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Unstable environments and habitats changing due to climate change force individuals to either respond by genetic adaptation, phenotypic plasticity or by dispersal to suitable environments. Theodoxus fluviatilis (Linneaus, 1758) is a good study organisms when researching phenotypic plasticity and genetic adaptation as it naturally appears in freshwater (FW) as well as brackish water (BW) and thus inhabits a wide range of environmental salinities (0-18‰). It is a euryhaline snail that can be found in shallow waters with stony ground or on Fucus spp. and has formed regional subgroups. The brackish water and the freshwater subgroups are spatially separated and the species cannot be found in areas inbetween, e.g. estuaries.
The species shows great variability in shell patterning and shell size and there is still debate whether the subgroups are distinguishable by these traits or not. The mitochdrial RNA marker cytochrome c subunit I did not show differences between the subgroups indicating that they must be closely related, but salinity tolerance has been observed to be higher in BW snails. This might be caused by the different protein expression patterns and osmolyte accumulation (measured as ninhydrin-positive substances) observed in this species in previous studies. The exact mechanisms regulating protein expression and osmolyte accumulation, however, are not fully understood yet.
Data collected for this thesis shows differences in shell size and suggests a less strict grouping of FW and BW individuals as shell sizes of one FW site are more similar to BW individuals than the other FW ones. A better salinity tolerance towards high salinities and a higher physiological salinity limit of BW snails was confirmed and extended by demonstrating an expanded tolerance range through slow acclimation to challenging salinities in snails from both subgroups. This was achieved by a shift in the slope of their reaction norms that was much more pronounced in BW snails than FW ones. S3 individuals showed a shift similar to that of BW individuals. The data for the salinity tolerance indicates that the underlying mechanism for these tolerances are a combination of phenotypic plasticity and genetic adaptation. Despite an acclimation and shift in the slope of the reaction norms and therefore an increased tolerance towards high salinities (plasticity) FW individuals from two collection sites were not able to cope with salinities as high as BW individuals (local adaptation). The general ability to mobilise free amino acids (FAA) as organic osmolytes was not the reason for this tolerance difference. Individuals from BW and FW sites were capable of accumulating quantities of FAAs equally well. Proline, alanine and urea were the most important components of the accumulated cocktail of organic osmolytes. Even though the total amount of FAAs accumulated under hyperosmotic conditions was the same in both subgroups, there were differences in the metabolic pathways involved in osmolyte accumulation in the foot muscle. The data indicates that the hydrolysis of storage proteins and the synthesis of proline and alanine are the main processes to avoid detrimental body volume shrinkage in T. fluviatilis. While FW individuals seemed to rely on the degradation of proteins and synthesis of alanine, BW individuals depended on newly synthesising proline and alanine and accumulating urea as a side product of transamination. The accumulation of urea is a new finding in aquatic living snails and has not been reported as a mechanism to avoid cell volume shrinkage in these animals.
Differing protein expression patterns were observed under control conditions across all collection sites. 9 spots showed volume changes in BW snails opposite to those of FW snails from collection sites S1 and S2. For 6 of those spots, S3 individuals showed patterns similar to those of BW individuals and for the remaining 3 they showed patterns similar to those of FW animals. The patterns observed when exposing snails to hypo- or hyperosmotic stress were not conclusive in relation to pinpointing individual spots that show the same pattern in all collection sites, but revealed the heterogeneity of protein expression in snails from the different collection sites and in the process of osmoregulation. It also showed the general tendency of protein reduction when snails where under osmotic stress of either kind (hypo- or hyperosmotic), which supports the hypothesis of storage protein degradation.
The investigation of an ANP-receptor showed two variations of the encoding sequence expressed in T. fluviatilis. S3 individuals as well as BW individuals were found to express one type, while FW individuals, with the exception of one sample expressed the other type. This showed that the FW subgroup of T. fluviatilis seems to be more heterogeneous than the BW subgroup, but also raises the question of the dispersal history of this species. The collected data indicates that T. fluviatilis individuals are firstly capable of surviving the acidity of a duck's gizzard and secondly can tolerate acute salinity changes to 16‰ when introduced into a new environment. Hence, if snails from the FW were to be transported to waters with a salinity of up to 16‰ by man, bird, drifting plants or some other means of transport, they would most likely survive and possibly be able to thrive and spread.
The rapid anthropogenic climate change that is projected for the 21st century is predicted to have severe impacts on ecosystems and on the provision of ecosystem services. With respect to the longevity of trees, forestry in particular has to adapt now to future climate change. This requires profound multidisciplinary knowledge on the direct and indirect climate sensitivity of forest ecosystems on various spatial scales. Predictions on growth declines due to increasing drought exposition during climate change are widely recognized for European beech (Fagus sylvatica L.), which is the major forest tree in European temperate deciduous forests. However, research from other continents or other biomes has shown that winter climate change may also affect forest growth dynamics due to declining snow cover and increased soil cooling. So far, this winter cold sensitivity is largely unexplored in Europe. Thus, particularly focussing on forest growth dynamics and winter cold sensitivity, the goal of this PhD-project was to explore how climate sensitivity of forest ecosystems differs regionally. By doing so, the project aimed to deliver insights about possibilities and limits of upscaling regional knowledge to a global understanding of climate sensitivity. To achieve these goals, this PhD-project integrated five studies (Manuscripts 1–5) that investigated the climate sensitivity of biogeochemical cycles, plant species composition in forests, and forest growth dynamics across spatial scales. In particular, a large-scale gradient-design field experiment simulated the influence of winter climate change on forest ecosystems by snow cover and soil temperature manipulations (Manuscript 1). This study indicated that soil cooling and decreased root nutrient uptake may indirectly reduce growth of adult forest trees. Moreover, this study indicated uniform ecological sensitivity to soil temperature changes across sites along a large winter temperature gradient (ΔT = 4 K across 500 km), irrespective of the site-specific history of snow cover conditions, which motivates upscaling from local winter climate change studies to the regional scale. Although regional climate drives growth of adult forest trees, local factors, such as site-specific edaphic conditions, might control plants in the forest understory. This assumption was tested by mapping the forest understory composition along the same winter temperature gradient as introduced above (Manuscript 2). Across sites, this study found that edaphic conditions explained the spatial turnover in the forest understory composition more than climate, which might moderate direct climate change impacts on the forest understory composition. However, edaphic conditions, forest structure, and climate are linked by triangular interactions. Thus, climate change might still indirectly affect the forest vegetation dynamics. Moreover, a dendroecological study focussed on the same winter temperature gradient from central to cold-marginal beech populations as above in order to identify gradual changes in summer drought and winter cold sensitivity in tree growth (Manuscript 3). Towards the cold distribution margin, the influence of drought on tree growth gradually decreased, while growth reductions were increasingly related to winter cold due to harsher winter climate. By a large-scale dendroecological network study assessed the relationship of growth dynamics to climate and reproductive effort in beech forests across Europe (Manuscript 4). Indeed, this study found the general pattern across the distribution range of beech that high temperature controlled growth indirectly via resource allocation to reproduction. However, the strong, direct drought signal that could be generally detected from dry-marginal to central populations vanished towards the cold-marginal populations, where the more focussed study of Manuscript 3 identified a stronger relationship of tree growth to winter cold. Further extending the scope of this PhD-thesis to global scales, litter decomposition rates were assessed across biomes (Manuscript 5). This study found a robust relationship between climate and decomposition rates, but it also demonstrated large within-biome variability on a local scale. These local scale differences might depend on habitat conditions that, in turn, could be modulated by climate change, which calls for a better exploration of indirect climate sensitivity. In conclusion, this PhD-thesis highlighted that multidisciplinary research can advance the understanding of ecological interactions in forest ecosystems under changing climate scenarios. In this PhD-project, a winter climate change experiment, where site-representative target trees were selected by means of dendroecology, contributed to a mechanistic understanding of winter cold sensitivity in forest growth dynamics. Dendroecological investigations then put the findings in a broader temporal and spatial context by describing local climate sensitivity of tree growth on different spatial scales. This thesis further shows that global generalizations about the relationship of climate and ecological processes in ecosystem models have to be critically reviewed for the need of local and regional adjustment because these processes might experience considerable regional- or local-scale variation. However, this thesis reports uniform sensitivity of ecological processes to altered winter soil temperature regimes across a large winter temperature gradient. Thus, upscaling from insights of previous winter climate change experiments to regional scales is encouraged.
Die klinischen Ergebnisse von Fusionsoperationen an der Lendenwirbelsäule sind von vielen Faktoren abhängig. Zwei Operationsverfahren stellen derzeit den Goldstandard bei dorsalen lumbalen interkorporellen Fusionsoperationen dar, das PLIF- und das TLIF-Verfahren.
Das Ziel der Entwicklung des neuen dPLIF-Operationsverfahrens und des hierfür entwickelten Cages und Werkzeugs war, die Vorteile der PLIF-Technik und der TLIF-Technik zu vereinen. Kern der Entwicklung war es, über den dorsomedialen PLIF-Zugang einen geraden Cage einzubringen und diesen sicher in eine diagonale Lage, entsprechend der Cagelage bei der TLIF-Technik, zu rotieren. In der Anwendungsbeobachtung sollte die technische Anwendbarkeit im operativen Regelbetrieb bei guten und zur Literatur vergleichbaren klinischen Ergebnissen nachgewiesen werden. Das Cagedesign und die Verfahrenstechnik wurden am Rinderkadaver entwickelt. Nach der CE-Zulassung wurde die prospektive Anwendungsbeobachtung zur lumbalen Fusion von der Ärztekammer genehmigt. Diese umfasste 105 Patienten zwischen 27 und 87 Jahren mit symptomatischer und radiologisch nachweisbarer Wirbelsäuleninstabilität. In 87 von 105 Fällen (82,9%) konnte der dPLIF-Cage in eine diagonale Lage rotiert werden. Wenn intraoperativ eine Cageinsertion oder -rotation aus anatomischen Gründen nicht durchführbar war, war der problemlose Umstieg auf die PLIF-Technik möglich. Es wurde eine Fusionsrate von 95,2% erzielt. In prä- und postoperativen Untersuchungen konnte eine Besserung der neurologischen Symptomatik, der Einschränkungen im Alltag (ODI) und der Schmerzen (VAS) verzeichnet werden. Die Patientenzufriedenheit lag bei 87,6%. Die vorliegende Anwendungsbeobachtung zeigt, dass es möglich ist, mit dem dPLIF-Operationsverfahren einen einzelnen Cage über einen dorsomedialen PLIF-Zugang so zu platzieren, dass seine diagonale Lage der eines TLIF-Cages entspricht. Die Wahl des Operationszugangs ermöglicht die Dekompression des Spinalkanals und die Cageinsertion von nur einer Seite und erspart einen gesonderten Zugang. Dies führt zu einer im Vergleich zur PLIF-Technik kürzeren Operationszeit. Alle klinischen Parameter entsprechen denen der bisherigen Verfahren. Die Daten der Anwendungsbeobachtung ergeben auch, dass die dPLIF-Operationstechnik als sicher zu bewerten ist.
Das Kohärenzgefühl im höheren Lebensalter -Entwicklung und Validierung eines Messinstrumentes-
(2018)
In unserer Gesellschaft vollzieht sich ein demografischer Wandel, der zu einer zunehmend alternden Bevölkerung führt. Dies erfordert, Menschen höheren Lebensalters vermehrt in den Fokus von Forschung und Medizin zu rücken, einem Anspruch, dem die vorliegende Arbeit gerecht werden möchte. Zielsetzung war die Entwicklung eines auf das von Antonovsky begründeten Konzeptes der Salutogenese ausgerichteten Messinstrumentes, zur Erfassung des Kohärenzgefühls im höheren Lebensalter. Die neue Skala sollte einerseits die testspezifischen Gütekriterien Objektivität, Reliabilität und Validität erfüllen, gleichzeitig aber auch forschungsökonomischen Prinzipien gerecht werden und das vor dem Hintergrund einer zielgruppenorientierten Ausrichtung.
Die Fragebogenentwicklung vollzog sich in mehreren Teilschritten. Als Einstieg diente eine explorative Vorstudie in Form von Gruppendiskussionen, die der Itemgenerierung diente. Hieraus entstand ein Pool von 90 Items, der im Anschluss einer Expertenbefragung hinsichtlich seiner Eignung für den Fragebogen unterzogen wurde. Als Resultat entstand eine 30 Items umfassende Sammlung, in der jede SOC-Komponente quantitativ gleich vertreten war. Diese wurde einer Gruppe von sechs Probanden zur Testung auf Verständlichkeit zugeführt. In der Folge wurde ein Item umformuliert, die anderen konnten unverändert in die vorläufige Fragebogenversion, Meine Lebensorientierung, übernommen werden. Diese wurde, eingebettet in eine umfangreiche Fragebogenbatterie, im Rahmen der Greifswalder Studie zur Lebensorientierung im Alter, im Oktober 2011 in drei Kleinstädten in Norddeutschland eingesetzt. Im Anschluss fand die statistische Datenauswertung statt. Mittels Itemanalyse wurden nicht geeignete Items identifiziert und aus der Sammlung eliminiert. Als Resultat entstand eine neue Skala, Das Kohärenzgefühl im höheren Lebensalter, mit 15 Items, jeweils fünf pro SOC-Komponente. In der durchgeführten Studie zeigte diese Skala eine gute interne Konsistenz. Hingegen ließen sich die theoriegeleiteten drei SOC-Komponenten faktorenanalytisch nicht reproduzieren, auch von dem Vorliegen eines Generalfaktors ist, als weitere wichtige Erkenntnis, nicht auszugehen. Die externe Validität wurde in der Untersuchung als mittelstark berechnet.
Abschließend lässt sich festhalten, dass die finale Skala, Das Kohärenzgefühl im höheren Lebensalter, ein reliables und valides Messinstrument darstellt, das zur ökonomischen Erfassung des Kohärenzgefühls, z. B. als Screening-Methode im Rahmen der hausärztlichen oder geriatrischen Betreuung, sinnvoll seinen Einsatz finden kann.
Background: Iodine deficiency disorders (IDD) represent a global health threat to individuals and societies. IDD prevention programmes have been introduced in many parts of the world. However, challenges remain, particularly in Europe due to fragmentation and diversity of approaches that are not harmonized. Objectives: This review is dedicated to the public-health impact of IDD prevention programmes. It sums up experiences collected by the EUthyroid consortium so far and provides information on stakeholders that should be involved in actions directed to improve the impact of IDD prevention. Methods: A joint European database for combining registry-based outcome and monitoring data as well as tools for harmonizing study methods were established. Methods for analyzing thyroglobulin from a dried blood spot are available for assessing the iodine status in the general population and at-risk groups. Mother-child cohorts are used for in-depth analysis of the potential impact of mild-to-moderate iodine deficiency on the neurocognitive development of the offspring. A decision-analytic model has been developed to evaluate the long-term effectiveness and cost effectiveness of IDD prevention programmes. Results: EUthyroid has produced tools and infrastructure to improve the quality of IDD monitoring and follows a dissemination strategy targeting policymakers and the general public. There are tight connections to major stakeholders in the field of IDD monitoring and prevention. Conclusions: EUthyroid has taken steps towards achieving a euthyroid Europe. Our challenge is to inspire a greater sense of urgency in both policymakers and the wider public to address this remediable deficit caused by IDD.
Intranasal Vaccination With Lipoproteins Confers Protection Against Pneumococcal Colonisation
(2018)
Streptococcus pneumoniae is endowed with a variety of surface-exposed proteins representing putative vaccine candidates. Lipoproteins are covalently anchored to the cell membrane and highly conserved among pneumococcal serotypes. Here, we evaluated these lipoproteins for their immunogenicity and protective potential against pneumococcal colonisation. A multiplex-based immunoproteomics approach revealed the immunogenicity of selected lipoproteins. High antibody titres were measured in sera from mice immunised with the lipoproteins MetQ, PnrA, PsaA, and DacB. An analysis of convalescent patient sera confirmed the immunogenicity of these lipoproteins. Examining the surface localisation and accessibility of the lipoproteins using flow cytometry indicated that PnrA and DacB were highly abundant on the surface of the bacteria. Mice were immunised intranasally with PnrA, DacB, and MetQ using cholera toxin subunit B (CTB) as an adjuvant, followed by an intranasal challenge with S. pneumoniae D39. PnrA protected the mice from pneumococcal colonisation. For the immunisation with DacB and MetQ, a trend in reducing the bacterial load could be observed, although this effect was not statistically significant. The reduction in bacterial colonisation was correlated with the increased production of antigen-specific IL-17A in the nasal cavity. Immunisation induced high systemic IgG levels with a predominance for the IgG1 isotype, except for DacB, where IgG levels were substantially lower compared to MetQ and PnrA. Our results indicate that lipoproteins are interesting targets for future vaccine strategies as they are highly conserved, abundant, and immunogenic.
Halsschmerzen gehören zu den häufigen Beratungsanlässen in der Hausarztpraxis und sind zu circa 90% viral bedingt. Um nicht-indizierte Behandlungen mit Antibiotika zu vermeiden gibt es symptomatische Therapieoptionen. AMC / DCBA (Amylmetacresol und 2,4-Dichlorbenzylalkohol) ist eine nicht verschreibungspflichtige Wirkstoffkombination, die in Lutschtabletten (z.B. Strepsils®) enthalten ist. Die Wirkung ist antiseptisch und lokalanästhetisch.
Wir durchsuchten die Datenbanken Medline, Cochraine und EMBASE nach randomisiert kontrollierten Studien, in denen AMC / DCBA gegen Placebo oder andere lokale Behandlungsmethoden getestet wurde. Zwei Gutachter prüften unabhängig Relevanz, Einschlusskriterien und Bias der Studien. Aus den Daten der eingeschlossenen Studien wurden die gewichteten mittleren Differenzen der Schmerzreduktion berechnet.
Diese Metaanalyse fast 3 RCTs mit insgesamt 660 Patienten zusammen und vergleicht AMC / DCBA (0,6 mg Amylmetacresol, 1,2 mg 2,4-Dichlorbenzylalkohol) mit wirkstofffreien Lutschtabletten bei der Behandlung von Halsschmerzen. Berechnet wurden die gewichteten mittleren Differenzen (SMD). Hauptstudienergebnis war die Reduktion der Schmerzintensität von -1,04 Punkten (-1,28 bis -0,79; p<.00001) nach 2 Stunden im Vergleich zum Ausgangswert, gemessen auf einer 11-Punkte Ordinalskala, zum Vorteil für AMC / DCBA. Für die Nebenergebnisse wurden die Schmerzlinderung auf einer 7-Punkte-Skala von 0,89 (1,04 bis 0,73; p<0,00001) und die Linderung der Schluckbeschwerden auf der VAS100 von -0,90 (-1,06 bis -0,75; p<0,00001) nach 2h beobachtet, ebenfalls zugunsten von AMC / DCBA.
In beiden Gruppen berichteten 2 bis 16% der Probanden von Nebenwirkungen, welche meist mild und bezogen auf die eigentliche Atemwegsinfektion waren. 3 Patienten jedoch berichteten von Ulzerationen im Mund, ein Zusammenhang mit der Studienmedikation kann jedoch nicht bewiesen werden [21-23].