Der Einfluss der SNPs rs4077515 des CARD9-Gens und rs3816527 des PTX3-Gens auf die Lungenerkrankung der Zystischen Fibrose

Die Zystische Fibrose (CF) ist in der kaukasischen Bevölkerung die häufigste genetisch bedingte Stoffwechselerkrankung. Sie betrifft viele Organe, vor allem den Gastrointestinaltrakt und die Lunge. Die ursächliche Störung verursacht der defekte Chloridkanal Cystic Fibrosis Transmembrane Conductance Regulator (CFTR). Die verschiedenen Ausprägungen der Erkrankung des Gastrointestinaltraktes, nicht jedoch der Lungenerkrankung, sind weitgehend auf Mutationen im CFTR-Gen zurückzuführen. Um die vielen unbekannten Ursachen der CF-Lungenerkrankung weiter zu erforschen, wurde in dieser Arbeit der Zusammenhang zwischen zwei SNPs von modifizierenden Genen und der Lungenfunktion sowie dem Erregerbefall untersucht. Die DNA von 528 CF-Patienten aus Deutschland und Österreich wurde mittels des Kits QIAamp DNA Mini Kit aus Vollblut extrahiert. Anhand der PCR, dem Restriktionsenzymverdau und der Agarosegelelektrophorese wurden die Genotypen der SNPs rs4077515 des CARD9-Gens und rs3816527 des PTX3-Gens ermittelt. Bei CF-Patienten entsprechen die Häufigkeiten der Genotypen der SNPs rs4077515 des CARD9-Gens und rs3816515 des PTX3-Gens den Genotyphäufigkeiten der Normalbevölkerung. Diese Arbeit legt nahe, dass die Genotypen des SNPs rs4077515 des Gens CARD9 bei CF-Patienten den C. albicans Befall in der Lunge beeinflussen. Des Weiteren konnte kein Zusammenhang zwischen P. aeruginosa, A. fumigatus sowie der Lungenfunktion anhand von FEV1(mean) und dem Slope bei rs4977515 des CARD9-Gens bestätigt werden. Ferner konnte genauso wenig eine Beeinflussung durch den SNP rs3816515 des PTX3-Gens und den Lungenerregern P.aeruginosa, A. fumigatus und C. albicans bei CF-Patienten erkannt werden. Auch die Lungenfunktion blieb durch die Genotypen von rs3816515 unbeeinflusst. Im Rahmen dieser Dissertation wurde herausgefunden, dass eine Beeinflussung durch die Genotypen eines SNPs des modifizierenden Genes CARD9 auf den C. albicans Befall in der Lunge von CF-Patienten vorliegt. Diese Erkenntnis kann als Ausgangspunkt für weitere Studien dienen, die einen Zusammenhang zwischen dem Erregerbefall durch C. albicans und der Lungenfunktion untersuchen. Gegebenenfalls könnten präventive oder frühzeitige Therapien bei genotypisch anfälligeren CF-Patienten für einen verbesserten Krankheitsverlauf sorgen

Zeugenschaft zwischen Ethik und Politik

Zeugenschaft ist heute wichtiger denn je – und das nicht trotz, sondern vielmehr gerade wegen der gewachsenen Möglichkeiten, jederzeit und überall das Geschehen technisch aufzunehmen und einer breiten Öffentlichkeit zugänglich zu machen. Zeugenschaft ist jedoch nicht nur eine epistemische Praxis, sondern auch eine Form sozialen Engagements, wie die sozialen Protestbewegungen der letzten Jahre gezeigt haben. In den aktuellen Debatten um Zeugenschaft ist allerdings eine gewisse Verengung hin auf die epistemischen Aspekte des Zeugnisgebens zu beobachten. Dagegen versucht der Artikel, Praktiken der Zeugenschaft auf ihre ethischen und politischen Implikationen hin zu befragen. Dabei gilt es, kritisch auf die Normen zu reflektieren, die Zeugenschaft ermöglichen oder verhindern. Zugleich impliziert jedes Zeugnis ein politisches Moment, insofern sich das Wahrsprechen des Zeugen bzw. der Zeugin selbst als politischer Akt interpretieren lässt. Zeugnisgeben erweist sich damit, so die These, nicht nur als eine epistemische, sondern auch als eine ethische und politische Praxis, ohne dass diese Elemente aufeinander reduzierbar wären

Kompetenzorientierung in modularisierten Studiengängen zur Schließung curricularer Lücken

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Synthetic biology in the view of European public funding organisations

We analysed the decisions of major European public funding organisations to fund or not to fund synthetic biology (SB) and related ethical, legal and social implication (ELSI) studies. We investigated the reaction of public organisations in six countries (Austria, France, Germany, the Netherlands, Switzerland and the UK) towards SB that may influence SB’s further development in Europe. We examined R&D and ELSI communities and their particular funding situation. Our results show that the funding situation for SB varies considerably among the analysed countries, with the UK as the only country with an established funding scheme for R&D and ELSI that successfully integrates these research communities. Elsewhere, we determined a general lack of funding (France), difficulties in funding ELSI work (Switzerland), lack of an R&D community (Austria), too small ELSI communities (France, Switzerland, Netherlands), or difficulties in linking existing communities with available funding sources (Germany), partly due to an unclear SB definition

Thermoanalytical Investigations on the Influence of Storage Time in Water of Resin-Based CAD/CAM Materials

New resin-based composites and resin-infiltrated ceramics are used to fabricate computer-aided design (CAD) and computer-aided manufacturing (CAM)-based restorations, although little information is available on the long-term performance of these materials. The aim of this investigation was to determine the effects of storage time (24 h, 90 days, 180 days) on the thermophysical properties of resin-based CAD/CAM materials. Thermogravimetric Analysis (TGA), differential scanning calorimetry (DSC) and dynamic mechanical analysis (DMA) were used in the study. TGA provided insight into the composition of the resin-based materials and the influence of internal plasticization and water sorption. Resin-based composites showed different decomposition, heat energy and mechanical behavior, which was influenced by storage time in water. Individual materials such as Grandio bloc showed lower influence of water storage while maintaining good mechanical properties

Balancing competing needs in kidney transplantation: does an allocation system prioritizing children affect the renal transplant function?

Children often merit priority in access to deceased donor kidneys by organ-sharing organizations. We report the impact of the new Swiss Organ Allocation System (SOAS) introduced in 2007, offering all kidney allografts from deceased donors <60 years preferentially to children. The retrospective cohort study included all paediatric transplant patients (<20 years of age) before (n = 19) and after (n = 32) the new SOAS (from 2001 to 2014). Estimated glomerular filtration rate (eGFR), urine protein-to-creatinine ratio (UPC), need for antihypertensive medication, waiting times to kidney transplantation (KTX), number of pre-emptive transplantations and rejections, and the proportion of living donor transplants were considered as outcome parameters. Patients after the new SOAS had significantly better eGFRs 2 years after KTX (Mean Difference, MD = 25.7 ml/min/1.73 m(2) , P = 0.025), lower UPC ratios (Median Difference, MeD = -14.5 g/mol, P = 0.004), decreased waiting times to KTX (MeD = -97 days, P = 0.021) and a higher proportion of pre-emptive transplantations (Odds Ratio = 9.4, 95% CI = 1.1-80.3, P = 0.018), while the need for antihypertensive medication, number of rejections and living donor transplantations remained stable. The new SOAS is associated with improved short-term clinical outcomes and more rapid access to KTX. Despite lacking long-term research, the study results should encourage other policy makers to adopt the SOAS approach

Baseline Chest Computed Tomography as Standard of Care in High-Risk Hematology Patients

Baseline chest computed tomography (BCT) in high-risk hematology patients allows for the early diagnosis of invasive pulmonary aspergillosis (IPA). The distribution of BCT implementation in hematology departments and impact on outcome is unknown. A web-based questionnaire was designed. International scientific bodies were invited. The estimated numbers of annually treated hematology patients, chest imaging timepoints and techniques, IPA rates, and follow-up imaging were assessed. In total, 142 physicians from 43 countries participated. The specialties included infectious diseases (n = 69; 49%), hematology (n = 68; 48%), and others (n = 41; 29%). BCT was performed in 57% (n = 54) of 92 hospitals. Upon the diagnosis of malignancy or admission, 48% and 24% performed BCT, respectively, and X-ray was performed in 48% and 69%, respectively. BCT was more often used in hematopoietic cell transplantation and in relapsed acute leukemia. European centers performed BCT in 59% and non-European centers in 53%. Median estimated IPA rate was 8% and did not differ between BCT (9%; IQR 5-15%) and non-BCT centers (7%; IQR 5-10%) (p = 0.69). Follow-up computed tomography (CT) for IPA was performed in 98% (n = 90) of centers. In high-risk hematology patients, baseline CT is becoming a standard-of-care. Chest X-ray, while inferior, is still widely used. Randomized, controlled trials are needed to investigate the impact of BCT on patient outcome

AGO Recommendations for the surgical therapy of breast cancer: update 2022

The recommendations of the AGO Breast Committee on the surgical therapy of breast cancer were last updated in March 2022 (www.ago-online.de). Since surgical therapy is one of several partial steps in the treatment of breast cancer, extensive diagnostic and oncological expertise of a breast surgeon and good interdisciplinary cooperation with diagnostic radiologists is of great importance. The most important changes concern localization techniques, resection margins, axillary management in the neoadjuvant setting and the evaluation of the meshes in reconstructive surgery. Based on meta-analyses of randomized studies, the level of recommendation of an intraoperative breast ultrasound for the localization of non-palpable lesions was elevated to “++”. Thus, the technique is considered to be equivalent to wire localization, provided that it is a lesion which can be well represented by sonography, the surgeon has extensive experience in breast ultrasound and has access to a suitable ultrasound device during the operation. In invasive breast cancer, the aim is to reach negative resection margins (“no tumor on ink”), regardless of whether an extensive intraductal component is present or not. Oncoplastic operations can also replace a mastectomy in selected cases due to the large number of existing techniques, and are equivalent to segmental resection in terms of oncological safety at comparable rates of complications. Sentinel node excision is recommended for patients with cN0 status receiving neoadjuvant chemotherapy after completion of chemotherapy. Minimally invasive biopsy is recommended for initially suspect lymph nodes. After neoadjuvant chemotherapy, patients with initially 1 – 3 suspicious lymph nodes and a good response (ycN0) can receive the targeted axillary dissection and the axillary dissection as equivalent options