@article{WagnerSlaghuisGoebeletal.2021, author = {Wagner, Martin and Slaghuis, J{\"o}rg and G{\"o}bel, Werner and V{\´a}zquez-Boland, Jos{\´e} Antonio and Rychli, Kathrin and Schmitz-Esser, Stephan}, title = {Virulence pattern analysis of three Listeria monocytogenes lineage I epidemic strains with distinct outbreak histories}, series = {Microorganisms}, volume = {9}, journal = {Microorganisms}, number = {8}, issn = {2076-2607}, doi = {10.3390/microorganisms9081745}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-245093}, year = {2021}, abstract = {Strains of the food-borne pathogen Listeria (L.) monocytogenes have diverse virulence potential. This study focused on the virulence of three outbreak strains: the CC1 strain PF49 (serovar 4b) from a cheese-associated outbreak in Switzerland, the clinical CC2 strain F80594 (serovar 4b), and strain G6006 (CC3, serovar 1/2a), responsible for a large gastroenteritis outbreak in the USA due to chocolate milk. We analysed the genomes and characterized the virulence in vitro and in vivo. Whole-genome sequencing revealed a high conservation of the major virulence genes. Minor deviations of the gene contents were found in the autolysins Ami, Auto, and IspC. Moreover, different ActA variants were present. Strain PF49 and F80594 showed prolonged survival in the liver of infected mice. Invasion and intracellular proliferation were similar for all strains, but the CC1 and CC2 strains showed increased spreading in intestinal epithelial Caco2 cells compared to strain G6006. Overall, this study revealed long-term survival of serovar 4b strains F80594 and PF49 in the liver of mice. Future work will be needed to determine the genes and molecular mechanism behind the long-term survival of L. monocytogenes strains in organs.}, language = {en} } @article{SahitiMorbachCejkaetal.2022, author = {Sahiti, Floran and Morbach, Caroline and Cejka, Vladimir and Tiffe, Theresa and Wagner, Martin and Eichner, Felizitas A. and Gelbrich, G{\"o}tz and Heuschmann, Peter U. and St{\"o}rk, Stefan}, title = {Impact of cardiovascular risk factors on myocardial work-insights from the STAAB cohort study}, series = {Journal of Human Hypertension}, volume = {36}, journal = {Journal of Human Hypertension}, number = {3}, issn = {1476-5527}, doi = {10.1038/s41371-021-00509-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-271770}, pages = {235-245}, year = {2022}, abstract = {Myocardial work is a new echocardiography-based diagnostic tool, which allows to quantify left ventricular performance based on pressure-strain loops, and has been validated against invasively derived pressure-volume measurements. Myocardial work is described by its components (global constructive work [GCW], global wasted work [GWW]) and indices (global work index [GWI], global work efficiency [GWE]). Applying this innovative concept, we characterized the prevalence and severity of subclinical left ventricular compromise in the general population and estimated its association with cardiovascular (CV) risk factors. Within the Characteristics and Course of Heart Failure STAges A/B and Determinants of Progression (STAAB) cohort study we comprehensively phenotyped a representative sample of the population of W{\"u}rzburg, Germany, aged 30-79 years. Indices of myocardial work were determined in 1929 individuals (49.3\% female, mean age 54 ± 12 years). In multivariable analysis, hypertension was associated with a mild increase in GCW, but a profound increase in GWW, resulting in higher GWI and lower GWE. All other CV risk factors were associated with lower GCW and GWI, but not with GWW. The association of hypertension and obesity with GWI was stronger in women. We conclude that traditional CV risk factors impact selectively and gender-specifically on left ventricular myocardial performance, independent of systolic blood pressure. Quantifying active systolic and diastolic compromise by derivation of myocardial work advances our understanding of pathophysiological processes in health and cardiac disease.}, language = {en} } @phdthesis{Wagner2022, author = {Wagner, Martin}, title = {Zyto- und Gentoxizit{\"a}t von Zinkoxid-Nanopartikeln in humanen mesenchymalen Stammzellen nach repetitiver Exposition und im Langzeitversuch}, doi = {10.25972/OPUS-27572}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-275726}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {Zinkoxid-Nanopartikel (ZnO-NP) finden in vielen Produkten des t{\"a}glichen Verbrauchs Verwendung. Daten {\"u}ber die toxikologischen Eigenschaften von ZnO-NP werden kontrovers diskutiert. Die menschliche Haut ist in Bezug auf die ZnO-NP Exposition das wichtigste Kontakt-Organ. Intakte Haut stellt eine suffiziente Barriere gegen{\"u}ber NP dar. Bei defekter Haut ist ein Kontakt zu den proliferierenden Stammzellen m{\"o}glich, sodass diese als wichtiges toxikologische Ziel f{\"u}r NP darstellen. Das Ziel dieser Dissertation war die Bewertung der genotoxischen und zytotoxischen Effekte an humanen mesenchymalen Stammzellen (hMSC) durch niedrig dosierte ZnO-NP nach 24 st{\"u}ndiger Exposition, repetitiven Expositionen und im Langzeitversuch bis zu 6 Wochen. Zytotoxische Wirkungen von ZnO-NP wurden mit 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromid-Test (MTT) gemessen. Dar{\"u}ber hinaus wurde die Genotoxizit{\"a}t durch den Comet-Assay bewertet. Zur Langzeitbeobachtung bis zu 6 Wochen wurde die Transmissionselektronenmikroskopie (TEM) verwendet. Zytotoxizit{\"a}t nach 24-st{\"u}ndiger ZnO-NP-Exposition war ab einer Konzentration von 50 µg/ml nachweisbar. Genotoxizit{\"a}t konnten bereits bei Konzentrationen von 1 und 10 µg/ml ZnO-NP beschrieben werden. Wiederholte Exposition verst{\"a}rkte die Zyto-, aber nicht die Genotoxizit{\"a}t. Eine intrazellul{\"a}re NP-Akkumulation mit Penetration der Zellorganelle wurde bei einer Exposition bis zu 6 Wochen beobachtet. Die Ergebnisse deuten auf zytotoxische und genotoxisches Effekte von ZnO-NP hin. Bereits geringe Dosen von ZnO-NP k{\"o}nnen bei wiederholter Exposition toxische Wirkungen hervorrufen sowie eine langfristige Zellakkumulation. Diese Daten sollten bei der Verwendung von ZnO-NP an gesch{\"a}digter Haut ber{\"u}cksichtigt werden.}, subject = {nanoparticle}, language = {de} } @article{YurdadoganMalschKotsevaetal.2021, author = {Yurdadogan, Tino and Malsch, Carolin and Kotseva, Kornelia and Wood, David and Leyh, Rainer and Ertl, Georg and Karmann, Wolfgang and M{\"u}ller-Scholden, Lara and Morbach, Caroline and Breuning, Margret and Wagner, Martin and Gelbrich, G{\"o}tz and Bots, Michiel L. and Heuschmann, Peter U. and St{\"o}rk, Stefan}, title = {Functional versus morphological assessment of vascular age in patients with coronary heart disease}, series = {Scientific Reports}, volume = {11}, journal = {Scientific Reports}, number = {1}, doi = {10.1038/s41598-021-96998-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265810}, year = {2021}, abstract = {Communicating cardiovascular risk based on individual vascular age (VA) is a well acknowledged concept in patient education and disease prevention. VA may be derived functionally, e.g. by measurement of pulse wave velocity (PWV), or morphologically, e.g. by assessment of carotid intima-media thickness (cIMT). The purpose of this study was to investigate whether both approaches produce similar results. Within the context of the German subset of the EUROASPIRE IV survey, 501 patients with coronary heart disease underwent (a) oscillometric PWV measurement at the aortic, carotid-femoral and brachial-ankle site (PWVao, PWVcf, PWVba) and derivation of the aortic augmentation index (AIao); (b) bilateral cIMT assessment by high-resolution ultrasound at three sites (common, bulb, internal). Respective VA was calculated using published equations. According to VA derived from PWV, most patients exhibited values below chronological age indicating a counterintuitive healthier-than-anticipated vascular status: for VA(PWVao) in 68\% of patients; for VA\(_{AIao}\) in 52\% of patients. By contrast, VA derived from cIMT delivered opposite results: e.g. according to VA\(_{total-cIMT}\) accelerated vascular aging in 75\% of patients. To strengthen the concept of VA, further efforts are needed to better standardise the current approaches to estimate VA and, thereby, to improve comparability and clinical utility.}, language = {en} } @article{WalterGrussNeidlingeretal.2020, author = {Walter, Steffen and Gruss, Sascha and Neidlinger, Jana and Stross, Isabelle and Hann, Alexander and Wagner, Martin and Seufferlein, Thomas and Walter, Benjamin}, title = {Evaluation of an Objective Measurement Tool for Stress Level Reduction by Individually Chosen Music During Colonoscopy—Results From the Study "ColoRelaxTone"}, series = {Frontiers in Medicine}, volume = {7}, journal = {Frontiers in Medicine}, doi = {10.3389/fmed.2020.00525}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-212337}, year = {2020}, abstract = {Background and Aims: Colonoscopy as standard procedure in endoscopy is often perceived as uncomfortable for patients. Patient's anxiety is therefore a significant issue, which often lead to avoidance of participation of relevant examinations as CRC-screening. Non-pharmacological anxiety management interventions such as music might contribute to relaxation in the phase prior and during endoscopy. Although music's anxiolytic effects have been reported previously, no objective measurement of stress level reduction has been reported yet. Focus of this study was to evaluate the objective measurement of the state of relaxation in patients undergoing colonoscopy. Methods: Prospective study (n = 196) performed at one endoscopic high-volume center. Standard colonoscopy was performed in control group. Interventional group received additionally self-chosen music over earphones. Facial Electromyography (fEMG) activity was obtained. Clinician Satisfaction with Sedation Instrument (CSSI) and Patients Satisfaction with Sedation Instrument (PSSI) was answered by colonoscopists and patients, respectively. Overall satisfaction with music accompanied colonoscopy was obtained if applicable. Results: Mean difference measured by fEMG via musculus zygomaticus major indicated a significantly lower stress level in the music group [7.700(±5.560) μV vs. 4.820(±3.330) μV; p = 0.001]. Clinician satisfaction was significantly higher with patients listening to music [82.69(±15.04) vs. 87.3(±15.02) pts.; p = 0.001]. Patient's satisfaction was higher but did not differ significantly. Conclusions: We conclude that self-chosen music contributes objectively to a reduced stress level for patients and therefore subjectively perceived satisfaction for endoscopists. Therefore, music should be considered as a non-pharmacological treatment method of distress reduction especially in the beginning of endoscopic procedures.}, language = {en} } @article{DenglerMaldanerGlaeskeretal.2016, author = {Dengler, Julius and Maldaner, Nicolai and Gl{\"a}sker, Sven and Endres, Matthias and Wagner, Martin and Malzahn, Uwe and Heuschmann, Peter U. and Vajkoczy, Peter}, title = {Outcome of Surgical or Endovascular Treatment of Giant Intracranial Aneurysms, with Emphasis on Age, Aneurysm Location, and Unruptured Aneuryms - A Systematic Review and Meta-Analysis}, series = {Cerebrovascular Diseases}, volume = {41}, journal = {Cerebrovascular Diseases}, number = {3-4}, organization = {Giant Intracranial Aneurysm Study Group}, issn = {1015-9770}, doi = {10.1159/000443485}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-196792}, pages = {187-198}, year = {2016}, abstract = {Background: Designing treatment strategies for unruptured giant intracranial aneurysms (GIA) is difficult as evidence of large clinical trials is lacking. We examined the outcome following surgical or endovascular GIA treatment focusing on patient age, GIA location and unruptured GIA. Methods: Medline and Embase were searched for studies reporting on GIA treatment outcome published after January 2000. We calculated the proportion of good outcome (PGO) for all included GIA and for unruptured GIA by meta-analysis using a random effects model. Results: We included 54 studies containing 64 study populations with 1,269 GIA at a median follow-up time (FU-T) of 26.4 months (95\% CI 10.8-42.0). PGO was 80.9\% (77.4-84.4) in the analysis of all GIA compared to 81.2\% (75.3-86.1) in the separate analysis of unruptured GIA. For each year added to patient age, PGO decreased by 0.8\%, both for all GIA and unruptured GIA. For all GIA, surgical treatment resulted in a PGO of 80.3\% (95\% CI 76.0-84.6) compared to 84.2\% (78.5-89.8, p = 0.27) after endovascular treatment. In unruptured GIA, PGO was 79.7\% (95\% CI 71.5-87.8) after surgical treatment and 84.9\% (79.1-90.7, p = 0.54) after endovascular treatment. PGO was lower in high quality studies and in studies presenting aggregate instead of individual patient data. In unruptured GIA, the OR for good treatment outcome was 5.2 (95\% CI 2.0-13.0) at the internal carotid artery compared to 0.1 (0.1-0.3, p < 0.1) in the posterior circulation. Patient sex, FU-T and prevalence of ruptured GIA were not associated with PGO. Conclusions: We found that the chances of good outcome after surgical or endovascular GIA treatment mainly depend on patient age and aneurysm location rather than on the type of treatment conducted. Our analysis may inform future research on GIA.}, language = {en} } @article{MuellerScholdenKirchhofMorbachetal.2019, author = {M{\"u}ller-Scholden, Lara and Kirchhof, Jan and Morbach, Caroline and Breunig, Margret and Meijer, Rudy and R{\"u}cker, Viktoria and Tiffe, Theresa and Yurdadogan, Tino and Wagner, Martin and Gelbrich, G{\"o}tz and Bots, Michiel L. and St{\"o}rk, Stefan and Heuschmann, Peter U.}, title = {Segment-specific association of carotid-intima-media thickness with cardiovascular risk factors - findings from the STAAB cohort study}, series = {BMC Cardiovascular Disorders}, volume = {19}, journal = {BMC Cardiovascular Disorders}, number = {84}, doi = {10.1186/s12872-019-1044-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-200720}, year = {2019}, abstract = {Background The guideline recommendation to not measure carotid intima-media thickness (CIMT) for cardiovascular risk prediction is based on the assessment of just one single carotid segment. We evaluated whether there is a segment-specific association between different measurement locations of CIMT and cardiovascular risk factors. Methods Subjects from the population-based STAAB cohort study comprising subjects aged 30 to 79 years of the general population from W{\"u}rzburg, Germany, were investigated. CIMT was measured on the far wall of both sides in three different predefined locations: common carotid artery (CCA), bulb, and internal carotid artery (ICA). Diabetes, dyslipidemia, hypertension, smoking, and obesity were considered as risk factors. In multivariable logistic regression analysis, odds ratios of risk factors per location were estimated for the endpoint of individual age- and sex-adjusted 75th percentile of CIMT. Results 2492 subjects were included in the analysis. Segment-specific CIMT was highest in the bulb, followed by CCA, and lowest in the ICA. Dyslipidemia, hypertension, and smoking were associated with CIMT, but not diabetes and obesity. We observed no relevant segment-specific association between the three different locations and risk factors, except for a possible interaction between smoking and ICA. Conclusions As no segment-specific association between cardiovascular risk factors and CIMT became evident, one simple measurement of one location may suffice to assess the cardiovascular risk of an individual.}, language = {en} } @article{TiffeMorbachRueckeretal.2019, author = {Tiffe, Theresa and Morbach, Caroline and R{\"u}cker, Viktoria and Gelbrich, G{\"o}tz and Wagner, Martin and Faller, Hermann and St{\"o}rk, Stefan and Heuschmann, Peter U.}, title = {Impact of patient beliefs on blood pressure control in the general population: findings from the population-based STAAB cohort study}, series = {International Journal of Hypertension}, volume = {2019}, journal = {International Journal of Hypertension}, doi = {10.1155/2019/9385397}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-200992}, pages = {9385397}, year = {2019}, abstract = {Background. Effective antihypertensive treatment depends on patient compliance regarding prescribed medications. We assessed the impact of beliefs related towards antihypertensive medication on blood pressure control in a population-based sample treated for hypertension. Methods. We used data from the Characteristics and Course of Heart Failure Stages A-B and Determinants of Progression (STAAB) study investigating 5000 inhabitants aged 30 to 79 years from the general population of W{\"u}rzburg, Germany. The Beliefs about Medicines Questionnaire German Version (BMQ-D) was provided in a subsample without established cardiovascular diseases (CVD) treated for hypertension. We evaluated the association between inadequately controlled hypertension (systolic RR >140/90 mmHg; >140/85 mmHg in diabetics) and reported concerns about and necessity of antihypertensive medication. Results. Data from 293 participants (49.5\% women, median age 64 years [quartiles 56.0; 69.0]) entered the analysis. Despite medication, half of the participants (49.8\%) were above the recommended blood pressure target. Stratified for sex, inadequately controlled hypertension was less frequent in women reporting higher levels of concerns (OR 0.36; 95\%CI 0.17-0.74), whereas no such association was apparent in men. We found no association for specific-necessity in any model. Conclusion. Beliefs regarding the necessity of prescribed medication did not affect hypertension control. An inverse association between concerns about medication and inappropriately controlled hypertension was found for women only. Our findings highlight that medication-related beliefs constitute a serious barrier of successful implementation of treatment guidelines and underline the role of educational interventions taking into account sex-related differences.}, language = {en} } @phdthesis{Wagner2019, author = {Wagner, Martin}, title = {Assoziations- und Haplotypenanalyse genetischer Ver{\"a}nderungen der Pannexin-Gengruppe bei Patienten mit schizophrenen Psychosen nach ICD-10 und der Klassifikation von Karl Leonhard}, doi = {10.25972/OPUS-18851}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-188512}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2019}, abstract = {Bestimmung von genetischen Ver{\"a}nderungen auf PANX 1-3 anhand von Einzelnukleotid Polymorphismen (SNP). Test auf Assoziation von Allelen und Haplotypen mit den schizophrenen Psychosen nach ICD-10 und der Klassifikation von Karl Leonhard in Form einer Fall-Kontroll-Studie mit 1163 Patienten und 479 Kontrollen.}, subject = {panx1}, language = {de} } @article{IckrathWagnerScherzadetal.2017, author = {Ickrath, Pascal and Wagner, Martin and Scherzad, Agmal and Gehrke, Thomas and Burghartz, Marc and Hagen, Rudolf and Radeloff, Katrin and Kleinsasser, Norbert and Hackenberg, Stephan}, title = {Time-Dependent Toxic and Genotoxic Effects of Zinc Oxide Nanoparticles after Long-Term and Repetitive Exposure to Human Mesenchymal Stem Cells}, series = {International Journal of Environmental Research and Public Health}, volume = {14}, journal = {International Journal of Environmental Research and Public Health}, number = {12}, doi = {10.3390/ijerph14121590}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-169932}, pages = {1590}, year = {2017}, abstract = {Zinc oxide nanoparticles (ZnO-NP) are widely spread in consumer products. Data about the toxicological characteristics of ZnO-NP is still under controversial discussion. The human skin is the most important organ concerning ZnO-NP exposure. Intact skin was demonstrated to be a sufficient barrier against NPs; however, defect skin may allow NP contact to proliferating cells. Within these cells, stem cells are the most important toxicological target for NPs. The aim of this study was to evaluate the genotoxic and cytotoxic effects of ZnO-NP at low-dose concentrations after long-term and repetitive exposure to human mesenchymal stem cells (hMSC). Cytotoxic effects of ZnO-NP were measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Furthermore, genotoxicity was evaluated by the comet assay. For long-term observation over 6 weeks, transmission electron microscopy (TEM) was applied. The results of the study indicated cytotoxic effects of ZnO-NP beginning at high concentrations of 50 μg/mL and genotoxic effects in hMSC exposed to 1 and 10 μg/mL ZnO-NP. Repetitive exposure enhanced cyto- but not genotoxicity. Intracellular NP accumulation was observed up to 6 weeks. The results suggest cytotoxic and genotoxic potential of ZnO-NP. Even low doses of ZnO-NP may induce toxic effects as a result of repetitive exposure and long-term cellular accumulation. This data should be considered before using ZnO-NP on damaged skin.}, language = {en} }