Entwicklung von forensisch-toxikologischen Untersuchungsverfahren für die Materialanalytik von ‚Spice‘-Produkten, Arznei- und Dopingmitteln

Für die Charakterisierung von forensisch-toxikologischen Materialien werden qualitative und/oder quantitative Ergebnisse benötigt. Einen entscheidenden Faktor spielt dabei die Analysenzeit (Probenvorbereitung, Messzeit) der verwendeten Methode. Aus diesem Grund befasst sich diese Arbeit mit der Analytik von Spice-, Doping- und Arzneiprodukten mittels Desorptions-Elektrospray-Ionisierung (DESI) gekoppelt an ein Ionenfallenmassenspektrometer (IT-MS). Durch die Verwendung der DESI-Technik ist eine direkte massenspektrometrische Untersuchung von festen Materialien möglich und die Verwendung eines IT-MS erlaubt die Differenzierung zwischen Regio- und Strukturisomeren. Neben diesen direkten Analysemöglichkeiten werden Methoden für die quantitative Analyse der vollsynthetischen Wirkstoffe in Spice-Produkten und die Quantifizierung einzelner Steroidester in öligen Dopingmittelzubereitungen beschrieben.<br/

Ureaplasma-Driven Neuroinflammation in Neonates: Assembling the Puzzle Pieces

Ureaplasma species (spp.) are commonly regarded as lowvirulence colonizers of the genitourinary tract. Intrauterine Ureaplasma infection, however, has been associated with chorioamnionitis and preterm birth. The overall impact of a neonatal Ureaplasma colonization is yet to be understood. High pathogen prevalence and frequent neurological morbidities particularly in immature preterm infants call for an assessment of the significance of Ureaplasma spp. in neonatal neuroinflammation. This narrative review summarizes clinical data, animal studies, and in vitro results to elucidate potential Ureaplasma-associated neurological morbidities as well as underlying mechanisms. Increasing evidence indicates an involvement of Ureaplasma spp. in invasive central nervous system infections, suggesting a meticulous ability of Ureaplasma spp. to interfere with immune defense mechanisms. Ultimately, Ureaplasma spp. should be considered as relevant pathogens in neonatal neuroinflammation

The Complexity of Homomorphism Reconstructibility

Representing graphs by their homomorphism counts has led to the beautiful theory of homomorphism indistinguishability in recent years. Moreover, homomorphism counts have promising applications in database theory and machine learning, where one would like to answer queries or classify graphs solely based on the representation of a graph $G$ as a finite vector of homomorphism counts from some fixed finite set of graphs to $G$. We study the computational complexity of the arguably most fundamental computational problem associated to these representations, the homomorphism reconstructability problem: given a finite sequence of graphs and a corresponding vector of natural numbers, decide whether there exists a graph $G$ that realises the given vector as the homomorphism counts from the given graphs. We show that this problem yields a natural example of an \mathsf{NP}^{#\mathsf{P}}-hard problem, which still can be $\mathsf{NP}$-hard when restricted to a fixed number of input graphs of bounded treewidth and a fixed input vector of natural numbers, or alternatively, when restricted to a finite input set of graphs. We further show that, when restricted to a finite input set of graphs and given an upper bound on the order of the graph $G$ as additional input, the problem cannot be $\mathsf{NP}$-hard unless $\mathsf{P} = \mathsf{NP}$. For this regime, we obtain partial positive results. We also investigate the problem's parameterised complexity and provide fpt-algorithms for the case that a single graph is given and that multiple graphs of the same order with subgraph instead of homomorphism counts are given

The interleukin-6 -174promoter polymorphism is associated with long-term kidney allograft survival

The interleukin-6 -174promoter polymorphism is associated with long-term kidney allograft survival.BackgroundTh1-dependent effector mechanisms may be responsible for allograft rejection. Recently, interleukin-6 (IL-6) has been shown to antagonize CD4+ T cells to effector Th2 cells and, in the process, differentiate them into Th1 cells.MethodsTo assess the role of IL-6 in long-term allograft survival, 158 patients after first cadaveric kidney transplantation were analyzed for the biallelic –174G→C promoter polymorphism of the IL-6 gene.ResultsCarriers of the –174C-allele (genotype GC/CC) had an inferior three-year graft survival (71/104 = 68.3%; P = 0.0059) with a 3.7-fold increased relative risk of graft loss compared to carriers of the –174GG-genotype (48/54 = 88.9%). The –174GC/CC-genotype retained its negative impact on graft survival when other established prognostic factors and further cytokine polymorphisms (-308TNF-α, TGF-β1 codon 10 & 25, -592/-819/-1082IL-10 and +874IFN-γ) were considered simultaneously.ConclusionsSince the clinical impact on transplant outcome seems as important as matching for histocompatibility antigens, genotyping of the IL-6 -174polymorphism may offer a new method for identifying patients at increased risk of allograft loss

Two Beer(s) or Not Two Beer(s): The eNose as an Instrument to Pacify the World.

BACKGROUND Science prizes that are not meant to be very serious, stand-up evenings, science slams or publications with a scientific twist: science comedy comes in very different forms. But all variants have one thing in common: humour. It can be used to hide the seriousness of life or, in this case, everyday scientific life for a brief moment. Moreover, serious social or ethical questions are also met. The GPP, a group of German, Austrian and Swiss Pediatric Pulmonologists (GPP) is a scientific society with regular annual meetings. Unsystematic observations and preliminary data suggest that beer consumption increased by some of the participants during this event. Recently, electronic nose (eNose) devices have been developed as a technology for disease screening using exhaled-breath analysis. Here we addressed the issue, if the eNose can be used to differentiate between real beer and fake beer. METHODS In this single-centre experimental study, 12 different "real beer" types and one "fake beer" were analyzed with regard to their emittance of volatile organic compounds (VOCs) with the eNose as an electronic VOC-sensing technology. RESULTS Every single beer type can be identified by a characteristic VOC-smell print using the eNose. Distinct clusters exist for bottom- and top-fermented ales. Intriguingly, "Sylter Hopfen", which is marketed as a "champagne-beer" and tested as representative of a "fake beer", can be clearly differentiated from all other genuine beer types. CONCLUSION Our study provides the first objective data of beer flavor. In the long term perspective the eNose might help to overcome the agonizing controversy about beer flavors and, consequently, pacify the World. In the short run, however, our results give support to more targeted and reserved beer consumption during our annual meeting, especially since one specific beer shows a very similar pattern to indoor air. HINTERGRUND UND FRAGESTELLUNG Sogenannte Stand-up-Abende, Science Slams oder Publikationen wie in der «Christmas-Edition» des "British Medical Journals" haben eines gemeinsam: Humor. Humor kann dabei helfen, der Ernsthaftigkeit des Alltags - auch der des Wissenschaftlers - für einen kurzen Moment zu entfliehen. Die wissenschaftliche Gesellschaft Pädiatrische Pneumologie (GPP e. V.) ist eine Gruppe deutscher, österreichischer und schweizer Kinderpneumolog:innen, die sich regelmässig zu ihrer Jahrestagung treffen. Nicht-systematisch erhobene Daten und persönliche Beobachtungen deuten darauf hin, dass der Bierkonsum von einigen der Teilnehmer:innen während dieser Veranstaltung signifikant ansteigt. Vor kurzem wurde mit der «eNose» eine sogenannte «elektronische Nase» entwickelt, die als Screening-Instrument zur Atemgasanalyse eingesetzt werden kann. Hier haben wir die Frage gestellt, ob die eNose verwendet werden kann, um unterschiedliche Biersorten zu unterscheiden und echte Biere von sogenannten «Fake-Bieren» zu diskriminieren. METHODEN In dieser monozentrischen, experimentellen Studie wurden 12 verschiedene "echte Biersorten" und ein "Fake-Bier" hinsichtlich ihrer Emission flüchtiger organischer Verbindungen (VOCs) mit der eNose als elektronische VOC-Sensortechnologie analysiert. ERGEBNISSE Jede einzelne Biersorte lässt sich anhand eines charakteristischen, reproduzierbaren VOC-Profils mit der eNose identifizieren. Dabei clustern sogenannte unter- und obergärige Biere mit einem spezifischen Muster. "Sylter Hopfen", das als "Champagner-Bier" vermarktet und als «Fake-Bier» getestet wurde, unterscheidet sich in seinem VOC-Profil von allen anderen «echten» Biersorten. SCHLUSSFOLGERUNG Unsere Studie liefert die ersten objektiven Daten zu spezifischen VOC-Mustern von verschiedenen Biersorten. Langfristig könnte die eNose dabei helfen, die emotionale Kontroverse um Bieraromen zu überwinden und damit die Welt zu befrieden. Kurzfristig stützen unsere Ergebnisse die Empfehlung nach einem zurückhaltenden Bierkonsum während unserer Jahrestagung, zumal spezifischen VOC-Mustern einiger Biere ein sehr ähnliches Muster wie Raumluft zeigen

Preterm birth and sustained inflammation: consequences for the neonate.

Almost half of all preterm births are caused or triggered by an inflammatory process at the feto-maternal interface resulting in preterm labor or rupture of membranes with or without chorioamnionitis ("first inflammatory hit"). Preterm babies have highly vulnerable body surfaces and immature organ systems. They are postnatally confronted with a drastically altered antigen exposure including hospital-specific microbes, artificial devices, drugs, nutritional antigens, and hypoxia or hyperoxia ("second inflammatory hit"). This is of particular importance to extremely preterm infants born before 28 weeks, as they have not experienced important "third-trimester" adaptation processes to tolerate maternal and self-antigens. Instead of a balanced adaptation to extrauterine life, the delicate co-regulation between immune defense mechanisms and immunosuppression (tolerance) to allow microbiome establishment is therefore often disturbed. Hence, preterm infants are predisposed to sepsis but also to several injurious conditions that can contribute to the onset or perpetuation of sustained inflammation (SI). This is a continuing challenge to clinicians involved in the care of preterm infants, as SI is regarded as a crucial mediator for mortality and the development of morbidities in preterm infants. This review will outline the (i) role of inflammation for short-term consequences of preterm birth and (ii) the effect of SI on organ development and long-term outcome

Immunization of preterm infants: current evidence and future strategies to individualized approaches

Preterm infants are at particularly high risk for infectious diseases. As this vulnerability extends beyond the neonatal period into childhood and adolescence, preterm infants beneft greatly from infection-preventive measures such as immunizations. However, there is an ongoing discussion about vaccine safety and efcacy due to preterm infants’ distinct immunological features. A signifcant proportion of infants remains un- or under-immunized when discharged from primary hospital stay. Educating health care professionals and parents, promoting maternal immunization and evaluating the potential of new vaccination tools are important means to reduce the overall burden from infectious diseases in preterm infants. In this narrative review, we summarize the current knowledge about vaccinations in premature infants. We discuss the specifcities of early life immunity and memory function, including the role of polyreactive B cells, restricted B cell receptor diversity and heterologous immunity mediated by a cross-reactive T cell repertoire. Recently, mechanistic studies indicated that tissue-resident memory (Trm) cell populations including T cells, B cells and macrophages are already established in the fetus. Their role in human early life immunity, however, is not yet understood. Tissue-resident memory T cells, for example, are diminished in airway tissues in neonates as compared to older children or adults. Hence, the ability to make specifc recall responses after secondary infectious stimulus is hampered, a phenomenon that is transcriptionally regulated by enhanced expression of T-bet. Furthermore, the microbiome establishment is a dominant factor to shape resident immunity at mucosal surfaces, but it is often disturbed in the context of preterm birth. The proposed function of Trm T cells to remember benign interactions with the microbiome might therefore be reduced which would contribute to an increased risk for sustained infammation. An improved understanding of Trm interactions may determine novel targets of vaccination, e.g., modulation of T-bet responses and facilitate more individualized approaches to protect preterm babies in the future

Glucocorticoid Receptor Gene Variants and Neonatal Outcome in Very-Low-Birth-Weight Preterm Infants

Background: Induction of lung maturation by prenatal steroid treatment has become the standard of care for pregnant women at risk for preterm birth. In addition to the beneficial effects on lung maturation, prenatal steroids have been shown to reduce the incidence of neonatal death, necrotizing enterocolitis, sepsis, and intraventricular hemorrhage. However, little is known about the role of interindividual differences in corticoid sensitivity arising from polymorphisms in the glucocorticoid receptor (GR) gene. Objectives: To assess the impact of GR polymorphisms N363S (rs56149945), R23K (rs6190), and BclI (rs41423247) on neonatal outcome. Methods: The GR polymorphisms N363S, R23K, and BclI were examined in 10,490 very-low-birth-weight (VLBW) preterm infants from 49 German tertiary level neonatal units (German Neonatal Network, GNN) with respect to neonatal outcome. Results: Infants carrying the BclI genotype were at higher risk to develop bronchopulmonary dysplasia (BPD) (OR 1.12 per BclI allele, 95% CI: 1.02-1.23, p = 0.013) in a logistic regression model adjusted for gestational age, mechanical ventilation, and small for gestational age status. A similar relative risk was seen in the children (89.4%) who received antenatal betamethasone treatment (OR 1.16, 95% CI: 1.05-1.27, p = 0.003), whereas no such effect was detectable in infants without antenatal steroids. N363S and R23K did not show any stable association with neonatal outcome parameters. Conclusion: Except for a slightly higher risk of BPD in carriers of the GRBclI variant, the GR gene polymorphisms BclI, N363S, and R23K did not affect neonatal outcome parameters in this large multicenter cohort of VLBW preterm infants

Psychological restoration depends on curiosity, motivation, and species richness during a guided bird walk in a suburban blue space

Urban and suburban green and blue spaces are important places for human recreation, and the impact of biodiversity on psychological and recalled restoration has received much attention. This study addresses the relationship between bird species richness and restoration in a controlled field experiment (guided bird walk) applying a battery of individual trait scales (need for cognition, personality) as predictors of restoration. We found a significant positive relationship between the number of bird species present and recalled restoration. Personality, bird species knowledge, bird related interest as test measures, demographics and birding specialization as self-report had no influence on psychological restoration. However, need for cognition correlated positively with psychological restoration, thus providing a new predictive variable. All subscales of the intrinsic motivation scale (enjoyment, perceived competence, perceived choice, pressure/tension) were positively correlated with restoration except of pressure/tension. Learning emotions like interest and well-being were positively related to restoration, while boredom was negatively related. Therefore, we suggest research to examine the restorative function of more cognitive-oriented programs because people may also need cognition when it comes to restoration. We also suggest a broader focus on education and cognitive aspects when it comes to linking biodiversity and health within the framework of ecosystem services

The Questionnaire "SFDP26-German": a reliable tool for evaluation of clinical teaching?

Aims: Evaluation of the effectiveness of clinical teaching is an important contribution for the quality control of medical teaching. This should be evaluated using a reliable instrument in order to be able to both gauge the status quo and the effects of instruction. In the Stanford Faculty Development Program (SFDP), seven categories have proven to be appropriate