Design of an anti-inflammatory coating for invasive medical devices

The prevention of material-mediated innate immune responses, which may lead to severe side effects, is an unsolved issue in invasive medicine. Neutrophil granulocytes are activated upon contact of blood with artificial material surfaces in medical devices. This unappreciated non-specific immune response provides a challenge for invasive medicine, since it may cause systemic inflammatory reactions and severe sequelae such as organ failure or even death. This thesis investigates the design an anti-inflammatory surface coating, which avoids or reduces material-mediated innate immune responses on the example of the material polymethylpentene (PMP). PMP is a polymer, which is used as hollow fibers in medical devices like oxygenators enabling the exchange of oxygen and carbon dioxide in the blood. Therefore, a biofunctional anti-inflammatory coating has been developed to avoid material-mediated neutrophil activation during respiratory support. The biofunctional anti-inflammatory coating is based on the covalent coupling of the agonistic FasL-molecule APO010, the covalent coupling of albumin (Recombumin® alpha) to passivate the coating and an amino acid-based stabilizing formulation to enable stability and functionality of the coating even after ethylenoxid (EtO)-sterilization and subsequent storage of the device. To investigate the stability and functionality of the coating, different methods were established: an ELISA to investigate the stable coupling of the biofunctional coating, a sandwich ELISA to detect detached APO010 and a chemotaxis assay to investigate the reduction of neutrophil activity after incubation with the coating. The novel coating has been upscaled from laboratory scale (bench setting) to a serial production scale, whereby the methods from this work were able to show a rapid reduction of neutrophil activation by approx. 10 % after contacting the surface in the second serial production run and the stability of the surface coating even after accelerated aging for up to 82 days at 55 °C in the third serial production run. Three upscaling steps were performed to generate homogeneous distribution of the coating on the PMP matrix. The biofunctional anti-inflammatory coating is a new technology to reduce unappreciated material-induced immunogenic responses. In principle, it should be possible to transfer this technology to other surfaces. This could allow for expansion of the positive effects to other medical devices in direct blood contact and can possibly show the way for new biofunctional coatings in the medical device sector

Design of an anti-inflammatory coating for invasive medical devices

The prevention of material-mediated innate immune responses, which may lead to severe side effects, is an unsolved issue in invasive medicine. Neutrophil granulocytes are activated upon contact of blood with artificial material surfaces in medical devices. This unappreciated non-specific immune response provides a challenge for invasive medicine, since it may cause systemic inflammatory reactions and severe sequelae such as organ failure or even death. This thesis investigates the design an anti-inflammatory surface coating, which avoids or reduces material-mediated innate immune responses on the example of the material polymethylpentene (PMP). PMP is a polymer, which is used as hollow fibers in medical devices like oxygenators enabling the exchange of oxygen and carbon dioxide in the blood. Therefore, a biofunctional anti-inflammatory coating has been developed to avoid material-mediated neutrophil activation during respiratory support. The biofunctional anti-inflammatory coating is based on the covalent coupling of the agonistic FasL-molecule APO010, the covalent coupling of albumin (Recombumin® alpha) to passivate the coating and an amino acid-based stabilizing formulation to enable stability and functionality of the coating even after ethylenoxid (EtO)-sterilization and subsequent storage of the device. To investigate the stability and functionality of the coating, different methods were established: an ELISA to investigate the stable coupling of the biofunctional coating, a sandwich ELISA to detect detached APO010 and a chemotaxis assay to investigate the reduction of neutrophil activity after incubation with the coating. The novel coating has been upscaled from laboratory scale (bench setting) to a serial production scale, whereby the methods from this work were able to show a rapid reduction of neutrophil activation by approx. 10 % after contacting the surface in the second serial production run and the stability of the surface coating even after accelerated aging for up to 82 days at 55 °C in the third serial production run. Three upscaling steps were performed to generate homogeneous distribution of the coating on the PMP matrix. The biofunctional anti-inflammatory coating is a new technology to reduce unappreciated material-induced immunogenic responses. In principle, it should be possible to transfer this technology to other surfaces. This could allow for expansion of the positive effects to other medical devices in direct blood contact and can possibly show the way for new biofunctional coatings in the medical device sector

Diabetes care and outcomes of pediatric refugees and migrants from Ukraine and Syria/Afghanistan with type 1 diabetes in German-speaking countries

IntroductionCurrently, over two million war refugees live in Germany. Exposure to war and flight is associated with a high burden of diseases, not limited to mental disorders and infections. We aimed to analyze diabetes treatment and outcomes of pediatric refugees and migrants from Ukraine and Syria/Afghanistan with type 1 diabetes (T1D) in German-speaking countries.Materials and methodsWe included patients with T1D documented between January 2013 and June 2023 in the German/Austrian/Luxembourgian/Swiss DPV registry, aged < 20 years, born in Ukraine [U], in Syria or Afghanistan [S/A], or without migration background [C]. Using logistic, linear, and negative binomial regression models, we compared diabetes technology use, BMI-SDS, HbA1c values, as well as severe hypoglycemia and DKA rates between groups in the first year of treatment in the host country. Results were adjusted for sex, age, diabetes duration, and time spent in the host country.ResultsAmong all patients with T1D aged < 20 years, 615 were born in Ukraine [U], 624 in Syria or Afghanistan [S/A], and 28,106 had no migration background [C]. Compared to the two other groups, patients from Syria or Afghanistan had a higher adjusted BMI-SDS (0.34 [95%-CI: 0.21–0.48] [S/A] vs. 0.13 [- 0.02–0.27] [U] and 0.20 [0.19–0.21] [C]; all p<0.001), a lower use of CGM or AID system (57.6% and 4.6%, respectively [S/A] vs. 83.7% and 7.8% [U], and 87.7% and 21.8% [C], all p<0.05) and a higher rate of severe hypoglycemia (15.3/100 PY [S/A] vs. 7.6/100 PY [C], and vs. 4.8/100 PY [U], all p<0.05). Compared to the two other groups, patients from Ukraine had a lower adjusted HbA1c (6.96% [95%-CI: 6.77–7.14] [U] vs. 7.49% [7.32–7.66] [S/A] and 7.37% [7.36–7.39] [C], all p<0.001).DiscussionIn their first treatment year in the host country, young Syrian or Afghan refugees had higher BMI-SDS, lower use of diabetes technology, higher HbA1c, and a higher rate of severe hypoglycemia compared to young Ukrainian refugees. Diabetologists should be aware of the different cultural and socioeconomic backgrounds of refugees to adapt diabetes treatment and education to specific needs

Acceptance of mobile payments among consumers: the case of Kosovo

Analysis of the genome of Bacillus halodurans strain C125 indicated that two pathways leading from a cytosine deoxyribonucleotide to dUMP, used for dTMP synthesis, were encoded by the genome of the bacterium. The genes that were responsible, the comEB gene and the dcdB gene, encoding dCMP deaminase and the bifunctional dCTP deaminase:dUTPase (DCD:DUT), respectively, were both shown to be expressed in B. halodurans, and both genes were subject to repression by the nucleosides thymidine and deoxycytidine. The latter nucleoside presumably exerts its repression after deamination by cytidine deaminase. Both comEB and dcdB were cloned, overexpressed in Escherichia coli, and purified to homogeneity. Both enzymes were active and displayed the expected regulatory properties: activation by dCTP for dCMP deaminase and dTTP inhibition for both enzymes. Structurally, the B. halodurans enzyme resembled the Mycobacterium tuberculosis enzyme the most. An investigation of sequenced genomes from other species of the genus Bacillus revealed that not only the genome of B. halodurans but also the genomes of Bacillus pseudofirmus, Bacillus thuringiensis, Bacillus hemicellulosilyticus, Bacillus marmarensis, Bacillus cereus, and Bacillus megaterium encode both the dCMP deaminase and the DCD:DUT enzymes. In addition, eight dcdB homologs from Bacillus species within the genus for which the whole genome has not yet been sequenced were registered in the NCBI Entrez database