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  • 1
    Publication Date: 2018-06-02
    Description: Background: Despite age and sex differences in fecal hemoglobin (f-Hb) concentrations, most fecal immunochemical test (FIT) screening programs use population-average cut-points for test positivity. The impact of age/sex-specific threshold on FIT accuracy and colonoscopy demand for colorectal cancer screening are unknown. Methods: Using data from 723,113 participants enrolled in a Taiwanese population-based colorectal cancer screening with single FIT between 2004 and 2009, sensitivity and specificity were estimated for various f-Hb thresholds for test positivity. This included estimates based on a "universal" threshold, receiver-operating-characteristic curve–derived threshold, targeted sensitivity, targeted false-positive rate, and a colonoscopy-capacity-adjusted method integrating colonoscopy workload with and without age/sex adjustments. Results: Optimal age/sex-specific thresholds were found to be equal to or lower than the universal 20 μg Hb/g threshold. For older males, a higher threshold (24 μg Hb/g) was identified using a 5% false-positive rate. Importantly, a nonlinear relationship was observed between sensitivity and colonoscopy workload with workload rising disproportionately to sensitivity at 16 μg Hb/g. At this "colonoscopy-capacity-adjusted" threshold, the test positivity (colonoscopy workload) was 4.67% and sensitivity was 79.5%, compared with a lower 4.0% workload and a lower 78.7% sensitivity using 20 μg Hb/g. When constrained on capacity, age/sex-adjusted estimates were generally lower. However, optimizing age/-sex-adjusted thresholds increased colonoscopy demand across models by 17% or greater compared with a universal threshold. Conclusions: Age/sex-specific thresholds improve FIT accuracy with modest increases in colonoscopy demand. Impact: Colonoscopy-capacity-adjusted and age/sex-specific f-Hb thresholds may be useful in optimizing individual screening programs based on detection accuracy, population characteristics, and clinical capacity. Cancer Epidemiol Biomarkers Prev; 27(6); 704–9. ©2018 AACR .
    Print ISSN: 1055-9965
    Electronic ISSN: 1538-7755
    Topics: Medicine
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  • 2
    Publication Date: 2018-06-15
    Description: Objectives Although sleep, chronic disease and its related mortality are extensively studied areas, the association between stroke and sleep duration is relatively unknown. The aim of this study was to investigate the association between long and short sleep duration and stroke prevalence. Design A cross-sectional survey study. Setting and participants Adult surveyees (aged ≥19 years) who answered items relating to sleep duration and stroke in the 2010–2014 Korean National Health and Nutrition Surveys (n=17 601). Outcome measures Participants were divided into three groups by sleep duration (short: ≤6 hours/day, normal: 7–8 hours/day and long: ≥9 hours/day). Stroke prevalence in each sleep duration group was compared using logistic regression analysis, and sociodemographic characteristics, medical history, lifestyle habits and mental health factors were set as confounding variables. Results On adjusting for sex and age, each sleep-duration group displayed significantly different health-related characteristics. The short sleep and long sleep duration groups indicated significantly higher psychological factors for stress perception, depressive symptoms and psychiatric counselling compared with the normal sleep duration group. On adjustment of various confounders, the long sleep duration group demonstrated significantly higher ORs for stroke compared with the normal sleep duration group (OR 1.96, 95% CI 1.06 to 3.61). Also, when stratified by sex, men did not exhibit differences in stroke prevalence by sleep duration, but women showed higher stroke prevalence in the long sleep duration group compared with normal sleep duration (OR 2.94, 95% CI 1.21 to 7.17). Conclusions Longer sleep duration was associated with higher stroke prevalence, and this trend was more pronounced in women.
    Keywords: Open access, Epidemiology
    Electronic ISSN: 2044-6055
    Topics: Medicine
    Published by BMJ Publishing
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  • 3
    Publication Date: 2018-06-19
    Description: Human Ag R (HuR) is an RNA binding protein in the ELAVL protein family. To study the neuron-specific function of HuR, we generated inducible, neuron-specific HuR-deficient mice of both sexes. After tamoxifen-induced deletion of HuR, these mice developed a phenotype consisting of poor balance, decreased movement, and decreased strength. They performed significantly worse on the rotarod test compared with littermate control mice, indicating coordination deficiency. Using the grip-strength test, it was also determined that the forelimbs of neuron-specific HuR-deficient mice were much weaker than littermate control mice. Immunostaining of the brain and cervical spinal cord showed that HuR-deficient neurons had increased levels of cleaved caspase-3, a hallmark of cell apoptosis. Caspase-3 cleavage was especially strong in pyramidal neurons and α motor neurons of HuR-deficient mice. Genome-wide microarray and real-time PCR analysis further indicated that HuR deficiency in neurons resulted in altered expression of genes in the brain involved in cell growth, including trichoplein keratin filament–binding protein, Cdkn2c, G-protein signaling modulator 2, immediate early response 2, superoxide dismutase 1, and Bcl2. The additional enriched Gene Ontology terms in the brain tissues of neuron-specific HuR-deficient mice were largely related to inflammation, including IFN-induced genes and complement components. Importantly, some of these HuR-regulated genes were also significantly altered in the brain and spinal cord of patients with amyotrophic lateral sclerosis. Additionally, neuronal HuR deficiency resulted in the redistribution of TDP43 to cytosolic granules, which has been linked to motor neuron disease. Taken together, we propose that this neuron-specific HuR-deficient mouse strain can potentially be used as a motor neuron disease model.
    Print ISSN: 0022-1767
    Electronic ISSN: 1550-6606
    Topics: Medicine
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  • 4
    Publication Date: 2018-07-04
    Description: Background/Aim: Human hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Patients with metastatic HCC (mHCC) show poor prognosis and high mortality. In previous reports, gelsolin-like actin-capping protein (CapG) has been demonstrated to regulate cancer invasion and metastasis in various human cancers. In this study, the expression of CapG was verified in normal and/or HCCs' specimens and HCC cell lines. Moreover, the bio-activity of CapG was also investigated. Materials and Methods: The expression of CapG was examined in HCC's tissue-array by immunohistochemical (IHC) staining. The mRNA and protein of CapG in three HCC cell lines were determined using real-time RT-PCR and western blot. Moreover, a trans-well migration model and a matrigel-trans-well invasion assay were used to address the bio-activity of CapG in HCC cell lines. Results: CapG was detected in the cytoplasm of normal liver tissue and HCC specimens. Importantly, CapG expression was elevated in the HCC specimens compared to normal cases and was significantly overexpressed in mHCC cases compared to normal cases. Moreover, patients with highly expressed CapG showed greater mortality in HCC cases. In addition, the RNA and protein levels of CapG among three HCC cell lines showed a positive association with cellular migration and invasive ability. CapG knockdown with shRNA in HCC cells also verified this finding. Conclusion: In the present study, it is demonstrated that CapG is expressed in the cytoplasm and could be used as a prognostic or diagnostic biomarker for mHCC in clinical specimens. Moreover, CapG might contribute to tumor motility and cancer-associated mortality.
    Print ISSN: 0250-7005
    Electronic ISSN: 1791-7530
    Topics: Medicine
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  • 5
    Publication Date: 2018-08-21
    Print ISSN: 0022-1767
    Electronic ISSN: 1550-6606
    Topics: Medicine
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  • 6
    Publication Date: 2018-04-20
    Description: Purpose The Health and Prevention Enhancement (H-PEACE) study was designed to investigate the association of diagnostic imaging results, biomarkers and the predisease stage of non-communicable diseases (NCDs), such as malignancies and metabolic diseases, in an average-risk population in Korea. Participants This study enrolled a large-scale retrospective cohort at the Healthcare System Gangnam Center, Seoul National University Hospital, from October 2003 to December 2014. Findings to date The baseline and follow-up information collected in the predisease stage of NCDs allows for evaluation of an individual’s potential NCD risk, which is necessary for establishing personalised prevention strategies. A total of 91 336 health examinees were included in the cohort, and we repeatedly measured and collected information for 50.9% (n=46 484) of the cohort members. All participants completed structured questionnaires (lifestyle, medical history, mini-dietary assessment index, sex-specific variables and psychiatric assessment), doctors’ physical examinations, laboratory blood and urine tests and digital chest X-ray imaging. For participants with available data, we also obtained information on specific diagnostic variables using advanced diagnostic tests, including coronary CT for coronary calcium scores, colonoscopy and brain MRI. Furthermore, 17 455 of the participants who provided informed consent and donated blood samples were enrolled into the Gene-environmental interaction and phenotype study, a subcohort of the H-PEACE, from October 2013, and we analysed genome-wide single-nucleotide polymorphism array data for 6579 of these blood samples. Future plans The data obtained from this cohort will be used to facilitate advanced and accurate diagnostic techniques related to NCDs while considering various phenotypes. Potential collaborators can access the dataset after receiving approval from our institutional review board. Applications can be submitted on the study homepage ( http://en-healthcare.snuh.org/HPEACEstudy ).
    Keywords: Open access, Epidemiology, Epidemiology
    Electronic ISSN: 2044-6055
    Topics: Medicine
    Published by BMJ Publishing
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  • 7
    Publication Date: 2018-02-09
    Description: Objective Animal studies showed that male subjects had lower activity of immune response to infections than female subjects, which may increase the risk of the development of tuberculosis in male population. This study intended to investigate the risk of incident tuberculosis in male and female adults in Taiwan. Design This is a retrospective cohort study. Setting The present analyses used data of Taiwan National Health Interview Survey 2001, 2005 and 2009, National Register of Deaths Dataset, and National Health Insurance Research Database from 2000 to 2013. Participants A total of 43 424 subjects with a mean age of 43.04 years were analysed. Primary outcome measures Incidence of tuberculosis. Results During 381 561 person-years of follow-up period, incident tuberculosis was recognised in 268 individuals. The incidence rates of tuberculosis were 97.56 and 43.24 per 100 000 person-years among male and female participants, respectively. Kaplan-Meier curves comparing male and female subjects showed statistical significance (log-rank test, P value〈0.01). After adjusting for subjects’ demographics and comorbidities, men showed increased risks of incident tuberculosis (adjusted HR, 1.68; 95% CI 1.21 to 2.34; P value〈0.01) compared with women. On subgroup analysis, after stratifying by age, smoking and alcohol use, men had a higher risk of incident tuberculosis than women in all patient subgroups, except those who were current smokers. Conclusions This study suggests that men had a higher risk of incident tuberculosis than women. Future tuberculosis control programmes should particularly target the male population.
    Keywords: Open access, Infectious diseases
    Electronic ISSN: 2044-6055
    Topics: Medicine
    Published by BMJ Publishing
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  • 8
    Publication Date: 2018-11-14
    Description: Nonalcoholic fatty liver disease (NAFLD) is an increasingly studied condition that can progress to end-stage liver disease. Although NAFLD was first described in 1980, a complete understanding of the mechanism and causes of this disease is still lacking. Six-transmembrane protein of prostate 2 (STAMP2) plays a role in integrating inflammatory and nutritional signals with metabolism. Our previous study suggested that STAMP2 may be a suitable target for treating NAFLD. In the current study, we performed a focused drug-screening and found that cilostazol could be a potential STAMP2 enhancer. Thus, we examined whether cilostazol alleviates NAFLD through STAMP2. The in vivo and in vitro pharmacological efficacies of cilostazol on STAMP2 expression and lipid accumulation were analyzed in NAFLD mice induced by high-fat diet (HFD) and in HepG2 cell lines treated by oleic acid (OA), respectively. Cilostazol increased the expression of STAMP2 through transcriptional regulation in vivo and in vitro. Cilostazol also dampened the STAMP2 downregulation caused by the HFD and by OA in vivo and in vitro, respectively. Cilostazol activated AMP-activated protein kinase (AMPK) in vivo and in vitro, and AMPK functions upstream of STAMP2, and reversed downregulation of STAMP2 expression through AMPK in the NAFLD model. Cilostazol ameliorates hepatic steatosis by enhancing hepatic STAMP2 expression through AMPK. Enhancing STAMP2 expression with cilostazol represents a potential therapeutic avenue for treatment of NAFLD.
    Print ISSN: 0026-895X
    Electronic ISSN: 1521-0111
    Topics: Chemistry and Pharmacology , Medicine
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  • 9
    Publication Date: 2018-02-02
    Description: The epidermal growth factor receptor (EGFR) is a member of the erbB family of receptors and is overexpressed in many tumor types. A repebody is a newly designed nonantibody protein scaffold for tumor targeting that contains leucine-rich repeat modules. In this study, 3 64 Cu-labeled anti-EGFR repebodies with different chelators were synthesized, and their biologic characteristics were assessed in cultured cells and tumor-bearing mice. Methods: Repebodies were synthesized with the chelators 2-( p -isothiocyanatobenzyl)-1,4,7-triazacyclononane- N,N',N,''- triacetic acid trihydrochloride ([ p -SCN-Bn]-NOTA), 2,2',2''-(10-(2-(2,5-dioxopyrrolidin-1-yloxy)-2-oxoethyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl) triacetic acid (DOTA- N -hydroxysuccinimide ester), or 1-( p -isothiocyanatobenzyl)diethylenetriamine pentaacetic acid trihydrochloride ([ p -SCN-Bn]-DTPA) in 1.0 M NaHCO 3 buffer (pH 9.2) for 24 h. Purified NOTA-, DOTA-, and DTPA-conjugated repebody were radiolabeled with 64 Cu in 0.1 M NH 4 OAc buffer (pH 5.5). To compare the EGFR-binding affinities of the repebodies, cellular uptake studies were performed with the human non–small cell lung cancer cell line H1650 (high expression of EGFR) and the human colon adenocarcinoma cell line SW620 (low expression of EGFR). Biodistribution and small-animal PET imaging studies were performed using H1650 tumor–bearing mice. Results: Radiochemical yields of the 64 Cu-labeled repebodies were approximately 70%–80%. Cellular uptake of the NOTA-, DOTA-, and DTPA-repebodies was over 4-fold higher in H1650 cells than in SW620 cells at 1 h. The 3 repebodies had accumulated specifically in H1650 tumor–bearing nude mice by 1 h after intravenous injection and were retained for over 24 h, as measured by the percentage injected dose per gram of tissue (%ID/g). Tumor uptake of all repebodies increased from 1 to 6 h (at 1 h, 6.28, 8.46, and 6.91 %ID/g for NOTA-, DOTA-, and DTPA-repebody, respectively; at 6 h, 9.4, 8.28, and 10.1 %ID/g, respectively). H1650 tumors were clearly visible after injection of each repebody, with high tumor-to-background ratios (at 1 h, 3.43, 4.89, and 2.38 for NOTA-, DOTA-, and DTPA-repebody, respectively; at 6 h, 3.05, 4.36, and 2.08; at 24 h, 3.81, 4.58, and 2.86). Conclusion: The 3 64 Cu-repebody complexes demonstrated specific and rapid uptake in EGFR-expressing tumors within 1 h and may have potential as novel EGFR imaging agents for PET.
    Print ISSN: 0022-3123
    Topics: Medicine
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  • 10
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background The importance of assessing health-related quality of life (HRQL) of patients with allergic rhinitis (AR) has been well established, but the specific roles of rhinitis-specific or general health instruments have not been delineated.Objective We analysed the psychometric properties of a disease-specific instrument, the Rhinoconjunctivitis Quality-of-Life Questionnaire (RQLQ) and the general health instrument, the Medical Outcome Short-Form 36 (SF-36) as they are employed in combination in patients with persistent AR in clinical practice.〈section xml:id="abs1-2"〉〈title type="main"〉Method We analysed the data collected from a prospective study of 43 newly diagnosed patients with persistent AR and 44 controls. We interviewed the patients four times, at baseline, weeks 4, 8 and 10.Results The RQLQ and SF-36 have good discriminative property, internal consistency, and test–retest reliability. The RQLQ is superior to the SF-36 as an evaluative instrument because more of its domains respond to change, the magnitude of change was greater, and the response was faster. The SF-36 is more susceptible to floor and ceiling effects. Both instruments are unsuitable for mildly symptomatic patients based on Rasch model analysis. Each questionnaire assesses a distinct and significant portion of the total HRQL of persistent AR.Conclusion The SF-36 and RQLQ are good for discriminating rhinitis patients from controls, but the former is poor for detecting changes in QOL. Both are inappropriate for mildly symptomatic patients. Each instrument measures non-overlapping halves of the measurable HRQL. For an assessment of the HRQL in persistent AR that is complete and responsive both instruments should be employed together.
    Type of Medium: Electronic Resource
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