33 results on '"Kreft, D"'
Search Results
2. Campylobacter jejuni capsular genotypes are related to Guillain–Barré syndrome
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Heikema, A.P., Islam, Z., Horst-Kreft, D., Huizinga, R., Jacobs, B.C., Wagenaar, J.A., Poly, F., Guerry, P., van Belkum, A., Parker, C.T., and Endtz, H.P.
- Published
- 2015
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3. Comparison of illumina versus nanopore 16s rRNA gene sequencing of the human nasal microbiota
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Heikema, A.P. (Astrid), Horst-Kreft, D. (Deborah), Boers, S.A. (Stefan), Jansen, R. (Rick), Hiltemann, S. (Saskia), Koning, W. (Willem) de, Kraaij, R. (Robert), Ridder, M.A.J. (Maria) de, van Houten, C.B. (Chantal B.), Bont, L.J. (Louis), Stubbs, A.P. (Andrew), Hays, J.P. (John), Heikema, A.P. (Astrid), Horst-Kreft, D. (Deborah), Boers, S.A. (Stefan), Jansen, R. (Rick), Hiltemann, S. (Saskia), Koning, W. (Willem) de, Kraaij, R. (Robert), Ridder, M.A.J. (Maria) de, van Houten, C.B. (Chantal B.), Bont, L.J. (Louis), Stubbs, A.P. (Andrew), and Hays, J.P. (John)
- Abstract
Illumina and nanopore sequencing technologies are powerful tools that can be used to determine the bacterial composition of complex microbial communities. In this study, we compared nasal microbiota results at genus level using both Illumina and nanopore 16S rRNA gene sequencing. We also monitored the progression of nanopore sequencing in the accurate identification of species, using pure, single species cultures, and evaluated the performance of the nanopore EPI2ME 16S data analysis pipeline. Fifty-nine nasal swabs were sequenced using Illumina MiSeq and Oxford Nanopore 16S rRNA gene sequencing technologies. In addition, five pure cultures of relevant bacterial species were sequenced with the nanopore sequencing technology. The Illumina MiSeq sequence data were processed using bioinformatics modules present in the Mothur software package. Albacore and Guppy base calling, a workflow in nanopore EPI2ME (Oxford Nanopore Technologies—ONT, Oxford, UK) and an in-house developed bioinformatics script were used to analyze the nanopore data. At genus level, similar bacterial diversity profiles were found, and five main and established genera were identified by both platforms. However, probably due to mismatching of the nanopore sequence primers, the nanopore sequencing platform identified Corynebacterium in much lower abundance compared to Illumina sequencing. Further, when using default settings in the EPI2ME workflow, almost all sequence reads that seem to belong to the bacterial genus Dolosigranulum and a considerable part to the genus Haemophilus were only identified at family level. Nanopore sequencing of single species cultures demonstrated at least 88% accurate identification of the species at genus and species level for 4/5 strains tested, including improvements in accurate sequence read identification when the basecaller Guppy and Albacore, and when flowcell versions R9.4 (Oxford Nanopore Technologies—ONT, Oxford, UK) and R9.2 (Oxford Nanopore Technologies—ONT, Oxf
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- 2020
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4. Guide-free Cas9 from pathogenic Campylobacter jejuni bacteria causes severe damage to DNA
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Saha, C. (Chinmoy), Mohanraju, P. (Prarthana), Stubbs, A.P. (Andrew), Dugar, G. (Gaurav), Hoogstrate, Y. (Youri), Kremers, G.J. (Gert-Jan), Cappellen, W.A. (Gert) van, Horst-Kreft, D. (Deborah), Laffeber, C., Lebbink, J.H.G. (Joyce), Bruens, S.T. (Serena), Gaskin, D. (Duncan), Beerens, D.M.J.M. (Dior), Klunder, M. (Maarten), Joosten, R. (Rob), Demmers, J.A.A. (Jeroen), Gent, D.C. (Dik) van, Mouton, J.W. (Johan), Spek, P.J. (Peter) van der, Oost, J. van der, Baarlen, P. (Peter) van, Louwen, R.P.L. (Rogier), Saha, C. (Chinmoy), Mohanraju, P. (Prarthana), Stubbs, A.P. (Andrew), Dugar, G. (Gaurav), Hoogstrate, Y. (Youri), Kremers, G.J. (Gert-Jan), Cappellen, W.A. (Gert) van, Horst-Kreft, D. (Deborah), Laffeber, C., Lebbink, J.H.G. (Joyce), Bruens, S.T. (Serena), Gaskin, D. (Duncan), Beerens, D.M.J.M. (Dior), Klunder, M. (Maarten), Joosten, R. (Rob), Demmers, J.A.A. (Jeroen), Gent, D.C. (Dik) van, Mouton, J.W. (Johan), Spek, P.J. (Peter) van der, Oost, J. van der, Baarlen, P. (Peter) van, and Louwen, R.P.L. (Rogier)
- Abstract
CRISPR-Cas9 systems are enriched in human pathogenic bacteria and have been linked to cytotoxicity by an unknown mechanism. Here, we show that upon infection of human cells, Campylobacter jejuni secretes its Cas9 (CjeCas9) nuclease into their cytoplasm. Next, a native nuclear localization signal enables CjeCas9 nuclear entry, where it catalyzes metal-dependent nonspecific DNA cleavage leading to cell death. Compared to CjeCas9, native Cas9 of Streptococcus pyogenes (SpyCas9) is more suitable for guide-dependent editing. However, in human cells, native SpyCas9 may still cause some DNA damage, most likely because of its ssDNA cleavage activity. This side effect can be completely prevented by saturation of SpyCas9 with an appropriate guide RNA, which is only partially effective for CjeCas9. We conclude that CjeCas9 plays an active role in attacking human cells rather than in viral defense. Moreover, these unique catalytic features may therefore make CjeCas9 less suitable for genome editing applications.
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- 2020
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5. Diabetic retinopathy screening in incident diabetes mellitus type 2 in Germany between 2004 and 2013-A prospective cohort study based on health claims data
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Pan, C-W, Kreft, D, McGuinness, MB, Doblhammer, G, Finger, RP, Pan, C-W, Kreft, D, McGuinness, MB, Doblhammer, G, and Finger, RP
- Abstract
OBJECTIVE: To assess factors associated with diabetic retinopathy (DR) screening uptake following a diagnosis of type 2 diabetes mellitus (type 2 diabetes) in Germany. MATERIALS AND METHODS: A nationally representative prospective sample of individual-level health claims data for 250,000 members from Germany's largest public insurance provider in 2004-2013 was assessed. In the sample, 26,560 persons with incident type 2 diabetes were identified. Factors associated with subsequent DR screening were assessed using descriptive statistics, Kaplan-Meier estimator, and Cox regression analysis. RESULTS: On average 27.6 visits to an ophthalmologist per 100 person-years in persons with incident type 2 diabetes occurred. Half of all incident cases (Kaplan-Meier estimator) had not seen an ophthalmologist after more than two years (2.25 years) following their diabetes diagnosis. In the multivariate analysis, an older age (from hazard ratio HR(70-74) = 0.93 [95%-CI: 0.89-0.97] to HR(90+) = 0.50 [95%-CI: 0.42-0.60] compared to persons aged 50-69 years) and a higher disability level (i.e. HR(disability level 3) = 0.30 [95%-CI: 0.25-0.36]) were associated with a lower likelihood, while female sex (HR = 1.12 [95%-CI: 1.08-1.15]), six or more comorbidities (HR = 1.26 [95%-CI: 1.15-1.37]), moderate (HR = 1.51 [95%-CI: 1.46-1.56]) or severe type 2 diabetes (HR = 1.53 [95%-CI: 1.45-1.61]) as well as being enrolled in a type 2 diabetes disease management program (HR = 1.78 [95%-CI: 1.69-1.87]) were associated with a higher likelihood of DR screening. CONCLUSIONS: A high proportion of newly diagnosed persons with type 2 diabetes did not follow current German recommendations for DR screening, impeding timely detection and management of potential complications. This was more apparent among persons who were men, older or had a disability. The uptake of screening was considerably greater among those enrolled in a diseases management program. These factors need to be considered when planning D
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- 2018
6. Der Einfluss sozioökonomischer Faktoren der Wohnregion auf Kompression und Expansion der Pflegebedürftigkeit in Deutschland 2001-2009
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Kreft, D, Doblhammer, G, Kreft, D, and Doblhammer, G
- Published
- 2018
7. Der Einfluss von sozio-ökonomischen und -strukturellen Bedingungen der Wohnregion auf das Risiko der Schwerhörigkeit und Taubheit - Eine Untersuchung basierend auf Daten der Allgemeinen Ortskrankenkassen
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Kreft, D, Doblhammer, G, Kreft, D, and Doblhammer, G
- Published
- 2018
8. Prävalenz , Inzidenz und Einflussfaktoren von Offenwinkel-Glaukomen in Deutschland – eine prospektive Kohortenstudie basierend auf Längsschnittdaten der Allgemeinen Ortskrankenkasse
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Kreft, D, Doblhammer, G, Guthoff, R, and Frech, S
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ddc: 610 ,610 Medical sciences ,Medicine - Abstract
Hintergrund: Glaukomerkrankungen zählen zu den häufigsten Augenerkrankungen und sind eine der Hauptursachen für Erblindungen. Die überwiegende Mehrheit von Glaukomen sind dabei die Offenwinkel-Glaukome. Aufgrund der Tatsache, dass Offenwinkel-Glaukomerkrankungen mit dem Alter zunehmen,[zum vollständigen Text gelangen Sie über die oben angegebene URL], 15. Deutscher Kongress für Versorgungsforschung
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- 2016
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9. Campylobacter jejuni capsular genotypes are related to Guillain-Barré syndrome
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Heikema, A P, Islam, Z, Horst-Kreft, D, Huizinga, R, Jacobs, B C, Wagenaar, J A, Poly, F, Guerry, P, van Belkum, A, Parker, C T, Endtz, H P, Heikema, A P, Islam, Z, Horst-Kreft, D, Huizinga, R, Jacobs, B C, Wagenaar, J A, Poly, F, Guerry, P, van Belkum, A, Parker, C T, and Endtz, H P
- Abstract
In about one in a thousand cases, a Campylobacter jejuni infection results in the severe polyneuropathy Guillain-Barré syndrome (GBS). It is established that sialylated lipo-oligosaccharides (LOS) of C. jejuni are a crucial virulence factor in GBS development. Frequent detection of C. jejuni with sialylated LOS in stools derived from patients with uncomplicated enteritis implies that additional bacterial factors should be involved. To assess whether the polysaccharide capsule is a marker for GBS, the capsular genotypes of two geographically distinct GBS-associated C. jejuni strain collections and an uncomplicated enteritis control collection were determined. Capsular genotyping of C. jejuni strains from the Netherlands revealed that three capsular genotypes, HS1/44c, HS2 and HS4c, were dominant in GBS-associated strains and capsular types HS1/44c and HS4c were significantly associated with GBS (p 0.05 and p 0.01, respectively) when compared with uncomplicated enteritis. In a GBS-associated strain collection from Bangladesh, capsular types HS23/36c, HS19 and HS41 were most prevalent and the capsular types HS19 and HS41 were associated with GBS (p 0.008 and p 0.02, respectively). Next, specific combinations of the LOS class and capsular genotypes were identified that were related to the occurrence of GBS. Multilocus sequence typing revealed restricted genetic diversity for strain populations with the capsular types HS2, HS19 and HS41. We conclude that capsular types HS1/44c, HS2, HS4c, HS19, HS23/36c and HS41 are markers for GBS. Besides a crucial role for sialylated LOS of C. jejuni in GBS pathogenesis, the identified capsules may contribute to GBS susceptibility.
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- 2015
10. Campylobacter jejuni capsular genotypes are related to Guillain-Barré syndrome
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dI&I I&I-4, LS Klinisch Onderzoek Wagenaar, Infection & Immunity, Heikema, A P, Islam, Z, Horst-Kreft, D, Huizinga, R, Jacobs, B C, Wagenaar, J A, Poly, F, Guerry, P, van Belkum, A, Parker, C T, Endtz, H P, dI&I I&I-4, LS Klinisch Onderzoek Wagenaar, Infection & Immunity, Heikema, A P, Islam, Z, Horst-Kreft, D, Huizinga, R, Jacobs, B C, Wagenaar, J A, Poly, F, Guerry, P, van Belkum, A, Parker, C T, and Endtz, H P
- Published
- 2015
11. Numerical Simulation of Light to Heat Conversion by Plasmonic Nanoheaters.
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Nevárez Martínez MC, Kreft D, Grzegorczyk M, Mahlik S, Narajczyk M, Zaleska-Medynska A, Morales DP, Hollingsworth JA, and Werner JH
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Plasmonic nanoparticles are widely recognized as photothermal conversion agents, i.e., nanotransducers or nanoheaters. Translation of these materials into practical applications requires quantitative analyses of their photothermal conversion efficiencies (η). However, the value of η obtained for different materials is dramatically influenced by the experimental setup and method of calculation. Here, we evaluate the most common methods for estimating η (Roper's and Wang's) and compare these with numerical estimates using the simulation software ANSYS. Experiments were performed with colloidal gold nanorod solutions suspended in a hanging droplet irradiated by an 808 nm diode laser and monitored by a thermal camera. The ANSYS simulations accounted for both heating and evaporation, providing η values consistent with the Wang method but higher than the Roper approach. This study details methods for estimating the photothermal efficiency and finds ANSYS to be a robust tool where experimental constraints complicate traditional methods.
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- 2025
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12. Coronary artery bypass grafting vs. drug-eluting stent implantation: the probabilities of reintervention, transition to severe care-need, nursing home, and death in patients with coronary artery disease within the first three years: evaluations based on health claims data in Germany.
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Georges D, Kreft D, and Doblhammer G
- Abstract
Background: Coronary artery bypass grafting (CABG) and drug-eluting stent implantation (DES) are established as central methods of revascularization for patients with coronary artery disease. This study aims to analyse the health trajectories of patients after first CABG or first, second or third DES within the first three years, with a focus on follow-up interventions, severe care need, transition into a nursing home, and death., Methods: Based on health claims data (n=11,581), we estimated age-and sex standardized probabilities of reintervention, and of transition to severe care need, nursing home and death following initial CABG (n=2,008) or DES (n=9,573) for patients aged 50 years and older using logistic regression models and direct standardization. Up to three follow-up DES interventions and one follow-up CABG were considered., Results: There was a fairly high probability of reintervention, particularly after a DES and within the first year. Follow-up interventions were more likely to involve DES than CABG. The probability of death was notably higher for CABG patients. The probabilities of severe care need and moving to a nursing home were slightly lower and similar across the revascularization methods and over time., Conclusions: DES and CABG are often associated with a need for follow-up interventions. Depending on the procedure, however, the risk of repeat surgery or adverse health outcomes varies. DES is associated with a relatively high probability of follow-up revascularization and a nearly constant probability of negative health outcomes in the short and medium term. In contrast, within three years after a CABG, follow-up reinterventions are rather rare. However, this procedure is particularly associated with an increased risk of mortality and short-term transition into a nursing home., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-251/coif). The authors have no conflicts of interest to declare., (2024 Journal of Thoracic Disease. All rights reserved.)
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- 2024
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13. Dinuclear complex-induced DNA melting.
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Biere N, Kreft D, Walhorn V, Schwarzbich S, Glaser T, and Anselmetti D
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- Nucleic Acid Denaturation, Base Pairing, Microscopy, Atomic Force methods, DNA chemistry
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Dinuclear copper complexes have been designed for molecular recognition in order to selectively bind to two neighboring phosphate moieties in the backbone of double strand DNA. Associated biophysical, biochemical and cytotoxic effects on DNA were investigated in previous works, where atomic force microscopy (AFM) in ambient conditions turned out to be a particular valuable asset, since the complexes influence the macromechanical properties and configurations of the strands. To investigate and scrutinize these effects in more depth from a structural point of view, cutting-edge preparation methods and scanning force microscopy under ultra-high vacuum (UHV) conditions were employed to yield submolecular resolution images. DNA strand mechanics and interactions could be resolved on the single base pair level, including the amplified formation of melting bubbles. Even the interaction of singular complex molecules could be observed. To better assess the results, the appearance of treated DNA is also compared to the behavior of untreated DNA in UHV on different substrates. Finally, we present data from a statistical simulation reasoning about the nanomechanics of strand dissociation. This sort of quantitative experimental insights paralleled by statistical simulations impressively shade light on the rationale for strand dissociations of this novel DNA interaction process, that is an important nanomechanistic key and novel approach for the development of new chemotherapeutic agents., (© 2023. The Author(s).)
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- 2023
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14. Stents versus bypass surgery: 3-year mortality risk of patients with coronary interventions aged 50+ in Germany.
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Nestler S, Kreft D, Donndorf P, Ince H, and Doblhammer G
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- Germany epidemiology, Humans, Quality of Life, Risk Factors, Stents adverse effects, Treatment Outcome, Coronary Artery Disease, Drug-Eluting Stents, Myocardial Infarction etiology, Percutaneous Coronary Intervention methods
- Abstract
Objectives: Due to demographic aging, the prevalence of coronary artery disease (CAD) is expected to increase in the future, resulting in a growing demand for stent and bypass interventions. This study aims to investigate the mortality risk of patients following conventional coronary artery bypass grafting (CABG) or endovascular procedure by the implantation of bare-metal stents (BMS) or drug-eluting stents (DES)., Methods: Based on a random sample of 250,000 members of Germany's largest health insurance 'Allgemeine Ortskrankenkassen' (AOK) from 2004 to 2015, incident CAD patients were analyzed by Cox Proportional-Hazard models. Risk adjustment was made for sex, age, other cardiac diseases, non-cardiovascular comorbidities and years since intervention. Due to later admission of DES and thus a shorter observation time, mortality was examined for 3 years since the intervention., Results: BMS represented the most frequent procedure (48%). We found similar proportions of CABG (19%) and DES interventions (23%). After risk adjustment, the models showed a 21% (p = 0.004) lower mortality risk of patients with DES and also a 21% (p = 0.002) lower mortality risk of CABG patients compared to persons with BMS., Conclusion: Based on a large-scale dataset, our study demonstrated survival advantages of CABG and DES interventions over BMS, with no differences between the DES and CABG groups. The results help to assess the risks of coronary interventions. Aspects of quality of life, severity of postoperative physical limitations, duration of rehabilitation, patients' preferences, and aspects of cost-effectiveness for hospitals and society should be further considered., (© 2022. The Author(s).)
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- 2022
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15. Social disparities in the first wave of COVID-19 incidence rates in Germany: a county-scale explainable machine learning approach.
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Doblhammer G, Reinke C, and Kreft D
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- Communicable Disease Control, Humans, Incidence, Machine Learning, SARS-CoV-2, United States, COVID-19
- Abstract
Objectives: Knowledge about the socioeconomic spread of the first wave of COVID-19 infections in Germany is scattered across different studies. We explored whether COVID-19 incidence rates differed between counties according to their socioeconomic characteristics using a wide range of indicators., Data and Method: We used data from the Robert Koch-Institute (RKI) on 204 217 COVID-19 diagnoses in the total German population of 83.1 million, distinguishing five distinct periods between 1 January and 23 July 2020. For each period, we calculated age-standardised incidence rates of COVID-19 diagnoses on the county level and characterised the counties by 166 macro variables. We trained gradient boosting models to predict the age-standardised incidence rates with the macrostructures of the counties and used SHapley Additive exPlanations (SHAP) values to characterise the 20 most prominent features in terms of negative/positive correlations with the outcome variable., Results: The first COVID-19 wave started as a disease in wealthy rural counties in southern Germany and ventured into poorer urban and agricultural counties during the course of the first wave. High age-standardised incidence in low socioeconomic status (SES) counties became more pronounced from the second lockdown period onwards, when wealthy counties appeared to be better protected. Features related to economic and educational characteristics of the young population in a county played an important role at the beginning of the pandemic up to the second lockdown phase, as did features related to the population living in nursing homes; those related to international migration and a large proportion of foreigners living in a county became important in the postlockdown period., Conclusion: High mobility of high SES groups may drive the pandemic at the beginning of waves, while mitigation measures and beliefs about the seriousness of the pandemic as well as the compliance with mitigation measures may put lower SES groups at higher risks later on., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2022
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16. Progression to severe visual impairment and blindness in POAG patients: pace and risk factors-a cohort study using German health claims data.
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Nestler S, Kreft D, Doblhammer G, Guthoff RF, and Frech S
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- Blindness epidemiology, Cohort Studies, Humans, Risk Factors, Vision Disorders complications, Glaucoma, Open-Angle complications, Vision, Low complications
- Abstract
Objective: Glaucoma is a leading cause of severe visual impairment and blindness (SVI/B) worldwide. Hence, it is of utmost importance to explore relevant risk factors and study the pace of progression to SVI/B., Methods and Analysis: We used a random sample of 250 000 persons from administrative individual-level health records of the Allgemeine Ortskrankenkassen between 2004 and 2015. We identified 3535 primary open-angle glaucoma (POAG) patients aged 55 and older and followed them for up to 10 years. Monocular and binocular SVI/B were defined by the ICD-10 classifications H54.0 and H54.4. Ophthalmological and chronic disease risk factors were analysed by applying a multivariable Cox proportional hazard model., Results: The risk of SVI/B in POAG patients was significantly increased by the presence of specific additional eye diseases such as secondary glaucoma (HR: 3.08, p<0.001), retinal vascular occlusion (HR: 3.00, p<0.001) or age-related macular degeneration (AMD) (HR: 2.26, p<0.001). The risk was highest in the first 2 years after the POAG diagnosis and significantly decreased after the fifth year (HR: 0.36, p=0.002). Ocular injuries, other ocular diseases, non-ophthalmological comorbidities, and age and sex had no significant influence (p>0.05)., Conclusion: Although progression to SVI/B is relatively rare in POAG patients in Germany, one must be aware of additional risk factors, such as secondary glaucoma, retinal vascular occlusion and AMD. Regular ophthalmological examinations help prevent the progression of SVI/B, especially in the first years after the POAG diagnosis. Specific, targeted, and timely treatments for the other eye diseases could help prevent or delay SVI/B., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2022
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17. Sex and Gender Differences in Environmental Influences on Dementia Incidence in Germany, 2014-2019: An Observational Cohort Study Based on Health Claims Data.
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Kreft D and Doblhammer G
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- Aged, Cohort Studies, Female, Germany epidemiology, Humans, Incidence, Male, Risk Factors, Sex Factors, Dementia diagnosis, Dementia epidemiology
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Background: There is an ongoing debate about whether environmental characteristics influence dementia risk like individual traits do, and whether these differ by sex and gender., Objective: This study examines the influence of regional characteristics on the incidence of dementia and explores sex and gender differences using individual-level health information and regional characteristics., Methods: Using a random sample of 250,000 people aged 70 + insured through Germany's largest German public health agency, we analyzed quarterly data about diagnoses and place of residence from 2014 to 2019. Using five-digit postal codes, we added data on various dimensions of regional characteristics offered by the INKAR database and the 2011 Census database. We used multilevel survival regressions to tease out regional incidence differences while accounting for spatial clustering., Results: After adjusting for multi-morbidity and relocation-related selection bias, we saw that people living in regions with the highest tertile of income (HR = 0.87, p < 0.001), and who had the highest tertile of remaining life expectancy at age 60 (HR = 0.93, p = 0.012) had lower dementia risks. There was no gender difference in the regional income effect, but the effect of education (HR = 0.91, p = 0.015) was significant only for men and remaining life-expectancy was significant only for women (HR = 0.93, p = 0.026)., Conclusion: Environmental characteristics related to wealth and health resources of a region influence the risk of dementia among the elderly in Germany. This effect is independent of the health profiles of the individuals and differs between the two genders. Health policies need to acknowledge these modifiable risk factors and consider how they affect men and women differently.
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- 2022
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18. Biomolecule sulphation and novel methylations related to Guillain-Barré syndrome-associated Campylobacter jejuni serotype HS:19.
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Heikema AP, Strepis N, Horst-Kreft D, Huynh S, Zomer A, Kelly DJ, Cooper KK, and Parker CT
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- Humans, Methylation, Serogroup, Campylobacter Infections complications, Campylobacter jejuni genetics, Guillain-Barre Syndrome etiology
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- 2021
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19. Regional Characteristics of the Second Wave of SARS-CoV-2 Infections and COVID-19 Deaths in Germany.
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Doblhammer G, Kreft D, and Reinke C
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- Germany epidemiology, Humans, Incidence, Income, SARS-CoV-2, COVID-19
- Abstract
(1) Background: In the absence of individual level information, the aim of this study was to identify the regional key features explaining SARS-CoV-2 infections and COVID-19 deaths during the upswing of the second wave in Germany. (2) Methods: We used COVID-19 diagnoses and deaths from 1 October to 15 December 2020, on the county-level, differentiating five two-week time periods. For each period, we calculated the age-standardized COVID-19 incidence and death rates on the county level. We trained gradient boosting models to predict the incidence and death rates by 155 indicators and identified the top 20 associations using Shap values. (3) Results: Counties with low socioeconomic status (SES) had higher infection and death rates, as had those with high international migration, a high proportion of foreigners, and a large nursing home population. The importance of these characteristics changed over time. During the period of intense exponential increase in infections, the proportion of the population that voted for the Alternative for Germany (AfD) party in the last federal election was among the top characteristics correlated with high incidence and death rates. (4) Machine learning approaches can reveal regional characteristics that are associated with high rates of infection and mortality.
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- 2021
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20. The Role of the Respiratory Microbiome and Viral Presence in Lower Respiratory Tract Infection Severity in the First Five Years of Life.
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Hoefnagels I, van de Maat J, van Kampen JJA, van Rossum A, Obihara C, Tramper-Stranders GA, Heikema AP, de Koning W, van Wermerskerken AM, Horst-Kreft D, Driessen GJA, Punt J, Smit FJ, Stubbs A, Noordzij JG, Hays JP, and Oostenbrink R
- Abstract
Lower respiratory tract infections (LRTIs) in children are common and, although often mild, a major cause of mortality and hospitalization. Recently, the respiratory microbiome has been associated with both susceptibility and severity of LRTI. In this current study, we combined respiratory microbiome, viral, and clinical data to find associations with the severity of LRTI. Nasopharyngeal aspirates of children aged one month to five years included in the STRAP study (Study to Reduce Antibiotic prescription in childhood Pneumonia), who presented at the emergency department (ED) with fever and cough or dyspnea, were sequenced with nanopore 16S-rRNA gene sequencing and subsequently analyzed with hierarchical clustering to identify respiratory microbiome profiles. Samples were also tested using a panel of 15 respiratory viruses and Mycoplasma pneumoniae , which were analyzed in two groups, according to their reported virulence. The primary outcome was hospitalization, as measure of disease severity. Nasopharyngeal samples were isolated from a total of 167 children. After quality filtering, microbiome results were available for 54 children and virology panels for 158 children. Six distinct genus-dominant microbiome profiles were identified, with Haemophilus -, Moraxella -, and Streptococcus -dominant profiles being the most prevalent. However, these profiles were not found to be significantly associated with hospitalization. At least one virus was detected in 139 (88%) children, of whom 32.4% had co-infections with multiple viruses. Viral co-infections were common for adenovirus, bocavirus, and enterovirus, and uncommon for human metapneumovirus (hMPV) and influenza A virus. The detection of enteroviruses was negatively associated with hospitalization. Virulence groups were not significantly associated with hospitalization. Our data underlines high detection rates and co-infection of viruses in children with respiratory symptoms and confirms the predominant presence of Haemophilus -, Streptococcus -, and Moraxella -dominant profiles in a symptomatic pediatric population at the ED. However, we could not assess significant associations between microbiome profiles and disease severity measures.
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- 2021
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21. Incidence, individual, and macro level risk factors of severe binocular visual impairment and blindness in persons aged 50 and older.
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Kreft D, Doblhammer G, Guthoff RF, and Frech S
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- Aged, Aged, 80 and over, Cohort Studies, Female, Germany epidemiology, Humans, Incidence, Longitudinal Studies, Male, Middle Aged, Prevalence, Risk Factors, Vision, Low epidemiology, Vision, Low etiology, Visual Acuity physiology, Visually Impaired Persons, Blindness epidemiology, Blindness etiology, Vision Disorders epidemiology, Vision Disorders etiology
- Abstract
Objective: This study aims to estimate the incidence of severe binocular vision impairment and blindness (SVI/B) and to identify eye diseases and regional risk factors of persons with SVI/B at ages 50 years and older., Methods: We designed an observational cohort study based on longitudinal, multifactorial, and administrative information of a random sample of 250,000 persons at ages 50+. All individuals were included in the process-produced health claims register of the Allgemeine Ortskrankenkasse in 2004, and were followed until 2015. We analyzed ten selected eye diseases and regional characteristics as risk factors for SVI/B using Cox models, adjusting for demographic characteristics and multi-morbidity., Results: The age-standardized incidence was 79 new diagnoses of SVI/B per 100,000 person-years (95%-CI: 76-82); 77 for males (72-82) and 81 for females (77-85). By adjusting for multiple factors, the model revealed and confirmed that individuals who were very old (Hazard ratio90+: 6.67; 3.59-12.71), male (1.18; 1.01-1.38), had multi-morbidities (three+ diseases: 3.36; 2.51-4.49), or had diabetes (1.26; 1.07-1.49) had an increased risk of SVI/B. Compared to persons without the particular eye disease (all p<0.001), persons diagnosed with secondary glaucoma had a multiple-adjusted 4.66 times (3.17-6.85) higher risk, those with retinal vascular occlusion had a 4.51 times (3.27-6.23) higher risk, and those with angle-closure glaucoma had a 4.22 times (2.60-6.85) higher risk. Population density was not a risk factor, while persons living in wealthier regions had 0.75 times (p=0.003) to 0.70 times (p<0.001) the risk of SVI/B than persons in the least wealthy regions of Germany., Conclusion: The study revealed and confirmed some profound risk factors of SVI/B at both the individual and the macro level. The sizes of the effects of the characteristics of the living context were smaller than those of the individual characteristics, especially for some severe eye diseases. While urbanity and access to health services had no effect, regional economic wealth was a risk factor for SVI/B. Future health care measures and advice by physicians should take these dimensions of inequalities in SVI/B into account., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2021
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22. Campylobacter jejuni Cas9 Modulates the Transcriptome in Caco-2 Intestinal Epithelial Cells.
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Saha C, Horst-Kreft D, Kross I, van der Spek PJ, Louwen R, and van Baarlen P
- Subjects
- CRISPR-Associated Protein 9 genetics, Caco-2 Cells, Campylobacter Infections genetics, Campylobacter Infections metabolism, Campylobacter jejuni genetics, Epithelial Cells metabolism, Epithelial Cells microbiology, Gene Expression Profiling, Humans, Intestines microbiology, CRISPR-Associated Protein 9 metabolism, Campylobacter Infections microbiology, Campylobacter jejuni metabolism, Epithelial Cells pathology, Gene Expression Regulation, Intestines pathology, Transcriptome
- Abstract
The zoonotic human pathogen Campylobacter jejuni is known for its ability to induce DNA-damage and cell death pathology in humans. The molecular mechanism behind this phenomenon involves nuclear translocation by Cas9, a nuclease in C . jejuni (CjeCas9) that is the molecular marker of the Type II CRISPR-Cas system. However, it is unknown via which cellular pathways CjeCas9 drives human intestinal epithelial cells into cell death. Here, we show that CjeCas9 released by C. jejuni during the infection of Caco-2 human intestinal epithelial cells directly modulates Caco-2 transcriptomes during the first four hours of infection. Specifically, our results reveal that CjeCas9 activates DNA damage (p53, ATM (Ataxia Telangiectasia Mutated Protein)), pro-inflammatory (NF-κB (Nuclear factor-κB)) signaling and cell death pathways, driving Caco-2 cells infected by wild-type C . jejuni , but not when infected by a cas9 deletion mutant, towards programmed cell death. This work corroborates our previous finding that CjeCas9 is cytotoxic and highlights on a RNA level the basal cellular pathways that are modulated.
- Published
- 2020
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23. Comparison of Illumina versus Nanopore 16S rRNA Gene Sequencing of the Human Nasal Microbiota.
- Author
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Heikema AP, Horst-Kreft D, Boers SA, Jansen R, Hiltemann SD, de Koning W, Kraaij R, de Ridder MAJ, van Houten CB, Bont LJ, Stubbs AP, and Hays JP
- Subjects
- Adolescent, Adult, Aged, Child, Child, Preschool, Computational Biology methods, DNA Primers genetics, DNA, Bacterial genetics, Female, Humans, Infant, Male, Middle Aged, Nanopores, Young Adult, Genes, rRNA genetics, High-Throughput Nucleotide Sequencing methods, Microbiota genetics, Nanopore Sequencing methods, Nasal Cavity microbiology, RNA, Ribosomal, 16S genetics
- Abstract
Illumina and nanopore sequencing technologies are powerful tools that can be used to determine the bacterial composition of complex microbial communities. In this study, we compared nasal microbiota results at genus level using both Illumina and nanopore 16S rRNA gene sequencing. We also monitored the progression of nanopore sequencing in the accurate identification of species, using pure, single species cultures, and evaluated the performance of the nanopore EPI2ME 16S data analysis pipeline. Fifty-nine nasal swabs were sequenced using Illumina MiSeq and Oxford Nanopore 16S rRNA gene sequencing technologies. In addition, five pure cultures of relevant bacterial species were sequenced with the nanopore sequencing technology. The Illumina MiSeq sequence data were processed using bioinformatics modules present in the Mothur software package. Albacore and Guppy base calling, a workflow in nanopore EPI2ME (Oxford Nanopore Technologies-ONT, Oxford, UK) and an in-house developed bioinformatics script were used to analyze the nanopore data. At genus level, similar bacterial diversity profiles were found, and five main and established genera were identified by both platforms. However, probably due to mismatching of the nanopore sequence primers, the nanopore sequencing platform identified Corynebacterium in much lower abundance compared to Illumina sequencing. Further, when using default settings in the EPI2ME workflow, almost all sequence reads that seem to belong to the bacterial genus Dolosigranulum and a considerable part to the genus Haemophilus were only identified at family level. Nanopore sequencing of single species cultures demonstrated at least 88% accurate identification of the species at genus and species level for 4/5 strains tested, including improvements in accurate sequence read identification when the basecaller Guppy and Albacore, and when flowcell versions R9.4 (Oxford Nanopore Technologies-ONT, Oxford, UK) and R9.2 (Oxford Nanopore Technologies-ONT, Oxford, UK) were compared. In conclusion, the current study shows that the nanopore sequencing platform is comparable with the Illumina platform in detection bacterial genera of the nasal microbiota, but the nanopore platform does have problems in detecting bacteria within the genus Corynebacterium . Although advances are being made, thorough validation of the nanopore platform is still recommendable.
- Published
- 2020
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24. Guide-free Cas9 from pathogenic Campylobacter jejuni bacteria causes severe damage to DNA.
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Saha C, Mohanraju P, Stubbs A, Dugar G, Hoogstrate Y, Kremers GJ, van Cappellen WA, Horst-Kreft D, Laffeber C, Lebbink JHG, Bruens S, Gaskin D, Beerens D, Klunder M, Joosten R, Demmers JAA, van Gent D, Mouton JW, van der Spek PJ, van der Oost J, van Baarlen P, and Louwen R
- Subjects
- CRISPR-Cas Systems, DNA genetics, Gene Editing, Humans, RNA, Guide, CRISPR-Cas Systems genetics, CRISPR-Associated Protein 9 genetics, CRISPR-Associated Protein 9 metabolism, Campylobacter jejuni genetics, Campylobacter jejuni metabolism
- Abstract
CRISPR-Cas9 systems are enriched in human pathogenic bacteria and have been linked to cytotoxicity by an unknown mechanism. Here, we show that upon infection of human cells, Campylobacter jejuni secretes its Cas9 (CjeCas9) nuclease into their cytoplasm. Next, a native nuclear localization signal enables CjeCas9 nuclear entry, where it catalyzes metal-dependent nonspecific DNA cleavage leading to cell death. Compared to CjeCas9, native Cas9 of Streptococcus pyogenes (SpyCas9) is more suitable for guide-dependent editing. However, in human cells, native SpyCas9 may still cause some DNA damage, most likely because of its ssDNA cleavage activity. This side effect can be completely prevented by saturation of SpyCas9 with an appropriate guide RNA, which is only partially effective for CjeCas9. We conclude that CjeCas9 plays an active role in attacking human cells rather than in viral defense. Moreover, these unique catalytic features may therefore make CjeCas9 less suitable for genome editing applications., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)
- Published
- 2020
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25. Prevalence and Mortality of Venous Leg Diseases of the Deep Veins: An Observational Cohort Study Based on German Health Claims Data.
- Author
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Kreft D, Keiler J, Grambow E, Kischkel S, Wree A, and Doblhammer G
- Subjects
- Aged, Aged, 80 and over, Cohort Studies, Female, Germany epidemiology, Humans, Leg Ulcer mortality, Male, Middle Aged, Postthrombotic Syndrome mortality, Prevalence, Venous Thrombosis mortality, Leg blood supply, Leg Ulcer epidemiology, Postthrombotic Syndrome epidemiology, Venous Thrombosis epidemiology
- Abstract
This study estimates the prevalence and mortality of diseases of the deep veins of the legs such as deep vein thrombosis (DVT), postthrombotic syndrome (PTS), and venous leg ulceration (VLU). We used a random sample of 250 000 patients at age 50+ years of the register of the Allgemeine Ortskrankenkasse from 2004 to 2015. Selected manifestations of venous diseases assumed as risk factors for mortality were analyzed using Cox models while adjusting for various basic demographic and health characteristics. The prevalence in 2004 was 0.05% for DVT of the femoral veins, 0.50% for DVT of any deep veins, 0.86% for PTS, and 0.91% for VLU. The mortality rate in 2004 to 2015 was 20.40 deaths/100 person-years for DVT of the femoral veins, 10.69 for DVT of any deep veins, 4.34 for PTS, and 7.02 for VLU. The model revealed a 35% higher risk ( p < .001) in patients with any DVT, an 88% higher mortality ( p < .001) for femoral DVT, a 23% higher risk ( p < .001) for VLU, and no health disadvantage in persons with PTS. Our study revealed an increased mortality for patients with VLU and DVT. Even after adjustment for embolic events and infections of the venous ulcers mortality remained significantly higher.
- Published
- 2020
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26. Antimicrobial activity of two novel antimicrobial peptides AA139 and SET-M33 against clinically and genotypically diverse Klebsiella pneumoniae isolates with differing antibiotic resistance profiles.
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van der Weide H, Vermeulen-de Jongh DMC, van der Meijden A, Boers SA, Kreft D, Ten Kate MT, Falciani C, Pini A, Strandh M, Bakker-Woudenberg IAJM, Hays JP, and Goessens WHF
- Subjects
- Drug Resistance, Bacterial, Genetic Variation, Genotype, Klebsiella pneumoniae classification, Klebsiella pneumoniae genetics, Microbial Sensitivity Tests, Microbial Viability drug effects, Anti-Infective Agents pharmacology, Antimicrobial Cationic Peptides pharmacology, Klebsiella pneumoniae drug effects
- Abstract
Colistin is an antimicrobial peptide (AMP) used as a drug of last resort, although plasmid-mediated colistin resistance (MCR) has been reported. AA139 and SET-M33 are novel AMPs currently in development for the treatment of multidrug-resistant (MDR) Gram-negative bacterial infections. As many AMPs have a similar mode of action to colistin, potentially leading to cross-resistance, the antimicrobial activity of AA139 and SET-M33 was investigated against a collection of 50 clinically and genotypically diverse Klebsiella pneumoniae isolates with differing antibiotic resistance profiles, including colistin-resistant strains. The collection was genotypically characterised and susceptibility to clinically relevant antibiotics was determined. Susceptibility to AA139 and SET-M33 did not differ among the collection despite differences in underlying mechanisms of resistance or susceptibility to colistin. For three colistin-susceptible and three colistin-resistant strains with distinct MDR profiles as well as an additional MCR-producing strain, the bactericidal activity of AA139, SET-M33 and colistin during 24 h of exposure was examined. Following 24 h of exposure to AA139, SET-M33 or colistin, the seven strains were tested for changes in susceptibility to the respective AMPs. AA139 and SET-M33 showed a concentration-dependent bactericidal effect irrespective of bacterial susceptibility to colistin. Exposure to low colistin concentrations resulted in the development of colistin resistance in colistin-susceptible strains, whereas susceptibility to AA139 and SET-M33 following exposure to the respective AMPs was maintained. The two novel AMPs remained effective against colistin-resistant strains and may be promising novel drugs for the treatment of clinically and genotypically diverse MDR K. pneumoniae infections, including infections associated with colistin-resistant bacteria., (Copyright © 2019 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.)
- Published
- 2019
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27. VNTR confirms the heterogeneity of Madurella mycetomatis and is a promising typing tool for this mycetoma causing agent.
- Author
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Lim W, Eadie K, Horst-Kreft D, Ahmed SA, Fahal AH, and van de Sande WWJ
- Subjects
- Africa, Cluster Analysis, Electrophoresis, Agar Gel, Genotype, Humans, India, Madurella isolation & purification, Peru, Polymerase Chain Reaction, Genetic Variation, Madurella classification, Madurella genetics, Minisatellite Repeats, Molecular Typing, Mycetoma microbiology, Mycological Typing Techniques
- Abstract
The neglected tropical disease mycetoma is a chronic granulomatous inflammatory and infectious disease affecting various body parts. The most common causative agent is the fungus Madurella mycetomatis. In order to study the genetic diversity of this fungus and to monitor any potential outbreaks, a good typing method that can be used in endemic settings is needed. Previous typing methods developed were not discriminative and not easy to perform in resource-limited laboratories. Variable-Number-Tandem-Repeat (VNTR) typing overcomes these difficulties and further enables interlaboratory data comparison. Therefore, in this study we developed a VNTR method for typing M. mycetomatis. Six tandem-repeats were identified in the genome of M. mycetomatis isolate MM55 using an online tandem repeats software. The variation in these repeats was determined by PCR and gel-electrophoresis on DNA obtained from 81 M. mycetomatis isolates obtained from patients. These patients originated from Sudan, Mali, Peru, and India. The 81 isolates were divided into 14 genotypes which separated into two main clusters with seven and five subdivisions, respectively. VNTR typing confirms the heterogeneity of M. mycetomatis strains and can be used to study the epidemiology of M. mycetomatis. The results presented in this article are made fully available to the scientific community on request from the Eumycetoma Working Group. We hope that this open resource approach will bridge scientific community working with mycetoma from all around the world and lead to a deeper understanding of M. mycetomatis., (© The Author(s) 2018. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)
- Published
- 2019
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28. Correction to: Binding mechanism of anti-cancer chemotherapeutic drug mitoxantrone to DNA characterized by magnetic tweezers.
- Author
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Kreft D, Wang Y, Rattay M, Toensing K, and Anselmetti D
- Abstract
Following publication of this article [1] we found a typographical error in the results reported in the abstract. The corrected sentences should read as below.
- Published
- 2019
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29. Binding mechanism of anti-cancer chemotherapeutic drug mitoxantrone to DNA characterized by magnetic tweezers.
- Author
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Kreft D, Wang Y, Rattay M, Toensing K, and Anselmetti D
- Subjects
- Magnetic Phenomena, Magnets, Models, Molecular, Nanotechnology, Thermodynamics, Antineoplastic Agents chemistry, DNA chemistry, Intercalating Agents chemistry, Mitoxantrone chemistry
- Abstract
Background: Chemotherapeutic agents (anti-cancer drugs) are small cytostatic or cytotoxic molecules that often bind to double-stranded DNA (dsDNA) resulting in modifications of their structural and nanomechanical properties and thus interfering with the cell proliferation process., Methods: We investigated the anthraquinone compound mitoxantrone that is used for treating certain cancer types like leukemia and lymphoma with magnetic tweezers as a single molecule nanosensor. In order to study the association of mitoxantrone with dsDNA, we conducted force-extension and mechanical overwinding experiments with a sensitivity of 10
-14 N., Results: Using this method, we were able to estimate an equilibrium constant of association Ka ≈ 1 × 105 M-1 as well as a binding site size of n ≈ 2.5 base pairs for mitoxantrone. An unwinding angle of mitoxantrone-intercalation of ϑ ≈ 16° was determined., Conclusion: Moreover, we observed a complex concentration-dependent bimodal binding behavior, where mitoxantrone associates to dsDNA as an intercalator and groove binder simultaneously at low concentrations and as a mere intercalator at high concentrations.- Published
- 2018
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30. Diabetic retinopathy screening in incident diabetes mellitus type 2 in Germany between 2004 and 2013 - A prospective cohort study based on health claims data.
- Author
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Kreft D, McGuinness MB, Doblhammer G, and Finger RP
- Subjects
- Aged, Comorbidity, Diabetes Mellitus, Type 2 diagnosis, Female, Germany epidemiology, Humans, Male, Middle Aged, National Health Programs, Prospective Studies, Diabetes Mellitus, Type 2 pathology, Diabetic Retinopathy diagnosis, Diabetic Retinopathy epidemiology, Mass Screening methods, Patient Compliance
- Abstract
Objective: To assess factors associated with diabetic retinopathy (DR) screening uptake following a diagnosis of type 2 diabetes mellitus (type 2 diabetes) in Germany., Materials and Methods: A nationally representative prospective sample of individual-level health claims data for 250,000 members from Germany's largest public insurance provider in 2004-2013 was assessed. In the sample, 26,560 persons with incident type 2 diabetes were identified. Factors associated with subsequent DR screening were assessed using descriptive statistics, Kaplan-Meier estimator, and Cox regression analysis., Results: On average 27.6 visits to an ophthalmologist per 100 person-years in persons with incident type 2 diabetes occurred. Half of all incident cases (Kaplan-Meier estimator) had not seen an ophthalmologist after more than two years (2.25 years) following their diabetes diagnosis. In the multivariate analysis, an older age (from hazard ratio HR(70-74) = 0.93 [95%-CI: 0.89-0.97] to HR(90+) = 0.50 [95%-CI: 0.42-0.60] compared to persons aged 50-69 years) and a higher disability level (i.e. HR(disability level 3) = 0.30 [95%-CI: 0.25-0.36]) were associated with a lower likelihood, while female sex (HR = 1.12 [95%-CI: 1.08-1.15]), six or more comorbidities (HR = 1.26 [95%-CI: 1.15-1.37]), moderate (HR = 1.51 [95%-CI: 1.46-1.56]) or severe type 2 diabetes (HR = 1.53 [95%-CI: 1.45-1.61]) as well as being enrolled in a type 2 diabetes disease management program (HR = 1.78 [95%-CI: 1.69-1.87]) were associated with a higher likelihood of DR screening., Conclusions: A high proportion of newly diagnosed persons with type 2 diabetes did not follow current German recommendations for DR screening, impeding timely detection and management of potential complications. This was more apparent among persons who were men, older or had a disability. The uptake of screening was considerably greater among those enrolled in a diseases management program. These factors need to be considered when planning DR screening services and/or referrals.
- Published
- 2018
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31. Pharmacoepidemiological assessment of adherence and influencing co-factors among primary open-angle glaucoma patients-An observational cohort study.
- Author
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Frech S, Kreft D, Guthoff RF, and Doblhammer G
- Subjects
- Aged, Aged, 80 and over, Cohort Studies, Comorbidity, Female, Germany epidemiology, Glaucoma, Open-Angle epidemiology, Humans, Male, Middle Aged, Multivariate Analysis, Pharmacoepidemiology, Prevalence, Risk Factors, Glaucoma, Open-Angle drug therapy, Medication Adherence
- Abstract
The goal of this study was to assess the adherence of primary open-angle glaucoma (POAG) patients to medication, and to determine co-factors influencing adherence, using a representative sample of members of the largest German public health insurer. The observational cohort study was based on a longitudinal data set from 2010-2013 and included 250,000 insured persons aged 50 and older with 10,120 diagnosed POAG patients. Uni- and multivariate analysis was performed to investigate several aspects of glaucoma, such as prevalence, adherence, and co-factors influencing adherence. The main outcome measured adherence with prescriptions filled within a year. Multivariate panel regression analysis was used to determine the co-factors influencing this adherence. Prevalence of POAG was 3.36% [CI: 3.28-3.43%], with 2.91% [CI: 2.81-3.01%] for males and 3.71% [CI: 3.61-3.81%] for females, increasing with age. The mean level of adherence in terms of prescriptions filled was 66.5% [CI: 65.50-67.60%]. The results of this analysis revealed a significant influence of age, duration of the disease, care need, distance to death, and multimorbidity as co-factors of non-adherence, whereas gender had no influence. The analysis provided detailed information about POAG health care aspects concerning prevalence and adherence. The most endangered risk groups for non-adherence were patients aged 50-59, patients older than 80 years, patients with a longer duration of POAG, patients with care needs, and patients with three or more severe diseases in addition to glaucoma. To know the predictors responsible for an increased risk to develop POAG is of importance for all persons involved in health care management. Therefore effective strategies to increase awareness of patients and medical care personnel about non-adherence and the importance of a regular and continuous medication to avoid further nerve fiber damage and possible blindness have to be developed.
- Published
- 2018
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32. OXA-Carbapenemases Present in Clinical Acinetobacter baumannii-calcoaceticus Complex Isolates from Patients in Kurdistan Region, Iraq.
- Author
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Ganjo AR, Maghdid DM, Mansoor IY, Kok DJ, Severin JA, Verbrugh HA, Kreft D, Fatah MH, Alnakshabandi AA, Dlnya A, Hammerum AM, Ng K, and Goessens W
- Subjects
- Acinetobacter Infections drug therapy, Acinetobacter Infections microbiology, Acinetobacter baumannii classification, Acinetobacter baumannii drug effects, Acinetobacter baumannii isolation & purification, Acinetobacter calcoaceticus classification, Acinetobacter calcoaceticus drug effects, Acinetobacter calcoaceticus isolation & purification, Adolescent, Adult, Aged, Anti-Bacterial Agents pharmacology, Bacterial Proteins classification, Bacterial Proteins metabolism, Child, Child, Preschool, Clone Cells, Cross Infection drug therapy, Cross Infection microbiology, Disk Diffusion Antimicrobial Tests, Electrophoresis, Gel, Pulsed-Field, Female, Humans, Imipenem pharmacology, Iraq epidemiology, Male, Middle Aged, Multilocus Sequence Typing, Phylogeny, Plasmids chemistry, Plasmids metabolism, Polymerase Chain Reaction, Prevalence, beta-Lactamases classification, beta-Lactamases metabolism, Acinetobacter Infections epidemiology, Acinetobacter baumannii genetics, Acinetobacter calcoaceticus genetics, Bacterial Proteins genetics, Cross Infection epidemiology, Drug Resistance, Multiple, Bacterial genetics, Gene Expression Regulation, Bacterial, beta-Lactamases genetics
- Abstract
In addition to intrinsic resistance in Acinetobacter baumannii, many different types of acquired resistance mechanisms have been reported, including the presence of VIM and IMP metallo β-lactamases and also of bla
OXA-23-like and blaOXA-58-like enzymes. In the Kurdistan region of Iraq, the multiresistant A. baumannii-calcoaceticus complex is prevalent. We characterized the different mechanisms of resistance present in clinical isolates collected from different wards and different hospitals from the Kurdistan region. One hundred twenty clinical nonduplicate A. baumannii-calcoaceticus complex isolates were collected from four hospitals between January 2012 and October 2013. The identification of the isolates was confirmed by MALDI-TOF. The susceptibility to different antibiotics was determined by disk diffusion and analyzed in accordance to EUCAST guidelines. By PCR, the presence of blaOXA-51-like , blaOXA-23-like , blaOXA-24-like , and blaOXA-58-like genes was determined as well as the presence of the insertion element ISAba1. Clonal diversity was analyzed by pulsed-field gel electrophoresis (PFGE) using the restriction enzyme ApaI and, in addition, multilocus sequence typing (MLST) was performed on a selected subset of 15 isolates. All 120 A. baumannii isolates harbored blaOXA-51-like genes. One hundred one out of 110 (92%) imipenem (IMP)-resistant A. baumannii-calcoaceticus complex isolates additionally carried the blaOXA-23-like gene and four isolates (3%) were positive for blaOXA-24-like. All 101 blaOXA-23-like -positive isolates had the ISAba1 insertion sequence, 1,600 bp upstream of the blaOXA-23-like gene. The blaOXA-58-like gene was not detected in any of the 110 IMP-resistant strains. Eight different PFGE clusters were identified and distributed over the different hospitals. MLST analysis performed on a subset of 15 representative isolates revealed the presence of the international clone ST2 (Pasteur). Besides ST2 (Pasteur), also many other STs (Pasteur) were encountered such as ST136, ST94, ST623, ST792, and ST793, all carrying the blaOXA-23 gene. In clinical A. baumannii-calcoaceticus complex isolates from Kurdistan-Iraq, the blaOXA-23 gene in combination with the upstream ISAba1 insertion element is largely responsible for carbapenem resistance. Several small clusters of identical genotypes were found from patients admitted to the same ward and during overlapping time periods, suggesting transmission within the hospital. Identification of source(s) and limiting the transmission of these strains to patients needs to be prioritized.- Published
- 2016
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33. Expansion or compression of long-term care in Germany between 2001 and 2009? A small-area decomposition study based on administrative health data.
- Author
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Kreft D and Doblhammer G
- Abstract
Background: Studies state profound cross-country differences in healthy life years and its time trends, suggesting either the health scenario of expansion or compression of morbidity. A much-discussed question in public health research is whether the health scenarios are heterogeneous or homogeneous on the subnational level as well. Furthermore, the question arises whether the morbidity trends or the mortality trends are the decisive drivers of the care need-free life years (CFLY), the life years with care need (CLY), and, ultimately, the health scenarios., Methods: This study uses administrative census data of all beneficiaries in Germany from the Statutory Long-Term Care Insurance 2001-2009. We compute the CFLY and CLY at age 65+ for 412 counties. The CFLY and CLY gains are decomposed into the effects of survival and of the prevalence of care need, and we investigate their linkages with the health scenarios by applying multinomial regression models., Results: We show an overall increase in CFLY, which is higher for men than for women and higher for severe than for any care need. However, spatial variation in CFLY and in CLY has increased. In terms of the health scenarios, a majority of counties show an expansion of any care need but a compression of severe care need. There is high spatial heterogeneity, with expansion-counties surrounding compression-counties and vice versa, which is mainly caused by divergent trends in the prevalence of care need. We show that mortality is responsible for the absolute changes in CFLY and CLY, while morbidity is the decisive driver that determines the health scenario of a county., Conclusion: Combining regionalized administrative data and advanced statistical methods permits a deeper insight into the complex relationship between health and mortality. Our findings demonstrate a compression of life years with severe care need, which however, depends on the region of residence. To attenuate regional inequalities, more efforts are needed that improve health by medical and infrastructural interventions and by the exchange of insights in the efficiency of small- and large-area policy measures between the vanguard and the rearguard counties. In future research, the underlying latent mechanisms should be investigated in more detail.
- Published
- 2016
- Full Text
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