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  • Ovid Technologies (Wolters Kluwer Health)  (46)
  • 1
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    Serum Levels of Mannose-Binding Lectin and the Risk of Future Coronary Artery Disease in Apparently Healthy Men and Women
    Ovid Technologies (Wolters Kluwer Health) ; 2006
    In:  Arteriosclerosis, Thrombosis, and Vascular Biology Vol. 26, No. 10 ( 2006-10), p. 2345-2350
    Details
    In: Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 26, No. 10 ( 2006-10), p. 2345-2350
    Kurzfassung: The purpose of this study was to determine the association between serum levels of mannose-binding lectin (MBL) and the risk of future coronary artery disease (CAD) in apparently healthy men and women. Elevated levels of MBL are associated with an increased risk of future CAD in apparently healthy men but not in women. The sex difference merits further exploration.
    Materialart: Online-Ressource
    ISSN: 1079-5642 , 1524-4636
    URL: Article
    DOI: 10.1161/01.ATV.0000240517.69201.77
    Sprache: Englisch
    Verlag: Ovid Technologies (Wolters Kluwer Health)
    Publikationsdatum: 2006
    ZDB Id: 1494427-3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 2
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    Abstract 3132: Paraoxonase-1 Activity Is not Independently Related with the Risk of Future Coronary Artery Disease
    Ovid Technologies (Wolters Kluwer Health) ; 2008
    In:  Circulation Vol. 118, No. suppl_18 ( 2008-10-28)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 118, No. suppl_18 ( 2008-10-28)
    Kurzfassung: Background Paraoxonase-1 (PON1) is a potent antioxidant enzyme bound to high-density lipoprotein (HDL). Its activity, but not its concentration, is controlled by the PON1 Q192R polymorphism. PON1 is considered to protect against atherogenesis, but it is unclear whether this relation is independent of its carrier, HDL. Objective To evaluate the predictive value of PON1 for coronary artery disease (CAD) we assessed PON1 activity and genotype (Q192R polymorphism) in a large cohort. Methods and results We performed a case-control study nested in the prospective EPIC-Norfolk cohort. Cases (n = 1138) were apparently healthy men and women aged 45–79 years who developed fatal or nonfatal CAD during a mean follow-up of 6 years. Controls (n=2237) were matched by age and sex. Serum PON1 activity was lower in cases vs. controls (59.9 ± 44.6 U/L vs. 63.4 ± 46.7 U/L, p=0.020) and correlated with HDL cholesterol (r= 0.16, p 〈 0.0001). Whereas the PON1 Q192R polymorphism strongly controlled PON1 activity (QQ: 27 ± 9, QR: 87 ± 27 and RR 152 ± 44 U/L), it was not related to the risk of future CAD (Odds Ratio [OR] per R allele 0.98 [0.84–1.15] , p=0.84). Using conditional logistic regression, quartiles of PON1 activity showed a modest inverse relation with CAD risk (OR for the highest vs. the lowest quartile 0.77 [0.63– 0.95], p=0.013; p for trend over quartiles 0.064). PON1 activity adjusted for Q192R genotype - a proxy for PON1 concentration -correlated better with HDL cholesterol (r=0.29, p 〈 0.0001) and strongly predicted CAD risk (OR for the highest versus the lowest quartile 0.72 (0.58 – 0.91), p for trend over quartiles = 0.005). However, this relation was abolished after adjustment for HDL related parameters (HDL particle number, HDL cholesterol, HDL size and apolipoprotein A-I; OR for highest vs. lowest quartile 0.87 [0.66 –1.16], p for trend over quartiles = 0.13). Conclusion In the largest prospective study to date, we show that PON1 activity inversely relates to CAD risk, but not independently of HDL, presumably due to its close association with the HDL particle. Since the Q192R polymorphism profoundly affects lifelong PON1 activity, our inability to demonstrate a relation between the Q192R polymorphism and CAD risk suggests that PON1 activity is not a causal factor in atherogenesis.
    Materialart: Online-Ressource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.118.suppl_18.S_1099
    Sprache: Englisch
    Verlag: Ovid Technologies (Wolters Kluwer Health)
    Publikationsdatum: 2008
    ZDB Id: 1466401-X
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 3
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    Effect of Vegan Fecal Microbiota Transplantation on Carnitine‐ and Choline‐Derived Trimethylamine‐N‐Oxide Production and Vascular Inflammation in Patients With Metabolic Syndrome
    Ovid Technologies (Wolters Kluwer Health) ; 2018
    In:  Journal of the American Heart Association Vol. 7, No. 7 ( 2018-04-03)
    Details
    In: Journal of the American Heart Association, Ovid Technologies (Wolters Kluwer Health), Vol. 7, No. 7 ( 2018-04-03)
    Kurzfassung: Intestinal microbiota have been found to be linked to cardiovascular disease via conversion of the dietary compounds choline and carnitine to the atherogenic metabolite TMAO (trimethylamine‐N‐oxide). Specifically, a vegan diet was associated with decreased plasma TMAO levels and nearly absent TMAO production on carnitine challenge. Methods and Results We performed a double‐blind randomized controlled pilot study in which 20 male metabolic syndrome patients were randomized to single lean vegan‐donor or autologous fecal microbiota transplantation. At baseline and 2 weeks thereafter, we determined the ability to produce TMAO from d 6 ‐choline and d 3 ‐carnitine (eg, labeled and unlabeled TMAO in plasma and 24‐hour urine after oral ingestion of 250 mg of both isotope‐labeled precursor nutrients), and fecal samples were collected for analysis of microbiota composition. 18 F‐fluorodeoxyglucose positron emission tomography/computed tomography scans of the abdominal aorta, as well as ex vivo peripheral blood mononuclear cell cytokine production assays, were performed. At baseline, fecal microbiota composition differed significantly between vegans and metabolic syndrome patients. With vegan‐donor fecal microbiota transplantation, intestinal microbiota composition in metabolic syndrome patients, as monitored by global fecal microbial community structure, changed toward a vegan profile in some of the patients; however, no functional effects from vegan‐donor fecal microbiota transplantation were seen on TMAO production, abdominal aortic 18 F‐fluorodeoxyglucose uptake, or ex vivo cytokine production from peripheral blood mononuclear cells. Conclusions Single lean vegan‐donor fecal microbiota transplantation in metabolic syndrome patients resulted in detectable changes in intestinal microbiota composition but failed to elicit changes in TMAO production capacity or parameters related to vascular inflammation. Clinical Trial Registration URL : http://www.trialregister.nl . Unique identifier: NTR 4338.
    Materialart: Online-Ressource
    ISSN: 2047-9980
    URL: Article
    DOI: 10.1161/JAHA.117.008342
    Sprache: Englisch
    Verlag: Ovid Technologies (Wolters Kluwer Health)
    Publikationsdatum: 2018
    ZDB Id: 2653953-6
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 4
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    Abstract 11043: Clinical Safety Outcomes in Relation to Lipoprotein(a) Concentration: Insights from the FOURIER Trial
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Circulation Vol. 144, No. Suppl_1 ( 2021-11-16)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 144, No. Suppl_1 ( 2021-11-16)
    Kurzfassung: Background: Lipoprotein(a) is believed to play a causal role in atherogenesis. Drugs are in development that directly target Lp(a) and lower levels by 〉 75%. Thus, the safety of low Lp(a) levels is of importance. Methods: FOURIER randomized 27,564 patients w/ stable ASCVD to evolocumab (EVO) vs placebo on background statin (median f/up 2.2 y); EVO lowered Lp(a) levels by 27%. The relationships between Lp(a) levels, change in Lp(a) and 5 safety outcomes of interest based on prior reports (diabetes [DM], serious bleeding, hemorrhagic stroke, neurocognitive events, malignancy) were examined. Analyses were conducted in the overall population and by treatment arm. Multivariable models included age, sex, race, region, clinical predictors, high-intensity statin, ezetimibe, baseline hs-CRP, “Lp(a)-corrected” LDL-C, and treatment arm. Results: Lp(a) was assessed in 25,083 participants at baseline (median 37nM, range 5-1451) and 25,686 at week 12. There was no association between baseline or achieved Lp(a) levels and risk of serious bleeding, hemorrhagic stroke, neurocognitive events, or malignancy, even in the 3271 patients with Lp(a) levels ≤6nM. There was an inverse association between baseline Lp(a) levels and prevalent or incident DM [OR 1.09, 95%CI 1.07-1.12, for every 50nM lower Lp(a) below 250nM]. However, absolute change in Lp(a) with EVO was not associated with subsequent DM risk (HR 1.03, 0.91-1.16, per 50nM) and EVO did not increase the risk of DM irrespective of baseline Lp(a) (P int=0.97), even in participants in the top decile of baseline Lp(a) (HR 0.91, 0.51-1.62) in whom EVO reduced Lp(a) by 63nM. Conclusion: Lp(a) concentration and changes in Lp(a) were not associated with serious bleeding, hemorrhagic stroke, neurocognitive events, or malignancy. Levels were inversely correlated with having DM, but Lp(a) lowering over a median of 2.2 years with EVO did not further increase the risk. These findings provide new insights for ongoing trials of Lp(a)-lowering drugs.
    Materialart: Online-Ressource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.144.suppl_1.11043
    Sprache: Englisch
    Verlag: Ovid Technologies (Wolters Kluwer Health)
    Publikationsdatum: 2021
    ZDB Id: 1466401-X
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 5
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    Helium Induces Preconditioning in Human Endothelium In Vivo  
    Ovid Technologies (Wolters Kluwer Health) ; 2013
    In:  Anesthesiology Vol. 118, No. 1 ( 2013-01-01), p. 95-104
    Details
    In: Anesthesiology, Ovid Technologies (Wolters Kluwer Health), Vol. 118, No. 1 ( 2013-01-01), p. 95-104
    Materialart: Online-Ressource
    ISSN: 0003-3022
    URL: Article
    DOI: 10.1097/ALN.0b013e3182751300
    RVK:
    XA 22600
    Sprache: Englisch
    Verlag: Ovid Technologies (Wolters Kluwer Health)
    Publikationsdatum: 2013
    ZDB Id: 2016092-6
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 6
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    Abstract 3151: Inflammatory Markers and Risk of Coronary Heart Disease in Relation to the Apob/Apoa-i Ratio in Healthy Men and Women; The Epic-Norfolk Population Study
    Ovid Technologies (Wolters Kluwer Health) ; 2008
    In:  Circulation Vol. 118, No. suppl_18 ( 2008-10-28)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 118, No. suppl_18 ( 2008-10-28)
    Kurzfassung: Studies have shown that individuals with an elevated apoB/apoA-I ratio are at increased risk for CHD. Presence of higher levels of inflammatory markers is also associated with increased CHD risk. The respective contributions of the apoB/apoA-I ratio and inflammatory markers to CHD risk are unknown. The apoB/apoA-I ratio and the plasma concentrations of an extensive panel of inflammatory markers including CRP, adiponectin, fibrinogen, myeloperoxidase, secretory phospholipase A2 (sPLA2) as well as lipoprotein-associated phospholipase A2 (Lp-PLA2) activity were measured in a prospective case-control study of 844 cases and 1762 matched controls (1651 men and 955 women) aged between 45–79 years who participated to the EPIC-Norfolk prospective population study. In both sexes, compared to participants in bottom apoB/apoA-I ratio tertile, participants in the top tertile had the highest levels of CRP (4.4 [3.7–5.0] vs. 2.8 [2.4 –3.2] mg/dL, p 〈 0.001 in men and 4.1 [3.4 – 4.8] vs. 3.1 [2.6 –3.6] mg/dL, p=0.03 in women), fibrinogen (3.2 [3.1–3.2] vs. 2.9 [2.8 –2.9] g/L, p 〈 0.001 in men and 3.2 [3.1–3.2] vs. 3.0 [2.9 –3.1] g/L, p 〈 0.001 in women) and the highest Lp-PLA2 activity (60.7 [59.3– 62.1] vs. 47.3 [46.0 – 48.6] nmol/min/mL, p 〈 0.001 in men and 55.6 [53.8 –57.4] vs. 41.5 [40.2– 42.8] nmol/min/mL, p 〈 0.001 in women) and the lowest adiponectin levels (7.9 [7.6 – 8.3] vs. 10.2 [9.7–10.6] μg/mL, p 〈 0.001 in men and 11.3 [12.7–13.5] vs. 15.5 [14.6 –16.1] μg/mL, p 〈 0.001). Myeloperoxidase and sPLA2 levels did not differ in apoB/apoA-I ratio tertiles. Compared to men in the bottom apoB/apoA-I ratio tertile and only 0 or 1 inflammatory markers in the top tertile (bottom for adiponectin), men in the top apoB/apoA-I ratio tertile had odds ratio (OR) for future CHD of 1.7 [95%CI 1.1–2.5], whereas those with 4, 5 or 6 inflammatory markers in the top tertile had an OR of 2.1 [1.4 –3.1] for future CHD. Among women, these OR for future CHD were of 1.7 [1.05–2.9] and 2.2 [1.2–3.9] . Men and women with an elevated apoB/apoA-I ratio also exhibited increased levels of inflammatory markers. The presence of additional elevated levels of multiple inflammatory markers was associated with an elevated CHD risk independent of higher levels of apoB/apoA-I ratio.
    Materialart: Online-Ressource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.118.suppl_18.S_1104
    Sprache: Englisch
    Verlag: Ovid Technologies (Wolters Kluwer Health)
    Publikationsdatum: 2008
    ZDB Id: 1466401-X
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 7
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    C‐Reactive Protein Identifies Low‐Risk Metabolically Healthy Obese Persons: The European Prospective Investigation of Cancer–Norfolk Prospective Population Study
    Ovid Technologies (Wolters Kluwer Health) ; 2016
    In:  Journal of the American Heart Association Vol. 5, No. 6 ( 2016-06-13)
    Details
    In: Journal of the American Heart Association, Ovid Technologies (Wolters Kluwer Health), Vol. 5, No. 6 ( 2016-06-13)
    Kurzfassung: Conflicting data exist about the cardiovascular risk of metabolically healthy obese persons. The prognostic value of C‐reactive protein ( CRP ) in this intriguing group is unknown. We assessed the association between CRP levels and the risk of coronary heart disease ( CHD ) in metabolically healthy persons with abdominal obesity. Methods and Results In the European Prospective Investigation of Cancer–Norfolk prospective cohort, CRP levels and information on metabolic syndrome criteria were available for 7279 participants, of whom 825 (11%) developed CHD during a follow‐up period of 10.9±1.8 years. There was a trend toward a higher multivariable‐adjusted hazard ratio for CHD in metabolically healthy obese participants with CRP levels 〉 2 mg/L compared with 〈 2 mg/L (hazard ratio 1.59, 95% CI 0.97–2.62, P =0.066). Metabolically unhealthy obese participants had significantly higher CHD risk compared with metabolically healthy obese participants with CRP levels 〈 2 mg/L (hazard ratio 1.88, 95% CI 1.20–2.94, P =0.006). Most important, we found that the risk of CHD among metabolically healthy obese persons with CRP levels 〈 2 mg/L was comparable to that of metabolically healthy nonobese persons (hazard ratio 0.91, 95% CI 0.60–1.39, P =0.674). Conclusions Among metabolically healthy obese persons, low CRP levels were associated with a CHD risk comparable to that of metabolically healthy nonobese persons. CRP appears to be an easy and widely available method for identifying a low‐risk subpopulation among metabolically healthy obese persons.
    Materialart: Online-Ressource
    ISSN: 2047-9980
    URL: Article
    DOI: 10.1161/JAHA.115.002823
    Sprache: Englisch
    Verlag: Ovid Technologies (Wolters Kluwer Health)
    Publikationsdatum: 2016
    ZDB Id: 2653953-6
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 8
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    apoB/apoA‐I Ratio and Lp(a) Associations With Aortic Valve Stenosis Incidence: Insights From the EPIC‐Norfolk Prospective Population Study
    Ovid Technologies (Wolters Kluwer Health) ; 2019
    In:  Journal of the American Heart Association Vol. 8, No. 16 ( 2019-08-20)
    Details
    In: Journal of the American Heart Association, Ovid Technologies (Wolters Kluwer Health), Vol. 8, No. 16 ( 2019-08-20)
    Kurzfassung: Apolipoprotein B/apolipoprotein A‐I (apoB/apoA‐I) ratio and lipoprotein(a) (Lp[a]) are associated with aortic valve stenosis ( AVS ) disease progression. Clinical characteristics such as age, sex, and presence of concomitant coronary artery disease may strongly modify these associations; however, these effects have not been well defined in longitudinal studies. We set out to assess these associations between apoB/apoA‐I ratio, Lp(a), and AVS incidence in a large population study. Methods and Results We analyzed data from 17 745 participants (mean age, 59.2±9.1 years; men, 44.9%) in the EPIC ‐Norfolk (European Prospective Investigation Into Cancer in Norfolk Prospective Population Study) population study in whom apoB/apoA‐I and Lp(a) levels were measured. Participants were identified as having incident AVS if they were hospitalized or died with AVS as an underlying cause. After a median follow‐up of 19.8 years (17.9–21.0 years) there were 403 (2.2%) incident cases of AVS . The hazard ratio for AVS risk was 1.30 (95% CI , 1.19–1.41; P 〈 0.001) per SD increase in apoB/apoA‐I. Adjusting for age, sex, and coronary artery disease, there was no significant association between apoB/apoA‐I and AVS incidence (hazard ratio, 1.06; 95% CI , 0.97–1.17 [ P =0.215]). Elevated Lp(a) ( 〉 50 mg/ dL ) remained an independent risk factor for AVS after adjustment for age, sex, low‐density lipoprotein cholesterol, and concomitant coronary artery disease (hazard ratio, 1.70; 95% CI , 1.33–2.19 [ P 〈 0.001]). Conclusions In this population study, apoB/apoA‐I ratio was associated with risk of AVS incidence, especially in younger and female participants and those without concomitant coronary artery disease. Lp(a) was an independent risk factor for AVS incidence. Interventional trials are needed to investigate whether modulating apoB/apoA‐I or lowering Lp(a) can prevent or slow down AVS .
    Materialart: Online-Ressource
    ISSN: 2047-9980
    URL: Article
    DOI: 10.1161/JAHA.119.013020
    Sprache: Englisch
    Verlag: Ovid Technologies (Wolters Kluwer Health)
    Publikationsdatum: 2019
    ZDB Id: 2653953-6
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 9
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    Abstract 12066: The Long-Term Safety and Efficacy of Evinacumab in Patients With Homozygous Familial Hypercholesterolemia
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Circulation Vol. 144, No. Suppl_1 ( 2021-11-16)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 144, No. Suppl_1 ( 2021-11-16)
    Kurzfassung: Background: Homozygous familial hypercholesterolemia (HoFH) is a rare genetic lipid disorder characterized by marked elevations in LDL-C and premature atherosclerotic cardiovascular disease (ASCVD). EU guidelines recommend LDL-C treatment goals of 〈 55 mg/dL and 〈 70 mg/dL for pts with HoFH with and without ASCVD, respectively. Evinacumab (EVIN; an angiopoietin-like 3 inhibitor) significantly reduced LDL-C and was generally well tolerated in pts with HoFH during the 24-week double-blind treatment period (DBTP) of a pivotal Phase 3 study (NCT03399786). Methods: This post-hoc analysis assessed the long-term effect of EVIN on LDL-C goal attainment in pts with HoFH who participated in the subsequent 24-week open-label treatment period (OLTP) of the pivotal Phase 3 study. All pts received intravenous EVIN 15 mg/kg every 4 weeks. Efficacy by background lipid lowering medication (LLM) subgroups and the effect of EVIN on eligibility for apheresis were also assessed. Results: In total, 65 pts entered the OLTP and 64 pts (98.5%) received OL EVIN. Overall, 50.0% achieved LDL-C 〈 100mg/dL, 31.7% achieved LDL-C 〈 70 mg/dL and 23.3% achieved LDL-C 〈 55 mg/dL at Week 48 (end of OLTP) (Figure 1). For the subgroup with ASCVD (n=36), 50.0%, 37.5% and 31.3% achieved LDL-C 〈 100 mg/dL, 〈 70 mg/dL and 〈 55 mg/dL, respectively. Overall, 43.1%, 24.6% and 38.5% of pts qualified for apheresis at baseline and did not qualify for apheresis at Week 48 (using new US, US and EU criteria); no patient discontinued apheresis. EVIN markedly reduced LDL-C, irrespective of background LLM. Overall, treatment-emergent adverse events (TEAEs) occurred in 47 pts (73.4%) during the OLTP. Serious AEs (all unrelated to EVIN) were reported by 7 pts (10.9%), none led to death or EVIN discontinuation. Conclusions: EVIN enabled 31.7% of all pts to achieve LDL-C 〈 70 mg/dL and 31.3% of those with ASCVD to achieve LDL-C 〈 55 mg/dL. EVIN markedly reduced the proportion of pts qualifying for apheresis.
    Materialart: Online-Ressource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.144.suppl_1.12066
    Sprache: Englisch
    Verlag: Ovid Technologies (Wolters Kluwer Health)
    Publikationsdatum: 2021
    ZDB Id: 1466401-X
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 10
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    Efficacy and Safety of Bempedoic Acid in Patients With Hypercholesterolemia and Statin Intolerance
    Ovid Technologies (Wolters Kluwer Health) ; 2019
    In:  Journal of the American Heart Association Vol. 8, No. 7 ( 2019-04-02)
    Details
    In: Journal of the American Heart Association, Ovid Technologies (Wolters Kluwer Health), Vol. 8, No. 7 ( 2019-04-02)
    Kurzfassung: See Editorial by Jia and Virani
    Materialart: Online-Ressource
    ISSN: 2047-9980
    URL: Article
    DOI: 10.1161/JAHA.118.011662
    Sprache: Englisch
    Verlag: Ovid Technologies (Wolters Kluwer Health)
    Publikationsdatum: 2019
    ZDB Id: 2653953-6
    Standort Signatur Einschränkungen Verfügbarkeit
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