Search

Introduction: The long-term impact of initial immunogenicity induced by different primary COVID-19 vaccine series remains unclear., Methods: A prospective cohort study was conducted at 10 tertiary hospitals in Korea from March 2021 to September 2022. Immunogenicity assessments included anti-spike protein antibody (Sab), SARS-CoV-2-specific interferon-gamma releasing assay (IGRA), and multiplex cytokine assays for spike protein-stimulated plasma. Spike proteins derived from wild-type SARS-CoV-2 and alpha variant (Spike 1 ) and beta and gamma variant (Spike 2 ) were utilized., Results: A total of 235 healthcare workers who had received a two-dose primary vaccine series of either ChAdOx1 or BNT162b2, followed by a third booster dose of BNT162b2 (166 in the ChAdOx1/ChAdOx1/BNT162b2 (CCB) group and 69 in the BNT162b2/BNT162b2/BNT162b2 (BBB) group, based on the vaccine series) were included. Following the primary vaccine series, the BBB group exhibited significantly higher increases in Sab levels, IGRA responses, and multiple cytokines (CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1β, interleukin (IL)-1ra, IFN-γ, IL-2, IL-4, and IL-10) compared to the CCB group (all P < 0.05). One month after the third BNT162b2 booster, the CCB group showed Sab levels comparable to those of the BBB group, and both groups exhibited lower levels after six months without breakthrough infections (BIs). However, among those who experienced BA.1/2 BIs after the third booster, Sab levels increased significantly more in the BBB group than in the CCB group (P < 0.001). IGRA responses to both Spike 1 and Spike 2 proteins were significantly stronger in the BBB group than the CCB group after the third booster, while only the Spike 2 response were higher after BIs (P = 0.007). The BBB group exhibited stronger enhancement of T-cell cytokines (IL-2, IL-4, and IL-17A) after BIs than in the CCB group (P < 0.05)., Conclusion: Differences in immunogenicity induced by the two primary vaccine series persisted, modulated by subsequent booster vaccinations and BIs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Recently improved techniques could provide snapshots of chromatin structure generated based on chromatin accessibility. Since chromatin accessibility determines transcriptional potential, it has been attempted in a variety of cell systems. However, there has been no genome-wide analysis of chromatin accessibility for the entire murine osteoclast (OC) differentiation process. We performed an Assay for Transposase-Accessible Chromatin (ATAC)-sequencing (seq) during RANKL-induced OC differentiation and found that global chromatin accessibility decreased, especially early in OC differentiation. The global histone H3K27Ac level, an active histone modification mark, was diminished during OC differentiation by western blot and histone extract experiments. Its genomic enrichment was also reduced based on publicly available H3K27Ac chromatin immunoprecipitation (ChIP)-seq data. ATAC-seq and H3K27Ac ChIP-seq data demonstrated that RANKL induced a less accessible chromatin state during OC differentiation. Restoration of reduced H3K27Ac, presumably representing accessible states upon acetate treatment, suppresses OC differentiation by provoking immune-related gene expression. Subsequential integrative analysis of ATAC-seq, RNA-seq after acetate treatment, and H3K27Ac ChIP-seq reveals that Irf8 and its downstream targets are the most vulnerable to chromatin accessibility changes and acetate supplementation. Taken together, our study generated chromatin accessibility maps during the whole OC differentiation and suggested perturbation of chromatin accessibility might be a potential therapeutic strategy for excessive OC diseases., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Invasive pneumococcal disease (IPD) is associated with substantial morbidity and mortality in children and elderly populations. Serotype distribution and antibiotic susceptibility of IPD isolates are changing with the implementation of pneumococcal vaccination and increasing antibiotic use worldwide. We aimed to determine serotype distribution, antibiogram, and molecular epidemiology of pneumococci in the late stage of PCV13 era., Methods: Prospective multicenter IPD surveillance study was conducted for adults aged ≥ 19 years from July 2019 to June 2021. Clinical and epidemiologic data were collected. In addition, antibiotic susceptibility test, serotype identification and multi-locus sequence typing (MLST) was taken for pneumococcal isolates., Results: A total of 160 IPD cases were collected with mean age of 65.1 years (male, 72.5%). Serotyping was taken for 116 available pneumococcal isolates. PCV13 and PPSV23 serotypes were 32.8% (n = 38) and 56.0% (n = 65), respectively. Serotype 3 (13.8%) and 19A (9.5%) were the most common causative agents of IPD, followed by serogroup 11 (6.9%), 23A (6.9%), 10A (4.3%), and 15B (4.3%). Notably, 32.5% of invasive pneumococcal isolates were non-susceptible to ceftriaxone. Serotypes 11A, 11E and 19A pneumococci showed high ceftriaxone non-susceptible rate (80%, 100% and 81.8% respectively), and they were related to sequence type (ST) 166 and ST320. In comparison, most serotype 3 isolates were ceftriaxone susceptible and related to ST180., Conclusions: PCV serotypes, especially 3 and 19A, are still prevalent in adult IPDs, suggesting that individual PCV13 immunization would be necessary for the elderly people and chronically ill patients. Ceftriaxone non-susceptible rate was remarkably high in invasive pneumococcal isolates., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: To investigate and compare the postoperative efficacy and complications of the transurethral resection of prostate (TURP) and holmium laser enucleation (HoLEP) using the nationwide insurance database of Korea., Methods: We created a cohort of benign prostatic hyperplasia (BPH) patients treated with TURP and HoLEP between 2011 and 2017 from the nationwide database of reimbursement. We compared the postoperative effects between the two surgical groups., Results: We retrieved a total of 58,346 patients (TURP 38,308 and HoLEP 20,038 patients). The mean follow-up duration was 51.6 and 47.6 months, respectively. The rate of reoperation was significantly higher in the TURP group (4.50%) than in the HoLEP group (1.27%) (P < .01). The postoperative use of alpha-blockers and dutasteride/finasteride was significantly higher in the TURP group until 24 months postoperatively. The rate of the postoperative use of medications for symptoms of overactive bladder was lower in the TURP group than in the HoLEP group until 12 months postoperatively, but it did not differ after 12 months postoperatively. Overall, urethral surgeries were less frequently performed in the TURP group than in the HoLEP group (P < .05); however, more severe cases required surgeries under general anesthesia in the TURP group (P < .05). Postoperative surgery for stress incontinence was performed in 0.10% and 0.31% of patients after TURP and HoLEP, respectively (P < .01)., Conclusion: This study showed the superiority of HoLEP compared to TURP in terms of postoperative efficacy and its inferiority in terms of complications of stress incontinence in real life practice., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Osteoclasts (OCs) have been well-known involved in the exacerbation of bone-related diseases. However, the role of metabolites on osteoclastogenesis has not been well characterized. Herein, we found osteoclastogenesis was negatively regulated by α-ketoglutarate (αKG) in vitro and in vivo (C57BL/6 mouse). Kinetic transcriptome analysis revealed the upregulation of solute carrier family 7 member 11 (Slc7a11), a subunit of the cysteine/glutamate antiporter, as well as the downregulation of typical OC maker genes through αKG treatment. Given that Slc7a11 could control ROS level through glutathione import, we measured intracellular ROS, then RANKL-induced ROS production was inhibited by αKG. Notably, we highlight that αKG plays an epigenetic co-factor at the Slc7a11 promoter by demethylating repressive histone H3K9 methylation and simultaneously increasing the nuclear factor erythroid 2-related factor (Nrf2) binding, a critical transcription factor through chromatin immunoprecipitation (ChIP) analysis. Together, we suggested that αKG could be a therapeutic strategy for OC activated diseases., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Hemorrhagic fever with renal syndrome is a serious health problem in Eurasian countries. This study aimed to evaluate the immunogenicity and safety of formalin-inactivated Hantaan virus vaccine (Hantavax®) with a 3 + 1 vaccination schedule., Methods: A phase III, multi-center clinical trial was conducted to evaluate the immunogenicity and safety of Hantavax® (three primary doses and a booster dose schedule at 0, 1, 2 and 13 months) among healthy adults. Immune responses were assessed using the plaque reduction neutralizing antibody test (PRNT) and immunofluorescent antibody assay (IFA). Systemic and local adverse events were assessed., Results: A total of 320 healthy subjects aged ≥19 years were enrolled. Following three primary doses of Hantavax®, the seroconversion rate was 80.97% and 92.81% by PRNT and IFA, respectively. With booster administration, seropositive rates were 67.47% and 95.68% at one-month post-vaccination according to PRNT and IFA, respectively. Solicited local and systemic adverse events were reported in 30.50-42.81% and 16.67-33.75% during the three primary dose vaccination, while those were reported 36.57% and 21.36% after the booster doses. Both local and systemic adverse events did not increase with repeated vaccinations., Conclusion: Hantavax® showed a high seroconversion rate after the three-dose priming, and additional dose administration with 11-month interval induced good booster effects. (ClinicalTrials.gov Identifier: NCT02553837)., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: South Korea has been providing 10-valent pneumococcal conjugate vaccine/(PCV10)/13-valent pneumococcal conjugate vaccine (PCV13) to children and 23-valent pneumococcal polysaccharide vaccine (PPSV23) to older adults as part of a national immunization program., Methods: From September 2015 to August 2017, a prospective cohort study was conducted for adults aged ≥19 years with community-acquired pneumonia (CAP) at four university hospitals. All-cause and pneumococcal CAP incidence and mortality rates were evaluated on the basis of hospital catchment population. Serotype distribution of pneumococcal CAP was also evaluated., Results: Among 2669 patients with CAP, 252 cases (9.4%) were pneumococcal CAP cases. The annual incidences of all-cause and pneumococcal CAP were 194.3 cases and 18.3 cases respectively, per 100,000 persons. Serotyped Streptococcus pneumoniae was identified in 107 cases (42.5%) through culture or a serotype-specific urinary antigen detection assay. Pneumococcal CAP caused by the PCV13 and PPSV23 serotypes were 50 cases (46.7% of serotyped pneumococcal CAP and 19.8% of pneumococcal CAP), and 83 cases (77.6% of serotyped pneumococcal CAP and 32.9% of pneumococcal CAP), respectively. The most prevalent serotype was 3 (n = 21, 19.6% of serotyped pneumococcal CAP), followed by 19A (n = 10, 9.3% of serotyped pneumococcal CAP) and 11A (n = 10, 9.3% of serotyped pneumococcal CAP). Compared with non-pneumococcal CAP patients, pneumococcal CAP patients were more likely to have a higher CURB-65 scores (P = 0.002). The overall 30-day mortality rate of pneumococcal CAP was higher than that of non-pneumococcal CAP (6.3% versus 5.6%; odds ratio [OR], 1.15; 95% confidence interval [CI], 0.67-1.96), but this trend was reversed in patients aged 65-74 years (4.2% versus 8.6%; OR, 0.47; 95% CI, 0.14-1.54)., Conclusions: The disease burden of PCV13-serotype pneumococcal CAP remains significantly high in Korean adults, particularly among elderly people, even after a high uptake of pediatric PCVs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: New influenza vaccine formulations are designed to improve vaccine effectiveness and protect those most vulnerable to infection. High dose trivalent inactivated influenza vaccine (HD-IIV3), licensed for ages ≥65 years, produces greater antibody responses and efficacy in clinical trials, but post-licensure vaccine effectiveness (VE) compared to standard dose (SD-IIV3/4) vaccine remains an open question., Methods: Using a test-negative, case control design and propensity analyses to adjust for confounding, US Influenza VE Network data from the 2015-2016 through 2018-2019 seasons were analyzed to determine relative VE (rVE) between HD-IIV3 and SD-IIV3/4 among outpatients ≥65 years old presenting with acute respiratory illness. Influenza vaccination status was derived from electronic medical records and immunization registries., Results: Among 3861 enrollees, 2993 (78%) were vaccinated; 1573 (53%) received HD-IIV3 and 1420 (47%) received SD-IIV3/4. HD-IIV3 recipients differed from SD-IIV3/4 recipients by race, previous vaccination, number of outpatient visits in the previous year and timing of vaccination, and were balanced in the propensity model except the timing of vaccination. Compared with no vaccination, significant protection against any influenza A was observed from both HD-IIV3 (VE = 29%; 95%CI = 10%, 44%) and SD-IIV3/4 (VE = 24%; 95%CI = 5%, 39%); rVE = 18% (95%CI = 0%, 33%, SD as referent). When stratified by virus type, against A/H1N1, HD-IIV3 VE was 30% (95%CI = -7%, 54%), SD-IIV3/4 VE was 40% (95%CI = 10%, 61%), and rVE = -32%; (95%CI = -94%, 11%); Against A/H3N2, HD-IIV3 VE was 31% (95%CI = 9%, 47%), SD-IIV3/4 VE was 19% (95%CI = -5%, 37%), and rVE = 27%; (95% CI = 9%, 42%)., Conclusions: Among adults ≥65 years of age, recipients of standard and high dose influenza vaccines differed significantly in their characteristics. After adjusting for these differences, high dose vaccine offered more protection against A/H3N2 and borderline significant protection against all influenza A requiring outpatient care during the 2015-2018 influenza seasons., Competing Interests: Declaration of Competing Interest RKZ has/had a research grant from Sanofi Pasteur, Inc. RKZ and MPN have/had research grant funding from Merck & Co, Inc. MLG has received institutional research grant from AstraZeneca-MedImmune. MLJ reports research funding from Sanofi Pasteur, unrelated to the present work. ASM reports consulting fees from Sanofi, Seqirus and Roche. ETM reports consulting fees from Pfizer. HQM reports research funding from Seqirus unrelated to the present work. The other authors have no conflicts to report., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Study of interactions between the nervous system and immunity offers insights into the pathogenesis of Parkinson's disease (PD) and potential therapeutic strategies for neurodegenerative diseases. Studies on rodents have revealed regulatory mechanisms of microglial activation and T lymphocyte recruitment in PD. However, the mechanisms underlying chronic T lymphocyte infiltration into the brain after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) injection into a non-human primate (NHP) model of PD remain unknown. This study aimed to investigate changes in serum RANTES (regulated on activation, normal T cell expression and secretion) and analyze the chronic infiltration of T lymphocytes into the brain and microglia activation in NHPs at 48 weeks post-MPTP administration. We found selective and local chronic infiltration of CD4+ and CD8+ T lymphocytes, loss of dopaminergic neurons, dopamine transporter expression, chronic normalization of RANTES in the peripheral blood, and altered microglial morphology at 48 weeks after MPTP injection. This study confirms the involvement of CD4+ and CD8+ T lymphocyte infiltration in MPTP-induced NHP models of PD. Additionally, we corroborated previous findings regarding the mechanisms of T lymphocyte-induced neurodegeneration. The findings of chronic infiltration of T lymphocytes in our NHP model of PD provide novel insights into PD pathogenesis and the development of preventive and therapeutic agents., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Annually, about 80% of the Korean elderly aged ≥65 years receive influenza vaccination. Repeated annual vaccination has been suggested as an important factor of poor influenza vaccine effectiveness (VE), though reported conflicting results., Methods: During the consecutive A/H3N2-dominant influenza seasons between 2012 and 2015, we comparatively evaluated the VE (repeated vs. current season only) against laboratory-confirmed influenza, pneumonia and hospitalization in the elderly aged ≥65 years with influenza-like illness (ILI). Clinical and demographic data were collected prospectively, and vaccination status of prior and current seasons was verified using the immunization registry data of Korean Centers for Disease Control and Prevention., Results: During the first A/H3N2-dominant season in 2012-2013, influenza vaccine showed statistically significant effectiveness against influenza A infection only and when vaccinated in the current season only (VE 53%, 95% CI 15-77). In the latter two seasons (2013-2015 years), the adjusted VE for influenza A was indistinguishable between repeated vaccination and vaccination in the current season only., Conclusion: During consecutive influenza A/H3N2 epidemics, poor influenza vaccine effectiveness may be more pronounced among the elderly population with a high annual vaccine uptake rate., (Copyright © 2019. Published by Elsevier Ltd.)

A multi-centre, randomised, double-blinded, active-controlled, parallel-group clinical trial was carried out to assess the immunogenicity and safety of NBP608-a newly developed live-attenuated zoster vaccine in Korea-relative to Zostavax® in healthy adults aged 50 years or older. Immune responses to the vaccine were evaluated by glycoprotein enzyme-linked immunosorbent assay (gpELISA) and enzyme-linked immunosorbent spot (ELISPOT) assays using the interferon (IFN)-γ and interleukin (IL)-2 FluoroSpot kit 6 weeks after vaccination. Safety was monitored for 26 weeks based on subjects' diaries, spontaneous reports from subjects, and history taking by the investigators. A total of 845 subjects participated in the screening, and 823 received the vaccination (413 in the NBP608 group and 411 in the comparator group). The gpELISA-determined geometric mean fold rise from baseline to post NBP608 vaccination was 2.75 [95% confidence interval, CI (2.57, 2.94)]. The gpELISA-determined adjusted geometric mean titers (GMTs) of NBP608 and the comparator were 1346.37 [95% CI (1273.99, 1422.87)] and 1674.94 [95% CI (1585.35, 1769.58)], respectively. The adjusted GMT ratio of NBP608 to the comparator was 0.80 [95% CI (0.75, 0.87)]. There was no statistically significant difference between two groups in terms of the geometric mean spot numbers determined by IFN-γ and IL-2 ELISPOT assays at 6 weeks post vaccination (P = 0.7232, 0.3844). The incidence of adverse events (AEs) within 6 weeks post vaccination was 49.82% overall (410/823, 941 cases), 50.73% (209/412, 474 cases) in the NBP608 group, and 48.91% (201/411, 467 cases) in the comparator group. The difference in AE rate between the two groups was not statistically significant (P = 0.6010). Most AEs were mild, with a rate of 83.12% in the NBP608 group and 75.37% in the comparator group. Thus, NBP608 is non-inferior to Zostavax® in terms of inducing the immune response and can be safely administered to adults aged 50 years or older. ClinicalTrials.gov Identifier: NCT03120364., (Copyright © 2019. Published by Elsevier Ltd.)

Background: While herd effects and serotype replacement by childhood pneumococcal protein conjugated vaccines (PCVs) continues to accumulate worldwide, direct effectiveness of 23-valent pneumococcal polysaccharide vaccine (PPV23) against pneumococcal diseases in the elderly has been challenged. We estimated the direct effectiveness of PPV23 in the elderly population., Methods: For a hospital-based case-control study, cases of invasive pneumococcal disease (IPD) and non-bacteremic pneumococcal pneumonia (NBPP) (adults ≥ 65 years) were identified in 14 hospitals participated in the pneumococcal surveillance program from March 2013 to October 2015, following implementation of PPV23 national immunization program (NIP) for the elderly in the Republic of Korea. Controls matched by age, sex, and hospital were selected at ratios of 1:2 (IPD) or 1:1 (NBPP). Clinical data and vaccination records were collected. Vaccine effectiveness was calculated as (1-adjusted odds ratio) × 100., Results: We enrolled 148 IPD and 557 NBPP cases, and 295 IPD and 557 NBPP controls for analyses. Overall effectiveness of PPV23 against IPD was 28.5% [95% confidence interval (CI) -5.8%-51.6%] and against NBPP was 10.2% (-15.1-30.6) in all patients ≥ 65 years. However, in subgroup analysis of patients aged 65-74 years, PPV23 was protective against IPD [effectiveness 57.4% (19.4-77.5)] and against NBPP [effectiveness 35.0% (2.3-56.7)]. Furthermore, serotype-specific effectiveness of PPV23 against IPD was 90.6% (27.6-98.8) for PPV23-unique serotypes and 81.3% (38.6-94.3) for PPV23 serotypes excluding serotype 3., Conclusions: This study indicates that PPV23 with broad serotype coverage might be beneficial in preventing IPD and NBPP due to non-PCV13 serotypes in the young-elderly, with potentially increasing effectiveness in the setting of childhood PCV NIP., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Due to the increased availability of digital human models, the need for knowing human movement is important in product design process. If the human motion is derived rapidly as design parameters change, a developer could determine the optimal parameters. For example, the optimal design of the door panel of an automobile can be obtained for a human operator to conduct the easiest ingress and egress motion. However, acquiring motion data from existing methods provides only unrealistic motion or requires a great amount of time. This not only leads to an increased time consumption for a product development, but also causes inefficiency of the overall design process. To solve such problems, this research proposes an algorithm to rapidly and accurately predict full-body human motion using an artificial neural network (ANN) and a motion database, as the design parameters are varied. To achieve this goal, this study refers to the processes behind human motor learning procedures. According to the previous research, human generate new motion based on past motion experience when they encounter new environments. Based on this principle, we constructed a motion capture database. To construct the database, motion capture experiments were performed in various environments using an optical motion capture system. To generate full-body human motion using this data, a generalized regression neural network (GRNN) was used. The proposed algorithm not only guarantees rapid and accurate results but also overcomes the ambiguity of the human motion objective function, which has been pointed out as a limitation of optimization-based research. Statistical criteria were utilized to confirm the similarity between the generated motion and actual human motion. Our research provides the basis for a rapid motion prediction algorithm that can include a variety of environmental variables. This research contributes to an increase in the usability of digital human models, and it can be applied to various research fields., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

This study identified 8-azaguanine (8-AG) as a novel immunomodulatory drug (IMiD) through a high-throughput screen of the Preswick Chemical Library in a model of human NK cell cytotoxicity against blood cancer cells. 8-AG, originally developed as an antineoplastic agent, significantly increased the cytotoxicity of NK cells and was superior in this activity to previously known IMiDs, such as fluoxetine and amphotericin B, identified from the same library. IFN-γ expression was also slightly increased by 8-AG. Mechanistically, 8-AG increased conjugate formation between NK and target cells and subsequent cytolytic granule polarization, but not calcium mobilization, regulation of activating receptors, or expression of perforin or granzyme B. Thus, the antineoplastic activity of 8-AG should be re-evaluated in light of this novel potentiating effect on NK cells., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Because H5N1 influenza viruses continuously threaten the public health, the WHO has prepared various clades of H5N1 mock-up vaccines as one of the measures for pandemic preparedness. The recent worldwide outbreak of H5Nx virus which belongs to clade 2.3.4.4 and of which H5N6 subtype belongs and already caused human infection also increases the need of pandemic vaccine for such novel emerging viruses. In this study, we evaluated the protective efficacy and immunogenicity of an egg-based and inactivated whole-virus H5N8 (IDCDC-RG43A) developed by CDC containing HA and NA gene of the parent virus A/gyrfalcon/Washington/41088-6/2014. Mice vaccinated two times elicited low to moderate antibody titer in varying amount of antigen doses against the homologous H5N8 vaccine virus and heterologous intra-clade 2.3.4.4 H5N6 (A/Sichuan/26221/2014) virus. Mice immunized with at least 3.0 µg/dose of IDCDC-RG43A with aluminum hydroxide adjuvant were completely protected from lethal challenge with the mouse-adapted H5N8 (A/Environment/Korea/ma468/2015, maH5N8) as well as cleared the viral replication in tissues including lung, brain, spleen, and kidney. Vaccinated ferrets induced high antibody titers against clade 2.3.4.4 H5N8/H5N6 viruses and the antibody showed high cross-reactivity to clade 2.2 H5N1 but not to clade 1 and 2.3.4 viruses as measured by hemagglutinin inhibition and serum neutralization assays. Furthermore, administration of the vaccine in ferrets resulted in attenuation of clinical disease signs and virus spread to peripheral organs including lung, spleen, and kidney from high dose challenge with maH5N8 virus. The protective and immunogenic characteristic of the candidate vaccine are essential attributes to be considered for further clinical trials as a pre-pandemic vaccine for a potential pandemic virus., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

We aimed to characterize the lineages of influenza B viruses obtained from clinical specimens during the 2007-2014 seasons in South Korea. RT-PCR for the partial hemagglutinin gene of influenza B virus was performed on laboratory-confirmed influenza B samples from the 2007-2008 season to 2013-2014 season. A phylogenetic tree was generated, and current influenza vaccine strains for the Northern Hemisphere were used as representative strains of Victoria and Yamagata lineages. A total of 571 influenza B virus sequences were analyzed. During the 2009-2010 season, most of the circulating influenza B viruses matched the vaccine strain; 91.0% (91/100) of viruses belonged to the Victoria lineage. In the 2007-2008, 2011-2012, and 2013-2014 seasons, co-circulation of each influenza B lineage was found with a match ratio to the vaccine strain of 53.2% (42/79), 40.9% (63/154), and 58.3% (134/230), respectively. Overall, 41.7% (238/571) of the circulating influenza B viruses belonged to the lineage mismatching the vaccine strain. During the seven influenza seasons, influenza B epidemics were substantial in four seasons in South Korea. Significant mismatches of the vaccine and lineage of the circulating influenza B viruses were found. The current trivalent influenza vaccine may not be fully suitable for effective protection against influenza B., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Mast cells are critical effector cells in IgE-mediated allergic responses. The aim of this study was to investigate the anti-allergic effects of 3-[(aminocarbonyl)amino]-5-(3-fluorophenyl)-N-(3S)-3-piperidinyl-2-thiophenecarboxamide (AZD7762) in vitro and in vivo. AZD7762 inhibited the antigen-stimulated degranulation from RBL-2H3 (IC 50 , ∼27.9 nM) and BMMCs (IC 50 , ∼99.3 nM) in a dose-dependent manner. AZD7762 also inhibited the production of TNF-α and IL-4. As the mechanism of its action, AZD7762 inhibited the activation of Syk and its downstream signaling proteins, such as Linker of activated T cells (LAT), phospholipase (PL) Cγ1, Akt, and mitogen-activated protein (MAP) kinases (Erk1/2, p38, and JNK) in mast cells. In in vitro protein kinase assay, AZD7762 inhibited the activity of Lyn and Fyn kinases, which are important for the activation of Syk in mast cells. Furthermore, AZD7762 also suppressed the degranulation of LAD2 human mast cells (IC 50 , ∼49.9 nM) and activation of Syk in a dose-dependent manner. As observed in experiments with mast cells in vitro, AZD7762 inhibited antigen-mediated passive cutaneous anaphylaxis in mice (ED 50 , ∼35.8 mg/kg). Altogether, these results suggest that AZD7762 could be used as a new therapeutic agent for mast cell-mediated allergic diseases., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Mast cells are critical cells that prompt various allergic response-inducing factors, contributing to allergic diseases. While used as an antibiotic for livestock, there is no study on the effect of furaltadone on allergic response. This study investigated the effect of furaltadone on mast cells and passive cutaneous anaphylaxis (PCA). Furaltadone inhibited the degranulation of mast cells stimulated by antigen (IC 50 , ~ 3.9 μM), and also suppressed the production of tumor necrosis factor (TNF)-α and interleukin (IL)-4 in a concentration dependent manner. In addition, furaltadone inhibited allergic responses in an acute allergy animal model, PCA. Further investigation on the mechanism for these inhibitory effects of furaltadone found that the activities of Lyn/Syk and Syk-dependent downstream proteins such as mitogen-activated protein (MAP) kinases were inhibited by furaltadone in mast cells. Taken together, this study demonstrates that furaltadone inhibits the activation of mast cells by antigen via the suppression of the Lyn/Syk pathway and ameliorates allergic responses in vivo., (Copyright © 2018 Elsevier B.V. All rights reserved.)

During the outbreaks of highly pathogenic avian influenza (HPAI) H5N6 viruses in 2016 in South Korea, novel H5N8 viruses were also isolated from migratory birds. Phylogenetic analysis revealed that the HA gene of these H5N8 viruses belonged to clade 2.3.4.4, similarly to recent H5Nx viruses, and originated from A/Brk/Korea/Gochang1/14(H5N8), a minor lineage of H5N8 that appeared in 2014 and then disappeared. At least four reassortment events occurred with different subtypes (H5N8, H7N7, H3N8 and H10N7) and a chicken challenge study revealed that they were classified as HPAI viruses according to OIE criteria., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Concomitant administration of influenza and pneumococcal vaccines could be an efficient strategy to increase vaccine uptake among older adults. Nevertheless, immune interference and safety issues have been a concern when more than one vaccines are administered at the same time., Methods: Subjects aged ⩾60years were randomized in a 1:1:1 ratio to receive MF59-adjuvanted trivalent inactivated influenza vaccine (MF59-aTIV)+13-valent pneumococcal conjugate vaccine (PCV13) (Group 1), PCV13 alone (Group 2), or MF59-aTIV alone (Group 3). Hemagglutination inhibition (HI) and opsonophagocytic activity (OPA) assays were used to compare immunogenicity after single or concomitant vaccination., Results: A total of 1149 subjects (Group 1, N=373; Group 2, N=394; Group 3, N=382) were available for the assessment of immunogenicity and safety. All groups met immunogenicity criteria for the influenza vaccine in older adults with similar seroprotection rates, seroconversion rates, and geometric mean titer (GMT) fold-increases, irrespective of concomitant vaccination. For each pneumococcal serotype, OPA titers increased markedly after the PCV13 vaccination, irrespective of the concomitant influenza vaccination. After concomitant administration, the non-inferiority criteria of GMT ratios were met for all three influenza subtypes and 13 pneumococcal serotypes. No vaccine-related serious adverse events occurred., Conclusions: Concomitant MF59-aTIV and PCV13 administration showed no interference with antibody response and showed good safety profiles. (Clinical Trial Number - NCT02215863)., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Introduction: American Indians have the highest cigarette smoking prevalence of any racial/ethnic group in the U.S. There is currently no effective empirically based smoking-cessation program for American Indians. The purpose of this study was to determine if a culturally tailored smoking-cessation program, All Nations Breath of Life (ANBL), is more effective than a non-tailored cessation program among American Indian smokers., Design: A multisite RCT was conducted from September 2009 to July 2014; analysis was conducted in 2015., Setting/participants: Participants were rural or reservation-based American Indian smokers aged ≥18 years., Intervention: Smokers were group randomized to either the culturally tailored ANBL or non-tailored current best practices (CBP) for a total enrolled sample size of 463 (ANBL, n=243; CBP, n=220)., Main Outcome Measures: The primary outcome of interest was salivary cotinine-verified 7-day point prevalence smoking abstinence at 6 months. Results for both responder-only and intent-to-treat analyses for self-reported and cotinine-verified abstinence are presented., Results: Intention-to-treat, imputing all non-responses as smokers, the self-reported point prevalence abstinence rates at 12 weeks were 27.9% in the ANBL arm and 17.4% in the CBP arm (p=0.028). There was a statistically significant difference in self-reported 6-month intent-to-treat point prevalence abstinence rates between ANBL (20.1%) and CBP (12.0%) arms (p=0.029). None of the cotinine-verified results were statistically significant., Conclusions: The culturally tailored smoking-cessation program ANBL may or may not be an effective program in promoting cessation at 12 weeks and 6 months. Participants in the culturally tailored ANBL program were approximately twice as likely to quit smoking at 6 months compared with the CBP program, using self-reported abstinence., (Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction: National data indicate a higher prevalence of obesity among American Indian (AI) populations and greater disparity of morbidity and mortality among younger age groups compared with other ethnicities. Diet and physical activity are important obesity preventive behaviors, but no published data exist that describe these behaviors in relation to obesity in AI young adults at tribal colleges. Study purposes were to: (1) identify fruit and vegetable intake and physical activity practices of AI young adults from three U.S. tribal colleges according to BMI categories; (2) identify the accuracy of body weight perceptions; and (3) identify predictor variables for weight misperception., Methods: In this observational study during 2011-2014, a total of 1,256 participants were recruited from three participating U.S. tribal colleges to complete an online survey addressing issues related to diet, physical activity, and weight perception. Reported height and weight were used to calculate BMI categories, and differences between BMI categories were examined. Gender differences related to accuracy of weight perception by BMI categories were also examined. Analyses were conducted in 2016., Results: Based on self-reported height and weight, 68% of the sample was overweight or obese (BMI ≥25) and mean BMI was 28.9 (SD=6.9). Most did not meet recommendations for fruit intake (78.7%), vegetable intake (96.6%), or physical activity (65.6%). More than half (53.7%%) who were overweight/obese underestimated their weight category. Men more often underestimated their weight category (54.2%) than women (35.1%)., Conclusions: Interventions are needed to improve weight-related lifestyle behaviors of AI tribal college students., (Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to examine the association between serum zinc levels and several body composition factors in Korean adults., Methods: We used data from the Korean National Health and Nutrition Examination Survey, a cross-sectional survey of Korean civilians. Data from 1896 adults were analyzed., Results: Serum zinc levels in men with elevated waist circumference were higher than in those with normal waist circumference (152.1 ± 3.7 μg/dL versus 137.8 ± 2.2 μg/dL; P < 0.001) and serum zinc levels increased with increasing tertiles of total body fat percentage (134.2 ± 2.8 μg/dL, 142 ± 2.9 μg/dL, and 148 ± 2.7 μg/dL; P = 0.001). Among men with a normal waist circumference, serum zinc levels of those with the highest total body fat percentage were higher than in those with the lowest or medium total body fat percentage values (145.4 μg/dL versus 135.2 μg/dL; P = 0.029). In contrast, in men with an elevated waist circumference, no difference in serum zinc levels according to total body fat percentage was detected. There was no relationship between serum zinc levels and body composition factors in women., Conclusions: Body zinc status might be associated with the quantity and distribution of body fat in Korean men. Additional sex-specific studies are needed to determine whether the relationship of body zinc status with abdominal obesity and total body fat affects metabolic disorders and cardiovascular diseases., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Cell culture-derived influenza vaccines (CCIVs) have several important advantages over egg-based influenza vaccines, including shorter production time, better preservation of wild-type virus antigenicity and large-scale production capacity., Methods: A randomized, double-blind, phase 3 trial was undertaken to evaluate the immunogenicity and safety of a novel cell culture-derived inactivated, subunit, trivalent influenza vaccine (NBP607, SK Chemicals, Seongnam, Korea) compared to the control vaccine (AgrippalS1, Novartis Vaccines and Diagnostics Srl, Siena, Italy) among healthy adults aged 19 years or older (Clinical trial Number-NCT02344134). Immunogenicity was determined at pre-vaccination, 1 month and 6 month post-vaccination by the hemagglutination inhibition assay. Solicited and unsolicited adverse events were assessed after vaccination., Results: A total of 1156 healthy subjects were recruited. NBP607 met all of the criteria of Committee for Medicinal Products for Human Use (CHMP) at 21 days post-vaccination. Contrary to NBP607, the control vaccine did not satisfy the seroconversion criteria for influenza B irrespective of age. Although the geometric mean titer for each influenza subtype declined gradually, seroprotection rate still remained ≥80% for all subtypes up to six month after NBP607 administration. NBP607 recipients met the seroprotection criteria for all three influenza subtypes up to 6 month post-vaccination. There was no significant difference in the occurrence of adverse events between the NBP607 and control groups., Conclusion: NBP607, a novel CCIV, showed excellent immunogenicity that lasted ≥6 months after vaccination and had tolerable safety profiles. In particular, NBP607 was more immunogenic against influenza B compared to the control, an egg-based subunit vaccine., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: To investigate the role of S100A3 and the effect of S100A3 inhibition on human castration-resistant prostate cancer (CRPC) cells by using in vitro and in vivo functional assays., Materials and Methods: Using human CRPC cells (PC3 and DU145), S100A3 expression levels were assessed by reverse transcription-polymerase chain reaction and Western blot analysis. After S100A3-specific small interfering ribonucleic acid (RNA) treatment, cell viability was determined by Cell Counting Kit-8 assay, and apoptotic cell fractions were evaluated by flow cytometry. The invasive properties of these cells and the expression pattern of matrix metalloproteinases (MMPs) were assessed using transwell migration assays, reverse transcription-polymerase chain reaction, and gelatin zymography. Finally, the in vivo efficacy of S100A3 inhibition on human CRPC cells was investigated using human tumor xenograft models in nude mice., Results: Human CRPC cells showed overexpression of S100A3, and its suppression reduced cell viability owing to apoptotic cell death. Additionally, S100A3 inhibition decreased the invasiveness of human CRPC cells. Moreover, MMP-2 and MMP-9 were downregulated in PC3, whereas only MMP-9 was downregulated in D145 after S100A3 inhibition. In human CRPC xenograft models, we noted a marked reduction in tumor growth in mice injected with S100A3 short hairpin RNA-transfected PC3 and DU145 cells., Conclusion: Human CRPC cells showed upregulation of S100A3 expression, and S100A3 inhibition reduced tumor cell viability. S100A3 inhibition reduced invasion capability with downregulation of MMP expression. More importantly, S100A3 inhibition resulted in tumor growth suppression in human CRPC xenograft models, suggesting S100A3 could serve as a novel therapeutic target for the treatment of human CRPC., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To evaluate the in vitro and in vivo effects of escin on human castration-resistant prostate cancer (CRPC) cells, PC-3 and DU-145., Materials and Methods: The inhibition of cell proliferation and its mechanism were assessed through a cytotoxicity assay, flow cytometry, and Western blot. The in vivo efficacy of escin in CRPC cells was assessed using a xenograft tumor model subcutaneously established in BALB/c nude mice., Results: The treatment with escin significantly reduced cell viability of CRPC cells in a dose- and time-dependent manner. Escin induced apoptosis in a time-dependent manner, which was accompanied by increases in pro-apoptotic (BCL-2 associated X protein, cleaved-caspase3, and cleaved-poly [adenosine diphosphate-ribose] polymerase) proteins and decreases in antiapoptotic (X-linked inhibitor of apoptosis protein, cellular inhibitor of apoptosis protein-1, cellular inhibitor of apoptosis protein-2B-cell leukemia/lymphoma-2, and B-cell lymphoma-extra large) proteins. Escin induced G2/M-phase cell cycle arrest and thus led to a significant decrease in the expression of cyclinB1 and its activating partner cyclin-dependent kinase 1, with the concomitant induction of p21. In addition, escin significantly inhibited the growth of CRPC cells in xenograft models., Conclusion: The results show that escin induced cytotoxic effects on CRPC cells through the induction of apoptosis and G2/M cell cycle arrest, indicating it may be a novel therapeutic agent for CRPC., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Introduction: Although the relationship between risk perceptions and quit intentions has been established, few studies explore the potential impact of smoking level on these associations, and none have done so among diversely-aged samples of multiple ethnicities., Methods: Participants, ranging in age from 25 to 81, were 1133 nondaily smokers (smoked ≥1 cigarette on 4 to 24days in the past 30days), 556 light daily smokers (≤10 cigarettes per day), and 585 moderate to heavy daily smokers (>10 cigarettes per day). Each smoking level comprised approximately equal numbers of African Americans, Latinos, and Whites. A logistic regression analysis, adjusted for sociodemographics, self-rated health, time to the first cigarette of the day and smoking level, was used to examine the association between risk perception (perceived risk of acquiring lung cancer, lung disease, and heart disease) and intention to quit (≤6months versus >6months/never). A second adjusted model tested moderation by smoking level with an interaction term., Results: Greater risk perception was associated with a higher odds of planning to quit within 6months (AOR=1.34, CI.95=1.24, 1.45). Smoking level did not moderate this association (p=.85)., Conclusions: Results suggest that educating all smokers, irrespective of their smoking level, about increased risk of developing smoking-related diseases might be a helpful strategy to enhance their intention to make a smoking quit attempt., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objective: To evaluate changes of nocturnal polyuria (NP) after holmium laser enucleation of the prostate (HoLEP) in patients with nocturia preoperatively., Patients and Methods: This retrospective study included patients who underwent HoLEP for benign prostatic hyperplasia and recorded 3-day frequency-volume chart strictly. Patients who had a history of prostate cancer, sleep apnea, renal failure, heart failure, or medication of desmopressin were excluded. Nocturia is defined as ≥ 1 void at night, and NP is defined by nocturnal polyuria index (NPI) >33%. Among 472 patients included in the final analysis, 352 men (74.6%) presented nocturia preoperatively. Among those, 205 men (58.2%) who had NP preoperatively were allocated to group NP, and 147 men who did not were allocated to group non-NP., Results: In total patients, nocturnal frequency was decreased significantly starting from 3 months after the HoLEP. In NP group, mean value of NPI decreased by 4.1% ± 10.7%, 6.0% ± 9.4%, 6.2% ± 9.5%, and 4.8% ± 11.4% at postoperative months 1, 3, 6, and 12, respectively. The proportion of patients who showed decreased NPI to the normal range (≤ 33%) were 32.5%, 36.1%, 37.7%, and 31.0% at postoperative months 1, 3, 6, and 12, respectively. On receiver operating characteristics curve analysis, an absolute reduction of NPI of ≥ 6.0% was shown as a significant predictor for improved nocturia (≥ 50% reduction of nocturnal frequency)., Conclusion: In our study, the improvement of NP after HoLEP was observed. This suggests that relieving lower urinary tract obstruction has a positive influence on NP, and it could be a new strategy for treatment of NP., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Introduction: American Indians (AI) have the highest smoking rates of any racial/ethnic group in the U.S. and have more difficulty quitting smoking. Little is known about the smoking characteristics of AI smokers. The present study compared the demographic and smoking characteristics of light (≤10 cigarettes per day; N=206) and moderate/heavy (11+ cigarettes per day; N=86) AI smokers participating in a cross-sectional survey about smoking and health., Methods: Multiple methods were used to recruit participants in attendance at powwows, health and career fairs, and conferences. A total of 998 AI (76% cooperation rate) completed a survey assessing general health, sociodemographics, traditional and commercial tobacco use, knowledge and attitudes related to cancer, source of health information and care and other health-related behaviors., Results: AI light smokers were younger and less likely to be married or living with a partner compared to moderate/heavy smokers. AI light smokers were less dependent on smoking and more likely to have home smoking restrictions. There were no differences with respect to number of quit attempts in the past year or the average length of their most recent quit attempt by light vs. moderate/heavy smoking. In addition, a similar proportion of light and heavy smokers reported using tobacco for traditional purposes such as ceremonial, spiritual and prayer., Conclusions: These findings highlight important differences between AI light and heavier smokers. Differences related to smoking characteristics such as level of dependence and home smoking restrictions have important implications for the treatment of AI smokers., (© 2013 Elsevier Ltd. All rights reserved.)

Angiogenesis in rheumatoid arthritis (RA) is one of the histological hallmarks, which is mediated by expression of vascular endothelial growth factor (VEGF) in RA synovium. VEGF expression is enhanced by TNF-α, the main pro-inflammatory cytokine in RA. B cell activating factor (BAFF) which plays a role in maturation and maintenance of B cells is also associated with autoimmune RA. Here, we investigated whether BAFF could regulate VEGF expression in TNF-α-stimulated synovium using MH7A synovial cells that are established by transfection with the SV40 T antigen. Changes in hBAFF and hVEGF were measured by western blotting, RT-PCR and luciferase promoter assay. When MH7A cells were treated with TNF-α, we observed that TNF-α increased the expression of hBAFF and hVEGF. TNF-α also increased transcriptional activity of hBAFF and hVEGF as judged by luciferase promoter assay. Inhibition of hBAFF expression with BAFF-siRNA decreased transcriptional level and activity of hVEGF. In addition, when c-fos expression was inhibited by the transfection of MH7A cells with c-fos-siRNA, data showed that transcriptional level and activity of both hBAFF and hVEGF were attenuated by the activation with TNF-α. Our results demonstrate for the first time that VEGF-mediated angiogenesis in RA could be controlled by TNF-α-induced BAFF expression through c-Fos. Data suggest that TNF-α-induced BAFF expression and BAFF-mediated VEGF expression in synovium may cooperate to maintain the capacity of such cells to protect B cells from apoptosis and the supply of nutrients and oxygen in inflammatory microenvironments., (Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: This is the first study to examine predictors of successful cessation in African American (AA) light smokers treated within a placebo-controlled trial of bupropion., Methods: We analyzed data from a randomized, double-blind, placebo-controlled trial of bupropion and health education for 540 African American light smokers. African American light smokers (≤10 cigarettes per day, cpd) were randomly assigned to receive 150mg bid bupropion SR (n=270) or placebo (n=270) for 7weeks. All participants received health education counseling at weeks 0, 1, 3, 5 and 7. Using chi-square tests, two sample t-tests, and multiple logistic regression analyses, we examined baseline psychosocial and smoking characteristics as predictors of cotinine-verified 7-day point prevalence smoking abstinence among study participants at the end treatment (Week 7) and at the end of follow-up (Week 26)., Results: Participants who received bupropion were significantly more likely to quit smoking compared to those who received placebo (OR=2.72, 95% CI=1.60-4.62, P=0.0002). Greater study session attendance (OR=2.47, 95% CI=1.76-3.46, P=0.0001), and smoking non-menthol cigarettes increased the likelihood of quitting (OR=1.84, 95% CI=1.01-3.36, P=0.05); while longer years of smoking (OR=0.98, 95% CI=0.96-1.00, P=0.05) and higher baseline cotinine (OR=0.97, 95% CI=0.95-0.99, P=0.002) significantly reduced the odds of quitting at Week 7. Conversely, at the end of follow-up (Week 26), treatment with bupropion vs. placebo (OR=1.14, 95% CI=0.65-2.02, P=0.64) was not significantly associated with quitting and type of cigarette smoked (menthol vs. non-menthol) did not appear in the final logistic regression model. Greater study session attendance (OR=1.96, 95% CI=1.44-2.66, P=0.0001); BMI (OR=1.03, 95% CI=1.00-1.07, P=0.04); and weight efficacy (OR=1.03, 95% CI=1.01-1.05, P=0.01) increased the likelihood of quitting at Week 26. Similar to our findings at Week 7, longer years of smoking (OR=0.96, 95% CI=0.94-0.99, P=0.01) and higher baseline cotinine (OR=0.97, 95% CI=0.95-0.99, P=0.02) significantly reduced the odds of quitting at Week 26., Conclusions: Baseline cotinine levels, number of years smoked and study session attendance are associated with both short- and long-term smoking cessation, while bupropion and the type of cigarette smoked were associated with quitting on short term only., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Influenza epidemics are accompanied by a considerable increase in hospitalization due to acute lower respiratory infection and exacerbation of underlying medical conditions. We estimated the effectiveness of the influenza vaccine at preventing hospitalization due to acute lower respiratory infection and new onset or acute exacerbation of chronic cardiopulmonary disease., Method: During the peak influenza period in 2010-2011, we performed a multicenter, case-control, retrospective cohort study of patients who were hospitalized due to newly developed pneumonia, bronchitis, and bronchiolitis, or new onset or acute exacerbation of asthma, COPD, ischemic heart disease, and CHF. Controls were selected from outpatients who visited study hospitals but who were not hospitalized during the same study period. Controls were matched 1:1 to cases based on age, gender, and date of hospital visit. Univariate and multivariate logistic regression analyses were used to determine the effectiveness of the influenza vaccine at decreasing hospitalization., Results: Between December 2010 and February 2011, 556 hospitalized subjects were identified. Age, gender, and body mass index (BMI) were similar between case and control groups. The influenza vaccination rate of the hospitalized and non-hospitalized patients was 42.4% and 52.2%, respectively (p<0.001). The overall vaccine effectiveness for preventing hospitalization was 32.5% (odds ratio 0.675, 95% confidence interval [CI] 0.486-0.937; p=0.019). Multivariate logistic analysis showed that influenza vaccination significantly reduced the risk of hospitalization, especially due to new onset or acute exacerbation of ischemic heart disease and CHF in patients aged 65 years and older (OR 0.274, 95% CI 0.114-0.658, p=0.004). The estimated vaccine effectiveness in these patients was 72.6%., Conclusion: Influenza vaccination reduced the rate of hospitalization among patients with underlying chronic heart disease, particularly those patients 65 years old and greater., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Osteoclasts, multinucleated bone-resorbing cells, are closely associated with bone diseases such as rheumatoid arthritis and osteoporosis. Osteoclasts are derived from hematopoietic precursor cells, and their differentiation is mediated by two cytokines, including macrophage colony stimulating factor and receptor activator of nuclear factor κB ligand (RANKL). Previous studies have shown that arctigenin exhibits an anti-inflammatory effect. However, the effect of arctigenin on osteoclast differentiation is yet to be elucidated. In this study, we found that arctigenin inhibited RANKL-mediated osteoclast differentiation in bone marrow macrophages in a dose-dependent manner and suppressed RANKL-mediated bone resorption. Additionally, the expression of typical marker proteins, such as NFATc1, c-Fos, TRAF6, c-Src, and cathepsin K, were significantly inhibited. Arctigenin inhibited the phosphorylation of Erk1/2, but not p38 and JNK, in a dose-dependent manner. Arctigenin also dramatically suppressed immunoreceptor tyrosine-based activation motif-mediated costimulatory signaling molecules, including Syk and PLCγ2, and Gab2. Notably, arctigenin inhibited the activation of Syk through RANKL stimulation. Furthermore, arctigenin prevented osteoclast differentiation in the calvarial bone of mice following stimulation with lipopolysaccharide. Our results show that arctigenin inhibits osteoclast differentiation in vitro and in vivo. Therefore, arctigenin may be useful for treating rheumatoid arthritis and osteoporosis., (Copyright © 2012 Elsevier B.V. All rights reserved.)

We describe a hydrogel patterning and transferring (HPT) method that facilitates the quantitative analysis of synthetically engineered genetic circuits within bacterial cells. The HPT method encapsulates cells in the alginate hydrogel patterns by using polydimethylsiloxane (PDMS) template. Then, the hydrogel-encapsulated cell patterns are transferred onto an agarose hydrogel substrate that encapsulates inducer chemicals or bacterial cells. Using the HPT method, we demonstrate that inducers in the agarose hydrogel substrate regulate gene expression of the patterned cells for qualitative analysis by activating the promoters of fluorescence protein genes. In addition, we demonstrate that the HPT method can be used for the analysis of the cross-talk between genetic circuits and the concentration-dependent gene expression and regulation because the agarose hydrogel substrate can produce concentration gradients of inducers. Lastly, we demonstrate that the HPT method can be applied to investigating intercellular communication between neighboring cells with a wide range of cell densities. Since the HPT method is simple to deal with but versatile and powerful to quantitatively analyze genetic circuits in living cells in many controllable manners, we believe that the method can be widely used for the rapid advancement of synthetic, molecular, and systems biology., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Smoking menthol cigarettes is more prevalent among African Americans (AA) compared to Whites. Menthol has been found to be inversely related to smoking cessation among AA, yet little is known about the factors associated with menthol smoking among AA light smokers. This study examines baseline demographic, psychological, and smoking factors associated with smoking menthol cigarettes among AA light smokers (≤10 cigarettes per day)., Methods: Participants (n=540) were enrolled in a double blind, placebo-controlled randomized trial of bupropion in combination with health education counseling for smoking cessation. Bivariate differences between menthol and non-menthol smokers were explored and baseline factors associated with smoking menthol cigarettes were identified., Results: Participants averaged 46.5 years in age, predominantly female (66.1%), and smoked an average of 8.0 cpd (SD=2.5). The majority (83.7%) smoked menthol cigarettes. In bivariate analysis, menthol cigarette smokers were younger (mean age: 45 vs. 52 years p<0.0001), were more likely to be female (68% vs. 52% p=0.003) and had smoked for shorter duration (28 vs. 34 years p<0.0001) compared to non-menthol smokers. While depression and withdrawal scores were slightly higher and exhaled carbon monoxide values were lower among menthol smokers, the differences were not statistically significant., Conclusions: Among AA light smokers, younger individuals and females were more likely to smoke menthol cigarettes and may be more susceptible to the health effects of smoking. Appropriately targeted health education campaigns are needed to prevent smoking uptake in this high-risk population., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

We utilized a commercially available materials printer to investigate synthetic multicellular cell-to-cell communication because inkjet printing technology makes it easy to print spatiotemporal patterns of soluble biomolecules and live cells. Since cells are genetically programmed to communicate with one another via synthetic biology, cell signaling molecules secreted by one cell microcolony can induce two neighboring cell microcolonies to respond by expressing or stopping the expression of fluorescent protein genes. In this work, we not only characterize the printing parameters such as the initial seeding numbers, spacing distances, microcolony sizes, printing timings, and printed patterns of cells but also demonstrate that the use of the proposed printing technology can provide a useful means for many synthetic biologists to simplify and speed up the investigation of cell-to-cell communication between synthetic bacterial cells., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

The 2009 influenza pandemic was caused by a novel triple-reassortant influenza A/H1N1 virus that was further recombined with a Eurasian pig flu virus. Vaccination is a key countermeasure for disease; however, little data assessing vaccine effectiveness (VE) against the pandemic H1N1 virus are available. We conducted a matched case-control study to assess effectiveness of the 2009 influenza A/H1N1 monovalent vaccine against laboratory-confirmed, medically attended influenza patients. Subjects included in the study were ≥ 10 years of age and were treated at five university hospitals in the Republic of Korea (ROK) from December 2009 through March 2010. For subjects visiting outpatient clinics with influenza-like illness (ILI), real time reverse transcription polymerase chain reaction (rRT-PCR) was used to diagnose 2009 H1N1 influenza virus infection. Subjects with positive rRT-PCR were classified as cases, while those testing negative were controls. A valid vaccination corresponded to ≥ 14 days between receiving a dose of vaccine and symptom onset. Overall, 416 ILI subjects were analyzed, and 60 (14.4%) were vaccinated with the 2009 influenza A/H1N1 monovalent vaccine. The overall VE against pandemic 2009 A/H1N1 virus illness after adjustment for age group and presence of chronic medical conditions was 73.4% (95% confidence interval [CI]=49.1-86.1%). Both vaccine formulations (unadjuvanted and MF-59 adjuvanted) showed a statistically significant VE. In conclusion, the 2009 influenza A/H1N1 monovalent vaccine was substantially protective against pandemic influenza in the ROK during the 2009-2010 season., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

In a pandemic, the development of an effective influenza vaccine is the most important subject from the view of public health. This study was performed to evaluate the immunogenicity and safety of inactivated, monovalent H1N1 2009 vaccine (Green Cross Corporation, Yongin, Korea) among healthy adults aged 19-64 years (Group 1) and the elderly aged ≥ 65 years (Group 2) in a two-dose regimen, 21 days apart. At baseline, 28 of 454 participants (6.1%) had hemagglutination-inhibition titers of ≥ 1:40 with no significant difference between age groups (p=0.27). There was an apparent dose-dependent antibody response; participants receiving the dose of 30 μg hemagglutinin (HA) showed higher geometric mean titers (GMTs) than the 15 μg HA group in both age groups. Despite the rates of seroprotection and seroconversion were significantly higher with 30 μg HA formulation than 15 μg HA formula in Group 2, there was no definite difference in Group 1 irrespective of vaccine formula. Significant GMT elevation after the second dose was not noted in either age group, regardless vaccine formulations. No deaths, vaccine-related serious adverse events, or immediate unsolicited adverse reactions occurred during the study periods., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

The elderly have been considered as the priority group for influenza vaccination, but their influenza vaccine-induced antibody was believed to decline more rapidly. Long-term immunogenicity of the influenza vaccine among the elderly was evaluated as compared to young adults. Serum hemagglutinin inhibition (HI) titers were determined at pre- and post-vaccination periods (at 1, 6, and 12 months after vaccination). Of the 1018 subjects, 716 (70.3%) were followed up during a 12-month period. Seroprotection rates at 1 month post-vaccination ranged from 70.1% to 90.3% depending on the age group and influenza vaccine virus strain. At 6 months post-vaccination, seroprotection rates for all three strains had declined significantly in adults >or=65 years (P<0.01), but still met the EMEA criteria. Low pre-vaccination HI titer (<1:40) and advanced age were associated with early decline of HI titers, falling below seroprotective levels around 6 months after vaccination., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Background: The occurrence of herpes zoster can deteriorate the quality of life considerably, resulting in high disease burden. While Korea is assumed to have high disease burden of herpes zoster, there has been no researches analyzing this., Objectives: We performed this study to investigate the disease burden of herpes zoster in the Korean population as a whole., Study Design: We used the database of the Health Insurance Review & Assessment Service of Korea and analyzed the data of patients who had herpes zoster as a principal diagnosis during the period from 2003 to 2007. We investigated the annual prevalence, rate of clinical visits, rate of hospitalization, and the pattern of medical services use. The socioeconomic burden of herpes zoster was calculated by a conversion into cost., Results: Rates of clinic visits and hospitalizations due to herpes zoster during the 5-year period from 2003 to 2007 were 7.93-12.54 per 1000 population and 0.22-0.32 per 1000 population, respectively. Prevalence rates according to age increased sharply after 50 years and reached a peak at 70 years. The total socioeconomic cost of herpes zoster was $75.9-143.8 million per year, increasing every year by 14-20%., Conclusions: There is a heavy socioeconomic burden due to herpes zoster in Korea and indicate that appropriate policies need to be established to reduce this burden. Additional researches are also necessary to assess the safety, efficacy and cost-effectiveness of a herpes zoster vaccine in the Korean population., (Copyright 2010 Elsevier B.V. All rights reserved.)

Mast cells are responsible for IgE-mediated allergic responses. Although dietary flavonoid morin has been known to suppress mast cell activation, its in vivo anti-allergic activity and the underlying mechanisms remain are largely unknown. In this study, we determine whether morin suppresses IgE-mediated allergic responses in an animal model and its mechanism of action. Morin suppressed IgE-mediated PCA in mice (ED50 23.9 mg/kg) and inhibited degranulation and production of tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-4 in antigen (Ag)-stimulated mast cells. The mechanism of action was a follows. Morin inhibited the activating phosphorylation of spleen tyrosine kinase (Syk) and linker for activation of T cells (LAT) in rat basophilic leukemia (RBL)-2H3 cells and bone marrow-derived mast cells (BMMCs). Akt and the mitogen-activated protein (MAP) kinases, p38, extracellular signal-regulated kinase (ERK)1/2, and c-Jun N-terminal kinase (JNK) were inhibited as well. In vitro kinase assay indicated that Fyn kinase, not Lyn and Syk, was inhibited by morin in a dose-dependent manner (IC50 5.7 microM). In conclusion, the results suggest that morin suppresses the IgE-mediated allergic response by primarily inhibiting Fyn kinase in mast cells.

Soluble intercellular adhesion molecule-1 (sICAM-1), a circulating form of ICAM-1, has been known to be involved in the development of vascular diseases that are associated with vascular smooth muscle cell migration, such as hypertension and atherosclerosis. Here we investigated the contributions of sICAM-1 in promoting vascular migration in rat aortic smooth muscle cells (RASMCs). sICAM-1 increased RASMC migration, and this response was stronger in spontaneously hypertensive rats (SHRs) than in Wistar Kyoto (WKY) rats. The CD11a, CD11b, and CD18 subunits of ICAM-1 receptors were expressed in both SHRs and WKY rats; however, the expression levels of CD18 and CD11b were greater in SHRs than in WKY rats. The neutralization of the receptor subunits with anti-CD11a and -CD18 antibodies abolished the sICAM-1-increased migration. The treatment of inhibitors of spleen tyrosine kinase (Syk) and p38 mitogen-activated protein kinase suppressed the sICAM-1-stimulated migration of RASMCs. sICAM-1 also increased the sprout formation in aortic rings on Matrigel, and this response was inhibited by treatment with these inhibitors. The results suggest that sICAM-1 play crucial roles in vascular cell function through Syk pathways, and that the altered responses of sICAM-1 in RASMCs from SHRs may be mediated by the increased expression of the CD18 receptor.

Nitric oxide (NO) is a widely recognized mediator of physiological and pathophysiological signal transmission. In an attempt to better understand the molecular actions of NO in astrocytes, stress protein expression in response to NO donor sodium nitroprusside was investigated. Heme oxygenase-1 (HO-1) has been identified as an inducer of manganese superoxide dismutase (MnSOD), playing a cytoprotective role under the condition of nitrosative stress. We present evidence that the sequential induction of HO-1 and MnSOD protects astrocytes from NO toxicity: (1) both HO-1 and MnSOD expression were induced by NO; (2) NO-mediated increase in MnSOD activity was partly abolished by HO-1 inhibitor Zn(II) protoporphyrin IX (ZnPP); (3) pretreatment of astrocytes with a nontoxic dose of NO protected the cells against the later treatment with a toxic dose of NO; (4) inhibition of HO-1 by ZnPP sensitized astrocytes to the nontoxic dose of NO resulting in a marked cytotoxicity; and (5) adenovirus-mediated overexpression of MnSOD protected astrocytes from the NO toxicity. The molecular action of NO in astrocytes appears to be dose-dependent. While a high dose of NO exerts cytotoxicity leading to the tissue damage in the central nervous system, a low dose of NO may act as an important signaling molecule in astrocytes with concurrent induction of cytoprotective proteins such as HO-1 and MnSOD.

This paper investigates how BST204, a fermented ginseng extract, affects the expression and mechanism of cyclooxygenase-2 (COX-2). BST204 was prepared by incubating crude ginseng extract with ginsenoside-beta-glucosidase. Unexpectedly, BST204 had no effect on the level of COX-2 protein in unstimulated RAW 264.7 cells, and it suppressed the level of COX-2 protein and PGE(2) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. It did not show any suppressive effect, though, on the COX-2 mRNA level. To investigate the suppressive mechanism of COX-2 protein, the activating phosphorylation of p70 S6 kinase and 4E-BP1, which are important for translation, were measured. The phosphorylation of p70 S6 kinase, not 4E-BP1, was increased by LPS in a time-dependent manner, and was inhibited by BST204 in a dose-dependent manner. The expression of COX-2 protein, however, was partially suppressed by rapamycin, an upstream inhibitor of p70 S6 kinase. Therefore, this paper suggests that the suppression of COX-2 protein by BST204 was partially correlated with the inhibition of p70 S6 kinase activation.

We examined the smoking relapse curves for African-American smokers by level of smoking to characterize nicotine dependence in this population of smokers. This analysis was conducted from data originally collected to study differences in level of smoking among African-Americans at an inner-city health center in Midwest. Relatively little research has been conducted to clarify smoking and quitting patterns among African-American smokers. The median number of cigarettes smoked currently was 7 cigarettes per day (cpd) for light smokers and 20 cpd for the moderate to heavy smokers. The heavier smokers reported smoking at this rate longer than light smokers, 11 and 5 years, respectively. The major finding in this study is that African-American light smokers have abstinence rates very similar to heavier smokers and the median length of their most recent quit attempts were also similar. Therefore, stable light smokers may also need smoking cessation interventions similar to those used for heavier smokers in order to successfully stop smoking.

Background: Recent studies have shown that tobacco advertising leads to the onset of smoking among adolescents. However, much more still remains to be learned about the impact of tobacco advertising in the later transitions, mainly from experimentation to established smoking. In this study, we focused on the influence of tobacco advertising and promotions on the transition from experimentation to established smoking., Methods: Data were derived from a longitudinal survey of adolescents in California. Adolescents who were classified as experimenters at baseline were included in the analyses (N=965). Receptivity to tobacco advertising and promotions refers to the development of a positive affective response to the communication (e.g., having a favorite tobacco advertisement or being willing to use a promotional item)., Results: Approximately 32% of adolescents who were experimenters at baseline in 1993, progressed to established smoking by follow-up in 1996. Progression was higher among Caucasian (37.3%) than Hispanic (21.9%) or African-American (17.6%) adolescents. Adolescents who perceived that most of their peers smoked, had poor relationships with family members, and were exposed to smoking friends and family members were more likely to progress to established smoking at follow-up in 1996. In addition, adolescents who were receptive to advertising and believed that they could quit anytime were more likely to progress to established smoking than those who did not think they could quit anytime. Adolescents who were willing to use a promotional item and who believed that they could quit anytime had the highest rate of progression to established smoking (52%)., Conclusions: This study provides evidence that receptivity to tobacco advertising and promotions is an important factor in progressing from experimentation to established smoking among adolescents. Because perceived ability to quit made adolescents more likely to progress, counter-tobacco marketing campaigns should incorporate messages about addiction and difficulties associated with quitting.

New sildenafil analogues possessing a carboxylic acid group in the 5'-sulfonamide of the phenyl ring, 9a-l, were prepared from the readily available starting compounds 6a-b and cyclic amines 3-5 in a three-step sequence. In the enzyme assays, it has been shown that all the target compounds 9a-l proved to be more potent in inhibiting phosphodiesterase type 5 (PDE5) than sildenafil by 4-38-fold. The effects on the IC(50) values were investigated by varying the alkoxy group (R) of the phenyl ring, the sulfonamide type (X), and the length of the methylene chain linking the carboxylic acid, and the results were discussed in detail. From this study, we have clearly demonstrated that introduction of a carboxylic acid group to the 5'-sulfonamide moiety of the phenyl ring greatly enhanced PDE5 inhibitory activity, probably by mimicking the phosphate group of cGMP. The piperidinyl propionic acid derivative 9i, which showed the highest PDE5 inhibitory activity and comparable to better selectivity over PDE isozymes in comparison with sildenafil, has been selected for more detailed biological investigations.

New sildenafil analogues with an N-acylamido group at the 5'-position of the phenyl ring, 6a--e, were prepared from the readily available starting compound 2 in four straightforward steps. Enzyme assays demonstrated that all the target compounds 6a-e showed higher PDE5 inhibitory activities than sildenafil. It was observed that the PDE5 inhibitory activity was enhanced as the chain length of R group increased, but introduction of the branched alkyl groups such as isopropyl (6d) and cyclohexyl (6e) resulted in the drop of potency compared with 6c. In particular the N-butyrylamido derivative 6c exhibited the highest PDE5 inhibitory activity, and was about 6-fold more potent than sildenafil. However, all the compounds exhibited somewhat weak selectivity (1--3-fold) over PDE6, indicating that the compounds 6a--e have intrinsically lower selectivity than sildenafil.

New sildenafil analogues containing an ether ring fused into the phenyl moiety, 6a--d and 7a--d, were efficiently synthesized from the readily available starting materials, 1a--d and 2, in five steps. Ab initio calculations indicated that introduction of a cyclic ether to the phenyl group might enhance the co-planarity of the molecule. The torsional angles were calculated to be 2--3 degrees for the 5-membered cyclic ether derivatives, 6a, 6c, 7a, and 7c, and 12--16 degrees for the 6-membered ones, 6b, 6d, 7b, and 7d. On the other hand, sildenafil showed the least co-planarity with the torsional angle of 23 degrees compared with the target compounds, 6a--d and 7a--d. In the enzyme assay, however, the in vitro PDE 5 inhibitory activity was found out to be inversely related to the degree of co-planarity. In other words, the least planar sildenafil showed the highest activity, and the most planar 5-membered cyclic ether derivatives were least active by 100--200-fold compared with sildenafil. Our study clearly demonstrated that the open chain 2'-alkoxy group of the phenyl ring, although less effective for inducing the co-planarity, seemed to act as a much better lipophilic requirement than the cyclic alkoxy moiety.

A series of 2-amino-9-(3-acyloxymethyl-4-alkoxycarbonyloxybut-1-yl)purin es (1-8) and 2-amino-9-(3-alkoxycarbonyl-oxymethyl-4-alkoxycarbonyloxybut -1-yl)purines (9-12) were synthesized as potential prodrugs of penciclovir. Treatment of 6-deoxypenciclovir with trimethyl orthoacetate or triethyl orthopropionate (1.2 equiv) in DMF in the presence of p-TsOH.H2O (0.1 equiv) followed by quenching with excess H2O gave the corresponding mono-O-acetyl or mono-O-propionyl compound, 17 or 18, in excellent yields of 95 and 92%, respectively. Reactions of 17 or 18 with an appropriate alkyl (Me, Et, n-Pr, and i-Pr) 4-nitrophenyl carbonate (1.2 equiv) in pyridine in the presence of a catalytic amount of DMAP (0.1 equiv) at 80 degrees C afforded the monoacyl, monocarbonate derivatives of 6-deoxypenciclovir, 1-8, in 86 94% yields. Similar reactions of 6-deoxypenciclovir with 2.1 equiv of alkyl 4-nitrophenyl carbonate produced the dicarbonate derivatives 9 12 in 81-83% yields. Of the prodrugs tested in rats, 2-amino-9-(3-acetoxymethyl-4-isopropoxycarbonyloxybut-1-yl)purine (4) achieved the highest mean urinary recovery of penciclovir (36%), followed in order by compounds 2 (35%), 6 (35%), 7 (34%), 10 (34%), 8 (32%), 3 (32%), and famciclovir (31%). The mean urinary recovery of penciclovir and concentrations of penciclovir in the blood from 4 in mice were also slightly higher than those from famciclovir. The in vivo antiviral efficacy of 4 in HSV-1-infected normal BALB/c mice was higher than those of famciclovir and valaciclovir in terms of mortality (100, 80, and 40%) and mean survival time ( > 21, 13+/-5.0 (SEM), and 13+/-1.6 days). Compound 4 demonstrated an effective anti-hepadnaviral response with intrahepatic viral load being reduced by 90%, the viral supercoiled DNA levels reduced by 70% and Pre-S expression inhibited by 30% against duck hepatitis B virus (DHBV) in vivo, and did not cause any significant hepatotoxicity after 4 weeks of treatment.