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Purpose The expression of major histocompatibility complex class I (MHC I) has previously been reported to be negatively associated with estrogen receptor (ER) expression. Furthermore, MHC I expression, level of tumor-infiltrating lymphocytes (TILs), and expression of interferon (IFN) mediator MxA are positively associated with one another in human breast cancers. This study aimed to investigate the mechanisms of association of MHC I with ER and IFN signaling. Materials and Methods The human leukocyte antigen (HLA)-ABC protein expression was analyzed in breast cancer cell lines. The expressions of HLA-A and MxA mRNAs were analyzed in MCF-7 cells in Gene Expression Omnibus (GEO) data. ER and HLA-ABC expressions, Ki-67 labeling index and TIL levels in tumor tissue were also analyzed in ER+/human epidermal growth factor receptor 2- breast cancer patients who randomly received either neoadjuvant chemotherapy or estrogen modulator treatment followed by resection. Results HLA-ABC protein expression was decreased after β-estradiol treatment or hESR-GFP transfection and increased after fulvestrant or IFN-γ treatment in cell lines. In GEO data, HLA-A and MxA expression was increased after ESR1 shRNA transfection. In patients, ER Allred score was significantly lower and the HLA-ABC expression, TIL levels, and Ki-67 were significantly higher in the estrogen modulator treated group than the chemotherapy treated group. Conclusion MHC I expression and TIL levels might be affected by ER pathway modulation and IFN treatment. Further studies elucidating the mechanism of MHC I regulation could suggest a way to boost TIL influx in cancer in a clinical setting. [ABSTRACT FROM AUTHOR]

BACKGROUNDIt is unclear whether the level of serum hepatitis B virus (HBV) DNA at baseline affects the on-treatment risk of hepatocellular carcinoma (HCC) in hepatitis B e antigen-positive (HBeAg-positive), noncirrhotic patients with chronic hepatitis B (CHB).METHODSWe conducted a multicenter cohort study including 2073 entecavir- or tenofovir-treated, HBeAg-positive, noncirrhotic adult CHB patients with baseline HBV DNA levels of 5.00 log10 IU/mL or higher at 3 centers in South Korea between January 2007 and December 2016. We evaluated the on-treatment incidence rate of HCC according to baseline HBV DNA levels.RESULTSDuring a median 5.7 years of continuous antiviral treatment, 47 patients developed HCC (0.39 per 100 person-years). By Kaplan-Meier analysis, the risk of HCC was lowest in patients with baseline HBV DNA levels of 8.00 log10 IU/mL or higher, increased incrementally with decreasing viral load, and was highest in those with HBV DNA levels of 5.00-5.99 log10 IU/mL (P < 0.001). By multivariable analysis, the baseline HBV DNA level was an independent factor that was inversely associated with HCC risk. Compared with HBV DNA levels of 8.00 log10 IU/mL or higher, the adjusted HRs for HCC risk with HBV DNA levels of 7.00-7.99 log10 IU/mL, 6.00-6.99 log10 IU/mL, or 5.00-5.99 log10 IU/mL were 2.48 (P = 0.03), 3.69 (P = 0.002), and 6.10 (P < 0.001), respectively.CONCLUSIONOn-treatment HCC risk increased incrementally with decreasing baseline HBV DNA levels in the range of 5.00 log10 IU/mL or higher in HBeAg-positive, noncirrhotic adult patients with CHB. Early initiation of antiviral treatment when the viral load is high (≥8.00 log10 IU/mL) may maintain the lowest risk of HCC for those patients.FUNDINGPatient-Centered Clinical Research Coordinating Center (PACEN) (grant no. HC20C0062) of the National Evidence-based Healthcare Collaborating Agency; National R&D Program for Cancer Control through the National Cancer Center (grant no. HA21C0110), Ministry of Health and Welfare, South Korea. [ABSTRACT FROM AUTHOR]

• Abalone myoinhibitory peptides (Hdh-MIPs) act as ligands for the MIP receptor. • WX 5-7 Wamide motif in Hdh-MIPs is critical for Hdh-MIP signaling. • Hdh-MIP precursor and Hdh-MIPR are mainly expressed in the neural ganglia. • Hdh-MIPs inhibits larval metamorphosis but stimulates spawning behavior in abalone. Myoinhibitory peptides (MIPs) affect various physiological functions, including juvenile hormone signaling, muscle contraction, larval development, and reproduction in invertebrates. Although MIPs are ligands for MIP and/or sex peptide receptors (MIP/SPRs) in diverse arthropods and model organisms belonging to Lophotrochozoa, the MIP signaling system has not yet been fully investigated in mollusks. In this study, we identified the MIP signaling system in the Pacific abalone Haliotis discus hannai (Hdh). Similar to the invertebrate MIPs, a total of eight paracopies of MIPs (named Hdh-MIP1 to Hdh-MIP8), harboring a WX 5-7 Wamide motif, except for Hdh-MIP2, were found in the Hdh-MIP precursor. Furthermore, we characterized a functional Hdh-MIPR, which responded to the Hdh-MIPs, except for Hdh-MIP2, possibly linked with the PKC/Ca2+ and PKA/cAMP signaling pathways. Hdh-MIPs delayed larval metamorphosis but increased the spawning behavior. These results suggest that the Hdh-MIP signaling system provides insights into the unique function of MIP in invertebrates. [ABSTRACT FROM AUTHOR]

Objective: External beam radiation therapy (EBRT) with concurrent chemotherapy followed by intracavitary brachytherapy is the standard treatment in locally advanced cervical cancer. This study examined the brachytherapy utilization rate and evaluated the effect of brachytherapy on survival in cervical cancer patients in Korea. Methods: In this study, data from the Korea Central Cancer Registry and Korean National Health Insurance Service and data on mortality from Statistics Korea were linked and used. Patients with other cancers, distant metastasis at diagnosis, or unknown stage or who underwent hysterectomy were excluded. A total of 12,721 cervical cancer patients were analyzed in this study. Results: The brachytherapy utilization rate (%) was calculated as the proportion of patients who received brachytherapy among those who received curative EBRT. The brachytherapy utilization rate decreased from 84% in 2005 to 78% in 2013 (p<0.001). Brachytherapy utilization rates varied by region, ranging from 72% to 100% except for in Jeju Island, where the rate was 56%. The brachytherapy utilization rate was lower in patients older than 80 years; patients with localized disease, non-squamous cell carcinoma, or Charlson comorbidity index 3 or more; patients diagnosed after 2010; patients from certain regions; patients receiving medical aid; and patients who underwent gynecologic procedures. Multivariable Cox regression analysis showed that brachytherapy when added to curative EBRT was independently associated with better cancer-specific survival (CSS) and overall survival (OS) than curative EBRT only. Conclusion: The brachytherapy utilization rate decreased from 2005 to 2013 and varied by region in Korea. Brachytherapy use is independently associated with significantly higher CSS and OS in cervical cancer. [ABSTRACT FROM AUTHOR]

Background: Despite clinical evidence indicating poor muscle health in subjects with primary aldosteronism (PA), it is still unclear whether the role of aldosterone in muscle metabolism is direct or mediated indirectly via factors, such as electrolyte imbalance or impaired glucose uptake. As one approach to clarify this issue, we investigated the effect of aldosterone on in vitro myogenesis and the potential mechanism explaining it. Methods: Myogenesis was induced in mouse C2C12 myoblasts with 2% horse serum. Immunofluorescence, quantitative reversetranscription polymerase chain reaction, Western blot, viability, and migration analyses were performed for experimental research. Results: Recombinant aldosterone treatment suppressed muscle differentiation from mouse C2C12 myoblasts in a dose-dependent manner, and consistently reduced the expression of myogenic differentiation markers. Furthermore, aldosterone significantly increased intracellular reactive oxygen species (ROS) levels in myotubes, and treatment with N-acetyl cysteine, a potent biological thiol antioxidant, reversed the decrease of myotube area, myotube area per myotube, nucleus number per myotube, and fusion index due to aldosterone through decreasing oxidative stress. A binding enzyme-linked immunosorbent assay confirmed that mineralocorticoid receptor (MR) interacted with aldosterone in C2C12 myoblasts, while eplerenone, an MR inhibitor, blocked aldosterone-stimulated intracellular ROS generation during myogenesis and markedly attenuated the suppression of in vitro myogenesis by aldosterone. Conclusion: These findings support the hypothesis that hypersecretion of aldosterone, like PA, directly contributes to muscular deterioration and suggest that antioxidants and/or MR antagonists could be effective therapeutic options to reduce the risk of sarcopenia in these patients. [ABSTRACT FROM AUTHOR]

Although research has demonstrated that introducing computational thinking (CT) benefits young children, there has been a lack of systematic professional development (PD) opportunities for preschool teachers. The current study investigated the impact of Teaching through Interaction-Plus (TTI-P) on preschool teachers’ self-efficacy in teaching CT to preschool children, which focuses on high-quality teacher-child interaction. A quasi-experimental design was used to train 23 in-service preschool teachers and 111 children in the TTI-P program for 15 weeks. A control group consisting of six teachers and 75 children was also included. The results showed that the TTI-P training effectively increased preschool teachers’ self-efficacy in teaching CT. Additionally, children in the experimental group showed better CT skills than those in the control group. Based on findings from the current study, we offer implications for supporting preschool teachers with high-quality interaction that promotes critical thinking and problem-solving skills during CT activities. [ABSTRACT FROM AUTHOR]

Background: The C-C motif chemokine ligand 11 (CCL11) has been receiving attention as a potential pro-aging factor. Accordingly, it may be involved in muscle metabolism and sarcopenia, a key component of aging phenotypes. To clarify this potential, we investigated the effects of CCL11 on in vitro muscle biology and its clinical relevance for sarcopenia parameters in older adults. Methods: Myogenesis was induced in mouse C2C12 myoblasts with 2% horse serum. Human blood samples were collected from 79 participants who underwent a functional assessment. Thereafter, CCL11 level was measured using a quantikine ELISA kit. Sarcopenia was defined using the Asian-specific guideline. Results: Recombinant CCL11 treatment significantly stimulated myogenesis in a dose-dependent manner, and consistently increased the expression of myogenic differentiation markers. Among the C-C chemokine receptors (CCRs), CCR5, not CCR2 and CCR3, was predominantly expressed in muscle cells. Further, the CCR5 inhibitor blocked recombinant CCL11-stimulated myogenesis. In a clinical study, serum CCL11 level was not significantly different according to the status of sarcopenia, low muscle mass, weak muscle strength, and poor physical performance, and was not associated with skeletal muscle index, grip strength, short physical performance battery score, gait speed, and time to complete 5 chair stands, after adjusting for sex, age, and body mass index. Conclusion: Contrary to expectations, CCL11 exerted beneficial effects on muscle metabolism at least in vitro system. However, its impact on human muscle health was not evident, suggesting that circulating CCL11 may not be a useful biomarker for sarcopenia risk assessment in older adults. [ABSTRACT FROM AUTHOR]

Online teaching and learning have become widespread in higher education over the past two decades, and accelerated during the pandemic. Although online learning is expanding and has many benefits, instructors teaching online courses must deal with a variety of demands in online learning environments. Formative assessment and sense of community have been recognized as significant factors for enhancing meaningful student learning in online platforms. While existing technological resources create opportunities for students to engage with course materials and collaborative tasks, it can be quite daunting for a single instructor to meet the needs of a diverse student population. Typically, online instructors often do not have learning assistants (LAs), and/or lack models for how to effectively deploy these human resources in online environments. In this paper we describe how the creation of online instructional teams with specialized LA roles (online learning researchers [OLRs] and online instructional managers [OIMs]) can support formative assessment and community building in online courses. The OLRs and OIMs were trained to fulfill specialized roles to support formative assessment and the development of a more cohesive community of learners had a positive impact on asynchronous online courses at our institution. [ABSTRACT FROM AUTHOR]

Purpose: Though the socioeconomic burden of cancer on patients is increasing in South Korea, there is little research regarding the type of cancer that incurs the highest costs. This study analyzed the socioeconomic burden on cancer patients from 2011 to 2015 according to sex and age. Materials and Methods: A prevalence-based approach was applied utilizing claim data of the National Health Insurance Service in Korea to estimate the socioeconomic burden of cancer on patients. Patients who received treatment for cancer from 2011 to 2015 were the study subjects. The total socioeconomic burden of their disease and treatment was divided into direct and indirect costs. Results: There was an increase of 50.7% for 5 years, from 821,525 to 1,237,739 cancer patients. The cancer costs for men and women increased $8,268.4 million to $9,469.7 million and $3,626.5 million to $4,475.6 million, respectively. Furthermore, the 50-59-year-old age group accounted for a large portion of the total disease cost. Liver, lung, stomach, and colorectal cancers created the heaviest economic burdens on patients. Conclusion: Overall, this study indicates new policies for cancer prevention, early detection, and postcancer treatment management are necessary to help limit the costs associated with cancer, especially in the elderly, and provides a foundation for establishing cancer-related health care policies, particularly by defining those cancers with heavier disease burdens. [ABSTRACT FROM AUTHOR]

Purpose The purpose of this study was to determine the rate and outcomes of pregnancies subsequent to breast cancer in Korea, and the effect of such pregnancies on the prognosis of women who survived breast cancer and subsequently conceived. Materials and Methods We followed a total of 31,761 Korean women 45 years of age or younger who were treated for primary breast cancer from 2002 to 2010. We also included follow-up surveys that were conducted through December 2011. We identified recurrence and mortality from breast cancer using data linked to the Korea National Health Insurance database. We used propensity score matching of the study cohort to analyze the risks of recurrence and mortality from breast cancer depending on pregnancy. Results Within our sample, 992 women (3.1%) became pregnant after receiving treatment for breast cancer. Of those, 622 (67.5%) successfully delivered; the remaining 370 (32.5%) failed to deliver. After propensity score matching, we found that the women who became pregnant after breast cancer did not have a different risk of recurrence (hazard ratio [HR], 0.503; 95% confidence interval [CI], 0.434 to 0.584) and death (HR, 0.520; 95% CI, 0.397 to 0.681), compared with those who did not conceive after breast cancer treatment. Conclusion Our study is the first to report outcomes for Korean women who survived breast cancer and subsequently conceived. Women who survived breast cancer and subsequently became pregnant did not show a poorer survival outcome, compared with those who did not become pregnant. [ABSTRACT FROM AUTHOR]

OBJECTIVES: It was suggested that normalization of serum alanine aminotransferase (ALT) levels at 1 year of antiviral treatment is associated with a lower risk of hepatic events in patients with chronic hepatitis B (CHB). However, it remains unclear whether earlier ALT normalization is associated with lower hepatocellular carcinoma (HCC) risk, independent of fatty liver or cirrhosis and on-treatment virological response (VR), in patients with CHB. METHODS: We analyzed 4,639 patients with CHB who initiated treatment with entecavir or tenofovir using landmark analysis and time-dependent Cox analysis. We defined normal ALT as £35 U/L (men) and £25 U/L (women) and VR as serum hepatitis B virus DNA <15 IU/mL. RESULTS: During a median 5.6 years of treatment, 509 (11.0%) patients developed HCC. ALT normalization occurred in 65.6% at 1 year and 81.9% at 2 years and was associated with a significantly lowerHCC risk in landmark (P < 0.001) and time-dependent Cox analyses (adjusted hazard ratio [AHR] 0.57; P < 0.001). Compared with ALT normalization within 6 months, delayed ALT normalization at 6-12, 12-24, and >24 months was associated with incrementally increasing HCC risk (AHR 1.40, 1.74, and 2.45, respectively; P < 0.001), regardless of fatty liver or cirrhosis at baseline and VR during treatment. By contrast, neither earlier VR (AHR 0.93; P 5 0.53) nor earlier hepatitis B e antigen seroclearance (AHR 0.91; P 5 0.31) was associated with a significantly lower HCC risk. DISCUSSION: In patients with CHB treated with entecavir or tenofovir, earlier ALT normalization was independently associated with proportionally lower HCC risk, regardless of fatty liver or cirrhosis at baseline and ontreatment VR. [ABSTRACT FROM AUTHOR]

Background/Aims: A meta-analysis of randomized trials performed in healthy asymptomatic individuals suggested that overall mortality may increase after Helicobacter pylori eradication despite a significant decrease in the gastric cancer incidence and mortality rates. This retrospective population-based cohort study investigated if H. pylori treatment is associated with an increase in overall mortality in patients with hypertension. Methods: From the database of the Korean National Health Insurance Sample Cohort, we selected 198,487 patients treated for hypertension between 2002 and 2010. Those who received H. pylori treatment (H. pylori treatment cohort, 5,541 patients) were matched to those who did not (nontreatment cohort, 11,082 patients) at the ratio of 1 to 2. The primary outcome was the risk of overall mortality. The secondary outcomes were the risks of mortality due to cardiovascular disease, cerebrovascular disease, and cancer. The outcomes were evaluated from 6 months after H. pylori treatment to December 2013. A Cox proportional hazard model was used to estimate the hazard ratios (HRs). Results: During a median follow-up period of 4.8 years, death from any cause was reported in 4.1% of the patients in the H. pylori treatment cohort and 5.5% of the patients in the nontreatment cohort. The adjusted HR (aHR) for overall mortality in the H. pylori treatment cohort was 0.70 (95% confidence interval [CI], 0.60 to 0.82; p<0.001). With regard to cause-specific mortality, compared with the nontreatment cohort, the H. pylori treatment cohort had a lower risk of mortality due to cerebrovascular disease (aHR, 0.46; 95% CI, 0.26 to 0.81; p=0.007). The risks of mortality due to cancer and cardiovascular disease were not different between the cohorts. Conclusions: H. pylori treatment is not associated with an increase in overall mortality in patients treated for hypertension. [ABSTRACT FROM AUTHOR]

Salivary gland tumors usually appear in solitary mass in single salivary gland. The coexistence of tumors with different histological types occurring within a unilateral parotid gland is an extremely rare event. We experienced a case which two different types of malignant tumors developed at different time points in same gland; metachronous tumors. The second tumor was excised widely and reconstruction was performed by free tissue transfer. Sensory and motor nerve to the left cheek appeared to be intact, and circulation was adequate. This rare case was presented in this article. [ABSTRACT FROM AUTHOR]

Probiotics including Lactobacillus and Bifidobacterium spp. have been known to control the balance of gut microbiota and are positively effective to host animals. In this study, 32 bacterial strains were isolated from Norwegian forest cat (castrated, 12 years old) and Persian cat (castrated, 10 years old) which were privately owned and had indoor access. Among them, Lactobacillus rhamnosus CACC612 (CACC612) and Bifidobacterium animalis subsp. Lactis CACC789 (CACC789) were selected as potential probiotics. From the characterization of the two strains, they showed equivalent acid tolerance, similar cell adhesion rate on HT-29 monolayer cell line, and superior bile salt tolerance, compared with Lactobacillus rhamnosus GG (LGG). Subsequently, they exhibited antibacterial activities against a broad spectrum of pathogenic bacteria such as E. coli KCTC 2617, Salmonella Derby NCCP 12238, Salmonella enteritidis NCCP 14546, Salmonella typhimurium NCCP 10328, Clostridium difficile JCM 1296T. From evaluating host effects, the viability of the feline macrophage cell line (Fcwf-4) increased with the treatment of CACC612 or CACC789 (P < 0.05). The induced expression of immune-related genes such as IFN-γ, IL1β, IL2, IL4, and TNF-α by immune stimulation was significantly attenuated by the treatment of CACC612 or CACC789 (P < 0.05). In addition, when 52 clinical factors of sera from 21 healthy cats were analyzed using partial least-squares discriminant analysis (PLS-DA), the animals were markedly clustered before and after CACC612 or CACC789 feeding. In addition, hemoglobin and Mean corpuscular hemoglobin concentration (MCHC) were significantly increased after CACC612 feeding (P < 0.05). Conclusively, these results could contribute to understanding the functional effects of feline-originated probiotics and supporting their industrial applications. [ABSTRACT FROM AUTHOR]

Dorsal augmentation with synthetic implants is themost commonly performedrhinoplasty procedure, especially in the East-Asian region. However, as in all other surgical procedures, complications are inevitable. Complications that need to be managed surgically include displacement, deviation, suboptimal aesthetic outcome, extrusion, inflammation, infection, and changes in skin quality. Most complications can be easily managed with revision surgery. After the removal of the synthetic implant fromthe nasal dorsum, different dorsal implant materials such as dermofat, alloderm, or fascia-wrapped diced cartilage, conchal cartilage with perichondrial attachment, and costal cartilage are preferred. An irreversible change in the skin/soft tissue envelope poses a challenge that usually requires reconstructive surgery with a local flap. Therefore, early detection and prompt management of the complication are essential for minimizing the severity of the deformity and the complexity of the surgical procedures. [ABSTRACT FROM AUTHOR]

Background Acetylsalicylic acid (aspirin) and non-steroidal anti-inflammatory drugs (NSAIDs) have been associated with reduced risks for certain human cancers. However, the effects of aspirin and NSAIDs on head and neck squamous cell carcinoma (HNSCC) remain controversial, and the prognostic effects of these drugs in patients with HNSCC are largely unknown. This study examined the clinical impact of aspirin and NSAIDs on disease recurrence and survival in patients with HNSCC. Methods This study analysed a cohort of 1392 consecutive patients who received definitive treatment for previously untreated HNSCC at our tertiary referral center. Aspirin or NSAID use was considered positive if the patients were receiving aspirin or NSAID medication from HNSCC diagnosis to at least 1 year after treatment initiation. Cox proportional hazard models were utilised to determine the association of aspirin and/or NSAID use with recurrence, survival, and second primary cancer occurrence. Results Of 1392 patients, 81 (5.8%) and 89 (6.4%) received post-diagnosis treatment with aspirin and NSAIDs, respectively. After controlling for clinical factors, aspirin and NSAIDs were not significantly associated with recurrence, survival, or second cancer occurrence (P > 0.05). The cumulative dose of aspirin or NSAIDs did not alter survival outcomes (P > 0.05). Conclusion Our data illustrated that the use of aspirin or NSAIDs has no effect on survival or recurrence in patients with HNSCC. [ABSTRACT FROM AUTHOR]

Objectives Curative resection is not indicated for non-small cell lung cancer (NSCLC) with pleural seeding, which is classified as stage IV (M1a) disease. However, some patients with a presumably resectable main tumor are diagnosed with localized pleural seeding during surgery. Methods A retrospective analysis was performed of 3,975 patients who underwent surgery for NSCLC from 2000 to 2011. Among these cases, 78 (2.0%) patients had unexpected pleural seeding detected during surgery. Exploration with pleural biopsy was performed in 42 of these patients (exploration-only group) and pulmonary resection, including for the main tumor, was performed in 36 cases (resection group; sublobar resection in 12, lobectomy in 21, and pneumonectomy in 3 patients). Survival and cancer progression rates were estimated using the Kaplan-Meier method. Cox proportional hazard regression was used to evaluate prognostic factors associated with survival. Results Adenocarcinoma was the predominant histological type in both the exploration and resection groups (88.1 and 86.1%, respectively). Epidermal growth factor receptor expression was detected in 22 (52.4%) patients of the exploration group and 21 (58.3%) patients of the resection group. Baseline characteristics including age, sex, comorbidity, pulmonary function, and clinical T/N status were not significantly different between the two groups. There were no postoperative deaths in either group but postoperative complications occurred in two (4.8%) patients of the exploration group and three (8.3%) patients of the resection group. The overall 3- and 5-year survival rates in the exploration group were 41.1 and 15.2%, respectively, with a median survival time (MST) of 33 months, whereas they were 66.7 and 42.7%, respectively, in the resection group, with a 52-month MST (p = 0.012). Local and regional progression-free rates were significantly different (p < 0.001 and p = 0.029, respectively) between groups, platinumwhereas no difference was seen in the distant metastasis rates (p = 0.957). In multivariate survival analysis, surgical resection was the only significant prognostic factor (p = 0.01). Conclusions Pulmonary resection including the main tumor, regardless of resection extent, may increase long-term survival for NSCLC patients with localized pleural seeding first detected during surgery, without a significant increase in hospital mortality or morbidity. [ABSTRACT FROM AUTHOR]

Background: Arginine vasopressin has been shown to affect social and emotional behaviors, which is mediated by the arginine vasopressin receptor (AVPR1A). Genetic polymorphisms in the AVPR1A promoter region have been identified to be associated with susceptibility to social deficits in autism spectrum disorder (ASD). We hypothesize that alleles of polymorphisms in the promoter region of AVPR1A may differentially interact with certain transcriptional factors, which in turn affect quantitative traits, such as sociality, in children with autism. Methods: We performed an association study between ASD and polymorphisms in the AVPR1A promoter region in the Korean population using a family-based association test (FBAT). We evaluated the correlation between genotypes and the quantitative traits that are related to sociality in children with autism. We also performed a promoter assay in T98G cells and evaluated the binding affinities of transcription factors to alleles of rs7294536. Results: The polymorphisms--RS1, RS3, rs7294536, and rs10877969--were analyzed. Under the dominant model, RS1-310, the shorter allele, was preferentially transmitted. The FBAT showed that the rs7294536 A allele was also preferentially transmitted in an additive and dominant model under the bi-allelic mode. When quantitative traits were used in the FBAT, rs7294536 and rs10877969 were statistically significant in all genotype models and modes. Luciferase and electrophoretic mobility-shift assays suggest that the rs7294536 A/G allele results in a Nf-κB binding site that exhibits differential binding affinities depending on the allele. Conclusion: These results demonstrate that polymorphisms in the AVPR1A promoter region might be involved in pathophysiology of ASD and in functional regulation of the expression of AVPR1A. [ABSTRACT FROM AUTHOR]

WNT1-inducible-signaling pathway protein-1 (WISP-1) belongs to the family of cysteine rich 61/connective tissue growth factor/nephroblastoma overexpressed matricellular proteins, which are involved in various biological processes, including cell adhesion, proliferation, differentiation, angiogenesis and carcinogenesis. In the present study, the expression of WISP-1 was investigated, and its association with clinicopathological factors and prognosis in patients with oral squamous cell carcinoma (OSCC) was evaluated. Additionally, the role of WISP-1 in invasion and apoptosis of human OSCC cells was evaluated. Immunoreactivity of WISP-1 was increased in OSCC tissue compared with adjacent normal tissue samples. High expression of WISP-1 protein was observed in 24/84 (28.57%) OSCC specimens. Additionally, high WISP-1 expression was significantly associated with treatment failure (P=0.042). The 5-year overall survival rate was 33% in patients with high WISP1 expression, and 66% in patients with low WISP-1 expression. WISP-1 expression in the human OSCC SCC-1483 cell line was observed. Furthermore, WISP-1 knockdown using small interfering (si)RNA significantly reduced cell invasion and induced apoptosis compared with control siRNA-transfected cells. These findings suggested that WISP-1 is associated with tumor progression and poor prognosis by increasing tumor cell invasion and inhibiting cell apoptosis in human OSCC. [ABSTRACT FROM AUTHOR]

Background: We aimed to evaluate the potential benefits of the Leadership and Coaching for Health (LEACH) program on physical activity (PA), dietary habits, and distress management in cancer survivors.Methods: We randomly assigned 248 cancer survivors with an allocation ratio of two-to-one to the LEACH program (LP) group, coached by long-term survivors, or the usual care (UC) group. At baseline, 3, 6, and 12 months, we used PA scores, the intake of vegetables and fruits (VF), and the Post Traumatic Growth Inventory (PTGI) as primary outcomes and, for secondary outcomes, the Ten Rules for Highly Effective Health Behavior adhered to and quality of life (QOL), the Hospital Anxiety and Depression Scale (HADS), and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30).Results: For primary outcomes, the two groups did not significantly differ in PA scores or VF intake but differed marginally in PTGI. For secondary outcomes, the LP group showed a significantly greater improvement in the HADS anxiety score, the social functioning score, and the appetite loss and financial difficulties scores of the EORTC QLQ-C30 scales from baseline to 3 months. From baseline to 12 months, the LP group showed a significantly greater decrease in the EORTC QLQ-C30 fatigue score and a significantly greater increase in the number of the Ten Rules for Highly Effective Health Behavior.Conclusion: Our findings indicate that the LEACH program, coached by long-term survivors, can provide effective management of the QOL of cancer survivors but not of their PA or dietary habits.Trial Registration: Clinical trial information can be found for the following: NCT01527409 (the date when the trial was registered: February 2012). [ABSTRACT FROM AUTHOR]

In order to characterize the female or male transcriptome of the Pacific abalone and further increase genomic resources, we sequenced the mRNA of full-length complementary DNA (cDNA) libraries derived from pooled tissues of female and male Haliotis discus hannai by employing the Iso-Seq protocol of the PacBio RSII platform. We successfully assembled whole full-length cDNA sequences and constructed a transcriptome database that included isoform information. After clustering, a total of 15,110 and 12,145 genes that coded for proteins were identified in female and male abalones, respectively. A total of 13,057 putative orthologs were retained from each transcriptome in abalones. Overall Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analyzed in each database showed a similar composition between sexes. In addition, a total of 519 and 391 isoforms were genome-widely identified with at least two isoforms from female and male transcriptome databases. We found that the number of isoforms and their alternatively spliced patterns are variable and sex-dependent. This information represents the first significant contribution to sex-preferential genomic resources of the Pacific abalone. The availability of whole female and male transcriptome database and their isoform information will be useful to improve our understanding of molecular responses and also for the analysis of population dynamics in the Pacific abalone. [ABSTRACT FROM AUTHOR]

Objective: The risk of neonatal respiratory morbidity between indicated deliveries vs. spontaneous deliveries has not been consistent in previous studies, in spite of the traditional belief that chronic intrauterine stress might have protective effect on fetal lung maturation. We hypothesized that the heterogeneous etiology of indicated preterm delivery may obscure the relationship between the etiologies of preterm birth and neonatal respiratory morbidity. To address this issue, we divided the indicated preterm birth (PTB) into medically-indicated (without fetal compromise) PTB and maternal/fetal-indicated PTB, and compared the neonatal respiratory morbidity according to the etiology of late PTB. Study design: Neonatal respiratory morbidities were examined in neonates who were delivered between 34+0 and 36+6 weeks of gestation according to the etiology of PTB: 1) medically-indicated PTB (but without fetal compromise), 2) maternal/fetal-indicated PTB, or 3) spontaneous PTB such as preterm labor or preterm premature rupture of membranes. Results: A total of 710 late preterm neonates were included in the study population, including 31 cases of medicallyindicated PTB, 202 cases of maternal/fetal-indicated PTB, and 477 cases of spontaneous PTB. The rate of composite respiratory morbidity in cases of medically-indicated PTB is higher than both maternal/fetal-indicated PTB and spontaneous PTB (19% in medically-indicated PTB, 6% in maternal/fetal-indicated PTB, and 7% in spontaneous PTB). This difference between medically-indicated PTB and maternal/fetal-indicated PTB remained significant after adjustment for confounding variables. Conclusion: The medically-indicated PTB is associated with highest risk of neonatal respiratory morbidity in late PTB [ABSTRACT FROM AUTHOR]

Background: We aimed to evaluate the prognostic value of quality of life (QOL) for predicting survival among disease-free survivors of surgically-treated lung cancer after the completion of cancer treatment.Methods: We administered the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), the Quality of Life Questionnaire Lung Cancer Module (QLQ-LC13), Hospital Anxiety and Depression Scale (HADS), and Posttraumatic Growth Inventory (PTGI) to 809 survivors who were surgically-treated for lung cancer at two hospitals from 2001 through 2006. We gathered mortality data by linkage to the National Statistical Office through December 2011. We used Cox proportional hazard models to compute adjusted hazard ratios (aHRs) and 95 % confidence intervals (CIs) to estimate the relationship between QOL and survival.Results: Analyses of QOL items adjusted for age, sex, stage, body mass index, and physical activity showed that scores for poor physical functioning, dyspnea, anorexia, diarrhea, cough, personal strength, anxiety, and depression were associated with poor survival. With adjustment for the independent indicators of survival, final multiple proportional hazard regression analyses of QOL show that physical functioning (aHR, 2.39; 95 % CI, 1.13-5.07), dyspnea (aHR, 1.56; 95 % CI, 1.01-2.40), personal strength (aHR, 2.36; 95 % CI, 1.31-4.27), and anxiety (aHR, 2.13; 95 % CI, 1.38-3.30) retained their independent prognostic power of survival.Conclusion: This study suggests that patient-reported QOL outcomes in disease-free survivors of surgically-treated lung cancer after the completion of active treatment has independent prognostic value for long-term survival. [ABSTRACT FROM AUTHOR]

Livin, a member of the human inhibitor of apoptosis protein (IAP) family, is expressed at high levels in various human cancer tissues and may have prognostic significance. The aim of the present study was to evaluate the effect of Livin on tumor cell behavior and oncogenic signaling pathways in human hypopharyngeal squamous cell carcinoma (HSCC). Reverse transcription-quantitative polymerase chain reaction and western blot analyses were used to determine the mRNA and protein expression levels, respectively. A cell proliferation assay and cell cycle analysis were used to assess the functional effects of small interfering RNA-mediated Livin knockdown. Livin was overexpressed in fresh HSCC tissues, compared with the adjacent normal mucosa. Livin knockdown led to significantly reduced cell proliferation and cell cycle arrest in the G1 phase of the human HSCC cells. The expression levels of c-myc, cyclin D1, cyclin D3, cyclin-dependent kinase (CDK)4 and CDK6 were decreased. The phosphorylation levels of extracellular signal-regulated kinase 1/2, p38, c-Jun N-terminal kinase and Akt were also decreased by Livin knockdown in the HSCC cells. Taken together, the results of the present study suggested that Livin may enhance tumorigenesis by modulating the mitogen-activated/Akt signaling pathways in human HSCC. [ABSTRACT FROM AUTHOR]

Background: The emotional status of cancer patients is associated with disease course and treatment outcomes. In this study, the authors evaluated associations between the presence of pretreatment depression and pretreatment quality of life (QOL), nutritional status, and survival outcomes in patients with head and neck squamous cell carcinoma (HNSCC).Methods: For this prospective study, 241 patients with previously untreated HNSCC who underwent curative treatments were enrolled. Patients completed the Beck Depression Inventory (BDI)-II, the European Organization for Research and Treatment of Cancer (EORTC) 30-item Core QOL Questionnaire (QLQ-C30), and the EORTC QLQ Head and Neck Cancer module (QLQ-H&N35). EORTC QLQ scores were compared between depressive and nondepressive patients, as determined according to pretreatment BDI-II scores ≥ 14 and <14, respectively. Univariate and multivariate analyses were performed to assess whether the presence of depression was associated with overall survival, disease-free survival (DFS), or posttreatment changes in nutritional status and laboratory data.Results: Pretreatment depression was present in 60 patients (24.9%). In depressive and nondepressive patients, the 3-year overall survival rates were 70.8% and 82.7%, respectively (P = .045), and the 3-year DFS rates were 63.5% and 79.1%, respectively (P = .015). After controlling for clinical factors, the presence of depression was predictive of 3-year DFS (P = .032). EORTC QLQ-C30 and QLQ-HN35 scores on all items except feeding tube, nutritional supplement, and problem with mouth opening differed between depressive and nondepressive patients (P < .05). Depressive patients had lower pretreatment serum albumin levels than nondepressive patients (P < .05).Conclusions: There was a significant correlation between pretreatment depression and pretreatment QOL, nutritional status, and survival outcomes in patients with HNSCC. [ABSTRACT FROM AUTHOR]

Background: In humans, sex-determining region-Y (SRY) related high-mobility-group box 4 (SOX4) is linked to development and tumorigenesis. SOX4 is over-expressed in several cancers and has prognostic significance. This study evaluated whether SOX4 affects oncogenic behavior and chemoradiotherapy response in head and neck squamous cell carcinoma (HNSCC) cells, and documented the relationship between its expression and prognosis in oral squamous cell carcinoma (OSCC).Methods: We used small interfering RNA in HNSCC cells to evaluate the effect of SOX4 on cell proliferation, apoptosis, chemoradiation-induced apoptosis, invasion, and migration. SOX4 expression in OSCC tissues was investigated by immunohistochemistry.Results: SOX4 knockdown (KO) decreased cell proliferation and induced apoptosis by activating caspases-3 and -7, and poly-ADP ribose polymerase and suppressing X-linked inhibitor of apoptosis protein in HNSCC cells; it also enhanced radiation/cisplatin-induced apoptosis; and suppressed tumor cell invasion and migration. Immunostaining showed SOX4 protein was significantly increased in OSCC tissues compared with adjacent normal mucosa. SOX4 expression was observed in 51.8 % of 85 OSCC tissues, and was significantly correlated with treatment failure (P = 0.032) and shorter overall survival (P = 0.036) in patients with OSCC.Conclusions: SOX4 may contribute to oncogenic phenotypes of HNSCC cells by promoting cell survival and causing chemoradioresistance. It could be a potential prognostic marker for OSCC. [ABSTRACT FROM AUTHOR]

Purpose This study estimates the socioeconomic cost and burden for breast cancer patients in Korea between 2007 and 2010. Materials and Methods This study used a prevalence-based approach to estimate the cost of breast cancer. Breast cancer patients were defined as those who were hospitalized or have visited an outpatient clinic during the period from 2007 to 2010. The socioeconomic costs of breast cancer were subdivided into two costs: direct and indirect. Results From 2007 to 2010, the prevalence of treated breast cancer increased from 7.9% to 20.4%. The total socioeconomic costs incurred by breast cancer increased by approximately 40.7% from US $668.49 million in 2007 to US $940.75 million in 2010. The direct medical care costs for 2010 were 1.4 times greater (US $399.22 million) than for 2007 (US $278.71 million). The direct non-medical costs rose from US $50.69 million in 2007 to US $75.83 million in 2010, a 49.6% increase. Regarding the economic burden of breast cancer, the total indirect costs were US $339.09 million in 2007 and increased by 37.3% to US $465.70 million in 2010. In the sensitivity analysis, with the annual discount rate for each year ranging from 0%-5%, the costs increased 1.1-1.2 times. Conclusion Due to the growing incidence of breast cancer, the annual prevalence and related costs are increasing. We must strive to reduce the socioeconomic burden of breast cancer through preventive measures and early screening.The processing and mechanical properties of potassium-based geopolymer (K20-Al203*4Si02-llH20) composites containing 1/2 inch long basalt chopped fiber reinforcement have been evaluated and compared to previous data for 1/4 inch long basalt fiber reinforcement. Geopolymer composite test samples were hand fabricated at ambient temperature and cured in a constant humidity, 50°C temperature/humidity chamber. The effects of varying weight percent of fiber reinforcement and heat treatment temperature for fixed fiber content were examined in this study. Reinforcement by ten weight percent basalt chopped fibers significantly improved the room temperature average bend strength over that of pure geopolymer from roughly 2 MPa to 27 MPa. The composite was able to preserve 75% bend strength after heat treatment to 200°C and 12% strength after heat treatment to 600°C, with only five weight percent of fiber reinforcement. Addition of 1/2 inch long fibers showed 20-50% strength increases over the use of 1/4 inch fibers. A Weibull statistical analysis was performed showing a significant increase in reliability with increasing amounts of chopped basalt fiber reinforcement. [ABSTRACT FROM AUTHOR]

Purpose: Previously, we found that the pressor response to muscle metaboreflex activation is enhanced in prehypertension and associated with peripheral vasoconstriction. However, mechanisms underlying this exaggerated response are not clear. Therefore, we tested the hypothesis that activation of this reflex is augmented owing to increased production of muscle metabolites (i.e., lactate, K+, and H+). Methods: Twenty-two men (11 normotensive and 11 prehypertensive) were studied. Changes in cardiac output (...), mean arterial pressure (MAP), and total peripheral resistance (TPR) were compared between the two groups during static exercise (SE) and postexercise muscular ischemia (PEMI). Subjects completed 2 min of SE at 50% of maximal voluntary contraction (MVC) followed by 2 min of PEMI. Venous blood samples for determination of metabolites and hormones (catecholamines, vasopressin, and plasma renin activity) were taken from the exercising and nonexercising arm, respectively. Results: Mean arterial pressure responses to SE (39 ± 3 vs 31 ± 2 mm Hg) and PEMI (24 ± 3 vs 19 ± 3 mm Hg) were significantly higher in the prehypertensive group. Increases in lactate and decreases in pH during PEMI were seen in both groups. However, changes in these variables were greater in the prehypertensive group (lactate, 50.1 ± 6.2 vs 32.8 ± 7.6 mg⋅dL-1; pH, -0.06 ± 0.02 vs -0.01 ± 0.01) (P < 0.05). Postexercise muscular ischemia did not evoke increases in hormones in either group. Conclusions: Compared to the normotensive group, the augmented pressor response to the metaboreflex in the prehypertensive group was associated with greater production of muscle metabolites that activate its afferent arm. The augmented response was not associated with activation of the vasopressin and renin-angiotensin systems and greater activation of the sympathetic nervous system was not apparent. Consequently, additional factors specific to prehypertension, such as arterial stiffness, may have been involved. [ABSTRACT FROM AUTHOR]

Heat shock factor 1 (HSF1) is a transcription factor for heat shock proteins (HSPs) expression that enhances the survival of cancer cells exposed to various stresses. HSF1 knockout suppresses carcinogen-induced cancer induction in mice. Therefore, HSF1 is a promising therapeutic and chemopreventive target. We performed cell-based screening with a natural compound collection and identified fisetin, a dietary flavonoid, as a HSF1 inhibitor. Fisetin abolished heat shock-induced luciferase activity with an IC50 of 14 μM in HCT-116 cancer cells. The treatment of HCT-116 with fisetin inhibited proliferation with a GI50 of 23 μM. When the cells were exposed to heat shock in the presence of fisetin, the induction of HSF1 target proteins, such as HSP70, HSP27 and BAG3 (Bcl-2-associated athanogene domain 3), were inhibited. HSP70/BAG3 complexes protect cancer cells from apoptosis by stabilizing anti-apoptotic Bcl-2 family proteins. The downregulation of HSP70/BAG3 by fisetin significantly reduced the amounts of Bcl-2, Bcl-xL and Mcl-1 proteins, subsequently inducing apoptotic cell death. Chromatin immunoprecipitation assays showed that fisetin inhibited HSF1 activity by blocking the binding of HSF1 to the hsp70 promoter. Intraperitoneal treatment of nude mice with fisetin at 30mg/kg resulted in a 35.7% (P < 0.001) inhibition of tumor growth. [ABSTRACT FROM AUTHOR]

Since the notion of community of practice was introduced in the early 1990s, it has been popular in various organizations with the recognition that knowledge sharing is important for organizational learning. It has emerged as a strategic approach to knowledge sharing and an innovative way to foster learning. Considering that the notion of community of practice can provide an intriguing framework for library services, this study explores the implications that community of practice suggests for libraries and the roles that librarians can take to foster communities of practice. [ABSTRACT FROM AUTHOR]

The article discusses a study related to antimicrobial efficacy of natural plant-derived compounds against Vibrio cholerae. Topics discussed include investigation of antibacterial activities in plant-derived natural compounds against Gram-negative enteric pathogens, induction pro-inflammatory responses generated by macrophages in response to lipopolysaccharides (LPS) and consideration of honokiol and magnolol as preventive food adjuncts for cholera.

The effects of strontium substitution for magnesium in a novel aluminum-free multicomponent glass composition for glass ionomer cements (GICs) were investigated. A series of glass compositions were prepared based on SiO2-P2O5-CaO-ZnO-MgO(1-X)-SrOX-CaF2 (X = 0, 0.25, 0.5 and 0.75). The mechanical properties of GICs prepared were characterized by compressive strength, flexural strength, flexural modules, and microhardness. Cell proliferation was evaluated indirectly by CCK-8 assay using various dilutions of the cement and rat mesenchyme stem cells. Incorporation of strontium instead of magnesium in the glasses has a significant influence on setting time of the cements and the properties. All mechanical properties of the GICs with SrO substitution at X = 0.25 were significantly increased, then gradually decreased with further increase of the amount of strontium substitution in the glass. The GIC at X = 0.25, also, showed an improved cell viability at low doses of the cement extracts in comparison with other groups or control without extracts. The results of this study demonstrate that the glass compositions with strontium substitution at low levels can be successfully used to prepare aluminum-free glass ionomer cements for repair and regeneration of hard tissues. [ABSTRACT FROM AUTHOR]

Objective Little is known about the long-term clinical outcome and durability of HBsAg seroclearance following nucleos(t)ide analogue (NUC) therapy in patients with chronic hepatitis B (CHB). Design During a median follow-up period of 6 years (33 567 patient-years) of 5409 CHB patients who were initially treated with lamivudine or entecavir, a total of 110 achieved HBsAg seroclearance (0.33% annual seroclearance rate) and were included in this study. Results Baseline alanine aminotransferase (ALT) level >5 times of upper limit of normal was associated with higher probability of HBsAg seroclearance (HR 1.80, p<0.01), while HBeAg positivity (HR 0.46, p<0.01), high HBV DNA level (log10 IU/mL; HR 0.61, p<0.01), and cirrhosis (HR 0.48, p<0.01) were inversely associated with the probability of HBsAg seroclearance by multivariable analysis. During follow-up for 287 patient-years after HBsAg seroclearance, only two patients with baseline cirrhosis developed hepatocellular carcinoma (HCC) or died (0.7% annual risk), which was of a significantly lower rate compared with propensity score-matched patients without HBsAg seroclearance (HR 0.09, p<0.01). HBsAg reversion and/or HBV DNA reversion occurred in 18 patients, most of which were transient with extremely low serum levels of HBsAg (0.05-1.00 IU/mL) and HBV DNA (17-1818 IU/mL). None required retreatment. The cumulative probability of anti-HBs seroconversion (detection of anti-HBs) at 4 years was 67.4% by Kaplan-Meier analysis. Selection for lamivudine-resistance HBV mutants during treatment was not associated with composite reversion (p=0.66). Conclusions HBsAg seroclearance achieved after NUC treatment was associated with favourable clinical outcomes and was durable in most cases during longterm follow-up. [ABSTRACT FROM AUTHOR]

Relapsing polychondritis (RP) is an uncommon disease that is characterized by inflammation and destruction of cartilaginous structures. When tracheobronchial tree is involved, respiratory obstructive symptoms can occur. A 35-year-old man, with a previous diagnosis of RP, was scheduled for rigid bronchoscopy to relieve dyspnea, caused by subglottic stenosis. After laser splitting of the subglottic web, the spontaneous respiration of the patient was insufficient, and hypercarbia developed progressively even with assisted ventilation. After 20 minutes of aggressive hyperventilation to reduce endtidal CO2 level, sudden extreme tachycardia and hypotension developed. Ventilation rate was reduced and prolonged expiration time was allowed to alleviate a near-tampon status from dynamic hyperinflation. After the hemodynamic status was stabilized, the patient was transferred to the ICU for mechanical ventilation. He received ICU care for 30 days, and now, he was on supportive care on a ward, considering Y stent insertion to prevent luminal collapse from tracheobronchomalacia. [ABSTRACT FROM AUTHOR]

Heat shock factor 1 (HSF1) enhances the survival of cancer cells under various stresses. The knock-out of HSF1 impairs cancer formation and progression, suggesting that HSF1 is a promising therapeutic target. To identify inhibitors of HSF1 activity, we performed cell-based screening with a library of marketed and experimental drugs and identified cantharidin as an HSF1 inhibitor. Cantharidin is a potent antitumor agent from traditional Chinese medicine. Cantharidin inhibited heat shock-induced luciferase activity with an IC50 of 4.2μM. In contrast, cantharidin did not inhibit NF-κB luciferase reporter activity, demonstrating that cantharidin is not a general transcription inhibitor. When the HCT-116 colorectal cancer cells were exposed to heat shock in the presence of cantharidin, the induction of HSF1 downstream target proteins, such as HSP70 and BAG3 (Bcl-2-associated athanogene domain 3), was sup- pressed. HSP70 and its co-chaperone BAG3 have been reported to protect cells from apoptosis by stabilizing anti-apoptotic Bcl-2 family proteins. As expected, treating HCT-116 cancer cells with cantharidin significantly decreased the amounts of BCL-2, BCL-xL, and MCL-1 protein and induced apoptotic cell death. Chromatin immunoprecipitation analysis showed that cantharidin inhibited the binding of HSF1 to the HSP70 promoter and subsequently blocked HSF1-dependent p-TEFb recruitment. Therefore, the p-TEFb-dependent phosphorylation of the C-terminal domain of RNA polymerase II was blocked, arresting transcription at the elongation step. Protein phosphatase 2A inhibition with PP2CA siRNA or okadaic acid did not blockHSF1 activity, suggesting that cantharidin inhibits HSF1 in a protein phosphatase 2A-independent manner. We show for the first time that cantharidin inhibitsHSF1 transcriptional activity. [ABSTRACT FROM AUTHOR]

A large body of literature provides compelling evidence for the role of evolutionarily conserved core histone residues in various biological processes. However, site-directed mutagenesis of individual residues that are known to be sites of posttranslational modifications often does not result in clear phenotypic defects. In some cases, the combination of multiple mutations can give rise to stronger phenotypes, implying functional redundancy between distinct residues on histones. Here, we examined the "histone redundancy hypothesis" by characterizing double deletion of all pairwise combinations of amino-terminal tails (N-tails) from the four core histones encoded in budding yeast. First, we found that multiple lysine residues on the N-tails of both H2A and H4 are redundantly involved in cell viability. Second, simultaneous deletion of N-tails from H2A and H3 leads to a severe growth defect, which is correlated with perturbed gross chromatin structure in the mutant cells. Finally, by combining point mutations on H3 with deletion of the H2A N-tail, we revealed a redundant role for lysine 4 on H3 and the H2A N-tail in hydroxyurea-mediated response. Altogether, these data suggest that the N-tails of core histones share previously unrecognized, potentially redundant functions that, in some cases are different from those of the widely accepted H2A/H2B and H3/H4 dimer pairs. [ABSTRACT FROM AUTHOR]

Background: To understand epidemiologic patterns of meningococcal disease in Asia, we performed a retrospective molecular analysis of cerebrospinal fluid (CSF) specimens collected in prospective surveillance among children aged < 5 years of age in China, South Korea, and Vietnam. Methods: A total of 295 isolates and 2,302 CSFs were tested by a meningococcal species- and serogroup-specific polymerase chain reaction (PCR) assay targeting the Neisseria meningitidis (Nm) ctrA gene. Multi-locus sequence typing (MLST) was performed in Nm gene amplification analysis and incidence rates for meningococcal meningitis were estimated. Results: Among 295 isolates tested, 10 specimens from Vietnam were confirmed as serogroup B and all were Sequence Type (ST) 1576 by MLST. Among the 2,032 CSF specimen tested, 284 (14%) were confirmed by PCR (ctrA gene), including 67 (23.6%) from China, 92 (32.4%) from Korea, and 125 (44.0%) from Vietnam. Neonates and infants aged < 6 months of age accounted for more than 50% of Nm-PCR positive CSF. Two CSF specimens from Vietnam were identified as serogroup B using MLST. In addition, 44 specimens underwent sequencing to confirm meningococcal serogroup; of these, 21 (48%) were serogroup C, 12 (27%) were serogroup X, 9 (20%) were serogroup Y and 2 (5%) were serogroup B. The incidence rates of meningococcal meningitis among children < 5 years of age was highest in Vietnam (7.4/100,000 [95% CI, 3.6-15.3] followed by Korea (6.8/100,000 [95% CI, 3.5- 13.5] and China (2.1/100,000) [95% CI, 0.7-6.2]). Conclusions: These results suggest that there is a previously undetected, yet substantial burden of meningococcal meningitis among infants and young children. Standardized, sensitive and specific molecular diagnostic assays with Nm serogrouping capacity are needed throughout Asia to understand the true burden of N. meningitidis disease. [ABSTRACT FROM AUTHOR]

Pneumonia and influenza are leading causes of morbidity and mortality across the globe. Korea has established the national health-insurance system to cover the entire Korean population since 1989. The aim of this study was to describe the epidemiologic trends in pneumonia and influenza-associated hospitalizations and deaths using the Korean National Health Insurance databases and national vital statistics. During 2002-2005, 989,472 hospitalizations and 10,543 deaths due to pneumonia and influenza were recorded. Eighty-one percent of the hospitalizations were related to diagnoses with unspecified aetiology. The average annual rate of hospitalizations due to pneumonia and influenza was 5.2 per 1,000 people [95% confidence interval (CI) 5.2-5.3], and the hospitalization rate increased by 28% (from 4.5 to 5.8 per 1,000 people) during the four-year study period. In addition, deaths due to pneumonia and influenza increased by 48% (2,829 during 2003, 3,522 during 2004, and 4,192 during 2005). Overall, the national burden of hospitalizations and deaths due to pneumonia and influenza in Korea was high, and it increased for all age-groups during the study period. A comprehensive review of potential interventions by the government authorities should aim to reduce the burden of pneumonia and influenza. [ABSTRACT FROM AUTHOR]

We employed glioblastoma (human-derived U87 cells) cells as an experimental model for our present investigation. Chlorophyll a and b, purified from Spinacia Oleracea, were incubated together with glioblastoma cells at concentrations ranging from 10 nM to 1 μM. Assessment of growth was determined by cell counting by using a hemocytometer or by WST-1 assay. Changes in survival signals (Akt, ERK, and p-ERK), apoptosis (Bax, caspase 3, and p21), levels of cell cycle cdk1/cdc2 protein and PTEN/p-P TEN were observed and Hoescht 33342 nuclear staining was also performed. Box plotting and Student t test was used for statistical analysis. It was observed that at concentrations higher than 10 nM, there was a decline in the rate of cell proliferation. At a concentration of 100 nM, proliferation of cells stopped with decreased phosphorylation of PTEN. Whereas, there were no changes in other cell survival related proteins. Chromatin condensation or nuclear fragmentation was not detected by Hoescht 33342 staining. Combination of chlorophylls a and b neither exhibited an additive nor any synergistic effect on the cells. In conclusion, chlorophylls inhibited the growth of cultured U87 glioblastoma cells, indicating, its function as a cytostatic agent. [ABSTRACT FROM AUTHOR]

Heat shock factor 1 (HSF1) is the master switch for heat shock protein (HSP) expression in eukaryotes. A synthetic chemical library was screened to identify inhibitors of HSF1 using a luciferase reporter under the control of a heat shock element. A compound named KRIBB11 (N2-( 1H-indazole-5-yl)-N6-methyl-3--nitropyridine-2,6-diamine) was identified for its activity in abolishing the heat shock-induced luciferase activity with an IC50 of 1.2 μmol/liter. When the cells were exposed to heat shock in the presence of KRIBB11, the induction of HSF1 downstream target proteins such as HSP27 and HSP70 was blocked. In addition, treatment of HCT-116 cells with KRIBB11 induced growth arrest and apoptosis. Markers of apoptosis, such as cleaved poly(ADP-ribose) polymerase, were detected after KRIBB11 treatment. Biotinyl-KRIBB11 was synthesized as an affinity probe for the identification of KRIBB11 target proteins. Using affinity chromatography and competition assays, KRIBB11 was shown to associate with HSF1 in vitro. Chromatin immuno-precipitation analysis showed that KRIBB11 inhibited HSF1-dependent recruitment of p-TEFb (positive transcription elongation factor b) to the hsp70 promoter. Finally, intraperitoneal treatment of nude mice with KRIBB11 at 50 mg/kg resulted in a 47.4% (p < 0.05) inhibition of tumor growth without body weight loss. Immunoblotting assays showed that the expression of HSP70 was lower in KRIBB11-treated tumor tissue than in control tissues. Because HSPs are expressed at high levels in a wide range of tumors, these results strengthen the rationale for targeting HSF1 in cancer therapy. [ABSTRACT FROM AUTHOR]

Background: We previously reported the anti-angiogenic activity of paeonol isolated from Moutan Cortex. In the present study, we investigated the negative effect of paeonol oxime (PO, a paeonol derivative) on basic fibroblast growth factor (bFGF)-mediated angiogenesis in human umbilical vein endothelial cells (HUVECs) (including tumor angiogenesis) and prosurvival activity in HT-1080 fibrosarcoma cell line. Methodology/Principal Findings: We showed that PO (IC50 = 17.3 μg/ml) significantly inhibited bFGF-induced cell proliferation, which was achieved with higher concentrations of paeonol (IC50 over 200 μg). The treatment with PO blocked bFGF-stimulated migration and in vitro capillary differentiation (tube formation) in a dose-dependent manner. Furthermore, PO was able to disrupt neovascularization in vivo. Interestingly, PO (25 μg/ml) decreased the cell viability of HT-1080 fibrosarcoma cells but not that of HUVECs. The treatment with PO at 12.5 μg/ml reduced the levels of phosphorylated AKT and VEGF expression (intracellular and extracelluar) in HT-1080 cells. Consistently, immunefluorescence imaging analysis revealed that PO treatment attenuated AKT phosphorylation in HT-1080 cells. Conclusions/Significance: Taken together, these results suggest that PO inhibits bFGF-induced angiogenesis in HUVECs and decreased the levels of PI3K, phospho-AKT and VEGF in HT-1080 cells. [ABSTRACT FROM AUTHOR]

We consider a nonlinear viscoelastic wave equation with nonlinear source term. Under suitable conditions on g, it is proved that any weak solution with negative initial energy blows up in finite time if p>2. [ABSTRACT FROM AUTHOR]

Objectives: To gain further insight into the defence mechanisms against triclosan in a mutant derived from an Escherichia coli strain carrying the triclosan-resistant target enzyme, FabI(G93V). [ABSTRACT FROM PUBLISHER]

The present study was undertaken to gain insight into the molecular mechanism of G2/M phase cell cycle arrest resulting from treatment of DU145 cells with diallyl trisulfide (DATS), a promising cancer chemopreventive constituent of garlic. Cell cycle distribution was determined by flow cytometry. Immunoblotting was performed to determine protein expression. Overexpression of wild-type or mutant Cdc25C was achieved by transient transfection. Nuclear and cytoplasmic localization of cyclin B1 and cyclin-dependent kinase 1 (cdk1) was studied by immunoblotting. Exposure of DU145 human prostate cancer cells to DATS resulted in concentration- and time-dependent accumulation of G2/M phase cells, which correlated with down-regulation as well as increased S216 phosphorylation of Cdc25C. Ectopic expression of wild-type or redox-insensitive mutants (C330S and C330S/C377S) or S216A mutant of Cdc25C failed to confer protection against DATS-induced G2/M phase arrest. The DATS-mediated G2/M phase cell cycle arrest was also independent of reduced complex formation between cdk1 and cyclin B1, but correlated with delayed nuclear translocation of cdk1. The present study indicates that the DATS-mediated G2/M phase cell cycle arrest in DU145 cells results from differential kinetics of nuclear localization of cdk1 and cyclin B1. [ABSTRACT FROM AUTHOR]

A novel method to coat electrospun poly(D,L-lactic-co-glycolic acid) (PLGA) fiber surfaces evenly and efficiently with low-crystalline carbonate apatite crystals using a poly(vinyl alcohol) (PVA) vehicle system carrying calcium ions was presented. A non-woven PLGA fabric was prepared by electrospinning: a 10 wt% PLGA solution was prepared using 1,1,3,3-hexafluoro-2-propanol as a solvent and electrospun under a electrical field of 1 kV/cm using a syringe pump with a flowing rate of 3 ml/h. The non-woven PLGA fabric, 12 mm in diameter and 1 mm in thickness, was cut and then coated with a PVA solution containing calcium chloride dihydrate (specimen PPC). As controls, pure non-woven PLGA fabric (specimen P) and fabric coated with a calcium chloride dihydrate solution without PVA (specimen PC) were also prepared. Three specimens were exposed to simulated body fluid for 1 week and this exposure led to form uniform and complete apatite coating layer on the fiber surfaces of specimen PPC. However, no apatite had formed to the fiber surfaces of specimen P and only inhomogeneous coating occurred on the fiber surfaces of specimen PC. These results were explained in terms of the calcium chelating and adhesive properties of PVA vehicle system. The practical implication of the results is that this method provides a simple but efficient technique for coating the fiber surface of an initially non-bioactive material with low-crystalline carbonate apatite. [ABSTRACT FROM AUTHOR]

Gravinol, a proanthocyanidin from grape seeds, has polyphenolic properties with powerful anti-oxidative effects. Although, increasing evidence strongly suggests that polyphenolic antioxidants suppress diabetic nephropathy that is causally associated with oxidative stress and inflammation, gravinol's protective action against diabetic nephropathy has not been fully explored to date. In the current study, we investigated the protective action of gravinol against oxidative stress and inflammation using the experimental diabetic nephropathy cell model, high glucose-exposed renal tubular epithelial cells. To elucidate the underlying actions of gravinol, several oxidative and inflammatory markers were estimated. Included are measurements of lipid peroxidation, total reactive species (RS), superoxide (ꔷO2), nitric oxide (NOꔷ), and peroxynitrite (ONOO−), as well as nuclear factor-kappa B (NF-κB) nuclear translocation. Results indicate that gravinol had a potent inhibitory action against lipid peroxidation, total RS, ꔷO2, NOꔷ, ONOO−, the reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio and more importantly, against NF-κB nuclear translocation. We propose that gravinol's strong protective effect against high glucose-induced renal tubular epithelial cell damage attenuates diabetic nephropathy by suppressing oxidative stress and inflammation. [Copyright &y& Elsevier]

In this article we prove the existence and uniform decay of the solution to the mixed problem for coupled Klein-Gordon-Schrödinger equation with memory term. The existence is proved by means of the Faedo-Galerkin method and the asymptotic behavior is obtained by making use of the multiplier technique combined with integral inequalities due to Komornik. [ABSTRACT FROM AUTHOR]

We study the existence and energy decay of solutions for the strongly damped nonlinear beam equation. We apply a method based on Nakao method to show that the solution decays exponentially, and to obtain precise estimates of the constants in the estimates. Finally, we discuss its applications in moving boundary. [ABSTRACT FROM AUTHOR]