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Supplemental Materials (jc.2023-00957)

Background and Objectives This work investigates the clinical characteristics of benign paroxysmal positional vertigo (BPPV) according to etiology by comparing idiopathic BPPV (iBPPV), BPPV occurring after head trauma (tBPPV) and BPPV associated with idiopathic sudden sensory neural hearing loss (sBPPV).Subjects and Method A total of 869 patients who were diagnosed and treated for BPPV were reviewed retrospectively. Patients were divided into three groups according to the probable etiology of BPPV: iBPPV vs. tBPPV vs. sBPPV. We investigated and compared demographics, the affected sides and canals, the number of canalith repositioning procedure (CRP) performed to achieve successful reposition, canal conversion and recurrence among the three groups. Among the three groups, BPPV patients who performed caloric test and/or video head impulse test (vHIT) were additionally evaluated and compared.Results The iBPPV group (n=787) had greater female preponderance (72%, 567/787) than the tBPPV (n=51) and sBPPV groups (n=31, p

Background/Aim: This study aimed to investigate the process of homeostatic restoration in the tracheal mucosa (TM) after thyroid surgery. Materials and Methods: Fifty-four rats were divided into normal controls (NC) and three experimental groups: (i) flap elevation (FE), (ii) thyroid exposure (TE), and (iii) thyroid isthmusectomy (TI). Expression of mRNA and proteins of key factors regulating homeostasis were evaluated in the TM obtained 3, 7, and 21 days after thyroid surgery. Results: Increased mRNA expression of transforming growth factor-β1 (TGF-β1), hypoxia-inducible factor-1α (HIF-1α), and matrix metalloproteinase-9 (MMP-9) were observed 21 days after thyroid surgery in all experimental groups compared to that of NC group. Conclusion: Thyroid surgery leads to an actual increase of TGF-β1, HIF-1α, and MMP-9 expression in the TM. This increased expression of key regulators of homeostatic restoration in the TM lasts for a considerable period of time after surgery, especially if the extent of surgery increased.

Background: Insulin resistance (IR) and inflammation are closely related to each other and share common pathophysiological and metabolic mechanisms. We aimed to investigate the combined effect of IR and inflammation on comorbidities of type 2 diabetes mellitus (T2DM). Methods: A total 3,758 patients with T2DM were recruited through Huh’s Diabetes Center from January 2003 to June 2009. Insulin sensitivity was measured by a rate constant for plasma glucose disappearance (Kitt , %/min) using short insulin tolerance test. High sensitivity C-reactive protein (hs-CRP) was used as a surrogate for inflammation.Results: Patients with the lowest tertile of Kitt (IR group) showed worse cardio-metabolic parameters while those with the highest tertile of hs-CRP levels had worse cardio-metabolic parameters. The prevalence of metabolic syndrome, fatty liver, albuminuria, and carotid atherosclerosis decreased with Kitt tertile, but increased with hs-CRP tertile. In multiple regression analysis, both Kitt and hs-CRP were independent risk factors for comorbidities of T2DM. In addition, they showed synergistic effects on these comorbidities. Conclusion: Both IR and inflammation were significantly associated with comorbidities of T2DM in a dose dependent manner. In addition, the coexistence of IR and inflammation may synergistically contribute to increased comorbidities of T2DM.

Seol A Jang,&ast; Su Jin Kwon,&ast; Chul Sik Kim, Seok Won Park, Kyoung Min Kim Division of Endocrinology, Department of Internal Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, South Korea&ast;These authors contributed equally to this workCorrespondence: Kyoung Min Kim, Division of Endocrinology, Department of Internal Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, South Korea, Tel +82 31-5189-8798, Fax +82 31-5189-8567, Email kyoungmin.kim@yonsei.ac.krPurpose: Falls are the leading cause of injury among hospitalized patients, particularly among older patients. We investigated the association between serum phosphate (s-phosphate) levels and the risk of in-hospital falls.Patients and Methods: This retrospective observational cohort study included all patients aged over 50 years who were admitted to Yongin Severance Hospital in South Korea between January 2018 and March 2021. Demographic, anthropometric, and biochemical parameters were recorded on admission. S-phosphate levels were classified into three groups: below normal (< 2.8 mg/dL), normal (2.8– 4.4 mg/dL), and above normal (≥ 4.5 mg/dL). The normal group was further stratified into tertiles (2.8– 3.2, 3.3– 3.7, and 3.8– 4.4 mg/dL). The incidence of in-hospital falls was compared between the five groups. Logistic regression analyses were performed to assess the association between s-phosphate levels and the incidence of falls during the hospital stay, with clinical factors included as covariates in the multivariable models.Results: A total of 15,485 patients (female: 52.1%) with a median age of 70.0 years (interquartile range: 60.0– 79.0 years) were included in the analysis, of whom 295 (1.9%) experienced a fall during the hospital stay. The incidence of falls was significantly higher among patients with lower s-phosphate levels, and this relationship also applied among patients with s-phosphate levels within the normal range as well. The association between lower s-phosphate levels and increased risk of falls remained significant in the adjusted analyses.Conclusion: A lower s-phosphate level on admission was independently associated with an increased risk of in-hospital falls. Further studies are needed to determine whether the s-phosphate level on admission could improve prediction of the risk of in-hospital falls.Keywords: in-hospital falls, older adults, blood biochemistry, risk prediction

Ambient air pollutants are considered significant factors that influence allergic diseases. This study aimed to evaluate the effect of ambient air pollution on the medical costs of allergic rhinitis (AR) through a time-series analysis.We used data from the Korean National Health Insurance Database from January 2016 to December 2019. The total cost for medical management and outpatient prescriptions for AR, estimated by the National Health Insurance Service for 25 districts, was summed as the total medical costs. The monthly concentrations of PMTime-series analysis revealed that the concentrations of PMThe monthly concentrations of PM1N/A Laryngoscope, 2022.

In this study, we developed a novel galloyl group-functionalized polydiacetylene (Galloyl-PDA) sensor for colorimetric and fluorescent detection of Pb

This study aimed to determine whether the patterns of diabetic complications differed when patients with type 2 diabetes mellitus (T2DM) were simply classified according to insulin sensitivity and beta-cell function. This observational study included 8861 patients with T2DM who underwent concurrent testing for fasting glucose, fasting insulin, and one or more diabetic complications. We categorized the patients into four groups according to insulin sensitivity and beta-cell function. Compared with the reference group (mild insulin resistance and beta-cell dysfunction), the “severe beta-cell dysfunction” group had lower odds of chronic kidney disease [adjusted odds ratios (aOR) 0.611]. The “severe insulin resistance” group had higher odds of carotid artery plaque presence (aOR 1.238). The “severe insulin resistance and beta-cell dysfunction” group had significantly higher odds of large fiber neuropathy (aOR 1.397, all p

Acute laryngitis and acute inflammatory diseases of either infectious or non-infectious causes have similarities with herpes zoster of the vagus nerve (VHZ). We present a case which was initially diagnosis wtih acute laryngitis but finally diagnosed as VHZ. A 41-year-old male presented with an ongoing fever, throat pain and right otalgia lasting for two days with worsening symptoms despite nonsteroidal anti-inflammatory drug medication. Initially, he was treated conservatively as acute laryngitis was suspected. However, VHZ was subsequently diagnosed in this patient after considering unilateral auricular and laryngeal vesicles which were followed by ipsilateral vocal fold paresis. An antiherpetic agent and prednisolone were administered upon the presentation of vocal fold paresis. Axonotmesis was discovered by laryngeal electromyography one week after the appearance of vocal fold paresis. All symptoms subsided after one month. These results highlight the importance of understanding vagus nerve function in developing a differential diagnosis for laryngitis and VHZ.

In addition to the phase-separated morphology of donor and acceptor, the internal field created by work-function difference between cathode and anode can also influence the exciton dissociation probability. In this study, we have demonstrated enhanced photovoltaic performance by increasing exciton dissociation efficiency. To improve both work-function modification effect and charge transport properties, we have incorporated novel carbon quantum dots (CQD) having NH2 ligands into the polyethyleneimine (PEI) work-function modifying layer as a dopant. A study of net photocurrent density as a function of effective voltage showed that devices with a CQD-doped PEI layer had a much higher charge separation probability compared to devices with a pristine PEI layer. A Kelvin-probe force microscopy study demonstrated that a CQD-doped PEI layer induced lower work-function of ITO than that of ITO with a pristine PEI, which induced a stronger internal field. This strengthened internal field induced better exciton dissociation efficiency, thereby improving solar cell performance.

Objectives. Human amniotic membrane extract (AME) is known to contain numerous bioactive factors and anti-inflammatory substances. However, the anti-inflammatory effects of AME on the middle ear (ME) mucosa are unclear. This study assessed the effects of AME on the growth of the ME mucosa in response to bacterially-induced otitis media (OM).Methods. OM was induced by inoculating nontypeable Haemophilus influenzae (NTHi) into the ME cavity of rats. ME mucosal explants were cultured in AME concentrations of 0, 5, 10, or 50 μg/mL. The area of explant outgrowth was measured in culture and analyzed at 1, 3, 5, and 7 days after explantation. The expression of Ki-67, mucin 5AC (MUC5AC), tumor necrosis factor-α (TNF-α), and interleukin-10 (IL-10) in the explants was also evaluated using quantitative polymerase chain reaction (PCR) and immunocytochemistry (ICC).Results. The NTHi-induced ME mucosa growth increased gradually over the 7-day culture period in all explants at different AME concentrations. There was a trend for mucosal growth inhibition at higher concentrations of AME, although the growth was not significantly different among the groups until day 5. The ME mucosal explants treated with the 50 μg/mL concentration of AME showed significantly suppressed growth on postexplantation day 7 compared with other explants on the same day. PCR and ICC staining revealed that the expression of Ki-67, MUC5AC, TNF-α, and IL-10 further decreased in the explants with higher concentrations of AME than in those with lower concentrations of AME.Conclusion. Our results showed that higher concentrations of AME reduced the mucosal proliferative response in bacterial OM in rats. These findings provide evidence that AME has an influence on the inflammatory and proliferative responses to NTHi infection in ME mucosa.

OBJECTIVE Obesity and type 2 diabetes are risk factors for cardiovascular diseases and mortality, and they commonly result in weight variabilities. We aimed to investigate the association between body weight variability and risk of major cardiovascular outcomes and mortality in individuals with type 2 diabetes using large-scale, nationwide cohort data on the Korean population. RESEARCH DESIGN AND METHODS We enrolled 624,237 individuals with type 2 diabetes who underwent health examinations provided by the Korean National Health Insurance System between 2009 and 2010, with three or more body weight measurements within 5 years since enrollment and followed up until the end of 2017. We assessed body weight variability using four indices, including variability independent of the mean (VIM). A multivariate-adjusted Cox proportional hazards regression analysis was performed. RESULTS During the follow-up, 15,832, 25,038, and 44,716 cases of myocardial infarction (MI), stroke, and all-cause mortality, respectively, were recorded. Body weight variability was associated with increased risks of major cardiovascular outcomes after adjusting for confounding variables. Compared with the hazard ratios (HRs) of the lowest quartile group, the HRs (95% CIs) of the highest quartile group of VIM for body weight were 1.15 (1.10–1.20), 1.22 (1.18–1.26), and 1.58 (1.53–1.62) for MI, stroke, and all-cause mortality, respectively. CONCLUSIONS Body weight variability was associated with increased risks of MI, stroke, and all-cause mortality in patients with type 2 diabetes and may be a predictor of cardiovascular outcomes in such patients. Appropriate interventions to maintain stable weight could positively influence health outcomes in patients with type 2 diabetes.

Objectives. The objectives of this study were to identify the clinical features and chest computed tomography (CT) findings of coronavirus disease 2019 (COVID-19) patients and to compare the characteristics of patients diagnosed in Wuhan and in other areas of China by integrating the findings reported in previous studies.Methods. We conducted a proportion meta-analysis to integrate the results of previous studies identified in online databases, and subsequently compared the overlapping of 95% confidence intervals (CIs) between locations of diagnosis. The heterogeneity of the results of the included studies was also demonstrated.Results. Nine studies with level IV evidence were considered to be eligible for the meta-analysis, and a comparative analysis was only possible between patients diagnosed in Wuhan and outside of Wuhan in China. Fever (84.8%; 95% CI, 78.5% to 90.1%) was identified as the most common clinical manifestation in all COVID-19 patients, and signs of respiratory infection were also frequently present in these patients. When comparing the clinical features according to the location of diagnosis, fever and dyspnea were less frequent in patients diagnosed outside of Wuhan (fever: 78.1%; 95% CI, 73.2% to 82.7%; dyspnea: 3.80%; 95% CI, 0.13% to 12.22%) than in patients diagnosed in Wuhan (fever: 91.7%; 95% CI, 88.0% to 94.8%; dyspnea: 21.1%; 95% CI, 13.2% to 30.3%). The chest CT findings exhibited no significant differences between the groups.Conclusion. Fever was found to be the most common symptom in COVID-19, and respiratory infection signs were also commonly present. Fever and dyspnea were less frequently observed in the patients diagnosed outside of Wuhan, which should be considered in COVID-19 screening programs. These results may be attributable to the earlier diagnosis of the disease and the younger age of patients outside of Wuhan although further analysis is needed. The role of chest CT in COVID-19 diagnosis is inconclusive based on this study.

BACKGROUND To evaluate the association between serum 25-hydroxyvitamin D (25(OH)D) at mid-pregnancy and postpartum glucose intolerance in women with gestational diabetes mellitus (GDM). METHODS We enrolled 348 pregnant women diagnosed with GDM from August 2012 to October 2016. We measured serum 25(OH)D levels at mid-pregnancy and carried out a 75-g oral glucose tolerance test at 6 to 12 weeks after delivery. Vitamin D deficiency was defined as serum 25(OH)D

Objective: This study investigated whether serum bilirubin levels can predict the progression of carotid atherosclerosis in individuals with type 2 diabetes mellitus (T2DM). Methods: This observational study included 1,381 subjects with T2DM in whom serial measurements of carotid intima-media thickness (CIMT) were made at 1- to 2-year intervals for 6–8 years. The progression of carotid atherosclerosis was defined as newly detected plaque lesions on repeat ultrasonography. After dividing total serum bilirubin levels into tertiles, the association between total serum bilirubin at baseline and plaque progression status was analyzed. Results: Among 1,381 T2DM patients, 599 (43.4%) were categorized as having plaque progression in their carotid arteries. Those with plaque progression were significantly older; showed a higher prevalence of hypertension, abdominal obesity, and chronic kidney disease; and had a longer duration of T2DM, higher levels of total cholesterol (TC), triglycerides, and insulin resistance, and lower total bilirubin concentrations than those with no plaque progression. When total serum bilirubin levels were divided into tertiles, the highest tertile group was younger than the lowest tertile group, with higher levels of TC and high-density lipoprotein cholesterol. Multiple logistic regression analysis demonstrated that higher serum bilirubin levels were associated with a significantly lower risk of CIMT progression (odds ratio, 0.584; 95% confidence interval, 0.392–0.870; p=0.008). Age (p

Polypyrrole nanoparticles (PPy-NPs) with excellent near-infrared absorption are commonly used as photothermal therapy (PTT) agents; however, PTT using PPy-NPs has a limitation in that it is difficult to maximize their therapeutic effect because of the lack of specific targeting. In this study, to overcome the difficulty of targeting, folic acid functionalized carbon dots (FA-CDs) with bright green fluorescence properties were combined with carboxylated PPy-NPs via the EDC/NHS coupling reaction to yield a PTT imaging agent. The synthesized FA-CD/PPy-NPs with excellent photostability performed folate receptor (FR) positive HeLa cancer cell imaging by green fluorescence signals of FA-CDs and exhibited high cell viability (above 90%) even at 500 μg/mL. The viability of HeLa cells incubated with 200 μg/mL FA-CD/PPy-NPs was dramatically decreased to 25.02 ± 1.85% by NIR laser irradiation, through photothermal therapeutic effects of FA-CD/PPy-NPs with high photothermal conversion efficiency (η = 40.80 ± 1.54%). The cancer cell death by FA-CD/PPy-NPs was confirmed by fluorescence imaging of FA-CDs as well as live/dead cell staining assay (calcein-AM/PI). These results demonstrate that the FA-CD/PPy-NPs can be utilized as multifunctional theranostic agents for specific bioimaging and treatment of FR-positive cancer cells.

Background Meta-analyses comparing the efficacy of sublingual immunotherapy (SLIT) and subcutaneous immunotherapy (SCIT) for house dust mite allergy are lacking. Objective To compare the efficacy of SLIT drops, SLIT tablets, and SCIT in patients with perennial allergic rhinitis through network analysis. Methods Frequentist network meta-analyses estimated the standardized mean difference (SMD) across the three immunotherapy modalities on allergic rhinitis symptom and medication score data from double-blind randomized clinical trials. Random effects models were investigated. Results We included 26 double-blind randomized clinical trials in this meta-analysis for the symptom score and 18 for the medication score. In the direct pairwise meta-analysis, a significant reduction of the symptom score was observed for all immunotherapy modalities compared with the placebo: pooled SMDs of –0.461 (95% confidence interval [CI], –0.795 to –0.127) for SLIT drop, –0.329 (95% CI, –0.426 to –0.231) for SLIT tablet, and –1.669 (95% CI, –2.753 to –0.585) for SCIT. For the medication score, a significant reduction was observed for all modalities. In network meta-analysis, the clinical efficacy of SCIT based on the symptom score was greater than for SLIT drop or SLIT tablet (SMD: –0.697, 95% CI, –1.105 to –0.288; and SMD: –0.819, 95% CI, –1.242 to –0.397). However, there was no significant difference in the symptom score between SLIT drop and SLIT tablet. Conclusions This study demonstrated the clinical efficacy of all house dust mite immunotherapy modalities and suggests that SCIT may be more effective than SLIT drops or tablets in controlling symptoms of allergic rhinitis.

Overexpression of collagenase, elastase, and tyrosinase is caused by external factors such as ultraviolet (UV) radiation and stress, resulting in wrinkle formation and freckles through the loss of skin elasticity and skin pigmentation. In this study, we developed novel carbon quantum dots (CQDs) with antioxidant and anti-aging properties using tannic acid as a carbon source through a simple microwave-assisted pyrolysis method. The synthesized tannic acid-derived CQDs (T-CQDs) showed bright blue fluorescence (QY = 28.2 ± 4.0%), exhibiting maximum emission at 430 nm under 350 nm excitation. Even though small amount of the T-CQDs (3μg ml-1) was used, they exhibited excellent free radical scavenging ability (82.8 ± 4.3%). Also, the T-CQDs (10μg ml-1) revealed remarkable inhibitory activity against skin aging-related collagenase (77.6 ± 4.8%), elastase (52.6 ± 1.0%), and tyrosinase (44.2 ± 1.3%), demonstrating their antioxidant and anti-aging effects. Furthermore, their antioxidant and anti-aging properties were superior to those of tannic acid, L-ascorbic acid, and quercetin used as positive controls. Finally, the T-CQDs effectively suppressed UV-induced reactive oxygen species generation by 30% at the cellular levels and showed high cell viability (99.7 ± 0.8%) even at 500μg ml-1. These results demonstrate that the T-CQDs with superior antioxidant, anti-aging properties, and low cytotoxicity can be utilized as novel anti-aging materials in cosmetic and nanomedicine fields.

Background There is increasing concern regarding cardiovascular risk in individuals with non-alcoholic fatty liver disease. This study was conducted to evaluate whether hepatic steatosis with or without fibrosis is associated with the progression of carotid atherosclerosis in patients with type 2 diabetes. Methods From a longitudinal cohort, we enrolled 1120 patients with type 2 diabetes who underwent repeated carotid artery ultrasonography every 1–2 years. Ultrasonographic findings at baseline and after 6–8 years were compared. Presence of hepatic steatosis was mainly assessed by abdominal ultrasonography; patients with hepatic steatosis were further evaluated for hepatic fibrosis according to fibrosis-4 index. We investigated the association between liver status and atherosclerosis progression. Results Of 1120 patients, 636 (56.8%) were classified as having hepatic steatosis at baseline. After 6–8 years, 431 (38.5%) showed atherosclerosis progression. Hepatic steatosis was significantly associated with atherosclerosis progression (adjusted odds ratio[AOR]: 1.370, 95% CI 1.025–1.832; p p p p Conclusions Hepatic steatosis with fibrosis is independently associated with the progression of carotid atherosclerosis in patients with type 2 diabetes.

Objectives The objective of this study was to evaluate the effects of allergic rhinitis (AR) on the development, progression, and recovery of acute otitis media (OM) in an animal model and investigate the secondary effects of bacterial infection. Methods BALB/c mice were divided into four groups: AR + OM, AR, OM, and control groups. AR + OM and AR groups were sensitized with ovalbumin (OVA) and alum and then challenged intranasally with OVA. Phosphate-buffered saline (PBS) was administered to the OM and control groups the same number of times. After AR induction, OM was induced by surgical inoculation of non-typeable Haemophilus influenza (NTHi) into the middle ear (ME) cavity of the mice in the AR + OM and OM groups. PBS was injected into the bulla in the AR and control groups. Each group was subdivided into sets of six mice, one for each of the four time points (0, 2, 7, and 10 days post-bacterial inoculation), at which point the mice were euthanized and ME and nasal cavity mucosa were obtained and evaluated. The occurrence of OM and the ME mucosa thickness were evaluated and compared among the four groups. Tissue expression of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) in infected ME mucosa was assessed by immunohistochemical staining. We also investigated IgE, IL-4, and IL-5 in the nasal mucosa. Results Most of the ears showed OM on post-inoculation day 2 in both AR + OM and OM groups. In the AR + OM group, 58.3% of ears still had OM on post-inoculation day 10, while only 16.7% of the OM group had OM. The ME mucosa of all groups increased, and the AR + OM group exhibited the thickest mucosa. The OM group showed peak thickness on post-inoculation day 2 and then decreased, whereas the ME mucosa thickness of the AR + OM group continued to increase to day 7. In the OM group, the expression of IL-1β, IL-6, and TNF-α in the ME also increased significantly, peaking on post-inoculation day 2, and then gradually decreased. In the AR + OM group, the expression of these proteins increased until day 7 and then decreased. The IgE and Th2 response (IL-4 and IL-5) cytokines were expressed at higher levels in the AR + OM and AR groups than in the OM and control groups. Conclusion The inflammatory reaction to NTHi was more intense and lasted longer in the allergic group, which indicates that AR affects the progression and subsequent recovery of acute bacterial OM.

Background/Aim: This study aimed to investigate changes in the tracheal mucosa after thyroidectomy, that can be a cause of post-thyroidectomy discomfort. Materials and Methods: Forty rats were divided into normal controls and 3 surgical groups: (i) thyroid isthmectomy with cauterization, (ii) isthmectomy by a cold instrument without hemostasis, and (iii) sham (exposure of the trachea and thyroid gland without thyroidectomy by dissection through pretracheal fascia). Animals were euthanized at 1 and 4 weeks. Mucosal edema and glandular hyperplasia were measured. Mucin production and basal cell activities were evaluated by mucin 5AC (MUC5AC) and keratin 5 (KRT5) using immunofluorescence staining. Results: Larger mucosal areas were observed in all surgical groups at 1 and 4 weeks. More submucosal glandular hyperplasia was noted in the group with isthmectomy without hemostasis. MUC5AC and KRT5 expressions were significantly higher in the surgical groups. Conclusion: The tracheal mucosa may change after surgery, which could explain postoperative discomfort after thyroidectomy.

In this paper, we first open on important issues regarding the Penn Korean Universal Treebank (PKT-UD) and address these issues by revising the entire corpus manually with the aim of producing cleaner UD annotations that are more faithful to Korean grammar. For compatibility to the rest of UD corpora, we follow the UDv2 guidelines, and extensively revise the part-of-speech tags and the dependency relations to reflect morphological features and flexible word-order aspects in Korean. The original and the revised versions of PKT-UD are experimented with transformer-based parsing models using biaffine attention. The parsing model trained on the revised corpus shows a significant improvement of 3.0% in labeled attachment score over the model trained on the previous corpus. Our error analysis demonstrates that this revision allows the parsing model to learn relations more robustly, reducing several critical errors that used to be made by the previous model., Comment: Accepted by The 16th International Conference on Parsing Technologies, IWPT 2020

The objective of this study was to investigate the expression and the role of surfactant protein A (SP-A) in the middle ear (ME) mucosa in response to bacterial infection in a rat model. Otitis media (OM) was induced by surgical inoculation of non-typeable Haemophilus influenza (NTHi) into the ME cavity of Sprague-Dawley rats. The rats were divided into an NTHi-induced OM group and a phosphate-buffered saline-injected control group. The NTHi-induced OM and control groups were subdivided into sets of 6 rats, one for each of the 6 time points (0, 1, 2, 4, 7, and 14 days post-inoculation), at which point the rats were euthanized after inoculation. The concentrations of SP-A in the ME effusion were determined by an enzyme-linked immunosorbent assay (ELISA). Tissue expression of SP-A, interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in infected ME mucosa was assessed by immunohistochemical staining. For mRNA expression quantification, RNA was extracted from the ME mucosa and SP-A expression was monitored and compared between the control and OM groups using quantitative polymerase chain reaction (PCR). Expression of IL-1β, IL-6, and TNF-α in the ME mucosa was also evaluated. SP-A expression was evaluated in the effusion of pediatric OM patients (70 ears) who received ventilation-tube insertion by ELISA. SP-A was detected in normal rat ME mucosa before bacterial inoculation. SP-A expression was up-regulated in the NTHi-induced OM group (p = 0.046). Immunohistochemical staining revealed increased SP-A expression on post-inoculation day 1, 2, and 4 in the OM group. Expression of proinflammatory cytokines (IL-1β, IL-6, and TNF-α) in the ME also increased significantly on post-inoculation day 1, 2, and 4 in the OM group. It correlated with changes in SP-A expression. Expression of SP-A was also identified in the ME effusion of humans. SP-A exists in the ME of the rat and was up-regulated in the ME of NTHi-induced OM. Expression of IL-1β, IL-6, and TNF-α was increased in the ME of the bacteria-induced OM in the rat model. The results suggest that SP-A may play a significant role in the early phase of OM induction and subsequent recovery from it.

Aim To investigate the efficacy and safety of evogliptin compared with linagliptin in patients with type 2 diabetes. Materials and Methods In this 12‐week, multicentre, randomized, double‐blind, active‐controlled, and 12‐week open‐label extension study, a total of 207 patients with type 2 diabetes who had HbA1c levels of 7.0%‐10.0% were randomized 1:1 to receive evogliptin 5 mg (n = 102) or linagliptin 5 mg (n = 105) daily for 12 weeks. The primary efficacy endpoint was the change from baseline HbA1c at week 12. The secondary endpoint was the change in the mean amplitude of glycaemic excursion (MAGE) assessed by continuous glucose monitoring. In the extension study conducted during the following 12 weeks, evogliptin 5 mg daily was administered to both groups: evogliptin/evogliptin group (n = 95) and linagliptin/evogliptin group (n = 92). Results After 12 weeks of treatment, the mean change in HbA1c in the evogliptin group and in the linagliptin group was −0.85% and −0.75%, respectively. The between‐group difference was −0.10% (95% CI: −0.32 to 0.11), showing non‐inferiority based on a non‐inferiority margin of 0.4%. The change in MAGE was −24.6 mg/dL in the evogliptin group and −16.7 mg/dL in the linagliptin group. These values were significantly lower than the baseline values in both groups. However, they did not differ significantly between the two groups. In the evogliptin/evogliptin group at week 24, HbA1c decreased by −0.94%, with HbA1c values of

BACKGROUND/AIMS This study aimed to investigate whether the apolipoprotein (Apo) B/ApoA-I ratio is associated with carotid intima-media thickness (CIMT) in type 2 diabetes mellitus (T2DM) subjects with low density lipoprotein cholesterol (LDL-C) levels less than 100 mg/dL. METHODS This cross-sectional study included 845 subjects aged with T2DM 40 to 75 years who had visited Huh's Diabetes Center in Seoul, Republic of Korea for CIMT measurement. Traditional fasting lipid profiles, ApoB and ApoA-I levels were examined. CIMT was measured at three points on the far wall of 1 cm long section of the common carotid artery in the proximity of the carotid bulb. The mean value of six measurements from right and left carotid arteries were used as the mean CIMT. In this study, carotid atherosclerosis was defined as having a focal plaque or diffuse thickening of the carotid wall (mean CIMT ≥ 1.0 mm). RESULTS The prevalence of carotid atherosclerosis increased with ApoB/ApoA-I ratio. The ApoB/ApoA-I ratio, expressed as both quartiles (odds ratio [OR], 2.14; 95% confidence interval [CI], 1.21 to 3.79; p for trend = 0.014) and continuous values (OR, 10.05; 95% CI, 3.26 to 30.97; p < 0.001), was significantly associated with a higher risk for carotid atherosclerosis, regardless of conventional cardiovascular disease risk factors. The optimal ApoB/ApoA-I ratio cutoff value for detecting carotid atherosclerosis was 0.57, based on receiver operating characteristic curve analysis with a sensitivity of 58.0% and a specificity of 55.1%. CONCLUSIONS A high ApoB/ApoA-I ratio was significantly associated with carotid atherosclerosis in T2DM patients with LDL-C levels less than 100 mg/dL.

A new polymer, P(BDT-fPPD), which incorporates 4,8-bis(2-ethylhexyloxy)benzo[1,2-b:4,5-bʹ]dithiophene (BDT) and 4,6-bis(furan-2-yl)-2,5-dioctylpyrrolo [3] , [4] 3,4-c]pyrrole-1,3(2H,5H)-dione (fPPD, furan π–bridged PPD) units, was prepared. The optoelectrical, crystalline, charge transport, backbone curvature, and photovoltaic properties of P(BDT-fPPD) were thoroughly studied. P(BDT-fPPD) was also compared to the polymer P(BDT-tPPD), comprising BDT and 4,6-bis(thiophen-2-yl)-2,5-dioctylpyrrolo [3] , [4] 3,4-c]pyrrole-1,3(2H,5H)-dione (tPPD, thiophene π–bridged PPD) units. This study demonstrates that the π–bridges, such as thiophene and furan, attached between the BDT and pyrrolo [3] , [4] 3,4-c]pyrrole-1,3(2H,5H)-dione (PPD) units greatly altered the properties of the resulting polymers. In particular, the backbone curvature of P(BDT-fPPD) was significantly different from that of P(BDT-tPPD), which resulted in P(BDT-fPPD) having a higher bandgap energy (Eg), deeper HOMO level, and higher crystallinity, but lower carrier mobility (μh) and relatively poor power conversion efficiency (PCE) compared to P(BDT-tPPD). For P(BDT-fPPD), the Eg, HOMO, μh, and PCE were determined as 2.20 eV, −5.44 eV, 1.19 × 10−5 cm−2 V−1 s−1, and 2.62%, respectively. The corresponding values for P(BDT-tPPD) were 2.11 eV, −5.39 eV, 2.95 × 10−4 cm−2 V−1 s−1 and 5.29%, respectively. Interestingly, the inclusion of a small amount of P(BDT-tPPD) in the PTB7-Th:PC70BM blend enhanced the PCE of the resulting ternary organic solar cells (OSCs), whereas the insertion of P(BDT-fPPD) lowered the PCE of the ternary OSCs. The lower mobility and PCE obtained for P(BDT-fPPD) are mainly attributed to its poor blending with PC70BM.

Levodopa has been a standard drug for treating Parkinson’s disease since the 1960s, but it has caused many side effects such as wearing-off, motor fluctuation, and dystonia. In this work, we developed glutathione-conjugated carbon quantum dots (GSH-CQDs) as a novel fluorescent sensor for sensitive and selective detection of levodopa. The GSH-CQDs were prepared by EDC/NHS coupling reaction of glutathione (GSH) with amine-functionalized CQDs (N-CQDs) synthesized using meta-phenylenediamine and ethylenediamine. The synthesized GSH-CQDs emitted bright green fluorescence with a high quantum yield (QY) of 22.42 ± 6.88%. However, upon the addition of levodopa to GSH-CQDs under alkaline conditions, the fluorescence of GSH-CQDs was quenched. Since levodopa is converted to dopaquinone in an alkaline environment, it is presumed that thiol groups of GHS-CQDs form covalent bonds with dopaquinone, causing fluorescence quenching through photoinduced electron transfer. Therefore, as the concentration of levodopa increased, the fluorescence intensity of GSH-CQDs was gradually decreased. Under optimal conditions, a linear response was observed in the range of 0.05–1 μM, and limit of detection (LOD) was determined to be 0.057 μM. The GSH-CQDs exhibited high specificity to levodopa over other non-target biological substances, quinone derivatives, and Parkinson’s medications. Furthermore, the capability of this GSH-CQDs sensor for monitoring levodopa in human serum were validated with excellent precision and recovery rates of 100.20–103.33%.

Background This study aimed to explore the time interval distribution pattern between the Physicians Order for Life-Sustaining Treatment (POLST) form completion and death at a tertiary hospital in South Korea. It also examined the association between various independent parameters and POLST form completion timing. Methods A total of 150 critically ill patients admitted to Korea University Guro Hospital between June 1, 2018 and December 31, 2018 who completed the POLST form were retrospectively analyzed and included in this study. Data were analyzed with descriptive statistics, and group comparisons were performed using the chi-square test for categorical variables. Fisher's exact test was also used to compare cancer versus non-cancer groups. Results More than half the decedents (54.7%) completed their POLST within 15 days of death and 73.4% within 30 days. The non-cancer group had the highest percentage of patients (77.8%) who died within 15 days of POLST form completion while the colorectal (39.1%) and other cancer (37.5%) groups had the lowest (P=0.336). Conclusion Our findings demonstrated a current need for more explicit guidance to assist physicians with initiating more timely, proactive end-of-life discussions.

Background and Aims: Evogliptin is a new dipeptidyl peptidase-4 (DPP-4) inhibitor. We investigated the efficacy and safety of Evogliptin compared with linagliptin in patients with type 2 diabetes (T2D). Materials and Methods: A total of 207 untreated patients with T2D (mean age, 56.1±10.4 years; body mass index, 26.1±3.4 kg/m2) who had HbA1c 7.0-10.0%, prior to the screening were randomized 1:1 for 5 mg Evogliptin (n=102) or 5 mg linagliptin (n=105) once daily for 12 weeks. The primary efficacy endpoint was the change from baseline HbA1c at week 12. The secondary endpoint included the change in mean amplitude of glycemic excursion (MAGE) assessed by 72-hour continuous glucose monitoring. In the extended study for another 12 weeks, open-label treatment with Evogliptin 5 mg qd was conducted in both groups; Evogliptin/Evogliptin group (n=95) and Linagliptin/Evogliptin group (n=92). Results: After 12 weeks of treatment, the mean changes in HbA1c of Evogliptin group and linagliptin group were −0.85% and −0.75%, respectively; the between-group difference was -0.10% (95% confidence interval, −0.32-0.11%), demonstrating non-inferiority, meeting the pre-specified margin of 0.40%. The changes in MAGE were −24.6 mg/dL in the Evogliptin group and −16.7 mg/dL in the linagliptin group, which were significantly lower compared with baseline values in both groups. In the Evogliptin/Evogliptin group at week 24, the mean changes from baseline in HbA1c was −0.94%, achieving HbA1c Conclusion: In this study, once-daily evoglipitin 5 mg treatment significantly decreased HbA1c levels by 0.94% at week 24 and improved glycemic variability without any serious adverse events in Korean patients with T2D (ClinicalTrials.gov Identifier: NCT02974504). Disclosure S. Lim: None. G. Kim: None. H. Kwon: None. I. Park: None. K. Ahn: None. C. Park: None. S. Kwon: None. H. Kim: None. S. Park: None. S. Kim: None. M. Moon: None. E. Kim: None. C.H. Chung: None. K. Won: None. K. Park: None. M. Kim: None. D. Chung: None. C. Lee: None. T. Kim: None. M. Lee: None.

The objective of this study was to evaluate the role of group 3 innate lymphoid cells (ILC3) in the middle ear (ME) mucosal response to bacterial infection in a rat model. To confirm the role of ILC3 in bacterially induced otitis media (OM), the serum concentrations of IL-17 and IL-22 were determined by ELISA, and the tissue expression of IL-17 and IL-22 in infected ME mucosa was assessed by immunohistochemical staining. Immunohistochemical staining of specific cell surface markers was also assessed to confirm the origin of the cells expressing IL-17 and IL-22. Twenty Sprague-Dawley rats were used in the surgically-induced animal model of OM. OM was induced by inoculation of non-typeable Haemophilus influenzae into the ME cavity of the rats. The rats were divided into four experimental groups: three infected groups and one control group. Infected groups were subdivided into sets of 5 rats, one for each of the three time points (1, 4 and 7 days post-inoculation). For determination of rat IL-17 and IL-22 levels in infected rats and control rats, infected or control ME mucosa sections were analyzed by immunohistochemistry with specific antibodies directed against IL-17 and IL-22. Immunohistochemical staining for CD3, RORγt, and NKp46 were also conducted on the samples to confirm the origin of cells expressing IL-17 and IL-22. IL-17 and IL-22 serum concentrations were significantly increased in the infected rats compared to control rats. Immunohistochemical staining revealed increased IL-17 and IL-22 expressions in all infected ME mucosae from the first day after inoculation. In addition, the results of tissue staining for the specific surface markers were negative for CD3 and NKp46, but were highly positive for RORγt. IL-17 and IL-22 revealed their association with the bacterially induced proliferative and hyperplastic responses of ME mucosa, which are characteristic features in pathogenesis of OM. Surface marker examination showed that the source cells for IL-17 and IL-22 seemed to be lymphoid tissue inducer (LTi) cells. The results suggest that LTi cells release IL-17 and IL-22, and play a significant role in both the early phase of OM induction and recovery from it.