Prognostic Implications of N-Terminal Pro-B-Type Natriuretic Peptide in Patients With Non-ST-Elevation Myocardial Infarction.

BACKGROUND: Limited data exist regarding the prognostic implications of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with non-ST-elevation myocardial infarction (NSTEMI) who undergo percutaneous coronary intervention (PCI).Methods and Results: Of 13,104 patients in the nationwide Korea Acute Myocardial Infarction Registry-National Institutes of Health, 3,083 patients with NSTEMI who underwent PCI were included in the present study. The primary endpoint was major adverse cardiovascular events (MACE) at 3 years, a composite of all-cause death, recurrent myocardial infarction, unplanned repeat revascularization, and admission for heart failure. NT-proBNP was measured at the time of initial presentation for the management of NSTEMI, and patients were divided into a low (<700 pg/mL; n=1,813) and high (≥700 pg/mL; n=1,270) NT-proBNP group. The high NT-proBNP group had a significantly higher risk of MACE, driven primarily by a higher risk of cardiac death or admission for heart failure. These results were consistent after confounder adjustment by propensity score matching and inverse probability weighting analysis. CONCLUSIONS: In patients with NSTEMI who underwent PCI, an initial elevated NT-proBNP concentration was associated with higher risk of MACE at 3 years, driven primarily by higher risks of cardiac death or admission for heart failure. These results suggest that the initial NT-proBNP concentration may have a clinically significant prognostic value in NSTEMI patients undergoing PCI.

Sinonasal seromucinous hamartoma: a single institution case series combined with a narrative review of the literature.

PURPOSE: This study aimed to investigate the clinical and histopathological characteristics of sinonasal seromucinous hamartomas (SHs). METHODS: Eight patients with sinonasal SH and treated at a tertiary hospital between November 2005 and September 2023 were included. Additionally, a systematic review of published articles was conducted, analyzing 48 cases of SH described in the literature. RESULTS: Among the eight patients treated at our institution, tumors originated from the posterior nasal cavity in four patients and middle turbinate and middle meatus were the primary origin in two patients each. Coexistence of inflammatory nasal polyps (NPs) was observed in four cases. Histopathologically, four patients exhibited focal respiratory epithelial adenomatoid hamartoma (REAH) features, and low-grade dysplasia was found in one patient. A combined analysis with previous literature revealed that 46.3% of all cases originated in the anterior nasal cavity. The proportions of cases accompanied by NPs and those with focal REAH features were 20.5% and 39.1%, respectively. Additionally, the frequencies of cases exhibiting dysplastic features (5.4%) and recurrence (2.1%) were low. Remarkably, tumors originating from the anterior region tended to have a higher frequency of dysplasia than those originating from the posterior region, although this difference was not statistically significant (p = 0.0996). CONCLUSION: Patients with sinonasal SH showed favorable treatment outcomes following surgical resection. Focal REAH features and accompanying NPs were frequently observed. A substantial proportion of cases originate in the anterior nasal cavity, and these tumors may exhibit a high tendency for dysplasia.

IL-4 drastically decreases deuterosomal and multiciliated cells via alteration in progenitor cell differentiation.

BACKGROUND: Allergic inflammation affects the epithelial cell populations resulting in goblet cell hyperplasia and decreased ciliated cells. Recent advances in single-cell RNA sequencing (scRNAseq) have enabled the identification of new cell subtypes and genomic features of single cells. In this study, we aimed to investigate the effect of allergic inflammation in nasal epithelial cell transcriptomes at the single-cell level. METHODS: We performed scRNAseq in cultured primary human nasal epithelial (HNE) cells and in vivo nasal epithelium. The transcriptomic features and epithelial cell subtypes were determined under IL-4 stimulation, and cell-specific marker genes and proteins were identified. RESULTS: We confirmed that cultured HNE cells were similar to in vivo epithelial cells through scRNAseq. Cell-specific marker genes were utilized to cluster the cell subtypes, and FOXJ1+ -ciliated cells were sub-classified into multiciliated and deuterosomal cells. PLK4 and CDC20B were specific for deuterosomal cells, and SNTN, CPASL, and GSTA2 were specific for multiciliated cells. IL-4 altered the proportions of cell subtypes, resulting in a decrease in multiciliated cells and loss of deuterosomal cells. The trajectory analysis revealed deuterosomal cells as precursor cells of multiciliated cells and deuterosomal cells function as a bridge between club and multiciliated cells. A decrease in deuterosomal cell marker genes was observed in nasal tissue samples with type 2 inflammation. CONCLUSION: The effects of IL-4 appear to be mediated through the loss of the deuterosomal population, resulting in the reduction in multiciliated cells. This study also newly suggests cell-specific markers that might be pivotal for investigating respiratory inflammatory diseases.

Keratinized tissue augmentation using collagen-based soft tissue substitute with/without epidermal growth factor on buccally positioned implants: a pilot preclinical study.

OBJECTIVES: To investigate the effect of epithelial growth factor (EGF) with collagen matrix (CM) on the gain of KT for buccally positioned implants in dogs. MATERIALS AND METHODS: In five dogs, four implants were placed buccally with the whole part of KT excision on the buccal side (two implants per each hemi-mandible). After one month, KT augmentation was performed: 1) free gingival grafts (FGG), 2) collagen matrix (CM) only, 3) CM soaked with 1 µg/g of EGF, and 4) CM soaked with 10 µg/g of EGF (n = 5 in each group). The experimental animals were sacrificed three months post-KT augmentation. Clinical, histologic, and histomorphometric analyses were performed. RESULTS: The clinical KT zone was the highest in group FGG (5.16 ± 1.63 mm). Histologically, all groups presented buccal bony dehiscence. Regarding newly formed KT, no specific difference was found among the groups, but robust rete pegs formation in some specimens in group FGG. Histomorphometric KT height (4.66 ± 1.81 mm) and length (5.56 ± 2.25 mm) were the highest in group FGG, whereas similar increases were noted in the rest. The buccal soft tissue thickness at the coronal part of the implant did not exceed 2 mm in all groups. CONCLUSION: All groups presented increased KT zone, but FGG treatment was more favored. The addition of EGF to CM appeared not to enhance KT formation. CLINICAL RELEVANCE: FGG treatment was more favorable to re-establish the KT zone than other treatment modalities.

Comparison of clinical features and surgical outcomes between hypopnea- and apnea-predominant obstructive sleep apnea.

OBJECTIVES: This study is aimed to investigate the differences in the clinical features and surgical outcomes between hypopnea- and apnea-predominant obstructive sleep apnea (OSA). DESIGN: Cohort study. SETTING: Single tertiary care centre. PARTICIPANTS: This study included 190 patients with OSA who underwent multilevel upper airway surgery between September 2012 and September 2021. The patients were divided into two groups according to the proportion of each respiratory event: hypopnea-predominant (n = 102) and apnea-predominant (n = 88). MAIN OUTCOME MEASURES: The primary outcome measure was the percentage improvement in the apnea-hypopnea index (AHI) from baseline AHI after surgery. RESULTS: The apnea-predominant group included more male patients and had higher AHI, respiratory disturbance index (RDI) and oxygen desaturation index (ODI) than the hypopnea-predominant group. Both groups showed significant improvements in AHI, apnea index, RDI, supine AHI, REM AHI, non-REM AHI, ODI, lowest O2 saturation and Epworth Sleepiness Scale scores following the surgery. Notably, hypopnea index increased after surgery in the apnea-predominant OSA group. Although the improvement in the absolute value of AHI by surgery was significantly greater in the apnea-predominant group than in the hypopnea-predominant group, the two groups showed no significant difference in the percentage improvement in AHI from baseline AHI. CONCLUSION: Patients with apnea-predominant OSA had more severe disease than those with hypopnea-predominant OSA; however, surgical outcomes, as evaluated by percentage AHI improvement, were comparable between the two groups. In addition, multilevel upper airway surgery may induce the transition from apnea to hypopnea in patients with apnea-predominant OSA.

LIF maintains mouse embryonic stem cells pluripotency by modulating TET1 and JMJD2 activity in a JAK2-dependent manner.

The LIF-JAK2-STAT3 pathway is the central signal transducer that maintains undifferentiated mouse embryonic stem cells (mESCs), which is achieved by the recruitment of activated STAT3 to the master pluripotency genes and activation of the gene transcriptions. It remains unclear, however, how the epigenetic status required for the master gene transcriptions is built into LIF-treated mESC cultures. In this study, Jak2, but not Stat3, in the LIF canonical pathway, establishes an open epigenetic status in the pluripotency gene promoter regions. Upon LIF activation, cytosolic JAK2 was translocalized into the nucleus of mESCs, and reduced DNA methylation (5mC levels) along with increasing DNA hydroxymethylation (5hmC) in the pluripotent gene (Nanog/Pou5f1) promoter regions. In addition, the repressive histone codes H3K9m3/H3K27m3 were reduced by JAK2. Activated JAK2 directly interacted with the core epigenetic enzymes TET1 and JMJD2, modulating its activity and promotes the DNA and histone demethylation, respectively. The JAK2 effects were attained by tyrosine phosphorylation on the epigenetic enzymes. The effects of JAK2 phosphorylation on the enzymes were diverse, but all were merged to the epigenetic signatures associated with open DNA/chromatin structures. Taken together, these results reveal a previously unrecognized epigenetic regulatory role of JAK2 as an important mediator of mESC maintenance.

Evaluation of the efficacy and safety of the 1064 nm picosecond Nd:YAG laser with a topically applied gold and diamond suspension for facial skin rejuvenation: A pilot study.

To investigate the efficacy and safety of combined treatment with a serum comprising a micro-diamond suspension and micro-gold cage with a 1064 nm picosecond neodymium-doped yttrium aluminum garnet (Nd:YAG) laser for facial skin rejuvenation. Topical serum was applied to the entire face and allowed to penetrate the skin and hair follicles for 20 min. Each participant was then treated with a 1064 nm picosecond Nd:YAG laser on the face. Photographs of each participant were taken at baseline, immediately after treatment, and 2 weeks after treatment using an imaging tool (Mark-Vu®; PSI PLUS, Suwon, Republic of Korea). Global improvement scores by two blinded investigators and participants' satisfaction scores were also assessed. The melanin index (MI), transepidermal water loss (TEWL), and skin hydration were evaluated using a device. Parameters associated with skin rejuvenation were assessed using Mark-Vu®. Adverse events were observed and reported by participants and physicians during the treatment and follow-up visit. At week 2, 40% (4/10) of the participants showed more than moderate clinical improvement in the investigator's global improvement assessment. No significant differences were observed in the MI, TEWL, skin hydration level, or skin parameters of Mark-Vu®. At week 2, 40% of the participants reported a high satisfaction score and minimal side effects. The novel topical facial serum comprising micro-diamond suspension and micro-gold cage is safe and effective when combined with laser treatment for facial rejuvenation.

Detecting serum galactomannan to diagnose acute invasive Aspergillus sinusitis: a meta-analysis.

PURPOSE: The serum galactomannan test has been used for diagnosing acute invasive fungal sinusitis (AIFS), especially invasive Aspergillus. We aimed to assess the accuracy of the test to diagnose acute invasive Aspergillus sinusitis (AIAS). METHODS: We searched all relevant articles published in PubMed, Embase, the Cochrane Library, and Web of Science databases up until September 14, 2020. The available data for serum galactomannan test to diagnose AIAS from selected studies were assessed. The diagnostic odds ratio (DOR), summary receiver operating characteristics (SROC), sensitivity, specificity, positive likelihood ratio (PLR), and negative likelihood ratio (NLR) were estimated. Additionally, we analysed four studies with a cut-off value of 0.5. RESULTS: Five eligible articles were selected in this study. The total number of enrolled patients was 118, and 62 patients had confirmed AIAS. Among these 62 patients, the summary estimates of the serum galactomannan assay were as follows: DOR, 3.37 (95% confidence interval [CI]: 1.47-6.66); sensitivity, 0.63 (95% CI 0.50-0.74); specificity, 0.65 (95% CI 0.51-0.76); PLR, 1.83 (95% CI 1.21-2.74); NLR, 0.58 (95% CI 0.39-0.83). The SROC was 0.68. CONCLUSION: In this current meta-analysis, the serum galactomannan test was classified as less accurate for purposes of diagnosing confirmed AIAS. These results suggest that the initial diagnosis of AIAS should not solely be dependent upon serum galactomannan test results. More studies of the test are needed in patients with AIAS to more accurately assess its diagnostic value.

Integrated genetic and epigenetic analyses uncover MSI2 association with allergic inflammation.

BACKGROUND: The relationship between allergic and eosinophilic inflammation, either systemic or local, in allergic diseases remains unclear. OBJECTIVE: We performed combined genome-wide association study (GWAS) and epigenome-wide (EWAS) for atopy and tissue eosinophilia to identify both genetic and epigenetic signatures between systemic and local allergic inflammation, and to capture global patterns of gene regulation. METHODS: We included 126 subjects for atopy analysis and 147 for tissue eosinophilia analysis, as well as 18 normal nasal tissue samples. We identified differentially methylated positions (DMPs) and genes associated with atopy and tissue eosinophilia. Furthermore, we performed mendelian randomization analysis and penalized regression along with replication in an independent cohort. RESULTS: EWAS identified genes, including Musashi RNA binding protein 2 (MSI2), associated with atopy, which contained enriched DMPs that genetically affect atopy. A direct association was observed between MSI2 single-nucleotide polymorphisms and atopy, as was a causal effect of changes in MSI2 expression and methylation on atopy, which was replicated in a Costa Rican population. Regarding tissue eosinophilia, EWAS identified genes with enriched DMPs directly contributing to tissue eosinophilia at the gene level, including CAMK1D. The gene ontology terms of the identified genes for both phenotypes encompassed immune-related terms. CONCLUSION: EWAS combined with GWAS identified novel candidate genes, especially the methylation of MSI2, contributing to systemic allergic inflammation. Certain genes displayed a greater association with either systemic or local allergic inflammation; however, it is expected that a harmonized effect of these genes influences immune responses.

Association between diabetes mellitus and chronic rhinosinusitis with nasal polyps: A population-based cross-sectional study.

OBJECTIVE: To investigate the association between physician-diagnosed diabetes mellitus (DM) and chronic rhinosinusitis (CRS) phenotypes in a national population-based study. STUDY DESIGN: Retrospective cross-sectional study. SETTING: Population-based survey data were collected by the Korean National Health and Nutrition Survey between January 2008 and December 2012. PARTICIPANTS AND METHODS: A total of 34 670 participants aged over 19 years were enrolled in the Korea National Health and Nutrition Examination Surveys from 2008 to 2012. The relationship of CRS prevalence, with and without nasal polyps, with physician-diagnosed DM and non-DM were assessed. Differences in sinonasal symptoms between patients with and without DM were analysed in this cross-sectional study. RESULTS: A significant association was observed between DM and CRS with nasal polyps after adjustment for multiple variables. No substantial association was observed between DM and CRS without nasal polyps. Among patients with CRS, olfactory dysfunction for >3 months was significantly more frequent in the DM group than in the non-DM group. CONCLUSION: We demonstrated significant associations between DM and CRS with nasal polyps and olfactory dysfunction among patients with CRS in a large national clinical cohort study. The direct mechanism of the association between DM and CRS with nasal polyps should be further investigated to clarify the pathogenesis of CRS with nasal polyps.

Th2 cytokines-DUOX2-ROS-HMGB1 translocation axis is important in the pathogenesis of allergic rhinitis.

The function of high-mobility group box 1 (HMGB1) varies according to its location. However, the translocation mechanism behind HMGB1 remains unclear. We hypothesize that type 2 helper T cell (Th2) cytokines are involved in the translocation of HMGB1 in the upper airway epithelium. We investigated the mechanism behind HMGB1 translocation using Th2 cytokine stimulation and examined the clinical significance of HMGB1 translocation in allergic rhinitis (AR). Cytoplasmic and extracellular HMGB1 were increased in AR. Inhibiting HMGB1 translocation with glycyrrhizic acid (GA) decreased the level of antigen-specific immunoglobulin E (IgE), the degree of Periodic Acid-Schiff (PAS), and Sirius Red staining in the murine model. The in vivo reactive oxygen species (ROS) level in the nasal mucosa was higher in the mice with AR than in the controls. Th2 cytokine-induced up-regulation of the ROS and translocation of HMGB1 by Th2 cytokines was dependent on the generated ROS. The ROS level also increased in the murine model. We suggest that the Th2 cytokine-dual oxidase (DUOX)2-ROS-HMGB1 translocation axis is important in AR pathogenesis.

Efficacy of Rhino-Protect ointment after endoscopic sinus surgery: a prospective, randomized, multicenter study.

OBJECTIVE: Blocking airflow into the sinonasal cavity after surgery may help to keep the cavity moist and thus decrease postoperative crusting. Here we investigated the efficacy of Rhino-Protect ointment following endoscopic sinus surgery (ESS). SUBJECTS AND METHODS: A total of 93 patients with chronic rhinosinusitis who underwent identical ESS were enrolled. After surgery, all patients were instructed to perform nasal saline irrigation and deliver a nasal spray to each nostril, then to apply Rhino-Protect ointment to one nostril only; the other nostril served as a control. Subjective symptoms, postoperative Lund-Kennedy (LK) endoscopic scores, and adverse reactions 14 and 28 days after treatment were evaluated. RESULTS: The Rhino-Protect ointment significantly reduced pain (p = 0.015 at 28 days), dryness (p = 0.009 at 14 days and p = 0.045 at 28 days), and crusting (p = 0.047 at 14 days), and was associated with significantly lower LK scores 14 and 28 days after treatment (p = 0.037 and p = 0.007, respectively). Statistically significant differences were noted in the LK edema subscore at 14 days (p = 0.043) and in LK crusting subscores at 14 and 28 days (p = 0.005 and p = 0.006, respectively). No patient reported any serious adverse event associated with Rhino-Protect use. CONCLUSION: Applying Rhino-Protect after ESS significantly reduced the formation of edema and crusts, leading to improving the patients' discomfort for pain, dryness, and crust.

Can the sensitisation to staphylococcal enterotoxin predict the severity of chronic rhinosinusitis?

BACKGROUND: Evidence is accumulating that Staphylococcus aureus plays an important role as a disease modifier in upper and lower airway disease. We aimed to assess the association of staphylococcal enterotoxins (SEs) with allergic multimorbidity as well as the severity of chronic rhinosinusitis. METHODS: We retrospectively reviewed the medical records of 97 subjects aged 6 years or older between March 2018 and June 2019 and analysed symptom scores, computed tomography scores, serum IgE levels to SEs, serum total and specific IgE levels to inhalant allergens. To evaluate eosinophilic chronic rhinosinusitis (ECRS), we used refractory ECRS score from the Japanese epidemiological survey. RESULTS: Of the 97 patients enrolled, 29 (29.9%) were non-sensitised, 33 (34.0%) were mono-sensitised, and 35 (36.1%) were poly-sensitised. Sensitisation to SEs was closely associated with poly-sensitisation to inhalant allergens. SE-sensitised participants had higher median values for total and specific IgE levels to inhalant allergens than did non-SE-sensitised participants. SE sensitisation was associated with allergic multimorbidity and severe allergic diseases, such as ECRS. CONCLUSIONS: This preliminary study suggested that sensitisation to SEs may play a role in the initiation of type-2 inflammatory responses, such as allergic rhinitis, ECRS, and allergic multimorbidity. Furthermore, sensitisation to SEs correlated with the severity of ECRS.

Efficacy and safety of rupatadine fumarate in the treatment of perennial allergic rhinitis: A multicenter, double-blinded, randomized, placebo-controlled, bridging study in Koreans.

BACKGROUND: The efficacy of rupatadine for the treatment of AR has been confirmed in numerous clinical studies, however there are very few studies on asian patients. OBJECTIVE: To assess the safety and efficacy of rupatadine fumarate in the treatment of Korean perennial allergic rhinitis (PAR) patients. METHODS: A multicenter, double-blind, randomized, placebo-controlled, comparative study of rupatadine fumarate and bepotastine besilate was conducted. Each group was administered rupatadine, bepotastine or placebo for 4 weeks. Primary parameters for efficacy included morning and evening symptom reduction from baseline at 4 weeks. Treatment safety and tolerability were evaluated according to a self-reported incidence and type of adverse events at each follow up visit. RESULTS: Rupatadine showed a significant reduction in symptoms at morning and evening evaluations, in both 5TSS (-5.69, P < 0.0006) and 4NTSS (-4.74, P < 0.0015) compared to placebo. There was a significant reduction from baseline for 5TSS (-65.4%, P = 0.002) and 4NTSS (-63.7%, P = 0.003) with rupatadine compared with placebo. At evening evaluations, there were significant reductions of 5TSS (-63.2%, P = 0.009) and 4NTSS (-61.6%, P = 0.013) for the rupatadine group. Compared with bepotastine, rupatadine showed greater reduction in the morning symptoms at 4 weeks. When individual symptoms were assessed with 12-hour reflective mean daily symptom score, rupatadine showed better efficacy than placebo in sneezing (P = 0.016) and rhinorrhea (P = 0.097). The rate of adverse events showed no statistical significance. CONCLUSIONS: Rupatadine is a safe and effective treatment option for Korean PAR patients and possibly a better choice over bepotastine for controlling morning symptom.

Role of specific IgE on staphylococcal enterotoxin B in chronic rhinosinusitis severity.

OBJECTIVE: To investigate the clinical significance of specific IgE-staphylococcal enterotoxin B (IgE-SEB) in CRS (chronic rhinosinusitis). DESIGN: Retrospective analysis of patients who were positive for specific IgE-staphylococcal enterotoxin B. SETTING: Tertiary rhinology clinic. PARTICIPANTS: A total of 965 patients who were tested for specific IgE-staphylococcal enterotoxin B from December 2016 to December 2017. MAIN OUTCOME MEASURES: We retrospectively reviewed the records of 965 patients who were tested for specific IgE-staphylococcal enterotoxin B from December 2016 to December 2017. Patient demographics, titre-specific IgE to staphylococcal enterotoxin B levels, MAST, serologic test and medical records were reviewed. RESULTS: IgE-SEB (KU/L) was higher in CRS patients than non-CRS patients (0.13 ± 0.37 vs 0.08 ± 0.22, respectively; P-value: .044), and the IgE-SEB (+, ≥0.35) rate was also higher (10.06% vs 4.46%, respectively; P-value: .030). IgE-SEB (KU/L) was higher in the CRS group than in the fungal sinusitis group (0.13 ± 0.37 vs 0.03 ± 0.05, respectively; P-value: <.001), and the IgE-SEB (+, ≥0.35) rate was also higher (10.06% vs 0%, respectively; P-value: .015). Between the CRSsNP (chronic rhinosinusitis without nasal polyps) and CRSwNP (chronic rhinosinusitis with nasal polyps) groups, there were no differences in IgE-SEB (KU/L) or IgE-SEB (+) rates. IgE-SEB positivity was not associated with the presence of polyps, concomitant asthma or postoperative recurrence. As the values of IgE-SEB (KU/L) and the IgE-SEB (+, >0.1) rate increased, the CRS severity also increased. CONCLUSIONS: IgE-SEB showed a positive correlation with Lund-Mackay CT severity score, but not with postoperative recurrence or nasal polyps. Further studies are needed to obtain clear evidence that IgE-SEB can be considered as an independent CRS endotype.

Huge Anterior Skull Base Defect Reconstruction on Communicating Between Cranium and Nasal Cavity: Combination Flap of Galeal Flap and Reverse Temporalis Flap.

INTRODUCTION: Traditionally, galeal flap or cranialization was often used to reconstruct the skull base defect caused by trauma or tumor removal. However, in the case of huge skull base defect, galeal flap is not enough to block the communication between nasal cavity and intracranial space. In this study, authors suggest combination flap of galea and reverse temporalis muscle as a method for reconstruction of huge skull base defect. MATERIALS AND METHODS: From 2016 to 2019, retrospective review was conducted, assessing 7 patients with bone defect which is not just opening of frontal sinus but extends to frontal sinus and cribriform plate. Reconstructions were done by combination of galeal flap and reverse temporalis muscle flap transposition. RESULTS: Defects were caused by nasal cavity tumor with intracranial extension or brain tumor with nasal cavity extension. There was no major complication in every case. During the follow up period, no patient had signs of complication such as ascending infection, herniation and CSF rhinorrhea. Postoperative radiologic images of all patients that were taken at least 6 months after the surgery showed that flaps maintained the lining and the volume well. DISCUSSION: Conventional reconstruction of skull base defect with galeal flap is not effective enough to cover the large sized defect. In conclusion, galeal flap in combination with reverse temporalis muscle flap can effectively block the communication of nasal cavity and intracranium.

Fms-Like Tyrosine Kinase 3-Independent Dendritic Cells Are Major Mediators of Th2 Immune Responses in Allergen-Induced Asthmatic Mice.

Dendritic cells (DCs) are the main mediators of Th2 immune responses in allergic asthma, and Fms-like tyrosine kinase 3 ligand (Flt3L) is an important growth factor for the development and homeostasis of DCs. This study identified the DC populations that primarily cause the initiation and development of allergic lung inflammation using Fms-like tyrosine kinase 3 (Flt3) knockout (KO) mice with allergen-induced allergic asthma. We observed type 2 allergic lung inflammation with goblet cell hyperplasia in Flt3 KO mice, despite a significant reduction in total DCs, particularly CD103+ DCs, which was barely detected. In addition, bone marrow-derived dendritic cells (BMDCs) from Flt3 KO mice directed Th2 immune responses in vitro, and the adoptive transfer of these BMDCs exacerbated allergic asthma with more marked Th2 responses than that of BMDCs from wild-type (WT) mice. Furthermore, we found that Flt3L regulated the in vitro expression of OX40 ligand (OX40L) in DCs, which is correlated with DC phenotype in in vivo models. In conclusion, we revealed that Flt3-independent CD11b+ DCs direct Th2 responses with the elevated OX40L and are the primary cause of allergic asthma. Our findings suggest that Flt3 is required to control type 2 allergic inflammation.

Efficient production of poly γ-d-glutamic acid from the bloom-forming green macroalgae, Ulva sp., by Bacillus sp. SJ-10.

Numerous studies on poly γ-d-glutamicacid (γ-PGA) production have investigated terrestrial renewable sources for reducing production costs, but there are no studies using waste marine resources so far. We aimed to develop a cost-effective production method of γ-d-PGA by Bacillus sp. SJ-10 using green macroalgae (Ulva sp.) as a major substrate without hydrolysis pretreatment. The SJ-10 was shown to not only cause immediate tissue degradation of the Ulva membrane but also grew well as a sole substrate. The γ-d-PGA yield was 6.29 ± 0.34 g/L under optimized conditions via the response surface method, and the produced γ-d-PGA had a thermal decomposition temperature of 310°C and molecular weight of 250-1780 kDa. The calculated cost efficiency for the final yield was 32% when compared with complex media. Therefore, the present study provided a strategy for promoting an ecofriendly and cost-effective means to produce γ-d-PGA via a marine renewable resource.

Patterns of failures after surgical resection in olfactory neuroblastoma.

INTRODUCTION: Patterns of failure in patients with olfactory neuroblastoma (ONB) according to two surgical approaches, craniofacial resection (CFR) and endoscopic surgery (ENDO), have yet to be analyzed. METHODS: We retrospectively reviewed 28 patients with surgically treated ONB between January 1995 and October 2017. Fourteen (50.0%) patients underwent CFR (9 CFR alone, 5 ENDO-assisted CFR) and 14 (50.0%) underwent ENDO. Nineteen (67.9%) patients underwent post-operative radiotherapy (RT). RESULTS: At a median follow-up of 53.8 months (range 10.4-195.3), the 5-year progression-free survival (PFS) and 10-year overall survival were 37.3% and 57.5%, respectively. Patients with adjuvant RT had a 5-year PFS of 46.7%, whereas those treated with surgery alone had a 5-year PFS of 19.4% (p = 0.01). Locoregional failure (LRF) occurred in ten patients (median 59.6 months after initial diagnosis; range 12.7-59.7). Neck node metastasis occurred in 25.0% (7 of 28). Five patients with ENDO showed LRF and underwent proper subsequent treatments with either surgery or adjuvant RT. Approximately 35.7% patients (five patients) in the CFR group experienced distant metastasis in the intracranial dura region (median 116.4 months after initial diagnosis; range 2.6-142.4). Three of four patients who developed LRF after CFR developed dura-based metastasis. CONCLUSIONS: Both dura-based and neck node metastasis in the delayed phase were distinct patterns of failure in ONB. Patterns of recurrence differed based on surgical approach; dura-based metastases were common after CFR. LRF was the distinct failure pattern in ENDO, but could be successfully salvaged. Treatment outcome was improved considerably with RT following surgical resection.