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To this day, the patient’s outcome after any form of cerebral ischemia is often mediocre
at best. The added damage that occurs at reperfusion after ischemia seems to be as
important as the ischemic injury itself. New therapeutic strategies targeted at this
critical issue are therefore crucial. P188, an amphiphilic triblock copolymer, has risen
to be one of the most promising pharmacological therapeutics, as its capability to insert
into injured cell membranes seems to perfectly fit the needed criteria to protect against
I/R injury. Lately, it has become apparent that mitochondrial function particularly profits
from P188 treatment after I/R injury. Therefore, the question arose, if P188 may
interact directly with mitochondria.
In the present study, rat isolated brain mitochondria were injured and then treated with
P188. The injury took place either in vivo by asphyxial cardiac arrest before isolation
of mitochondria or in vitro after isolation by addition of the ROS H2O2. After treatment
with P188, mitochondrial function was evaluated through the assessment of ATP
synthesis, O2 consumption and CRC.
10 or 15 min of asphyxia in vivo as well as 200 μM H2O2 for 10 min in vitro significantly
impaired mitochondrial function. Furthermore, a damaging effect of RT on isolated
mitochondria became apparent. Contrary to the underlying hypothesis, P188 did not
preserve mitochondrial function independently of the injury mechanism chosen.
In conclusion, in the context of studying P188, two new methods of I/R injury
simulation, namely asphyxial cardiac arrest in vivo and the injury with H2O2 in isolated
mitochondria in vitro, have been established. However, it is not yet conclusive, if P188
does or does not directly improve mitochondrial function after I/R injury. Further
research looking at different injuring methods as well as modulating the treatment
method is needed to ultimately clarify this question.
Potential of nitrous oxide sedation in pedodontics to reduce the need of dental general anesthesia
(2022)
Aim: To investigate the possible reduction of the need for dental general anesthesia (DGA) through nitrous oxide sedation (NOS), when is used in combination with behavior management techniques among patients younger than 12 years of age referred to a specialized pedodontics practice due to the high dental treatment need and poor cooperation level.
Materials and methods: Retrospective analysis was performed of the digital medical records of all children treated under NOS in a specialized pedodontics clinic between 2012 and 2017. The potential reduction of the need for dental general anesthesia was assessed depending on the success rate of NOS on patient-level with relations to multiple related factors such as age, reason of referral and treatment need.
Results: out of 510 patients, 228 meet the inclusion criteria. Nitrous oxide was used in 406 dental treatment sessions on 228 pre-cooperative and/or anxious patients aged 3-12 years (mean 6.4±1.7; 43.4% female). 91.9% of the NOS sessions were successful in achieving the intended dental treatment. Complete oral rehabilitation was possible for 84% of the patients using NOS without the need of DGA. Regarding the age, DGA reduction among pre-school children was lower than in schoolchildren (77.8% and 87.9%, respectively).
Conclusion: A high fraction of anxious or semi-cooperative children with high dental treatment needs can be treated without the use of DGA when a comprehensive concept of caries management is combined with the use of NOS and behavior management techniques. NOS should, therefore, always be considered as an option for dental treatment of semi-cooperative children with high dental treatment needs before making a decision towards DGA.
Pharmaceutical residues are found in increasing concentrations in the environment and in potable water where they have verifiable effects on aquatic life. Conventional methods for water treatment are not able to sufficiently abate these generally stable compounds. It was found that physical plasma generated directly in water can degrade several of these recalcitrant organic pollutants. Studies on the basic plasma chemical processes for the model system of phenol showed that the degradation is primarily caused by hydroxyl radicals. This was confirmed by reaction chemistry and spin trap enhanced electron paramagnetic resonance spectroscopy (EPR). The degradation of diclofenac and its by-products were investigated in detail to perform a first risk-assessment of the new technology. Findings are not limited to the application of plasma but applicable to other advanced oxidation processes (AOP) that are based on the generation of hydroxyl radicals as well. Additionally, pulsed corona plasma and pulsed electric fields were assessed for their capacity to kill Legionella pneumophila in water. Whereas it was possible to kill L. Pneumophila with both methods, plasma treatment resulted in an enhanced bacterial killing. Therefore, advanced oxidation processes (AOP) and plasma treatment in particular are some of the few feasible approaches to decompose recalcitrant compounds in water.
Dendrochronology, the science of tree-rings is a tool which has been widely used for many years for understanding changes in the environment, as trees react to environmental changes over time. In the contemporary situation, where climate warming in the Arctic is unequivocal and its effects on the Alpine and tundra ecosystems are seen pronouncedly in the past decade, the role of dendro-studies and the use of trees and shrubs alike as proxies of change has become critical. Studies clearly indicate that warming in the Arctic and Alpine tundra has resulted in increased vegetation in recent years. Shrubs, in these sensitive ecosystems, have proven to be highly instrumental as they likely benefit from this warming and hence are good indicators and auditees of this change. Therefore, in this study, we investigate the potential of shrubs in the evolving field of dendro-ecology/climatology.
Studies from classical dendrochronology used annual rings from trees. Further, because of shrub sensitivity to contemporary change, shrub-based dendrochronological research has increased at a notable scale in the last decade and will likely continue. This is because shrubs grow even beyond the tree line and promise environmental records from areas where tree growth is very limited or absent. However, a common limitation noted by most shrub studies is the very hard cross-dating due to asynchronous growth patterns. This limitation poses a major hurdle in shrub-based dendrochronological studies, as it renders weak detection of common signals in growth patterns in population stands. This common signal is traced by using a ‘site-chronology’.
In this dissertation, I studied shrub growth through various resolutions, starting from understanding radial growth within individuals along the length of the stem, to comparison of radial growth responses among male and female shrubs, to comparing growth responses among trees and shrubs to investigation of biome-wide functional trait responses to current warming. Apart from Chapter 4 and Chapter 6, I largely used Juniperus communis sp. for investigations as it is the most widely distributed woody dioecious species often used in dendro-ecological investigations in the Northern Hemisphere.
Primarily, we investigated radial growth patterns within shrubs to better understand growth within individuals by comparing different stem-disks from different stem heights within individuals. We found significant differences in radial growth from different stem-disks with respect to stem heights from same individuals. Furthermore, we found that these differences depending on the choice of the stem-disk affect the resulting site-chronology and hence climate-sensitivity to a substantial extent and that the choice of a stem-disk is a crucial precursor which affects climate-growth relationships.
Secondly, we investigated if gender difference – often reported causing differential radial growth in dioecious trees – is an influential factor for heterogeneous growth. We found that at least in case of Juniperus communis. L and Juniperus communis ssp nana. WILLD there is no substantial gender biased difference in radial growth which might affect the site-chronology. We did find moderate differences between sexes in an overall analysis and attribute this to reproductive effort in females.
In our study to test the potential of shrubs for reconstruction, we used a test case of Alnus viridis ssp crispa. We found a strong correlation between ring-width indices and summer temperature. Initially, the model failed the stability tests when we tested the stability of this relation using a response function model. However, using wood-anatomical analysis we discovered that this was because of abnormal cell-wall formation resulting in very thin rings in the year 2004. Pointer year analysis revealed that the thin rings were caused because of a moth larval outbreak and when corrected for these rings the model passed all stability tests.
Furthermore, to see if trees and shrubs growing in same biomes react to environmental changes similarly, a network analysis with sites ranging from the Mediterranean biome to the Ural Mountains in Russia was carried out. We found that shrubs react better to the current climate warming and have a decoupled divergent temperature response as compared to coexisting trees. This outcome reiterated the importance of shrub studies in relation to contemporary climate change. Even though trees and shrubs are woody forms producing annual rings, they have very different growth patterns and need different methods for analysis and data treatment.
Finally, in a domain-wide network analysis from plant-community vegetation survey, we investigated functional relationships between plant traits (leaf area, plant height, leaf nitrogen content, specific leaf area (SLA), and leaf dry matter content (LDMC)) and abiotic factors viz. temperature and soil moisture. We found a strong relation between summer temperature and community height, SLA and LDMC on a spatial scale. Contrarily, the temporal-analysis revealed SLA and LDMC lagged and did not respond to temperature over the last decade. We realized that there are complex interactions between intra-specific and inter-specific plant traits which differ spatially and temporally impacting Arctic ecosystems in terms of carbon turn over, surface albedo, water balance and heat-energy fluxes. We found that ecosystem functions in the Arctic are closely linked with plant height and will be indicative of warming in the short term future becoming key factors in modelling ecosystem projections.
Background
Telephone-Cardiopulmonary Resuscitation (T-CPR) significantly increases rate of bystander resuscitation and improves patient outcomes after out-of-hospital cardiac arrest (OHCA). Nevertheless, securing correct execution of instructions remains a difficulty. ERC Guidelines 2021 recommend standardised instructions with continuous evaluation. Yet, there are no explicit recommendations on a standardised wording of T-CPR in the German language. We investigated, whether a modified wording regarding check for breathing in a German T-CPR protocol improved performance of T-CPR.
Methods
A simulation study with 48 OHCA scenarios was conducted. In a non-randomised trial study lay rescuers were instructed using the real-life-CPR protocol of the regional dispatch centre and as the intervention a modified T-CPR protocol, including specific check for breathing (head tilt-chin lift instructions). Resuscitation parameters were assessed with a manikin and video recordings.
Results
Check for breathing was performed by 64.3% (n = 14) of the lay rescuers with original wording and by 92.6% (n = 27) in the group with modified wording (p = 0.035). In the original wording group the head tilt-chin manoeuvre was executed by 0.0% of the lay rescuers compared to 70.3% in the group with modified wording (p < 0.001). The average duration of check for breathing was 1 ± 1 s in the original wording group and 4 ± 2 s in the group with modified wording (p < 0.001). Other instructions (e.g. check for consciousness and removal of clothing) were well performed and did not differ significantly between groups. Quality of chest compression did not differ significantly between groups, with the exception of mean chest compression depth, which was slightly deeper in the modified wording group.
Conclusion
Correct check for breathing seems to be a problem for lay rescuers, which can be decreased by describing the assessment in more detail. Hence, T-CPR protocols should provide standardised explicit instructions on how to perform airway assessment. Each protocol should be evaluated for practicability.
In general, concepts such as chemical equilibria and classical analytical chemistry, as well as instrumental methods such as potentiometry and flow injection analysis (FIA), are taught separately in the curricula of chemistry-related degree programs. However, FIA provides an opportunity to connect all of these important topics. This article shows how simple experiments can be used to link the fundamentals of FIA and potentiometry to the fundamentals of chemical equilibria and teach them in a sustainable way. The experiments were designed for undergraduate environmental science students with basic knowledge of chemical equilibria and classical analytical chemistry and minimal knowledge of electrochemistry. However, they can also be integrated into various courses on instrumental analysis in chemistry-related degree programs.
Für den erfolgreichen Erhalt von Natur und Landschaft sowohl in Schutzgebieten als außerhalb davon ist die Akzeptanz der jeweiligen Gebietsbewohner notwendig und ihr aktives Engagement hilfreich. Häufig gibt es jedoch Widerstand gegenüber Naturschutzmaßnahmen und wenige aktiv Engagierte. Ein Grund wird in der überwiegend naturwissenschaftlichen Argumention gesehen, die offenbar die Bedeutung von Natur und Landschaft für die Bevölkerung nicht ausreichend widerspiegelt. In der vorliegenden Arbeit wird daher der Frage nachgegangen, ob und wie ästhetische und emotionale Wertschätzungen das Portfolio von Argumenten für den Natur- und Landschaftserhalt bereichern können. Das empirische Material wurde im Rahmen eines Forschungsprojektes (gefördert von der Deutschen Bundesstiftung Umwelt, DBU, 2009-2012) gewonnen, dessen Ziel die Entwicklung und Erprobung von Erhebungsmethoden für ein sozioökonomisches Monitoring in den vier UNESCO-Biosphärenreservaten Mittelelbe, Schaalsee, Schorfheide-Chorin und Südost-Rügen war. Der zentrale Fokus der vorliegenden Arbeit mit soziologischer Forschungsperspektive liegt darauf, wie die Bewohner der vier untersuchten Biosphärenreservate ihre Region emotional und ästhetisch wertschätzen. Neben geographischen wurden vor allem die soziologischen Theorieansätze Social Identity Theory (SIT) und die Identity Process Theory (IPT) erörtert, um mögliche emotionale und ästhetische Argumente fundiert einordnen zu können. Es wurde eine quantitative CATI-Befragung mit mindestens 300 Interviews pro Biosphärenreservat auf der Grundlage einer Zufallsstichprobe durchgeführt. Die Daten wurden neben deskriptiven Untersuchungen mittels binär logistischer Regressionsanalysen und Varianzpartitionierungen als schließende statistische Methoden untersucht. Ein grundlegendes Ergebnis der Analysen ist, dass die Bewohner in allen vier Gebieten eine hohe regionale Verbundenheit aufweisen. Weiterhin scheinen Natur und Landschaft maßgeblich zur emotionalen Verbundenheit zur Region beizutragen. Außerdem stellte sich heraus, dass regionale Verbundenheit sowohl allgemein als auch mit explizitem Landschaftsbezug wichtige Themen für viele Menschen sind und kein Nischenthema einer speziellen Personengruppe darstellen. Denn zwar scheinen einige soziodemographische und andere Faktoren die emotionale Verbundenheit zu verstärken, diverse Parameter, wie etwa Geschlecht und ehrenamtliches Engagement, spielen dagegen aber kaum eine Rolle. Aus den Ergebnissen wurden folgende Handlungsempfehlungen für die Argumentation für Natur- und Landschaftserhalt abgeleitet: (1) Natur und Landschaft haben eine hohe emotionale und ästhetische Bedeutung für viele Bewohner, daher sollten alle raumwirksamen Aktivitäten umfangreich und so zeitig wie möglich erläutert und diskutiert werden. (2) Landschaftliche Vielfalt wird geschätzt und Natur und Landschaft werden nicht als rein stereotype Ansammlung von Landschaftselementen wahrgenommen, sondern mit regionsspezifischen Charakteristika. Wenn Maßnahmen in Natur und Landschaft zu diesen ästhetischen Werten beitragen haben sie ein großes Potenzial, die Unterstützung für Naturerhalt zu erhöhen. Daher wird empfohlen, diese Einflüsse der Maßnahmen besonders zu betonen. (3) Der Bildungsstand scheint grundsätzlich ein besonders wichtiger Faktor für die untersuchten Phänomene zu sein. Daher wird geraten, wenn möglich, die zielgruppenspezifische Kommunikation mit ästhetischen und emotionalen Argumenten sowie Angebote für ein Engagement so auszugestalten, dass Personen aus verschiedenen Bildungsmilieus erreicht werden. (4) Um Menschen für ein naturerhaltendes Engagement zu motivieren wird empfohlen, allgemein an der Region interessierte Personen zu suchen und anzusprechen. (5) Es scheint ratsam, bei der Formulierung von emotionalen Argumenten für den Erhalt von Natur und Landschaft auf den Begriff Stolz zu verzichten. Der Terminus findet unter Akademikern weniger Zustimmung, wenngleich sie eine hohe regionale Verbundenheit haben können. Der Heimatbegriff sollte nur benutzt werden, solange er sich auf kollektiv geteilte, eudaimonistische Werte bezieht und zukunftsgerichtet verwendet wird. (6) Neben der regionalen Verbundenheit können besonders die eudaimonistischen Werte Ruhe, Erholung und andere nicht mit Naturschutzzwecken konfligierende Freizeitnutzungen zielführend in der Argumentation für den Naturerhalt sein. Insgesamt wird für den Natur- und Landschaftserhalt tätigen Akteuren empfohlen, das offensichtlich bestehende Potenzial ästhetischer und emotionaler Argumente stärker zu nutzen und naturwissenschaftliche Argumente damit sinnvoll zu ergänzen. Die in dieser Arbeit diskutierten Ergebnisse liefern dafür eine fundierte Grundlage, da sich aus der nun vorliegenden vergleichenden Analyse von vier unterschiedlichen UNESCO-Biosphärenreservaten in Deutschland belastbare Empfehlungen ableiten lassen, die deutlich über die Untersuchungsgebiete hinaus anwendbar sind.
In this work, studies with respect to the exhaust problem were performed
in the stellarator experiment Wendelstein 7-X with different target concepts and different magnetic field geometries. Different infrared cameras were used to study the heat flux from the plasma onto the PFC. In the first publication, the limiter set-up was used with a simpler magnetic topology in the plasma edge. The radial fall-off of the parallel heat flux for inboard limiters in W7-X shows, similar to inboard limiters in tokamaks, two different radial fall-off lengths, a short (narrow) one, characterizing the near-SOL, and a long (broad) characterizing the far-SOL. For the far-SOL, the heating power and connection length have been identified as the main scaling parameters, while for the near-SOL, the electron temperature close to the LCFS has been identified as the main scaling parameter. The two fall-off lengths differ by a factor 10, and the found scalings for both regimes differ from known models and experimental scalings in tokamaks. A turbulent-driven feature was discussed in the publication as a possible explanation for the behavior of the fall-off length in W7-X.
The gained information and data have been further used to support many
other publications, covering the symmetry of the heat loads, the
energy balance of the machine, and seeding experiments.
The heat exhaust in W7-X with an island divertor was studied in the second
and third publication. Definitions of parameters such as peaking factor and
wetted area were applied for the heterogeneous heat flux pattern on the
W7-X divertor. It was shown that the island divertor concept is capable
of spreading out the heat efficiently, resulting in large wetted areas of up to 1.5 m2. The reached values for the wetted area are comparable to the ones of the larger tokamak JET but with a much smaller ratio of wetted
area to the area of the last closed flux surface. Furthermore, a positive
scaling of the wetted area with the power in the SOL was observed. This
scaling is beneficial for future reactors but needs further investigation of the involved transport processes. The peaking factor (discussed in the second publication) describes how concentrated the heat load is within the region of the strike line. It was shown that this factor is decreasing for increasing densities without affecting the wetted area. The present work paves the way for further analysis of the transport processes of the heat flux towards the island divertor of Wendelstein 7-X.
Aim
To determine the long-term effects of the use of powered tooth brush (PTB) in comparison to manual tooth brush (MTB) on periodontitis severity, coronal caries experience, and the number of missing teeth using in a population-based cohort study.
Materials and Methods
Using 7-year follow-up data of 2214 participants of the Study of Health in Pomerania (SHIP-TREND), comprehensively adjusted linear models using generalized least squares and ordinal regression models estimated the effects of PTB usage on dental outcomes in complete case and imputed data.
Results
At follow-up, PTB users had lower medians for mean probing depth (PD; 2.21 mm) and mean clinical attachment levels (1.73 mm) than MTB users (2.30 and 1.96 mm, respectively). Adjusted models revealed the beneficial effects of PTB usage on follow-up levels of plaque, bleeding on probing, mean PD, percentage of sites with PDs ≥4 mm, mean clinical attachment levels (all, interdental, and non-interdental sites, respectively), and the number of missing teeth. For the number of missing teeth, the effects were more pronounced in participants aged ≥50 years. No significant effects of PTB usage on the number of decayed or filled surfaces (all and interdental sites) were found.
Conclusions
A recommendation of PTB usage in dental practice could contribute to the long-term promotion of oral health.
Riociguat is one of several approved therapies available for patients with pulmonary arterial hypertension (PAH). Treatment should be initiated and monitored at an expert center by a physician experienced in treating PAH, and the dose adjusted in the absence of signs and symptoms of hypotension. In certain populations, including patients with hepatic or renal impairment, the elderly, and smokers, riociguat exposure may differ, and dose adjustments should therefore be made with caution according to the established scheme. Common adverse events are often easily managed, particularly if they are discussed before starting therapy. Combination therapy with riociguat and other PAH-targeted agents is feasible and generally well tolerated, although the coadministration of phosphodiesterase type 5 inhibitors (PDE5i) and riociguat is contraindicated. An open-label, randomized study is currently ongoing to assess whether patients who do not achieve treatment goals while receiving PDE5i may benefit from switching to riociguat. In this review, we provide a clinical view on the practical management of patients with PAH receiving riociguat, with a focus on the opinions and personal experience of the authors.
The reviews of this paper are available via the supplemental material section.
In den letzten Jahrzehnten hat sich durch randomisiert-kontrollierte Studien (RCTs) eine breite Evidenzbasis von Psychotherapie mit mittleren bis großen Effekten für verschiedene psychische Störungen gebildet. Neben der Bestimmung dieser Wirksamkeit („Efficacy“) ebneten Studien zur Wirksamkeit unter alltäglichen Routinebedingungen („Effectiveness“) historisch den Weg zur Entwicklung eines praxisorientierten Forschungsparadigmas. Im Beitrag wird argumentiert, dass im Rahmen dieses Paradigmas praxisbasierte Studien eine wertvolle Ergänzung zu RCTs darstellen, da sie existierende Probleme in der Psychotherapieforschung adressieren können. In der gegenwärtigen praxisorientierten Forschung liefern dabei neue Ansätze aus der personalisierten Medizin und Methoden aus der ‚Computational Psychiatry‘ wichtige Anhaltspunkte zur Optimierung von Effekten in der Psychotherapie. Im Kontext der Personalisierung werden bspw. klinische multivariable Prädiktionsmodelle entwickelt, welche durch Rückmeldeschleifen an Praktiker_innen kurzfristig ein evidenzbasiertes Outcome-Monitoring ermöglicht und langfristig das Praxis-Forschungsnetzwerk in Deutschland stärkt. Am Ende des Beitrags werden zukünftige Richtungen für die praxisorientierte Forschung im Sinne des ‘Precision Mental Health Care’ -Paradigmas abgeleitet und diskutiert.
Background
The ‘wallflower’ hypothesis proposes females mate indiscriminately to avoid reproductive delays. Post-copulatory mechanisms may then allow ‘trading up’, favouring paternity of future mates. We tested links between pre- and post-copulatory choice in Latrodectus geometricus female spiders paired sequentially with two males. These females copulate as adults or as subadults and store sperm in paired spermathecae. Choosy adults have a higher risk of delays to reproduction than subadults.
Results
We predicted low pre-copulatory, but high post-copulatory choice at first matings for adults and the opposite for subadults. At second matings, we expected all females would prefer males superior to their first. We found all females mated indiscriminately at their first pairing, but in contrast to subadults, adults usually allowed only a single insertion (leaving one of their paired spermatheca empty); a mechanism of post-copulatory choosiness. Adult-mated females were more likely to remate than subadult-mated females when they became adults, showing a preference for larger males, while subadult-mated females tended to prefer males of greater size-corrected mass.
Conclusions
Our results show that the ‘wallflower’ effect and ‘trading up’ tactics can be utilized at different life stages, allowing females to employ choice even if rejecting males is costly.
Abstract
Background
The CRISPR/Cas9 system has opened new perspectives to study the molecular basis of cerebral cavernous malformations (CCMs) in personalized disease models. However, precise genome editing in endothelial and other hard‐to‐transfect cells remains challenging.
Methods
In a proof‐of‐principle study, we first isolated blood outgrowth endothelial cells (BOECs) from a CCM1 mutation carrier with multiple CCMs. In a CRISPR/Cas9 gene correction approach, a high‐fidelity Cas9 variant was then transfected into patient‐derived BOECs using a ribonucleoprotein complex and a single‐strand DNA oligonucleotide. In addition, patient‐specific CCM1 knockout clones were expanded after CRISPR/Cas9 gene inactivation.
Results
Deep sequencing demonstrated correction of the mutant allele in nearly 33% of all cells whereas no CRISPR/Cas9‐induced mutations in predicted off‐target loci were identified. Corrected BOECs could be cultured in cell mixtures but demonstrated impaired clonal survival. In contrast, CCM1‐deficient BOECs displayed increased resistance to stress‐induced apoptotic cell death and could be clonally expanded to high passages. When cultured together, CCM1‐deficient BOECs largely replaced corrected as well as heterozygous BOECs.
Conclusion
We here demonstrate that a non‐viral CRISPR/Cas9 approach can not only be used for gene knockout but also for precise gene correction in hard‐to‐transfect endothelial cells (ECs). Comparing patient‐derived isogenic CCM1+/+, CCM1+/−, and CCM1−/− ECs, we show that the inactivation of the second allele results in clonal evolution of ECs lacking CCM1 which likely reflects the initiation phase of CCM genesis.
Abstract
Alkali ion beams are among the most intense produced by the ISOLDE facility. These were the first to be studied by the ISOLTRAP mass spectrometer and ever since, new measurements have been regularly reported. Recently the masses of very neutron-rich and short-lived cesium isotopes were determined at ISOLTRAP. The isotope 148Cs was measured directly for the first time by Penning-trap mass spectrometry. Using the new results, the trend of two-neutron separation energies in the cesium isotopic chain is revealed to be smooth and gradually decreasing, similar to the ones of the barium and xenon isotopic chains. Predictions of selected microscopic models are employed for a discussion of the experimental data in the region.
The rapid neutron-capture or the r-process is responsible for the origin of about half of the neutron-rich atomic nuclei in the universe heavier than iron. For the calculation of the abundances of those nuclei, atomic masses are required as one of the input parameters with very high precision. In the present work, the masses of the neutron-rich Zn isotopes (A=71 to 81) lying in the r-process path have been measured in the ISOLTRAP experiment at ISOLDE/CERN. The mass of 81Zn has been measured directly for the first time. The half-lives of the nuclides ranged from 46.5 h (72Zn) down to 290 ms (81Zn). In case of all the nuclides, the relative mass uncertainty (∆m/m) achieved was in the order of 1E-8 corresponding to a 100-fold improvement in precision over previous measurements.
The aim of this study was to analyse the predictive power of several clinical baseline parameters and the de-/remineralisation properties of in vivo etched sites measured with quantitative light-induced fluorescence (QLF) for subsequent 2-year caries increment. At baseline, in 44 children (8.23 ± 1.5 years) two areas (diameter 2 mm) of the buccal surface of a primary posterior tooth were etched with 36% phosphoric acid gel for 1 and 4 min, respectively. The etched sites were analysed immediately after etching (ΔQ1) and 24 h (ΔQ2) later by QLF. Additionally, caries status (deft/DMFT and initial caries), approximal plaque, bleeding on probing, and the patient’s current use of fluorides were recorded. In the 2-year follow-up, 29 children were re-assessed. After clinical examination, the caries increment was calculated (ΔDMFT) and correlated with the baseline clinical variables and the QLF readings. Results showed a significant positive correlation between ΔQ<sub>1 min</sub> and the ΔDMFT (r = 0.44, p = 0.02). The ΔDMFT was significantly correlated with the baseline deft (r = 0.56, p = 0.002), cavitated active caries lesions (r = 0.52, p = 0.003), and filled teeth (r = 0.53, p = 0.003). In a regression analysis the use of fluoridated salt (SC = –0.10) and fluoride gel (SC = –0.14) were negatively associated with ΔDMFT. In conclusion, these findings suggest that the demineralisation properties of the etched sites and the outcome of the 24-hour measurements with QLF are significantly associated with caries increment. Previous caries experience strongly correlated with caries increment in this group of children.
Predicting complications in pediatric Crohn's disease patients followed in CEDATA-GPGE registry
(2023)
Background
Complications of Crohn's disease (CD) often impair patients' quality of life. It is necessary to predict and prevent these complications (surgery, stricturing [B2]/penetrating [B3] disease behavior, perianal disease, growth retardation and hospitalization). Our study investigated previously suggested and additional predictors by analyzing data of the CEDATA-GPGE registry.
Methods
Pediatric patients (< 18 years) diagnosed with CD with follow up data in the registry were included in the study. Potential risk factors for the selected complications were evaluated by performing Kaplan-Meier survival curves and cox regression models.
Results
For the complication surgery, the potential risk factors older age, B3 disease, severe perianal disease and initial therapy with corticosteroids at the time of diagnosis were identified. Older age, initial therapy with corticosteroids, low weight-for-age, anemia and emesis predict B2 disease. Low weight-for-age and severe perianal disease were risk factors for B3 disease. Low weight-for-age, growth retardation, older age, nutritional therapy, and extraintestinal manifestations (EIM) of the skin were identified as risk factors for growth retardation during the disease course. High disease activity and treatment with biologicals were predictors for hospitalization. As risk factors for perianal disease, the factors male sex, corticosteroids, B3 disease, a positive family history and EIM of liver and skin were identified.
Conclusion
We confirmed previously suggested predictors of CD course and identified new ones in one of the largest registries of pediatric CD patients. This may help to better stratify patients’ according to their individual risk profile and choose appropriate treatment strategies.
(1) Background: Predicting chronic low back pain (LBP) is of clinical and economic interest as LBP leads to disabilities and health service utilization. This study aims to build a competitive and interpretable prediction model; (2) Methods: We used clinical and claims data of 3837 participants of a population-based cohort study to predict future LBP consultations (ICD-10: M40.XX-M54.XX). Best subset selection (BSS) was applied in repeated random samples of training data (75% of data); scoring rules were used to identify the best subset of predictors. The rediction accuracy of BSS was compared to randomforest and support vector machines (SVM) in the validation data (25% of data); (3) Results: The best subset comprised 16 out of 32 predictors. Previous occurrence of LBP increased the odds for future LBP consultations (odds ratio (OR) 6.91 [5.05; 9.45]), while concomitant diseases reduced the odds (1 vs. 0, OR: 0.74 [0.57; 0.98], >1 vs. 0: 0.37 [0.21; 0.67]). The area-under-curve (AUC) of BSS was acceptable (0.78 [0.74; 0.82]) and comparable with SVM (0.78 [0.74; 0.82]) and randomforest (0.79 [0.75; 0.83]); (4) Conclusions: Regarding prediction accuracy, BSS has been considered competitive with established machine-learning approaches. Nonetheless, considerable misclassification is inherent and further refinements are required to improve predictions.
The effects of climate change lead to increasing social injustice and hence justice is intrinsically linked to a socio-ecological transformation. In this study, we investigate whether justice sensitivity motivates pro-environmental intention (PEI) and behavior (PEB) and, if so, to what extent emotions and moral disengagement determine this process. For this purpose, we conducted two quota-sampling surveys (Study 1: N = 174, Study 2: N = 880). Multiple regression analyses in both studies suggest that a higher perception of injustice from a perpetrator’s, beneficiary’s, and observer’s perspective is associated with an increased PEI. However, moral disengagement best predicted PEB and PEI. Guilt and authentic pride were found to be emotional predictors of PEI. Additionally, mediation analyses demonstrated that guilt mediates the connection between both perpetrator and beneficiary sensitivity and PEI. These results suggest that when the predominant originators of climate change (i.e., individuals from industrialized countries) perceive global climate injustice from the perspective of a beneficiary or a perpetrator, they experience guilt and have a higher PEI. Based on this mechanism, it seems promising to render global injustice more salient to those responsible for activities that lead to climate change to motivate them to adapt their behavior. The role of moral disengagement and victim sensitivity as barriers to pro-environmental behavior is discussed in this context.
The therapeutic efficacy of a cardiovascular device after implantation is highly dependent on the host-initiated complement and coagulation cascade. Both can eventually trigger thrombosis and inflammation. Therefore, understanding these initial responses of the body is of great importance for newly developed biomaterials. Subtle modulation of the associated biological processes could optimize clinical outcomes. However, our failure to produce truly blood compatible materials may reflect our inability to properly understand the mechanisms of thrombosis and inflammation associated with biomaterials. In vitro models mimicking these processes provide valuable insights into the mechanisms of biomaterial-induced complement activation and coagulation. Here, we review (i) the influence of biomaterials on complement and coagulation cascades, (ii) the significance of complement-coagulation interactions for the clinical success of cardiovascular implants, (iii) the modulation of complement activation by surface modifications, and (iv) in vitro testing strategies.
Background: Biomarkers for gains of evidence based interventions for upper limb motor training in the subacute stage following stroke have rarely been described. Information about these parameters might help to identify patients who benefit from specific interventions and to determine individually expected behavioral gains for a certain period of therapy.
Objective: To evaluate predictors for hand motor outcome after arm ability training in the subacute stage after stroke selected from known potentially relevant parameters (initial motor strength, structural integrity of the pyramidal tract and functional motor cortex integrity).
Methods: We applied the arm ability training (AAT) over 3 weeks to a subpopulation of stroke patients with mild arm paresis, i.e., in 14 patients on average 4 weeks after stroke. The following biomarkers were measured before therapy onset: grip strength on the affected hand, transcranial magnetic stimulation recruitment curve steepness over the primary motor hand area [slope ratio between the ipsilesional hemisphere (IH) and contralesional hemisphere (CH)], and diffusion weighted MRI fractional anisotropy (FA) in the posterior limb of the internal capsule (PLIC; determined as a lateralization index between IH and CH). Outcome was assessed as the AATgain (percentage improvement over training). The “Test d'Evaluation des Membres Supérieurs de Personnes Âgées” (TEMPA) was assessed before and after training to test for possible associations of AAT with activity of daily living.
Results: A stepwise linear regression identified the lateralization index of PLIC FA as the only significant predictor for AAT-gain (R2 = 0.519; P = 0.029). AAT-gain was positively associated (r = 0.59; P = 0.028) with improvement in arm function during daily activities (TEMPA).
Conclusions: While all mildly affected patients achieved a clinically relevant therapeutic effect, pyramidal tract integrity nevertheless had a modifying role for clinical benefit.
Prediction of high caries increment in adults – a 5-year longitudinal study from North-East Germany
(2013)
The aim of this study is to develop an easily applicable prediction model for high coronal caries increment in adults (20-79 years) from a representative sample (N=2,565) to identify a high risk-group for specific caries prevention. The data from SHIP-0 (1997-2001) and the 5-year follow-up SHIP-1 (2002-2006) is used for analyses. The oral health examination was conducted according to WHO criteria [1997]. The drop-out analysis reveals that drop-outs are significantly older, have a lower school education, are more frequently current smokers, but have a better self-perception of their teeth. The majority of the study-population (76%) has caries incidence in this 5-year period. Caries increment shows a polarized distribution, as the high caries increment group (≥9 surfaces in half-mouth, 11.4% of the sample) comprise 40% of the total increment. The variables male gender, age ≥40 years, lower school education or lower income, current smoking, pain-associated dental visit, baseline caries experience and a non-satisfying self-perception of teeth show a statistically significant influence on high caries increment. The prediction model allows a fair to good prediction on an epidemiological level for men (AUC=0.75). The factors smoking, school education and pain-associated visit only have a significant impact on the prediction of high caries increment in men. Due to very high caries prevalence and increment a population-based prevention in adults should be optimized first, before risk-group specific preventive programmes might be implemented.
Background:
Post-stroke delirium (PSD) is a modifiable predictor for worse outcome in stroke. Knowledge of its risk factors would facilitate clinical management of affected patients, but recently updated national guidelines consider available evidence insufficient.
Aims:
The study aimed to establish risk factors for PSD incidence and duration using high-frequency screening.
Methods:
We prospectively investigated patients with ischemic stroke admitted within 24 h. Patients were screened twice daily for the presence of PSD throughout the treatment period. Sociodemographic, treatment-related, and neuroimaging characteristics were evaluated as predictors of either PSD incidence (odds ratios (OR)) or duration (PSD days/unit of the predictor, b), using logistic and linear regression models, respectively.
Results:
PSD occurred in 55/141 patients (age = 73.8 ± 10.4 years, 61 female, National Institutes of Health Stroke Scale (NIHSS) = 6.4 ± 6.5). Age (odds ratio (OR) = 1.06 (95% confidence interval (CI): 1.02–1.10), b = 0.08 (95% CI = 0.04–0.13)), and male gender (b = 0.99 (95% CI = 0.05–1.93)) were significant non-modifiable risk factors. In a multivariable model adjusted for age and gender, presence of pain (OR < sub > mvar </sub >= 1.75 (95% CI = 1.12–2.74)), urinary catheter (OR < sub > mvar </sub > = 3.16 (95% CI = 1.10–9.14)) and post-stroke infection (PSI; OR < sub > mvar </sub > = 4.43 (95% CI = 1.09–18.01)) were predictors of PSD incidence. PSD duration was impacted by presence of pain (b < sub > mvar </sub >= 0.49 (95% CI = 0.19–0.81)), urinary catheter (b < sub > mvar </sub > = 1.03 (95% CI = 0.01–2.07)), intravenous line (b < sub > mvar </sub >= 0.36 (95% CI = 0.16–0.57)), and PSI (b < sub > mvar </sub >= 1.60 (95% CI = 0.42–2.78)). PSD (OR = 3.53 (95% CI = 1.48–5.57)) and PSI (OR = 5.29 (95% CI = 2.92–7.66)) independently predicted inferior NIHSS at discharge. Insular and basal ganglia lesions increased the PSD risk about four- to eight-fold.
Discussion/Conclusion:
This study identified modifiable risk factors, the management of which might reduce the negative impact PSD has on outcome.
Preisbündelung - Eine Analyse von Zahlungsbereitschaften und Variablen des Konsumentenverhaltens
(2010)
Das Konzept der Preisbündelung als Alltagsphänomen verdient eine verhaltenswissenschaftliche Untersuchung. Eine Verbindung preistheoretischer Ansätze, Theorien der Wahrnehmung von Preisen und Eigenschaften sowie Aspekte des Konsumentenverhaltens werden in der vorliegenden Arbeit simultan miteinander in Verbindung gesetzt. Die Arbeit ist in die Theorie des Behavioral Pricings einzuordnen. Die Hauptfragestellung ist zum Einen, wie unterschiedliche Preisbündel durch den Konsumenten wahrgenommen und hinsichtlich des Nutzens beurteilt werden, zum Anderen, welche Motive und Intentionen des Konsumenten hinsichtlich der Nutzenstiftung durch ein Preisbündel relevant sind. Das Ergebnis zeigt Framingwirkungen der Wahrnehmung ausgehend von der Angebotsdarstellung auf. Ebenso werden preistheoretische Annahmen hinsichtlich der Vorteilhaftigkeit eines Preisbündels aus der Sicht des Anbieters aufgegriffen und von Seiten des Konsumenten her untersucht. Die Wahrnehmung von Preisgünstigkeit, Bequemlichkeit, Problemlösung und Transaktionskostenreduktion stehen auf der einen Seite bei dem Angebot von Preisbündeln, auf der anderen treten allerdings eine geringere Wahlfreiheit, geringere Variantenvielfalt und eine geringere Durchschnittsqualität in den Vordergrund. Diese Wahrnehmung von Eigenschaften des Preisbündels im Vergleich zu denselben angebotenen Einzelleistungen wird mit Kaufverhaltensvariablen hinsichtlich der Präferenzbildung für den Kauf eines Preisbündels in Verbindung gesetzt. Diese Variablen umfassen das Preisbewusstsein, das Produktinvolvement, impulsives Kaufverhalten und das Variety Seeking. Ein theoretischer Ansatzpunkt bietet hierbei die Präferenz bzw. Nutzenbewertung von Preisbündeln durch Konsumenten. In diesem Rahmen wird das Konzept der maximalen Zahlungsbereitschaft aufgegriffen und hinsichtlich der Beurteilung des wahrgenommenen und antizipierten Konsumnutzens des Nachfragers anhand verschiedener Modelle erläutert. Ebenfalls wird das Thema der Präferenzoperationalisierung anhand des Sequenzenmodells aufgegriffen. Ein Simultanmodell, bestehend aus Elementen der Wahrnehmung, Motiven und der monetären Nutzenbewertung sowie des Präferenzausdrucks, wird aus bestehenden Theorien und Modellansätzen entwickelt und empirisch anhand eines Praxisbeispiels, welches in der Hotellerie eingebettet ist, überprüft und validiert. Zur Auswertung werden Verfahren von Kausalmodellen bzw. Strukturgleichungsanalysen eingesetzt.
This is the first study to analyze the association of accelerometer-measured patterns of habitual physical activity (PA) and sedentary behavior (SB) with serum BDNF in individuals with coronary heart disease. A total of 30 individuals (M = 69.5 years; 80% men) participated in this pre-post study that aimed to test a multi-behavioral intervention. All participants underwent standardized measurement of anthropometric variables, blood collection, self-administered survey, and accelerometer-based measurement of PA and SB over seven days. Serum BDNF concentrations were measured using enzyme-linked immunosorbent assay kit. We applied separate multiple linear regression analysis to estimate the associations of baseline SB pattern measures, light and moderate-to-vigorous PA with serum BDNF (n = 29). Participants spent 508.7 ± 76.5 min/d in SB, 258.5 ± 71.2 min/d in light PA, and 21.2 ± 15.2 min/d in moderate-to-vigorous PA. Per day, individuals had 15.5 ± 3.2 numbers of 10-to-30 min bouts of SB (average length: 22.2 ± 2.1 min) and 3.4 ± 1.2 numbers of > 30 min bouts of SB (average length: 43.8 ± 2.4 min). Regression analysis revealed no significant associations between any of the accelerometer-based measures and serum BDNF. The findings of this study did not reveal an association of accelerometer-measured PA and SB pattern variables with serum BDNF in individuals with coronary heart disease. In addition, our data revealed a considerable variation of PA and SB which should be considered in future studies.
Background
Postoperative pancreatic fistula (POPF) is the most critical complication after pancreatoduodenectomy (PD). Preoperative identification of high-risk patients and optimal pancreatic reconstruction technique can be a way to reduce postoperative complications.
Methods
A series of 386 patients underwent PD over a 10-year period (2009–2019). On routinely performed preoperative computed tomography (CT) images, the ventro-dorsal diameters of duct (D) and parenchyma (P) were measured in the cutting plane at the superior mesenteric vein. Then, the ratio of both values was calculated (D/P ratio) Double-layer pancreatojejunostomy with alignment of duct and mucosa (ADAM) by two monofilament threads (MFT) was performed in 359 patients and pancreatogastrostomy (PG) in 27 patients. The incidence of POPF was diagnosed according to the International Study Group for Pancreatic Fistula criteria.
Results
The overall rate of POPF was 21% (n = 80), and the rate of clinically relevant type B/C fistulas 6.5% (n = 25). A D/P ratio of <0.2 was significantly associated with type B/C fistula (11%, p < 0.01). In low-risk patients (D/P ratio >0.2), type B/C fistula occurred only in 2%, and in high-risk patients (D/P ratio <0.2) in 9%. ADAM anastomosis was performed safely by two different surgeons. A PG anastomosis had double-digit POPF rates in all groups.
Conclusion
Preoperative CT imaging with D/P measurement may predict the risk of POPF development. A cut off D/P ratio of <0.2 was significantly associated with clinical relevant POPF. ADAM anastomosis may be an option for pancreatojejunostomy. However, preoperative knowledge of the D/P ratio could guide decision-making for primary pancreatectomy when pancreatic reconstruction is critical.
The present study focused on a new formulation approach to improving the solubility of drugs with poor aqueous solubility. A hot melt extrusion (HME) process was applied to prepare drug-loaded solid self-nanoemulsifying drug delivery systems (S-SNEDDS) by co-extrusion of liquid SNEDDS (L-SNEDDS) and different polymeric carriers. Experiments were performed with L-SNEDDS formulations containing celecoxib, efavirenz or fenofibrate as model drugs. A major objective was to identify a polymeric carrier and process parameters that would enable the preparation of stable S-SNEDDS without impairing the release behavior and storage stability of the L-SNEDDS used and, if possible, even improving them further. In addition to commercially available (co)polymers already used in the field of HME, a particular focus was on the evaluation of different variants of a recently developed aminomethacrylate-based copolymer (ModE) that differed in Mw. Immediately after preparation, the L-SNEDDS and S-SNEDDS formulations were tested for amorphicity by differential scanning calorimetry. Furthermore, solubility and dissolution tests were performed. In addition, the storage stability was investigated at 30 °C/65% RH over a period of three and six months, respectively. In all cases, amorphous formulations were obtained and, especially for the model drug celecoxib, S-SNEDDS were developed that maintained the rapid and complete drug release of the underlying L-SNEDDS even over an extended storage period. Overall, the data obtained in this study suggest that the presented S-SNEDDS approach is very promising, provided that drug-loaded L-SNEDDS are co-processed with a suitable polymeric carrier. In the case of celecoxib, the E-173 variant of the novel ModE copolymer proved to be a novel polymeric carrier with great potential for application in S-SNEDDS. The presented approach will, therefore, be pursued in future studies to establish S-SNEDDS as an alternative formulation to other amorphous systems.
Rice husk, one of the main side products in the rice production, and its sustainable management represent a challenge in many countries. Herein, we describe the use of this abundant agricultural bio‐waste as feedstock for the preparation of silver‐containing carbon/silica nano composites with antimicrobial properties. The synthesis was performed using a fast and cheap methodology consisting of wet impregnation followed by pyrolysis, yielding C/SiO2 composite materials doped with varying amounts of silver from 28 to 0.001 wt %. The materials were fully characterized and their antimicrobial activity against ESKAPE pathogens, namely E. faecium, S. aureus, K. pneumoniae, A. baumannii, P. aeruginosa, and E. coli, and the pathogenic yeast C. albicans was investigated. Sensitivities of these strains against the prepared materials were demonstrated, even with exceptional low amounts of 0.015 m% silver. Hence, we report a straightforward method for the synthesis of antimicrobial agents from abundant sources which addresses urgent questions like bio‐waste valorization and affordable alternatives to increasingly fewer effective antibiotics.
The release of DNA by cells during extracellular trap (ET) formation is a defense function of neutrophils and monocytes. Neutrophil ET (NET) formation in term infants is reduced compared to adults. Objective: The aim was to quantify NET and monocyte ET (MET) release and the respective key enzymes myeloperoxidase (MPO) and neutrophil elastase (NE) in preterm infants. In this prospective explorative study, ET induction was stimulated by N-formylmethionine-leucyl-phenylalanine (fMLP), phorbol 12-myristate 13-acetate (PMA), lipopolysaccharide (LPS), and lipoteichoic acid (LTA) in the cord blood of preterm infants (n = 55, 23–36 weeks) compared to term infants and adults. METs were quantified by microscopy, and NETs by microscopy and flow cytometry. We also determined the MPO levels within NETs and the intracellular concentrations of NE and MPO in neutrophils. The percentage of neutrophils releasing ET was significantly reduced for preterm infants compared to adults for all stimulants, and with a 68% further reduction for PMA compared to term infants (p = 0.0141). The NET area was not reduced except for when fMLP was administered. The amount of MPO in NET-producing cells was reduced in preterm infants compared to term infants. For preterm infants, but not term infants, the percentage of monocytes releasing ETs was significantly reduced compared to healthy adults for LTA and LPS stimulation. Conclusion: In preterm infants, ETs are measurable parts of the innate immune system, but are released in a reduced percentage of cells compared to adults.
Pretransplant Tolerance Induction Reduces the Islet Mass Required to Reverse Diabetes in NOD Mice
(2007)
Islet transplantation can restore normoglycemia in diabetic patients. However, its application is limited by the high number of islets required to reverse diabetes. As the mass and potency of most human islet preparations are marginal, a large impact on the applicability of islet transplantation is expected from the implementation of strategies that improve engraftment of these islet preparations. The roles of adaptive immunity and immunosuppression on islet engraftment are not well studied. Therefore, the effects of currently used immunosuppression with antilymphocyte serum, tacrolimus and sirolimus on islet engraftment were separated from their impact on immunity and diabetes reversal rates were compared after islet allotransplantation in immunosuppressed and chimeric, non-immunosuppressed NOD mice. Both strategies prevented rejection of islet allografts and reduced the frequency of donor-specific, IFN-gamma-secreting T cells. However, in order to achieve stable diabetes reversal with a probability of about 80% after islet allotransplantation in diabetic NOD mice, a fourfold higher islet mass (400 islets) was required in immunosuppressed recipients, compared with non-immunosuppressed recipients made tolerant pretransplant by induction of mixed hematopoietic chimerism (100 islets). The failure of immunosuppressed mice to become normoglycemic after low-dose islet transplantation primarily resulted from the inhibitory effects of tacrolimus combined with sirolimus on islet engraftment and not from the inhibitory effects of this combination on islet graft function. These data suggest that immunotherapeutic strategies that control adaptive immunity without interfering with islet neovascularization or other processes critical to islet engraftment are likely to improve the success rate of marginal mass human islet allografts.
The objectives of this study were to ascertain the fecal ESBL/AmpC-E. coli prevalence and to detect risk factors for their occurrence in young pre-weaned calves and their dams on large dairy farms in Germany. From 2018–2019 we investigated 2816 individual fecal samples from pre-weaned dairy calves and their dams, representing seventy-two farms (mean = 667 milking cows) from eight German federal states. To assess possible risk factors associated with ESBL/AmpC-E. coli prevalence in calves and dams, a questionnaire was performed, collecting management data. We observed an ESBL/AmpC-E. coli prevalence of 63.5% (95% CI: 57.4–69.5) among the sampled calves and 18.0% (95% CI: 12.5–23.5) among the dams. On all farms, at least one positive sample was obtained. To date, this is the highest ESBL/AmpC-E. coli prevalence observed in dairy herds in Europe. Feeding with waste milk was identified as a significant risk factor for a high prevalence of ESBL/AmpC-E. coli in calves. Many calves at large dairies in Germany are fed with waste milk due to the large amounts generated as a result of antibiotic dry-off routines and mastitis treatment with antibiotics. Other notable risk factors for high ESBL/AmpC-E. coli in calves were the general fitness/health of dams and calves, and the quality of farm hygiene. Taken together, these findings suggest that new or improved approaches to animal health management, for example, antibiotic dry cow management (selective dry cow therapy) and mastitis treatment (high self-recovery), as well as farm hygiene, should be researched and implemented.
This study primarily aims to determine the frequency of life-threatening conditions among pediatric patients served by the DRF, a German helicopter emergency service (HEMS) provider. It also seeks to explore the necessity of invasive procedures in this population, discussing the implications for HEMS crew training and service configuration based on current literature. We analyzed the mission registry from 31 DRF helicopter bases in Germany, focusing on 7954 children aged 10 or younger over a 5-year period (2014–2018). Out of 7954 identified children (6.2% of all primary missions), 2081 (26.2%) had critical conditions. Endotracheal intubation was needed in 6.5% of cases, while alternative airway management methods were rare (n = 14). Half of the children required intravenous access, and 3.6% needed intraosseous access. Thoracostomy thoracentesis and sonography were only performed in isolated cases.
Conclusions: Critically ill or injured children are infrequent in German HEMS operations. Our findings suggest that the likelihood of HEMS teams encountering such cases is remarkably low. Besides endotracheal intubation, life-saving invasive procedures are seldom necessary. Consequently, we conclude that on-the-job training and mission experience alone are insufficient for acquiring and maintaining the competencies needed to care for critically ill or injured children.
Due to the wide range of reported prevalence of Molar-Incisor-Hypomineralisation (MIH) found in regional studies, the aim of this study was to determine the prevalence of MIH in school children at different areas in Germany and to compare the findings to other studies. In the compulsory dental school examination, the first permanent molars, permanent incisors and second primary molars were examined for the presence of MIH according to EAPD criteria (Lygidakis et al., 2010; Weerheijm et al., 2003) in 2395 children attending 2nd to 4th grade (mean age 8.1 ±0.8 years, range 7- 10 years) in four regions in Germany. Examinations were performed by five calibrated examiners (Kappa> 0.9) on clean teeth after brushing. The MIH prevalence at the four regions differed considerably (Düsseldorf 14.6 %, Hamburg 14.0 %, Heidelberg 6.0 %, Greifswald 4.3%) with a mean prevalence of 10.1 % (10.7 % boys, 9.5 % girls, χ2-test: p= 0.57). The caries prevalence was low in general, but children with MIH exhibited statistically significantly higher caries experience in the primary and permanent dentition (MIH group: dmft 2.0 ±2.5; DMFT 0.2 ±0.6; other children: dmft 1.5 ±2.2; DMFT 0.1 ±0.5; t-test: p= 0.001 and p< 0.001, respectively). The mean number of permanent teeth affected by MIH was 2.8 (±1.7). 12.0 % of the children with MIH also had at least one affected primary molar which resulted in a statistically significant correlation for MIH in primary and permanent teeth (p< 0.01, Spearmans correlation). Most of the affected teeth had demarcated opacities (81.2 %), but more than half of the affected children showed at least one tooth with a severe form of MIH characterized by breakdown of the tooth, atypical restorations or pain during brushing or eating. In conclusion, MIH is a clinically and epidemiologically relevant problem in German school children. The prevalence which is highly varying in different regions requires more research on the aetiology of MIH. The high rate of severe forms is of clinical concern. The findings of the present study stress the need for educating present and future dentists and pediatric specialists in MIH, as well as for developing public health policies for the prevention and adequate treatment of MIH.
Introduction
Bipolar disorder (BD) is characterized by recurrent episodes of depression and mania and affects up to 2% of the population worldwide. Patients suffering from bipolar disorder have a reduced life expectancy of up to 10 years. The increased mortality might be due to a higher rate of somatic diseases, especially cardiovascular diseases. There is however also evidence for an increased rate of diabetes mellitus in BD, but the reported prevalence rates vary by large.
Material and Methods
85 bipolar disorder patients were recruited in the framework of the BiDi study (Prevalence and clinical features of patients with Bipolar Disorder at High Risk for Type 2 Diabetes (T2D), at prediabetic state and with manifest T2D) in Dresden and Würzburg. T2D and prediabetes were diagnosed measuring HBA1c and an oral glucose tolerance test (oGTT), which at present is the gold standard in diagnosing T2D. The BD sample was compared to an age-, sex- and BMI-matched control population (n = 850) from the Study of Health in Pomerania cohort (SHIP Trend Cohort).
Results
Patients suffering from BD had a T2D prevalence of 7%, which was not significantly different from the control group (6%). Fasting glucose and impaired glucose tolerance were, contrary to our hypothesis, more often pathological in controls than in BD patients. Nondiabetic and diabetic bipolar patients significantly differed in age, BMI, number of depressive episodes, and disease duration.
Discussion
When controlled for BMI, in our study there was no significantly increased rate of T2D in BD. We thus suggest that overweight and obesity might be mediating the association between BD and diabetes. Underlying causes could be shared risk genes, medication effects, and lifestyle factors associated with depressive episodes. As the latter two can be modified, attention should be paid to weight changes in BD by monitoring and taking adequate measures to prevent the alarming loss of life years in BD patients.
Objectives
During the corona pandemic, dental practices temporarily closed their doors to patients except for emergency treatments. Due to the daily occupational exposure, the risk of SARS-CoV-2 transmission among dentists and their team is presumed to be higher than that in the general population. This study examined this issue among dental teams across Germany.
Materials and methods
In total, 2784 participants provided usable questionnaires and dry blood samples. Dry blood samples were used to detect IgG antibodies against SARS-CoV-2. The questionnaires were analyzed to investigate demographic data and working conditions during the pandemic. Multivariable logistic mixed-effects models were applied.
Results
We observed 146 participants with positive SARS-CoV-2 IgG antibodies (5.2%) and 30 subjects with a borderline finding (1.1%). Seventy-four out of the 146 participants with SARS-CoV-2 IgG antibodies did not report a positive SARS-CoV-2 PCR test (50.7%), while 27 participants without SARS-CoV-2 IgG antibodies reported a positive SARS-CoV-2 PCR test (1.1%). Combining the laboratory and self-reported information, the number of participants with a SARS-CoV-2 infection was 179 (6.5%). Though after adjustment for region, mixed-effects models indicated associations of use of rubber dams (OR 1.65; 95% CI: 1.01–2.72) and the number of protective measures (OR 1.16; 95% CI: 1.01–1.34) with increased risk for positive SARS-CoV-2 status, none of those variables was significantly associated with a SARS-CoV-2 status in fully adjusted models.
Conclusions
The risk of SARS-CoV-2 transmission was not higher among the dental team compared to the general population.
Clinical relevance.
Following hygienic regulations and infection control measures ensures the safety of the dental team and their patients.
Background
Primary muscular disorders (metabolic myopathies, including mitochondrial disorders) are a rare cause of dyspnea. We report a case of dyspnea caused by a mitochondrial disorder with a pattern of clinical findings that can be classified in the known pathologies of mitochondrial deletion syndrome.
Case presentation
The patient presented to us at 29 years of age, having had tachycardia, dyspnea, and functional impairment since childhood. She had been diagnosed with bronchial asthma and mild left ventricular hypertrophy and treated accordingly, but her symptoms had worsened. After more than 20 years of progressive physical and social limitations was a mitochondrial disease suspected in the exercise testing. We performed cardiopulmonary exercise testing (CPET) with right heart catheterization showed typical signs of mitochondrial myopathy. Genetic testing confirmed the presence of a ~ 13 kb deletion in mitochondrial DNA from the muscle. The patient was treated with dietary supplements for 1 year. In the course of time, the patient gave birth to a healthy child, which is developing normally.
Conclusion
CPET and lung function data over 5 years demonstrated stable disease. We conclude that CPET and lung function analysis should be used consistently to evaluate the cause of dyspnea and for long-term observation.
Primary Pan-CT is associated with improved clinical course and outcome in polytrauma patients
(2012)
The early clinical management of patients with polytrauma remains challenging. Clinical examination is unreliable in identifying the presence and severity of injuries, and diagnostic imaging plays a central role in the evaluation of the injury pattern. In the last decade, whole body multi slice computed tomography (Pan-CT) performed immediately after admission gained recognition in Europe and United States. Its utility and value, given the lack of accuracy data and concerns about unnecessary exposure to radiation, is undefined. The primary objective of this retrospective cohort study was to compare survival of multiple trauma (polytrauma) patients (Injury Severity Score [ISS] ≥ 16) prior to (1999 - 2002) and after (2002 - 2004) the introduction of a Pan-CT-based trauma resuscitation algorithm at a maximum care university medical centre. Secondary objectives were to compare the complication rates and duration of intensive care treatment. The study included 123 patients (mean age 34.6 years [SD 16.8], mean ISS 26.7 [SD 8.7]) in the control and 104 (mean age 39.8 years [SD 20.0], mean ISS 28.6 [SD 10.5]) patients in the intervention period. Die Baseline criteria were well balanced amongst both cohorts except for age (34.6 versus 39.8 years, p = 0.034). Both cohorts had a similar predicted probability of survival using the TRISS method (77.5 versus 77.6%, p = 0.979). Raw mortality decreased markedly but not statistically significantly in Pan-CT cohort (17.9 versus 11.5%, risk ratio (RR) 0.65, 95% confidence interval (CI) 0.34 - 1.24). However, after adjustment for injury severity, by mortality odds ratio of 0.40 (95% CI 0.17 – 0.95, p = 0.038) Pan-CT patients were 2.5 times more likely to survive. The mean difference in the duration of ICU treatment (5.1, 95% CI 1.2 – 9.0 days), days on respirator (5.3, 95% CI 2.0 - 8.6), and number of complications (0.4, 95% CI 0.2 – 0.8) was statistically significant and in favour of the Pan-CT-period.
Introduction
The co-occurrence of health risk behaviours (HRBs, ie, tobacco smoking, at-risk alcohol use, insufficient physical activity and unhealthy diet) increases the risks of cancer, other chronic diseases and mortality more than additively; and applies to more than half of adult general populations. However, preventive measures that target all four HRBs and that reach the majority of the target populations, particularly those persons most in need and hard to reach are scarce. Electronic interventions may help to efficiently address multiple HRBs in healthcare patients. The aim is to investigate the acceptance of a proactive and brief electronic multiple behaviour change intervention among general hospital patients with regard to reach, retention, equity in reach and retention, satisfaction and changes in behaviour change motivation, HRBs and health.
Methods and analysis
A pre–post intervention study with four time points is conducted at a general hospital in Germany. All patients, aged 18–64 years, admitted to participating wards of five medical departments (internal medicine A and B, general surgery, trauma surgery, ear, nose and throat medicine) are systematically approached and invited to participate. Based on behaviour change theory and individual HRB profile, 175 participants receive individualised and motivation-enhancing computer-generated feedback at months 0, 1 and 3. Intervention reach and retention are determined by the proportion of participants among eligible patients and of participants who continue participation, respectively. Equity in reach and retention are measured with regard to school education and other sociodemographics. To investigate satisfaction with the intervention and subsequent changes, a 6-month follow-up is conducted. Descriptive statistics, multivariate regressions and latent growth modelling are applied.
Ethics and dissemination
The local ethics commission and data safety appointee approved the study procedures. Results will be disseminated via publication in international scientific journals and presentations on scientific conferences.
Trial registration numberNCT05365269.
Die vorliegende Studie vergleicht die Problemlösefähigkeiten von 30 Bulimikerinnen, 30 BED-Patientinnen, 30 Angstpatientinnen und 30 Kontrollpersonen. Aufbauend auf dem klassischen Problemlösemodell von D'ZURILLA und NEZU (1971) und geleitet durch eine Konzeptualisierung von D’ZURILLA und MAYDEU-OLIVARES (1995) werden zur Realisierung einer Prozess- und Outcome-Messung von Problemlösefähigkeiten empirisch überprüfte Fragebogenverfahren eingesetzt. Hierbei handelt es sich um das Problem-Solving-Inventory (PSI) von HEPPNER und PETERSEN (1982), das Social-Problem-Solving-Inventory (SPSI-R) von D’ZURILLA und NEZU (1990), das Means-End-Problem-Solving-Verfahren (MEPS) von PLATT und SPIVAK (1975) in der deutschen Bearbeitung von KÄMMERER (1983) und das Inventar-zur-Erfassung-interpersonaler-Probleme (IIP) von HOROWITZ, STRAUSS und KORDY (1994). Die Ergebnisse zeigen signifikant eingeschränkte Problemlösefähigkeiten aller drei Patientengruppen im Vergleich zur gesunden Kontrollgruppe. Unter Berücksichtigung des Depressionsgrades der Probandinnen trat eine Abschwächung, teilweise sogar eine Nivellierung der Effekte auf. Die Patientengruppen unterscheiden sich in ihren Problemlösefähigkeiten nicht untereinander. Problemlösefähigkeiten können sowohl störungsspezifische als auch störungsunspezifische klinische Kennwerte der Patientengruppen vorhersagen. Eine Berücksichtigung von Problemlösefähigkeiten in einem biopsychosozialen Störungsmodell, in Diagnostik und Behandlung von Bulimia Nervosa und "Binge-Eating"-Störung wird durch die Ergebnisse dieser Studie empirisch fundiert.
Innerhalb einer Schulstudie, die an 4 Gymnasien in Vorpommern mit Hilfe eines speziell erarbeiteten anonymen Fragebogen zu Konsumgewohnheiten von legalen und illegalen Drogen und zum diesbezüglichen Problembewusstsein im Zusammenhang mit dem Straßenverkehr durchgeführt wurde, erfolgte die Befragung von 205 SchülerInnen der 9. und 12. Jahrgangsstufe. 80 % der teilnehmenden SchülerInnen stellten zusätzlich Urinproben zur Verfügung. Bei den 15 Jahre alten SchülerInnen ist der Anteil der Raucher unter den Jugendlichen so groß wie bei den 18-Jährigen, nämlich fast 50 %. Darunter befindet sich der größte Anteil bei den weiblichen Raucherinnen. Das Problembewusstsein wird durch das Rauchverbot in der Schule fast überhaupt nicht angesprochen, da 86 % aller SchülerInnen der 9. Klasse auch in der Schule rauchen. Durchschnittlich 88 % der befragten Jugendlichen trinken in ihrer Freizeit Alkohol. Besonders beliebt sind alkoholische Mixgetränke, die überwiegend am Wochenende, auf Partys und Diskotheken oder anderen Feierlichkeiten getrunken werden. Bestimmte Verhaltensmuster im Straßenverkehr wurden besonders durch Fragen zum Fahr- bzw. Mitfahrverhalten bei Alkoholkonsum geprüft. Die Ergebnisse zeigen, dass ein Konsum von relativ geringen Mengen Alkohol (1-2 Gläser Bier) zwar beim Selbstfahren für 71 % der Befragten einen Hinderungsgrund für das Benutzen des Autos darstellen würde, dass man aber bei anderen, gleich stark alkoholisierten Personen durchaus bereit ist mitzufahren, u.a. auch wenn man den Fahrer für fahrtauglich hält oder nicht mehr anders nach Hause kommt. Erst bei einem größeren Alkoholkonsum (3-5 Gläser Bier) des potentiellen Fahrers würden 81 % der Jugendlichen nicht mehr ins Auto steigen. Die Ergebnisse beinhalten auch die Auswertung der Fragen nach den Erfahrungen und Erlebnissen jugendlicher Gymnasiasten mit illegalen Drogen. Bei den 15-jährigen Jugendlichen hatten bereits 40,2 % und bei den 18-Jährigen bereits 32,6 % Erfahrungen mit Cannabisprodukten. Zusätzlich zeigte sich, dass sich inzwischen auch das Einstiegsalter nicht nur für Zigaretten und Alkohol sondern auch für Drogen stark nach vorn verlagert hat. Die befragten 15-jährigen SchülerInnen waren mit 12-13 Jahren etwa 2 Jahre jünger bei erstem Drogenkontakt als die 18-jährigen Jugendlichen. Überwiegend konnten Cannabinoide - aber auch Amphetamine - in 10 % der Urinproben nachgewiesen werden. Andere Konsumdrogen waren in der Befragung z.B. Pilze, Leim, Kokain oder Lachgas. Hier zeigten sich auffällige Unterschiede bei den SchülerInnen von Schule zu Schule, so dass man vermuten darf, dass es bereits schulspezifische Konsummuster gibt. Die meisten SchülerInnen sind aus Neugier zum Drogenkonsum gekommen, sie wollten es einfach mal ausprobieren oder Freunde haben sie dazu verleitet. Im Zusammenhang mit dem Straßenverkehr würde die überwiegende Mehrzahl der Jugendlichen weder ein Fahrzeug selbst unter Drogeneinfluss führen noch bei einem Drogenkonsumenten ins Auto einsteigen. Trotzdem würden 12 % der SchülerInnen selbst noch nach dem Konsum von Drogen ein Auto fahren und 34 % würden sogar zu einem Dogenkonsumenten als Beifahrer ins Auto einsteigen und mitfahren. Bei der Frage nach dem „Warum“ spielte auf der einen Seite die Einschätzung der eigenen Fahrtüchtigkeit bzw. die des Fahrers eine Rolle, auf der anderen Seite steht gerade bei den jüngeren SchülerInnen die Frage, wie man sonst nach Hause kommen soll, im Vordergrund .
Thiol or sulfhydryl groups are highly reactive functional groups in cellular systems. Molecules carrying thiol groups are mostly derivatives of the amino acid cysteine and are grouped as low molecular weight (LMW)-thiols: coenzyme A (CoA), glutathione (GSH) or bacillithiol (BSH). LMW-thiols can help in the maintenance of the reduced cellular environment as so called redox-buffers. Additionally, they act as co-factors in enzyme reactions or help in the detoxification of reactive oxygen or nitrogen species, electrophilic compounds or thiophilic metalloids (arsenite, tellurite). In proteins from different organisms cysteine is underrepresented compared to other amino acids, but still overtakes diverse roles. It is an important determinant in the tertiary and quaternary structure of proteins. The nucleophilic character of the thiol or thiolate group, respectively, makes cysteine the catalytically active amino acids of different enzymes. As a precursor cysteine participates in the formation of Fe-S clusters and coordinates different co-factors like heme, iron or zinc. The main goal of this study was the investigation of the different cellular thiol pools, now defined as the thiolome. The thiolome is the entity of the cellular thiol pools, i.e. LMW-thiols and protein thiols, and the dynamics between these pools. In Bacillus subtilis and Staphylococcus aureus mixed disulfides between protein thiols and free LMW-thiols, so called S-thiolations, were identified in different proteins in response to the thiol specific reagent diamide. Some of these S-thiolations were located at catalytically active cysteine residues. Subsequent analysis of metabolites supports this: the S-thiolation of the cobalamine-independent methionine-synthase MetE led to a decrease of the cellular methionine content. Additionally, the conversion of threonine to different branched-chain amino acids (BCAAs) was disrupted by the S-thiolation of the branched-chain amino acid aminotransferase YwaA, thereby probably inducing the synthesis of ppGpp, the alarmon of the stringent response. In addition to the identification of S-thiolations a technique was established which allowed the discrimination between intra- and intermolecular disulfides. The non-reducing/ reducing diagonal gel electrophoresis was applied to B. subtilis and S. aureus and confirmed known existing disulfide bonds, e.g. in alkyl hydroperoxide reductase AhpC or the thiol peroxidase Tpx. In response to diamide an increase of specific disulfide bonds in different proteins was observed. The analysis of the LMW-thiol content by an HPLC-approach allowed the observation of the dynamics of the thiolome. In response to diamide the reduced LMW-thiol content decreased by 75%, reduced protein thiols by 60%. Collaborations with other working groups allowed the identification of BSH in this approach. Additionally, an unknown thiol was found that is likely a derivative of BSH. Screening of the LMW-thiol content of different S. aureus-strains under various growth conditions revealed that strains 8325-4 and SH1000 lack BSH. The lack of BSH was attributed to an 8 bp-duplication in the bshC-gene that encodes the last enzyme of the BSH-synthesis. BSH-production was restored by transducing plasmid-borne functional BshC from strain Newman into strains 8325-4 and SH1000. The reconstitution of the BSH-synthesis aided in the resistance to the antibiotic fosfomycin but did not increase the resistance to different oxidants (diamide, sodium hypochlorite, hydrogen peroxide). The production of BSH had also positive effects on the survival of S. aureus inside human bronchial epithelial cells and murine macrophages in phagocytosis assays. Additionally, a GSH-uptake was observed into S. aureus which has before been known as a GSH-free bacterium. Taken together, this thesis provides the first insights into both, the LMW-thiol- and protein thiol pool of low GC, Gram-positive bacteria under different conditions. A plethora of different methodologies was used to describe the thiolome. The bacterial thiolome is a sophisticated system which is tightly regulated, but also flexible enough to not rely on determined molecules like BSH. The influences of the thiolome are not restricted to its own system and regulation, but also affect different branches of cellular physiology like the metabolism of BCAAs.
This thesis presents the production of polyanionic clusters within two ion storage devices:
Considering a Penning trap, the accessible range of polyanionic aluminium clusters has been expanded up to the 10th charge state. In particular, abundance curves for clusters with 5 to 9 excess electrons have been measured for the first time and analysed with respect to their lifetime-dependent appearance sizes. These sizes reveal a nearly quadratic dependency on the charge state for experimentally accessible lifetimes.
Additionally, the production of polyanionic clusters has been enabled in a radiofrequency ion trap. Therefore, the transition from a harmonic to a digital 2- and 3-state guiding signal has been investigated with respect to the ion storage. The passing of electrons through the trap during field-free periods of the guiding signal led to the first production of polyanionic clusters within a radiofrequency ion trap.