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.

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.

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.

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.

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.

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.

Association of Cotinine-Verified Cigarette Exposure with Chronic Rhinosinusitis in Korean Adults.

Chronic rhinosinusitis is known to be influenced by cigarette exposure; however, this relationship is based on the presence of nasal polyps, and objective measurements of cigarette exposure in chronic rhinosinusitis are not well established. This study aimed to estimate the association between chronic rhinosinusitis and smoking status based on self-reported questionnaires and urinary cotinine levels according to the presence of nasal polyps. We analyzed a total of 23,621 participants who participated from the fifth Korea National Health and Nutrition Examination Survey (2010-2012). Serum total and specific IgE level were measured. Higher prevalence of chronic rhinosinusitis with nasal polyps was associated with current smoking status (OR = 1.43, 95% CI = 1.00-2.03). This association was prevalent in participants aged ≤ 50 years (OR = 1.76, 95% CI = 1.01-3.05), and higher urinary cotinine level showed correlation with higher prevalence of chronic rhinosinusitis with nasal polyps in this age group (OR = 1.04, 95% CI = 1.00-1.08). In addition, positive correlation between serum total IgE and urinary cotinine levels was greater in patients with chronic rhinosinusitis (ß = 0.493, 95% CI = 0.071-0.916) than in controls (ß = 0.062, 95% CI = 0.021-0.103). Aggressive smoking interventions should be performed in patients with chronic rhinosinusitis with nasal polyp, especially in cases of young adults or high serum IgE levels.

Exosomal miRNA-19a and miRNA-614 Induced by Air Pollutants Promote Proinflammatory M1 Macrophage Polarization via Regulation of RORα Expression in Human Respiratory Mucosal Microenvironment.

Air pollution exposure leads to various inflammatory diseases in the human respiratory system. Chronic rhinosinusitis is an inflammatory disease caused by viruses, bacteria, or air pollutants. However, the underlying molecular mechanisms through which air particulate matter (PM) causes inflammation and disease remain unclear. In this article, we report that the induction of exosomal microRNAs (miRNAs) from human nasal epithelial cells upon airborne PM exposure promotes proinflammatory M1 macrophage polarization via downregulated RORα expression. Exposure of human nasal epithelial cells to PM results in inflammation-related miRNA expression, and more miRNA is secreted through exosomes delivered to macrophages. Among these, miRNA-19a and miRNA-614 directly bind to the 3'-untranslated region of RORα mRNA and downregulate RORα expression, which leads to inflammation due to inflammatory cytokine upregulation and induces macrophages to a proinflammatory M1-like state. Finally, we showed enhanced expression of miRNA-19a and miRNA-614 but reduced RORα expression in a chronic rhinosinusitis patient tissue compared with the normal. Altogether, our results suggest that PM-induced exosomal miRNAs might play a crucial role in the proinflammatory mucosal microenvironment and macrophage polarization through the regulation of RORα expression.

Creation of a High-Yield AAV Vector Production Platform in Suspension Cells Using a Design-of-Experiment Approach.

Recombinant adeno-associated virus (rAAV) vectors are a leading gene delivery platform, but vector manufacturing remains a challenge. New methods are needed to increase rAAV yields and reduce costs. Past efforts to improve rAAV production have focused on optimizing a single variable at a time, but this approach does not account for the interactions of multiple factors that contribute to vector generation. Here, we utilized a design-of-experiment (DOE) methodology to optimize rAAV production in a HEK293T suspension cell system. We simultaneously varied the transgene, packaging, and helper plasmid ratios, the total DNA concentration, and the cell density to systematically evaluate the impact of each variable across 52 conditions. The results revealed a unique set of parameters with a lower concentration of transgene plasmid, a higher concentration of packaging plasmid, and a higher cell density than previously described protocols. Using this DOE-optimized protocol, we achieved unpurified yields approaching 3 × 1014 viral genomes (VGs)/L of cell culture. Additionally, we incorporated polyethylene glycol (PEG)-based virus precipitation, pH-mediated protein removal, and affinity chromatography to our downstream processing, enabling average purified yields of >1 × 1014 VGs/L for rAAV-EGFPs across 13 serotypes and capsid variants.

Oral health and gastrointestinal cancer: A nationwide cohort study.

AIMS: Poor oral hygiene is closely associated with bacteraemia and systemic inflammation, which are known mediators of cancer development. We investigated the relationship between oral hygiene indicators and the risk of gastrointestinal cancer in a nationwide population-based cohort. MATERIALS AND METHODS: This study was conducted on data from 150,774 subjects from the Korean National Health Screening Cohort. The occurrence of gastrointestinal cancer was analysed according to the presence of periodontal disease and oral hygiene indicators: frequency of toothbrushing, dental visits for any reason, professional dental cleanings and number of missing teeth. Gastrointestinal cancer was defined using International Statistical Classification of Diseases-10 codes C15-C26. RESULTS: During a median 11.6 years of follow-up, the estimated 10-year event rate for gastrointestinal cancer was 6.76%. In a multivariable analysis, after adjusting for age, sex, income level, regular exercise, alcohol consumption, smoking status, body mass index, history of comorbidities, systolic blood pressure and laboratory findings, frequent toothbrushing (≥3/day) was significantly associated with a reduced risk for gastrointestinal cancer (hazard ratio: 0.91, 95% confidence interval (0.86-0.96), p < .001, p for trend < .001). CONCLUSIONS: Good oral hygiene behaviour, especially frequent toothbrushing, could be associated with a lower risk of gastrointestinal cancer.

The Biology of Prostaglandins and Their Role as a Target for Allergic Airway Disease Therapy.

Prostaglandins (PGs) are a family of lipid compounds that are derived from arachidonic acid via the cyclooxygenase pathway, and consist of PGD2, PGI2, PGE2, PGF2, and thromboxane B2. PGs signal through G-protein coupled receptors, and individual PGs affect allergic inflammation through different mechanisms according to the receptors with which they are associated. In this review article, we have focused on the metabolism of the cyclooxygenase pathway, and the distinct biological effect of each PG type on various cell types involved in allergic airway diseases, including asthma, allergic rhinitis, nasal polyposis, and aspirin-exacerbated respiratory disease.

Association between subjective olfactory dysfunction and female hormone-related factors in South Korea.

An association between olfactory dysfunction and female hormone level has been reported; however, no previous studies have investigated the correlation with life-long female hormone exposure. The aim of this study was to estimate the association between subjective olfactory dysfunction and various endogenous and exogenous female hormone-related factors including age at menarche and menopause, number of pregnancies and deliveries, age at first and last delivery, duration of breastfeeding, use of oral contraceptives, and use of hormone therapy. The study analysed a total of 3863 female participants using data from the Korean National Health and Nutrition Examination Survey V (2010-2012). The prevalence of olfactory dysfunction was 3.5% for premenopausal participants and 6.2% for postmenopausal women. Among premenopausal women (compared to women breastfed less than 12 months), the 12-24-month group (OR = 4.690, 95% CI = 1.431-15.369) and the 25-48-month group (OR = 6.548, 95% CI = 1.758-24.394) had higher rates of olfactory dysfunction. In postmenopausal women, starting menopause at a younger age was positively associated with olfactory dysfunction (OR = 0.939, 95% CI = 0.887-0.993). These data suggest that a longer duration of endogenous oestrogen deprivation is associated with subjective olfactory dysfunction.

Association of Sinonasal Factors With Chronic Laryngitis in Korean Adults.

IMPORTANCE: Allergic laryngitis is underdiagnosed owing to overlapping clinical manifestations that arise from other causes of laryngitis. Sinonasal conditions associated with chronic laryngitis, including allergic laryngitis, have not been reported using population-based epidemiologic data. OBJECTIVE: To estimate the association of the prevalence of chronic laryngitis with various sinonasal symptoms and endoscopic findings, and to identify which of the sinonasal factors are particularly associated with allergic cause of chronic laryngitis. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional, population-based study of 11 283 participants 18 years and older who had undergone laryngoscopic and nasal endoscopic examination used data from 2010 through 2012 in the fifth edition of the Korea National Health and Nutrition Examination Survey, a nationwide survey of South Korea. Participants were extracted by stratified, multistage, clustered sampling to comprise a nationally representative sample. Data were analyzed in September 2017. EXPOSURES: Sociodemographic characteristics, smoking status, alcohol use, questionnaires for voice change and sinonasal symptoms, and nasal endoscopic examinations before and after shrinkage of the nasal mucosa. MAIN OUTCOMES AND MEASURES: Chronic laryngitis diagnosed by laryngoscopic examination, and allergic cause of laryngitis determined by specific serum immunoglobulin E tests. RESULTS: Of the 11 283 participants included in the study, the mean (SD) age was 50.1 (16.6) years, and 6365 (56.4%) were women. In total, 343 participants (3.0%) were diagnosed with chronic laryngitis through results of laryngoscopic examination. Chronic laryngitis was associated with a higher rate of rhinitis symptoms (odds ratio [OR], 1.54; 95% CI, 1.21-1.96), anterior/posterior nasal drip (OR, 2.03; 95% CI, 1.38-2.98), nasal congestion (OR, 1.49; 95% CI, 0.99-2.25), endoscopic findings of pale mucosa (OR, 1.74; 95% CI, 1.33-2.28), mucous or puslike discharge (OR, 1.53; 95% CI, 1.08-2.18), and puslike discharge in the middle meatus (OR, 1.85; 95% CI, 1.19-2.88), especially in female participants and participants older than 50 years. Subgroup analysis revealed that all participants with allergic laryngitis showed sensitization to Dermatophagoides farinae, and the allergic laryngitis group (n = 9) had a higher presence of rhinitis symptoms (n = 5; 56%) than did the nonallergic laryngitis group (n = 1 of 12; 8%) among participants younger than 50 years (risk difference, 47%; 95% CI, 4%-78%). CONCLUSIONS AND RELEVANCE: The association of various sinonasal factors with chronic laryngitis were prominent in female participants, as well as those 50 years and older. Nevertheless, the presence of rhinitis symptoms in patients with chronic laryngitis was associated with allergic cause of laryngitis solely in participants younger than 50 years. In young adults, presence of rhinitis symptoms might aid in considering allergic laryngitis.

Life-long endogenous estrogen exposure is associated with prevalence of allergic rhinitis in postmenopausal women.

OBJECTIVES: The aim of the study was to investigate the influence of life-long endogenous estrogen exposure on prevalence of chronic rhinitis including allergic rhinitis (AR) in the postmenopausal period. METHODS: In this cross-sectional study, a total of 3,043 postmenopausal women who participated in the Korea National Health and Nutrition Examination Survey V were included. Participants with symptoms including sneezing, rhinorrhea, nasal obstruction, or nasal itching were considered to have chronic rhinitis. In subgroup analysis, the AR group comprised participants with rhinitis with positive findings in at least one of three specific immunoglobulin E. Univariable and multivariable logistic analyses were performed to evaluate the relationship between rhinitis and estrogen-related factors including age at menarche, age at menopause, age at first delivery, parity, and duration of breast-feeding. RESULTS: Participants with chronic rhinitis (17.6%) had higher parity (odd ratio [OR] = 1.17, P = 0.0135) and shorter duration of breast-feeding (OR = 0.98, P = 0.0388) than controls. In subgroup analysis, participants with AR (7.1%) had younger age at menarche (OR = 0.56, P = 0.0028) and older age at menopause (OR = 1.42, P = 0.0060) after adjustment of confounding factors. There was a positive association between age at menopause and specific immunoglobulin E for both cockroach (OR = 1.38, P = 0.0132) and dogs (OR = 1.38, P = 0.0302). Longer postmenopausal duration was positively associated with cockroach allergen sensitization (OR = 1.25, P = 0.201). CONCLUSIONS: Longer duration of reproductive period was associated with higher prevalence of AR and aeroallergen sensitization in the postmenopausal period. Moreover, cockroach allergen sensitization was associated with a longer postmenopausal period.

Executive Summary of Stroke Statistics in Korea 2018: A Report from the Epidemiology Research Council of the Korean Stroke Society.

Despite the great socioeconomic burden of stroke, there have been few reports of stroke statistics in Korea. In this scenario, the Epidemiologic Research Council of the Korean Stroke Society launched the "Stroke Statistics in Korea" project, aimed at writing a contemporary, comprehensive, and representative report on stroke epidemiology in Korea. This report contains general statistics of stroke, prevalence of behavioral and vascular risk factors, stroke characteristics, pre-hospital system of care, hospital management, quality of stroke care, and outcomes. In this report, we analyzed the most up-to-date and nationally representative databases, rather than performing a systematic review of existing evidence. In summary, one in 40 adults are patients with stroke and 232 subjects per 100,000 experience a stroke event every year. Among the 100 patients with stroke in 2014, 76 had ischemic stroke, 15 had intracerebral hemorrhage, and nine had subarachnoid hemorrhage. Stroke mortality is gradually declining, but it remains as high as 30 deaths per 100,000 individuals, with regional disparities. As for stroke risk factors, the prevalence of smoking is decreasing in men but not in women, and the prevalence of alcohol drinking is increasing in women but not in men. Population-attributable risk factors vary with age. Smoking plays a role in young-aged individuals, hypertension and diabetes in middle-aged individuals, and atrial fibrillation in the elderly. About four out of 10 hospitalized patients with stroke are visiting an emergency room within 3 hours of symptom onset, and only half use an ambulance. Regarding acute management, the proportion of patients with ischemic stroke receiving intravenous thrombolysis and endovascular treatment was 10.7% and 3.6%, respectively. Decompressive surgery was performed in 1.4% of patients with ischemic stroke and in 28.1% of those with intracerebral hemorrhage. The cumulative incidence of bleeding and fracture at 1 year after stroke was 8.9% and 4.7%, respectively. The direct costs of stroke were about ₩1.68 trillion (KRW), of which ₩1.11 trillion were for ischemic stroke and ₩540 billion for hemorrhagic stroke. The great burden of stroke in Korea can be reduced through more concentrated efforts to control major attributable risk factors for age and sex, reorganize emergency medical service systems to give patients with stroke more opportunities for reperfusion therapy, disseminate stroke unit care, and reduce regional disparities. We hope that this report can contribute to achieving these tasks.

Efficiency of intraoperative neuromonitoring on voice outcomes after thyroid surgery.

OBJECTIVE: Voice disturbance is an important problem after thyroidectomy. The aim of this study was to evaluate the efficiency of intraoperative neuromonitoring (IONM) in reducing early phonation change by comparing postoperative voice outcomes. METHODS: The study retrospectively enrolled 68 consecutive female patients who had undergone IONM thyroidectomy for papillary thyroid carcinoma occurring between January 2014 and November 2014. A historical group of 117 similar female patients not receiving IONM thyroidectomy was used as an external control. Voice analyses were performed preoperatively and at 1 week, 1 month, and 3 months postoperatively. Voice outcomes between the IONM group and no IONM group were compared in patients who underwent hemithyroidectomy and total thyroidectomy. RESULTS: In patients who underwent IONM, there were significantly smaller changes in the fundamental frequency at postoperative 1 month and in the maximum voice pitch of the voice range profile at postoperative 1 week irrespective of the extent of thyroid surgery. CONCLUSION: IONM during thyroid surgery resulted in better outcomes regarding fundamental frequency and high-pitch voice in the early postoperative period. IONM appears to be an effective method to reduce temporary phonation alteration after thyroid surgery.

Comprehensive code stroke program to reduce reperfusion delay for in-hospital stroke patients.

BACKGROUND: Stroke may occur during hospital admission (in-hospital stroke). Although patients with in-hospital stroke are potentially good candidates for reperfusion therapy, they often do not receive treatment as rapidly as expected. AIMS: We investigated the effect of a code stroke program for in-hospital stroke, which included the use of computerized physician order entry, specific evaluation and treatment protocols for in-hospital stroke patients, and regular education of medical staffs. METHODS: We implemented the program in the cardiology and cardiovascular surgery departments/wards (target-ward group) in November 2008. We compared time intervals from symptom onset to evaluation and reperfusion treatment before and after program implementation between the target-ward and other departments/wards (other-ward group). RESULTS: Among 70 consecutive in-hospital stroke patients who received reperfusion therapy between July 2002 and February 2015, 28 and 42 were treated before and after program implementation, respectively. After program implementation, time intervals from symptom onset to neurology notification (50 min vs. 28 min; P = 0.033), symptom onset to brain imaging (91 min vs. 41 min; P < 0.001), and symptom recognition to notification (22 min vs. 9 min; P = 0.011) were reduced in the target-ward group. Finally, times from symptom onset to intravenous tissue plasminogen activator administration and to arterial puncture were reduced by 55 min (120 min vs. 65 min; P < 0.001) and 130 min (295 min vs. 165 min; P < 0.001), respectively. However, time reductions in the other-ward group were not significant. CONCLUSIONS: The comprehensive program for in-hospital stroke that included the use of computerized physician order entry was effective in reducing time intervals to evaluation and reperfusion therapy.

The extent of inferior displacement of the mastoid tegmen is related to the severity of congenital aural atresia.

CONCLUSION: The extent of inferior displacement of the mastoid tegmen is related to the severity of congenital aural atresia (CAA). OBJECTIVE: To analyze anatomic variations observed on high-resolution temporal bone computed tomography (TBCT) in patients with CAA, the extent of inferior displacement of the mastoid tegmen and the size of the incudo-stapedial (IS) joint angle were compared with surgical parameters for atresiaplasty, such as Jahrsdoerfer score and hearing acuity. METHODS: Sixty-one patients with unilateral CAA underwent high-resolution TBCT and hearing tests. We evaluated TBCTs in terms of Jahrsdoerfer criteria and analyzed the relationships among the inferior displacement of the mastoid tegmen, size of the IS joint angle, hearing acuity, and the Jahrsdoerfer score on the atretic side. RESULTS: IS joint angle on the atretic side was found to be 120.6 ± 11°, which was significantly greater than the corresponding value of 103.4 ± 5.4° on the normal side. Cholesteatoma occurred significantly more often in CAA patients with narrow external auditory canals (EACs) (9/27; 33.3%), compared with CAA patients with no EAC opening (2/34; 5.9%). There was a significant relation between the extent of inferior displacement of the mastoid tegmen (28.9% in the atretic side and 17.3% in the normal side) and the Jahrsdoerfer score (p < 0.0001).

Palmitoylation and polymerization of hepatitis C virus NS4B protein.

Hepatitis C Virus (HCV) NS4B protein induces a specialized membrane structure which may serve as the replication platform for HCV RNA replication. In the present study, we demonstrated that NS4B has lipid modifications (palmitoylation) on two cysteine residues (cysteines 257 and 261) at the C-terminal end. Site-specific mutagenesis of these cysteine residues on individual NS4B proteins and on an HCV subgenomic replicon showed that the lipid modifications, particularly of Cys261, are important for protein-protein interaction in the formation of the HCV RNA replication complex. We further demonstrated that NS4B can undergo polymerization. The main polymerization determinants were mapped in the N-terminal cytosolic domain of NS4B protein; however, the lipid modifications on the C terminus also facilitate the polymerization process. The lipid modification and the polymerization activity could be two properties of NS4B important for its induction of the specialized membrane structure involved in viral RNA replication.