA-dependent intracellular redox homeostasis facilitated by Ndh2 for survival and virulence.

Listeria monocytogenes is a remarkably well-adapted facultative intracellular pathogen that can thrive in a wide range of ecological niches. L. monocytogenes maximizes its ability to generate energy from diverse carbon sources using a respiro-fermentative metabolism that can function under both aerobic and anaerobic conditions. Cellular respiration maintains redox homeostasis by regenerating NAD+ while also generating a proton motive force. The end products of the menaquinone (MK) biosynthesis pathway are essential to drive both aerobic and anaerobic cellular respirations. We previously demonstrated that intermediates in the MK biosynthesis pathway, notably 1,4-dihydroxy-2-naphthoate (DHNA), are required for the survival and virulence of L. monocytogenes independent of their role in respiration. Furthermore, we found that restoration of NAD+/NADH ratio through expression of water-forming NADH oxidase could rescue phenotypes associated with DHNA deficiency. Here, we extend these findings to demonstrate that endogenous production or direct supplementation of DHNA restored both the cellular redox homeostasis and metabolic output of fermentation in L. monocytogenes. Furthermore, exogenous supplementation of DHNA rescues the in vitro growth and ex vivo virulence of L. monocytogenes DHNA-deficient mutants. Finally, we demonstrate that exogenous DHNA restores redox balance in L. monocytogenes specifically through the recently annotated NADH dehydrogenase Ndh2, independent of its role in the extracellular electron transport pathway. These data suggest that the production of DHNA may represent an additional layer of metabolic adaptability by L. monocytogenes to drive energy metabolism in the absence of respiration-favorable conditions.

Intensive vs Conventional Blood Pressure Lowering After Endovascular Thrombectomy in Acute Ischemic Stroke: The OPTIMAL-BP Randomized Clinical Trial.

Importance: Optimal blood pressure (BP) control after successful reperfusion with endovascular thrombectomy (EVT) for patients with acute ischemic stroke is unclear. Objective: To determine whether intensive BP management during the first 24 hours after successful reperfusion leads to better clinical outcomes than conventional BP management in patients who underwent EVT. Design, Setting, and Participants: Multicenter, randomized, open-label trial with a blinded end-point evaluation, conducted across 19 stroke centers in South Korea from June 2020 to November 2022 (final follow-up, March 8, 2023). It included 306 patients with large vessel occlusion acute ischemic stroke treated with EVT and with a modified Thrombolysis in Cerebral Infarction score of 2b or greater (partial or complete reperfusion). Interventions: Participants were randomly assigned to receive intensive BP management (systolic BP target <140 mm Hg; n = 155) or conventional management (systolic BP target 140-180 mm Hg; n = 150) for 24 hours after enrollment. Main Outcomes and Measures: The primary outcome was functional independence at 3 months (modified Rankin Scale score of 0-2). The primary safety outcomes were symptomatic intracerebral hemorrhage within 36 hours and death related to the index stroke within 3 months. Results: The trial was terminated early based on the recommendation of the data and safety monitoring board, which noted safety concerns. Among 306 randomized patients, 305 were confirmed eligible and 302 (99.0%) completed the trial (mean age, 73.0 years; 122 women [40.4%]). The intensive management group had a lower proportion achieving functional independence (39.4%) than the conventional management group (54.4%), with a significant risk difference (-15.1% [95% CI, -26.2% to -3.9%]) and adjusted odds ratio (0.56 [95% CI, 0.33-0.96]; P = .03). Rates of symptomatic intracerebral hemorrhage were 9.0% in the intensive group and 8.1% in the conventional group (risk difference, 1.0% [95% CI, -5.3% to 7.3%]; adjusted odds ratio, 1.10 [95% CI, 0.48-2.53]; P = .82). Death related to the index stroke within 3 months occurred in 7.7% of the intensive group and 5.4% of the conventional group (risk difference, 2.3% [95% CI, -3.3% to 7.9%]; adjusted odds ratio, 1.73 [95% CI, 0.61-4.92]; P = .31). Conclusions and Relevance: Among patients who achieved successful reperfusion with EVT for acute ischemic stroke with large vessel occlusion, intensive BP management for 24 hours led to a lower likelihood of functional independence at 3 months compared with conventional BP management. These results suggest that intensive BP management should be avoided after successful EVT in acute ischemic stroke. Trial Registration: ClinicalTrials.gov Identifier: NCT04205305.

Listeria monocytogenes requires DHNA-dependent intracellular redox homeostasis facilitated by Ndh2 for survival and virulence.

Listeria monocytogenes is a remarkably well-adapted facultative intracellular pathogen that can thrive in a wide range of ecological niches. L. monocytogenes maximizes its ability to generate energy from diverse carbon sources using a respiro-fermentative metabolism that can function under both aerobic and anaerobic conditions. Cellular respiration maintains redox homeostasis by regenerating NAD + while also generating a proton motive force (PMF). The end products of the menaquinone (MK) biosynthesis pathway are essential to drive both aerobic and anaerobic cellular respiration. We previously demonstrated that intermediates in the MK biosynthesis pathway, notably 1,4-dihydroxy-2-naphthoate (DHNA), are required for the survival and virulence of L. monocytogenes independent of their role in respiration. Furthermore, we found that restoration of NAD + /NADH ratio through expression of water-forming NADH oxidase (NOX) could rescue phenotypes associated with DHNA deficiency. Here we extend these findings to demonstrate that endogenous production or direct supplementation of DHNA restored both the cellular redox homeostasis and metabolic output of fermentation in L. monocytogenes . Further, exogenous supplementation of DHNA rescues the in vitro growth and ex vivo virulence of L. monocytogenes DHNA-deficient mutants. Finally, we demonstrate that exogenous DHNA restores redox balance in L. monocytogenes specifically through the recently annotated NADH dehydrogenase Ndh2, independent of the extracellular electron transport (EET) pathway. These data suggest that the production of DHNA may represent an additional layer of metabolic adaptability by L. monocytogenes to drive energy metabolism in the absence of respiration-favorable conditions.

Analysis of age-related prevalence and risk factors of chronic rhinosinusitis with asthma.

OBJECTIVE: To determine age-related risk factors for chronic rhinosinusitis (CRS) with asthma. METHODS: Data were obtained from a national survey of non-hospitalized civilians conducted by the Korean Center for Disease Control and Prevention. CRS diagnosis was based on the guidelines of the European Position Paper on Rhinosinusitis and Nasal Polyps 2020. Asthma was judged based on whether the patient had been diagnosed with asthma in the past. Of the 45,811 survey participants, 26,335 were included in the cross-sectional study. Participants included in the study were divided into the control, CRS, and CRS with asthma groups. Age-related risk factors were analyzed in patients aged < 60 or > 60 years. Univariate logistic analyses were performed to evaluate the relationship between groups. Risk factors included age, sex, household income, residence, education level, occupation, and body mass index (BMI). RESULTS: Education level (Odds Ratio [OR]: 0.342, P = .0003), BMI (OR: 1.09, P = .0082), and total IgE (TIgE) levels (OR: 5.582, P = .003) were significantly different between the control and the CRS with asthma group. Education level (OR: 0.478, P = .0016) and TIgE levels (OR: 4, P = .0218) were significantly different between the CRS and CRS with asthma groups under 60 years of age. BMI (OR: 1.087, P = .0443; OR: 1.104, P = .0224) showed a significant difference between all three groups with age > 60 years. CONCLUSION: Progression to CRS with asthma is influenced by education level, occupation, and TIgE levels in patients under 60 years of age. BMI was the only influencing factor associated with the progression to CRS with asthma in those aged > 60 years.

Association between Concentration of Air Pollutants and Prevalence of Inflammatory Sinonasal Diseases: A Nationwide Cross-sectional Study.

BACKGROUND: Air pollution is a serious health concern and affects inflammatory sinonasal diseases such as allergic rhinitis (AR) and chronic rhinosinusitis (CRS). Clarifying the relationship between air pollutants and upper respiratory diseases could help the patients. OBJECTIVE: To evaluate the association between the concentration of air pollutants and the prevalence of AR and CRS among South Koreans. METHODS: In this cross-sectional study, nationwide data were reviewed for participants of the Korean National Health and Nutrition Examination Survey (KNHANES) 2008 to 2012. Participants were surveyed with health questionnaires, examined with endoscopies by otolaryngologists, and tested with serum immunoglobulin E levels. The concentrations of sulfur dioxide (SO2), nitrogen dioxide (NO2), ozone (O3), and particulate matter with aerodynamic diameters ≤10 µm (PM10) were measured in 16 areas of South Korea. Air pollutant concentrations of geographic districts were matched to each participant's residence. Logistic regression analysis was performed. RESULTS: Among 27 863 eligible adults, 3359 and 1606 participants had AR or CRS, respectively. In multivariable logistic regression analysis for AR, PM10 showed statistically significant results (odds ratio [OR] = 1.145, 95% confidence interval [CI] = 1.042-1.258). No air pollutants showed statistically significant differences in the prevalence of CRS. In AR, PM10 (OR = 1.458, 95% CI = 1.201-1.770) was associated with endoscopic findings of watery rhinorrhea, whereas SO2 (OR = 1.202, 95% CI = 1.100-1.313) was associated with pale mucosa. CONCLUSION: The prevalence of AR was significantly associated with PM10 concentration. In patients with AR, endoscopic findings of watery rhinorrhea were associated with PM10. However, CRS was not associated with the air pollutant concentrations. Lower concentration of PM10 might help managing the clinical symptoms in patients of AR.

Simultaneously Occurring Ischemic Stroke, Leg Artery Occlusion, and Pulmonary Embolism Induced by a Uterine Myoma.

OBJECTIVES: Paradoxical embolism from venous thrombosis through the patent foramen ovale is a rare but well-known cause of stroke in young adults. Here, we report a case of simultaneous middle cerebral artery infarction, multiple occlusions of the leg arteries, and pulmonary thromboembolism from the venous thrombus, all due to compression of the external iliac vein by a uterine leiomyoma. MATERIALS AND METHODS (CASE PRESENTATION): A 44-year-old woman presented with left hemiparesis and central-type left facial palsy. She denied a history of hypertension, diabetes mellitus, previous cerebral infarction, myocardial infarction, smoking, or oral contraceptive use. The patient recovered completely after injection of tissue plasminogen activator. Brain diffusion-weighted imaging showed an acute right middle cerebral artery infarction. Transcranial Doppler with saline agitation test revealed a right-to-left shunt, suggesting a patent foramen ovale. Chest computed tomography revealed multiple pulmonary thromboembolisms. Lower extremity sonography and lower extremity computed tomography revealed a multifocal thrombus in the major veins and arteries of the left leg. Moreover, a large uterine myoma compressing the left external iliac vein was noted on lower extremity computed tomography. RESULTS: After the treatment of pulmonary thromboembolism and venous thrombosis with rivaroxaban, surgical thrombectomy of the left popliteal artery, patent foramen ovale closure, and total hysterectomy were performed. Subsequently, she had no recurrent paradoxical embolism or pulmonary thromboembolism. CONCLUSION: Structural abnormalities in the pelvic cavity are not commonly suspected as stroke etiology. However, examination of the pelvic cavity is advisable in young female stroke patients with pulmonary thromboembolism or other paradoxical embolisms.

Agreement and Reliability Analysis of Machine Learning Scaling and Wireless Monitoring in the Assessment of Acute Proximal Weakness by Experts and Non-Experts: A Feasibility Study.

Assessing the symptoms of proximal weakness caused by neurological deficits requires the knowledge and experience of neurologists. Recent advances in machine learning and the Internet of Things have resulted in the development of automated systems that emulate physicians' assessments. The application of those systems requires not only accuracy in the classification but also reliability regardless of users' proficiency in the real environment for the clinical point-of-care and the personalized health management. This study provides an agreement and reliability analysis of using a machine learning-based scaling of Medical Research Council (MRC) proximal scores to evaluate proximal weakness by experts and non-experts. The system trains an ensemble learning model using the signals from sensors attached to the limbs of patients in a neurological intensive care unit. For the agreement analysis, we investigated the percent agreement of MRC proximal scores and Bland-Altman plots of kinematic features between the expert- and non-expert scaling. We also analyzed the intra-class correlation coefficients (ICCs) of kinematic features and Krippendorff's alpha of the observers' scaling for the reliability analysis. The mean percent agreement between the expert- and the non-expert scaling was 0.542 for manual scaling and 0.708 for autonomous scaling. The ICCs of kinematic features measured using sensors ranged from 0.742 to 0.850, whereas the Krippendorff's alpha of manual scaling for the three observers was 0.275. The autonomous assessment system can be utilized by the caregivers, paramedics, or other observers during an emergency to evaluate acute stroke patients.

Predictive Value of Radiologic Central Compartment Atopic Disease for Identifying Allergy and Asthma in Pediatric Patients.

INTRODUCTION: Central compartment atopic disease (CCAD) has recently been suggested as a phenotype of chronic rhinosinusitis (CRS). This study aims to investigate the prevalence of the radiologic CCAD phenotype in CRS within a pediatric population and identify its ability to predict comorbid allergy and asthma. METHODS: Computed tomography and endoscopic examination were conducted on pediatric patients with CRS either with or without nasal polyps. Allergen sensitization was determined with the multiple-allergen simultaneous test and skin prick test. Serum total immunoglobulin E (IgE), peripheral blood eosinophil percentage, and presence of asthma were also evaluated. RESULTS: A total of 82 pediatric patients were enrolled. Overall, 55 (67.1%) of the participants demonstrated aeroallergen sensitization, and 31 (18.9%) of the 164 sides of sinuses were radiologically defined to fit the CCAD phenotype. Patients having CRS with the CCAD phenotype had a higher prevalence of aeroallergen sensitization (87.1% vs 62.4%, P = .008), particularly house dust mite (74.2% vs 53.4%, P = .035), and a higher incidence of asthma (16.1% vs 3.8%, P = .010). Additionally, patients having CRS with the CCAD phenotype demonstrated a high serum total IgE levels (51.6% vs 30.1%, P = .023) in comparison to patients having CRS without CCAD. CONCLUSION: In pediatric CRS, the radiological CCAD phenotype was associated with allergen sensitization and asthma. Furthermore, the CCAD phenotype was associated with high serum total IgE levels, suggesting allergy etiology should be considered with this type of pediatric patients with CRS.

Outcome in Patients Treated with Intra-arterial thrombectomy: The optiMAL Blood Pressure control (OPTIMAL-BP) Trial.

RATIONALE: Very early stage blood pressure (BP) levels may affect outcome in stroke patients who have successfully undergone recanalization following intra-arterial treatment, but the optimal target of BP management remains uncertain. AIM: We hypothesized that the clinical outcome after intensive BP-lowering is superior to conventional BP control after successful recanalization by intra-arterial treatment. SAMPLE-SIZE ESTIMATES: We aim to randomize 668 patients (334 per arm), 1:1. METHODS AND DESIGN: We initiated a multicenter, prospective, randomized, open-label trial with a blinded end-point assessment (PROBE) design. After successful recanalization (thrombolysis in cerebral infarction score ≥ 2 b), patients with elevated systolic BP level, defined as the mean of two readings ≥ 140 mmHg, will be randomly assigned to the intensive BP-lowering (systolic BP < 140 mm Hg) group or the conventional BP-lowering (systolic BP, 140-180 mm Hg) group. STUDY OUTCOMES: The primary efficacy outcomes are from dichotomized analysis of modified Rankin Scale (mRS) scores at three months (mRS scores: 0-2 vs. 3-6). The primary safety outcomes are symptomatic intracerebral hemorrhage and death within three months. DISCUSSION: The OPTIMAL-BP trial will provide evidence for the effectiveness of active BP control to achieve systolic BP < 140 mmHg during 24 h in patients with successful recanalization after intra-arterial treatment. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04205305.

A novel therapeutic modality using CRISPR-engineered dendritic cells to treat allergies.

Despite the important roles of dendritic cells (DCs) in airway allergies, current therapeutic strategies such as drugs, allergen immunotherapy and biologics haven't been targeted at them. In this study, we established a promising DC-based therapeutic approach for the alleviation of allergic rhinitis (AR)-associated allergic reactions, using clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-mediated targeted gene disruption. RNA sequencing analysis revealed upregulation of vacuolar protein sorting 37 B (VPS37B) in AR-derived DCs, indicating a novel molecular target. Following antigen presentation, VPS37A and VPS37B enabled endocytosis of the mannose receptor, which recognizes the house dust mite (HDM) allergen Der p 1. DCs with targeted disruption of VPS37A/B alleviated Th2 cytokine production when co-cultured in vitro with allogeneic naïve CD4+ T cell from patients with AR. Furthermore, nasal administration of Vps37a/b-disrupted bone marrow DCs to a mouse model of AR resulted in strongly reduced AR-related symptoms. Thus, this novel modality using genetically engineered DCs can provide an effective therapeutic and preventative strategy for allergic diseases.

Association of Allergic Diseases and Related Conditions with Dietary Fiber Intake in Korean Adults.

An association between fiber intake and allergic diseases in children has been reported; however, many studies have not been conducted to assess this association in adults. We aimed to evaluate the association between dietary fiber intake and allergic diseases (asthma, allergic rhinitis, and atopic dermatitis) among 10,479 adults using data from the Korean National Health and Nutrition Examination Survey (2010-2011). As dietary fiber intake increased, the prevalence of asthma (Q4 adjusted odds ratio (OR): 0.656; 95% confidence interval (CI): 0.48-0.91, p for trend < 0.0001) and atopic dermatitis (Q3 crude OR: 0.746; 95% CI: 0.57-0.98; Q4 adjusted OR: 0.712; 95% CI: 0.50-1.01, p for trend < 0.0001) decreased. The prevalence of allergic rhinitis (Q2 adjusted OR: 0.840; 95% CI: 0.70-1.00, p for trend < 0.0001) tended to decrease, especially in males. Subgroup analysis revealed that fiber intake reduced allergic rhinitis symptoms, including watery rhinorrhea (Q3 adjusted OR: 0.734; 95% CI: 0.55-0.97; Q4 adjusted OR: 0.722; 95% CI: 0.54-0.97) and dog allergen sensitization (Q3 adjusted OR: 0.319; 95% CI: 0.13-0.82; Q4 adjusted OR: 0.338; 95% CI: 0.13-0.86), exclusively in males. Thus, dietary fiber intake influences allergic diseases in adults, especially males.

Current Perspective on Nasal Delivery Systems for Chronic Rhinosinusitis.

Chronic rhinosinusitis is an upper respiratory disease during which topical drug treatment via the nasal cavity is the most actively utilized therapeutic strategy. In addition to steroids, antibiotics, and antifungal agents, which are widely used in clinical practice, research on novel topical agents to improve the bacterial biofilm or mucociliary clearance remains ongoing. Moreover, owing to the complex structure of the nasal cavity, the effects of nasal drug delivery vary depending on factors related to delivery fluid dynamics, including device, volume, and compounds. In this article, we review methods and compounds that have been applied to chronic rhinosinusitis management and introduce recent advances and future perspectives in nasal drug delivery for upper respiratory diseases.

Association between allergic rhinitis-related factors and sleep duration in adolescents: Korea National Health and Nutrition Examination Survey V (2010-2012).

OBJECTIVES: Previous studies have shown that sleep and allergic rhinitis (AR) is closely associated, bidirectionally affecting each other. Adolescence is a period that adequate sleep is essential, and the burden of AR increases, both of which greatly affect the quality of life. The aim of the present study was to investigate the correlation between inappropriate sleep duration and each AR-related subjective/objective factor in Korean adolescents. METHODS: We analyzed the data of 1936 adolescents aged between 12 and 18 years who participated in the Korea National Health and Nutrition Examination Survey from 2010 to 2012. Data on sleep duration, physician-diagnosed AR, and presence of rhinitis symptoms were collected using a self-administered questionnaire. Nasal endoscopic findings, including watery rhinorrhea and pale inferior turbinate mucosa, and aeroallergen sensitization based on serum specific immunoglobulin E levels were examined. RESULTS: There was a higher prevalence of AR (23.68%) in the inappropriate sleep duration group than in the control group (16.56%; odds ratio = 1.56, p = 0.0024). The presence of endoscopic findings of AR showed a positive association with inappropriate sleep duration in males (odds ratio = 1.52, p = 0.008). In addition, in all three indoor allergens investigated, aeroallergen sensitization was not associated with inappropriate sleep duration. CONCLUSION: Inappropriate sleep duration was associated with increased prevalence of AR in Korean adolescents. Especially, this association was relevant in nasal endoscopic findings in male.

Advances in the Knowledge of the Underlying Airway Remodeling Mechanisms in Chronic Rhinosinusitis Based on the Endotypes: A Review.

Chronic rhinosinusitis (CRS) is a chronic inflammatory condition of the nasal and paranasal sinus mucosa that affects up to 10% of the population worldwide. CRS is the most representative disease of the upper respiratory tract where airway remodeling occurs, including epithelial damage, thickening of the basement membrane, fibrosis, goblet cell hyperplasia, subepithelial edema, and osteitis. CRS is divided into two phenotypes according to the presence or absence of nasal polyps: CRS with nasal polyp (CRSwNP) and CRS without nasal polyps (CRSsNP). Based on the underlying pathophysiologic mechanism, CRS is also classified as eosinophilic CRS and non-eosinophilic CRS, owing to Type 2 T helper (Th2)-based inflammation and Type 1 T helper (Th1)/Type 17 T helper (Th17) skewed immune response, respectively. Differences in tissue remodeling in CRS are suggested to be based on the clinical phenotype and endotypes; this is because fibrosis is prominent in CRSsNP, whereas edematous changes occur in CRSwNP, especially in the eosinophilic type. This review aims to summarize the latest information on the different mechanisms of airway remodeling in CRS according to distinct endotypes.

Colonic Mucosal Immune Activation in Mice with Ovalbumin-Induced Allergic Airway Disease: Association between Allergic Airway Disease and Irritable Bowel Syndrome.

Recent studies on the pathophysiology of irritable bowel syndrome (IBS) have focused on the role of mast cells (MCs) in intestinal mucosal immunity. A link between allergic airway diseases (AADs) and IBS has been suggested because both diseases have similar pathophysiology. We aimed to investigate whether the induction of AAD in mice could lead to inflammation of the colonic mucosa, similar to IBS. We also evaluated whether this inflammatory response could be suppressed by administering a therapeutic agent. Mice were divided into three groups: control, AAD-induced, and salbutamol-treated. An AAD mouse model was established by intraperitoneal injection and nasal challenge with ovalbumin. Mice with AAD were intranasally administered salbutamol. Analyses of cytokine levels, MC count, and tryptase levels in the intestinal mucosa were performed to compare the changes in inflammatory responses among the three groups. Inflammation was observed in the intestinal mucosa of mice in the AAD group. This inflammation in AAD mice was suppressed after salbutamol treatment. Our study demonstrates that AAD induces an inflammatory response similar to that in IBS, suggesting a possible association between IBS and AADs. In patients with IBS with such allergic components, salbutamol may have the potential to alleviate the inflammatory response.

TRPV4-Mediated Epithelial Junction Disruption in Allergic Rhinitis Triggered by House Dust Mites.

BACKGROUND: Epithelial barrier disruption is a crucial feature of allergic rhinitis (AR). Previous reports have indicated the role of transient receptor potential vanilloid (TRPV) 4 in regulating the intercellular junctions in various cells. However, the role of TRPV4 and its regulation by T helper 2 cell cytokines in the epithelial cells of patients with AR remains unclear. OBJECTIVE: We aimed to elucidate the expression of TRPV4 in nasal epithelial cells and its cytokine-induced regulation, and to reveal its role in house dust mite-induced junction disruption in AR. METHODS: The expression of TRPV4 in nasal epithelial cells was measured using real-time polymerase chain reaction, western blot, and immunohistochemical assays, and the expression levels were compared between the patients with AR and healthy controls. Altered expression of TRPV4 was induced in cultured nasal epithelial cells by stimulation of interleukin (IL) 4, IL-13, and tumor necrosis factor alpha. In addition, expression of E-cadherin and zonula occludens 1 was induced in Der p 1-stimulated epithelial cells by treatment with either a TRPV4 agonist (GSK1016790A) or a TRPV4 antagonist (RN1734). RESULTS: TRPV4 expression was increased in epithelial cells harvested from the affected turbinates compared to those from the normal turbinates. The stimulation of cultured epithelial cells with IL-4 and IL-13 resulted in TRPV4 upregulation. Additionally, E-cadherin and zonula occludens 1 expression levels decreased in the cultured epithelial cells treated with GSK1016790A after stimulation with Der p 1, whereas Der p 1 stimulation alone showed no effect on junctional protein expression. CONCLUSIONS: Increased TRPV4 expression occurred in epithelial cells harvested from patients with AR and epithelial cells stimulated by Th2 cytokines. Decreased junctional protein expression in epithelial cells after the stimulation by house dust mite allergen with TRPV4 agonist indicates a possible role of TRPV4 in the pathogenesis of allergen-induced epithelial barrier disruption in AR.