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  • 1
    Keywords: LUNG-CANCER ; RISK ; SUSCEPTIBILITY LOCUS ; INITIATION ; DEPENDENCE ; GENOME-WIDE ASSOCIATION ; Adolescent ; NICOTINIC RECEPTOR GENES ; HEAVY SMOKING ; ADULT RATS
    Abstract: Context: Recent studies have shown an association between cigarettes per day (CPD) and a nonsynonymous single-nucleotide polymorphism in CHRNA5, rs16969968. Objective: To determine whether the association between rs16969968 and smoking is modified by age at onset of regular smoking. Data Sources: Primary data. Study Selection: Available genetic studies containing measures of CPD and the genotype of rs16969968 or its proxy. DataExtraction: Uniform statistical analysis scripts were runlocally. Starting with 94 050 ever-smokers from 43 studies, we extracted the heavy smokers (CPD 〉20) and light smokers (CPD 〈= 10) with age-at-onset information, re-ducing the sample size to 33 348. Each study was stratified into early-onset smokers (age at onset 〈= 16 years) and late-onset smokers (age at onset 〉16 years), and a logistic regression of heavy vs light smoking with ther s16969968 genotype was computed for each stratum. Meta-analysis was performed within each age-at-onset stratum. Data Synthesis: Individuals with 1 risk allele at rs16969968 who were early-onset smokers were significantly more likely to be heavy smokers in adulthood (odds ratio [OR]=1.45; 95% CI, 1.36-1.55; n=13 843) than were carriers of the risk allele who were late-onset smokers (OR=1.27; 95% CI, 1.21-1.33, n=19 505) (P=.01). Conclusion: These results highlight an increased genetic vulnerability to smoking in early-onset smokers.
    Type of Publication: Journal article published
    PubMed ID: 22868939
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  • 2
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    German Medical Science; Düsseldorf, Köln
    In:  68. Jahrestagung der Deutschen Gesellschaft für Unfallchirurgie, 90. Tagung der Deutschen Gesellschaft für Orthopädie und Orthopädische Chirurgie und 45. Tagung des Berufsverbandes der Fachärzte für Orthopädie; 20041019-20041023; Berlin; DOC04dguE6-1693 /20041019/
    Publication Date: 2004-10-20
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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  • 3
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  Deutscher Kongress für Orthopädie und Unfallchirurgie; 72. Jahrestagung der Deutschen Gesellschaft für Unfallchirurgie, 94. Tagung der Deutschen Gesellschaft für Orthopädie und Orthopädische Chirurgie, 49. Tagung des Berufsverbandes der Fachärzte für Orthopädie; 20081022-20081025; Berlin; DOCEF13-1491 /20081016/
    Publication Date: 2008-10-17
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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  • 4
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    German Medical Science; Düsseldorf, Köln
    In:  Deutscher Kongress für Orthopädie und Unfallchirurgie; 70. Jahrestagung der Deutschen Gesellschaft für Unfallchirurgie, 92. Tagung der Deutschen Gesellschaft für Orthopädie und Orthopädische Chirurgie und 47. Tagung des Berufsverbandes der Fachärzte für Orthopädie; 20061002-20061006; Berlin; DOCE.1.3-1562 /20060928/
    Publication Date: 2007-03-09
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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  • 5
    Publication Date: 2018-11-14
    Description: The organic anion transporting polypeptides (OATPs) are important membrane proteins that mediate the cellular uptake of drugs and endogenous substances. OATP1A2 is widely distributed in many human tissues that are targeted in drug therapy; defective OATP1A2 leads to altered drug disposition influencing therapeutic outcomes. 5'-AMP-activated protein kinase (AMPK) signaling plays an important role in the pathogenesis of the metabolic syndrome characterized by an increased incidence of type II diabetes and nonalcoholic fatty liver disease. This study investigated the regulatory role of AMPK in OATP1A2 transport function and expression. We found that the treatment of AMPK-specific inhibitor compound C (dorsomorphin dihydrochloride) decreased OATP1A2-mediated uptake of estrone-3-sulfate in a concentration- and time-dependent manner. The impaired OATP1A2 function was associated with a reduced V max [154.6 ± 17.9 pmol x ( μ g x 4 minutes) –1 in compound C–treated cells vs. 413.6 ± 52.5 pmol x ( μ g x 4 minutes) –1 in controls]; the K m was unchanged. The cell-surface expression of OATP1A2 was decreased by compound C treatment, but total cellular expression was unchanged. The impaired cell-surface expression of OATP1A2 was associated with accelerated internalization and impaired targeting/recycling. Silencing of the AMPK α 1-subunit using specific small interfering RNA corroborated the findings with compound C and revealed a role for AMPK in regulating OATP1A2 protein stability. Overall, this study implicated AMPK in the regulation of the function and expression of OATP1A2, which potentially impacts on the disposition of OATP1A2 drug substrates that may be used to treat patients with the metabolic syndrome and other diseases.
    Print ISSN: 0026-895X
    Electronic ISSN: 1521-0111
    Topics: Chemistry and Pharmacology , Medicine
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  • 6
    Publication Date: 2018-07-05
    Description: Pathogens entering the marine environment as pollutants exhibit a spatial signature driven by their transport mechanisms. The sea otter ( Enhydra lutris ), a marine animal which lives much of its life within sight of land, presents a unique opportunity to understand land–sea pathogen transmission. Using a dataset on Toxoplasma gondii prevalence across sea otter range from Alaska to California, we found that the dominant drivers of infection risk vary depending upon the spatial scale of analysis. At the population level, regions with high T. gondii prevalence had higher human population density and a greater proportion of human-dominated land uses, suggesting a strong role for population density of the felid definitive host of this parasite. This relationship persisted when a subset of data were analysed at the individual level: large-scale patterns in sea otter T. gondii infection prevalence were largely explained by individual exposure to areas of high human housing unit density, and other landscape features associated with anthropogenic land use, such as impervious surfaces and cropping land. These results contrast with the small-scale, within-region analysis, in which age, sex and prey choice accounted for most of the variation in infection risk, and terrestrial environmental features provided little variation to help in explaining observed patterns. These results underscore the importance of spatial scale in study design when quantifying both individual-level risk factors and landscape-scale variation in infection risk.
    Keywords: ecology, health and disease and epidemiology
    Electronic ISSN: 2054-5703
    Topics: Natural Sciences in General
    Published by Royal Society
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  • 7
    Publication Date: 2018-03-06
    Description: Background Untargeted active screening and treatment programmes for tuberculosis (TB) have not been shown to be more effective than passive screening and isoniazid preventive therapy (IPT) for reducing TB incidence. In this manuscript, we compare the efficacy of targeting screening and IPT on high-risk household contacts of diagnosed TB cases, with less-targeted active screening approaches in Lima, Peru. Methods We conducted a population-based prospective cohort study within households of TB cases in Lima. We identified all adults diagnosed with incident pulmonary TB from 2009 through 2012 at 106 participating public health centres (HC) within our catchment area of ∼3.3 million inhabitants. We estimated combined effects of community and household exposure on the risk of latent TB infection (LTBI) and incident TB disease. We used simulation modelling to assess the efficacy of TB screening programmes for reducing the risk of incident TB in these contacts. Results Individuals with household exposure to TB are more likely to present with LTBI and TB disease than those without this exposure, despite wide variation in community exposure. Simulations suggest that more cases are prevented by 1000 administrations of IPT to tuberculin skin test (TST)-positive household contacts of identified TB cases (30, 95% CI = 16,47) than from blanket screening and treatment in the community (7, 95% CI = 2,17). Conclusions Household exposure remains a major driver of incident TB risk among household contacts of identified TB cases. Targeting interventions on these individuals is likely to prevent more cases of TB than blanket screening of individuals in the community.
    Print ISSN: 0300-5771
    Electronic ISSN: 1464-3685
    Topics: Medicine
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  • 8
    Publication Date: 2018-02-10
    Description: Background: Quantifying circulating nucleic acids is an important new approach to cancer diagnosis/monitoring. Methods: We compared the suitability of serum versus plasma for measuring miRNAs using qRT-PCR and assessed how preanalytic variables that can affect circulating tumor DNA (ctDNA) quantification in plasma also influence miRNA levels. Results: Across 62 blood-derived specimens, plasma samples in EDTA, Streck-DNA, and Streck-RNA tubes showed significantly higher C t values for multiple housekeeping miRNAs, compared with serum samples. For the EDTA-plasma tubes, this difference was only seen when including the high-speed centrifugation protocol used to optimize ctDNA extraction. In plasma samples derived from blood stored at room temperature for up to 14 days (conditions that typically apply to samples processed for biobanking), levels of endogenous housekeeping miRNAs gradually increased, in parallel with the hemolysis marker hsa-miR-451a, consistent with release from blood cells/platelets. It was necessary to normalize levels of the housekeeping miRNAs to those of hsa-miR-451a, to obtain the stable values needed for referencing test miRNA levels. Conclusions: Our data indicate that plasma samples prepared for ctDNA extraction are suboptimal for miRNA quantification and require the incorporation of multiple data normalization steps. For prospective studies designed to measure both miRNAs and ctDNA, the most suitable approach would be to obtain both serum (for miRNAs) and plasma (for ctDNA). If only plasma can be collected, we recommend an initial low-speed centrifugation step, followed by aliquoting the supernatant into parallel samples, one for direct miRNA quantification, and the other for a further high-speed centrifugation step to optimize ctDNA retrieval. Impact: These recommendations will help "future-proof" clinical studies in which quantification of circulating miRNAs is a component. Cancer Epidemiol Biomarkers Prev; 27(2); 208–18. ©2017 AACR .
    Print ISSN: 1055-9965
    Electronic ISSN: 1538-7755
    Topics: Medicine
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  • 9
    ISSN: 1432-1955
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Experimental infections of calves were carried out with either isolates of predominantlyOstertagia ostertagi, pureO. leptospicularis or a mixed isolate of equal numbers of both these species. The total worms established on day 21 for the mixed species from a total inoculum of 100000 infective larvae, was 1.2 times greater than from 100000 larvae of theO. ostertagi isolate and 3.3 times that of the pureO. leptospicularis isolate. The increased establishment in the mixed inoculum referred to bothO. ostertagi andO. leptospicularis (days 17 and 21). These differences were both highly significant (P〈0.01). The severity of the pathological changes was also greater in the mixed infections. It is suggested that these findings must be taken into account when control measures involving alternate grazing of sheep and cattle are being employed.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Hoboken, NJ [u.a.] : Wiley-Blackwell
    Journal of Orthopaedic Research 2 (1984), S. 272-280 
    ISSN: 0736-0266
    Keywords: Normal slow walking ; Electromyography ; Gait kinematics ; Life and Medical Sciences
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Kinematics and electromyographic (EMG) activity were recorded in seven normal women during walking at slow, free, and fast speeds. Speed-related differences were found in the stride dimensions, temporal components, and most of the simultaneous displacement patterns of body segments measured. For most of the muscles tested, the amplitude of normalized EMG activity decreased as walking speed decreased. The findings emphasize the importance of accounting for the effect of speed itself on measurements of gait.
    Additional Material: 9 Ill.
    Type of Medium: Electronic Resource
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