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Psychological health is a result of the effective interplay between explicit and implicit attempts to regulate ones’ emotions (Koole & Rothermund, 2011). Emotion regulation refers to processes that influence the intensity, the duration and the type of emotion experienced (Gross & Thompson, 2007). While explicit emotion regulation comprises effortful mental processes, implicit emotion regulation refers to processes that require no monitoring and terminate automatically (Gyurak, Gross, & Etkin, 2011).
In the present thesis, explicit and implicit strategies to regulate emotions were investigated. In Study 1, a well-established paradigm (Gross & Levenson, 1993) was adapted to examine the up- and down-regulation of positive and negative emotions using two different explicit emotion regulation strategies. To infer on the neurobiological correlates, blood oxygen level dependent (BOLD) brain activity was recorded using functional magnetic resonance tomography. Furthermore, as a trait marker for the individual ability to regulate emotions, heart rate variability (HRV) was acquired during rest. In Study 2, implicit emotion regulation was examined. Therefore, a well-established fear extinction paradigm was compared to a novel approach based on the integration of new information during reconsolidation (Schiller et al., 2010). Autonomic arousal was measured via the skin conductance response during fear acquisition, fear extinction and after fear reinstatement. In Study 3, two dysfunctional emotion regulation strategies —worrying and rumination— were investigated. Excessive worrying and rumination are pathogenic characteristics of psychological disorders. Behavioral, autonomic and BOLD activity was recorded during worried and ruminative thinking as well as during neutral thinking.
The results showed that explicit emotion regulation was associated with modulated BOLD activity in the amygdala according to the regulation direction independent of the applied strategy and the valence of the emotion. In addition, increased dorsolateral prefrontal cortex (dlPFC) activity was observed during regulation compared to passively viewing emotional pictures. The findings are in line with previous research (Eippert etal., 2007; Kim &Hamann, 2007; Ochsner etal., 2004) and support the key role of the dlPFC during the explicit regulation of emotions. Similarly, implicit emotion regulation was associated with a decreased autonomic fear response, which was sustained after fear extinction during reconsolidation. The findings underscore the notion, that this novel technique might alter the initial fear memory resulting in a permanently diminished fear response (Nader, Schafe, & LeDoux, 2000; Schiller et al., 2010). Dysfunctional emotion regulation was associated with increased autonomic activity and fear potentiated startle (during worry) as well as increased BOLD activity in the insula (during worry and rumination) and increased BOLD activity in the amygdala (during rumination). In addition, neural activity in brain areas associated with the default mode network was observed. These findings stress the preserved negative emotional activity and the self-referential nature of the examined dysfunctional strategies. The results of all three studies are integrated into a neuro-biological model of emotion regulation focusing on the interplay between subcortical and prefrontal brain areas.
There is multiple evidence that emotionally arousing events are preferentially processed, and better remembered than neutral events. In the present dissertation I investigated whether those strong emotional memories are affected by acute and chronic stress. Moreover, I was interested in whether already established emotional memories can be changed by behavioral intervention. According to the modulation hypothesis, emotionally arousing events promote attention and memory processes via noradrenergic and glucocorticoid actions. Recent models suggest that stress hormones differentially impact mnemonic processing, namely encoding, (re-) consolidation and memory retrieval, depending on timing and duration of the stressor relative to the learning experience. Acute stress around the time of encoding has been found to enhance memory, whereas chronic stress has been associated with memory impairments. Furthermore, consolidated memories are not resistant to modifications. Following reactivation, memories can turn into an unstable state and undergo a process called reconsolidated in order to persist. During this vulnerable state, memories are prone to modification, for instance by pharmacological blockade or interference learning. Here, the modulation of newly formed emotional and neutral memories as well as existing emotional and neutral memories was investigated in a well-established picture viewing and recognition memory paradigm using behavioral and neurophysiological measures (event-related potential, ERPs). More elaborative processing of emotional, relative to neutral stimuli has been related to the late positive potential (LPP). During encoding of emotional and neutral pictures, enhanced LPPs (starting at about 400 ms after stimulus onset) are usually observed for emotionally arousing relative to neutral pictures, indicating preferential attention allocation and processing. During recognition, correctly recognized old items evoke larger ERP amplitudes than correctly identified new items. This difference, the ERP old/new effect, was used to measure mnemonic processing during retrieval. The ERP old/new effect over centro-parietal sensor sites (400-800 ms) has been associated with recollection processes, and is enhanced for emotional, compared to neutral materials. Three studies are presented, that investigated 1) the influence of acute stress prior to encoding on long-term memory and its neural correlates, 2) the impact of chronic stress on encoding and memory, and 3) the influence of interference on already established memories (reconsolidation), always contrasting emotionally arousing and neutral scenes. Study 1 investigated subsequent recognition memory after encoding following acute stress using a socially evaluated cold pressure test, while study 2 tested the influence of chronic stress investigating breast cancer survivors about two years after cancer treatment. In study 3, one day after encoding, reconsolidation of the reactivated picture memory was targeted with an interfering learning task. In all three studies, recognition memory was tested one week later. High-density electroencephalograms (EEGs; 257 electrodes) were recorded to measure brain potentials. The results showed, in line with previous research, that emotionally arousing scenes were preferentially processed, as indicated by larger LPPs, and were better remembered than neutral scenes, as indicated by enhanced memory performance and larger ERP old/new differences. Experiencing acute stress prior to encoding enhanced the centro-parietal ERP old/new effect for emotionally arousing pictures at recognition, corroborating that acute stress facilitates memory for emotional scenes (Study 1). In contrast, attenuated LPPs for unpleasant pictures and impaired memory performance for arousing pictures were observed in breast cancer survivors (Study 2), indicating altered attention to emotion and subsequent emotional memory storage in chronically stressed individuals. When memory reactivation was followed by an interfering learning task, recognition memory and ERP old/new differences were attenuated for emotionally arousing scenes, selectively, showing the possibility that emotional memories might be modulated by behavioral interventions (Study 3). The results of all three studies are discussed and integrated into a model of memory modulation by stress and interference. The results highlight the importance of understanding the role of emotional arousal in the processes of memory formation, retrieval and reconsolidation. Moreover, shedding light on the differential effects of acute and chronic stress, interference and their possible interactions might help to prevent and even modify impairing memories that are one of the major concerns in stress- and fear-related mental disorders.
Interoceptive sensations, that means, perceptions of the physiological body state, play an important role in the generation and expression of emotion. The focus of the research presented here is on respiratory sensations as specific interoceptive signals. Such respiratory sensations (like the feeling of dyspnea) play an important role in symptom perception in somatic (e.g., asthma) as well as in mental disorders (e.g., anxiety disorders). There are several different ways to manipulate respiratory sensations in an experimental environment, but many of them did not equal sensations in daily life. Here, stimuli (inspiratory resistive loads, caffeine) were used that trigger nearly naturally occurring interoceptive sensations. Taking into account that the elicited interoceptive experience also induces an unpleasant feeling state it is most likely that individuals show defensive physiological responding to such cues and try to avoid them. According to a bidirectional motivational system defensive behaviors are regulated by a defensive motivational system that is activated by threatening cues. From research with exteroceptive stimuli it is known that defensive responding is typically characterized by heightened autonomic arousal, increased respiration, and a potentiated startle eyeblink response. In contrast, only a few studies using interoceptive stimuli have incorporated the measurement of physiological data in their experimental designs. If included, studies show also heightened autonomic responding, whilst a heterogeneous respiratory as well as startle eyeblink responding is observed. Thus, the studies presented here were designed to clarify the factors that mediate defensive responding to interoceptive sensations. Study 1 investigated the influence of anxiety on the subjective, respiratory, and autonomic response to an individually determined inspiratory resistive load, while study 2 focuses on the effect of attentional modulation of the startle eyeblink response to a mild respiratory threat. In study 3 the modulation of subjective, respiratory and autonomic reactions by arousal expectations was examined. Therefore, caffeine, a respiratory stimulant, or a placebo were administered without the participants’ knowledge. The fourth study examined the influence of the process of worrying, a strategy to deal with unpleasant body symptoms, on defensive responding. Depending on the study design subjective, respiratory and autonomic (skin conductance level, heart rate) parameters were assessed as marker for defensive mobilization. In study 2 and 4 the startle eyeblink response was measured as further index of defensive activation. Besides that in study 2 also the P3 component of the event-related potential, as an index for attentional allocation, was recorded. The main findings of the presented dissertation are the following: Study 1 revealed that 1) only high anxiety sensitive individuals reporting also high suffocation fear respond to lower stimulus intensities with stronger defensive responding, and 2) that this group demonstrated a maladaptive compensatory breathing pattern. Additionally, study 2 exhibited that 1) the startle eyeblink response is relatively inhibited during a mild interoceptive threat, and 2) this inhibition corresponds to an attention allocation towards breathing as indicated by a reduced P3 amplitude to the startle noise as well as subjective report. Furthermore, highly anxiety sensitive individuals showed a more pronounced defensive responding if the interoceptive sensations were unexpected (study 3). Recently, study 4 demonstrated that worry led to an increased defensive response mobilization. All studies are discussed in the context of the theoretical background of the defensive response modulation to exteroceptive and interoceptive sensations with respect to mediating factors. Showing exaggerated defensive responding and maladaptive adaptation processes in high anxious individuals the results point towards the important role of interoceptive sensations in the etiology, maintenance and therapy of mental disorders, especially the anxiety disorders.
Lead-cluster investigations
(2017)
In this thesis, investigations on lead clusters stored in a Penning trap are presented. The measurements are performed at the ClusterTrap setup at the Institute of Physics of the University of Greifswald. A Penning trap with a superconducting magnet (B=12 Tesla) makes up the central part of the experiment. In this trap, singly positively or negatively charged lead clusters (a group of lead atoms) are stored, their amplitudes of motion are cooled, and a specific cluster size is selected. Thus, clusters of only a single size are prepared for experimental investigation. After interactions with electrons and/or photons, the trap content is extracted and analyzed by time-of-flight mass spectrometry.
In the first experiment, the size-selected clusters are excited by a frequency-doubled Nd:YAG laser, which leads to fragmentation processes. The preferred fragmentation pathway, which is observed to be break-off of a seven-atom neutral cluster is unusual for metal clusters, which typically evaporate monomers. Furthermore, the already known magic cluster sizes are observed.
In a subsequent experiment, positively charged lead clusters with 31 atoms are irradiated with laser light and fragmentation processes are time resolved investigated. The assumption that lead clusters fragment by break-off of neutral heptamers is confirmed.
In the following experiment, an electron beam is guided through the Penning trap to ionize pulsed-in argon atoms. While the positive argon ions leave the trap, the secondary electrons are trapped together with the selected lead clusters. This allows the electrons to attach to the singly charged lead clusters, which leads to multiply negatively charged lead clusters. The relative abundance of multiply-charged clusters is measured with respect to the cluster size, from which the appearance sizes of di- and trianions can be calculated. In addition to the attachment of electrons, fragmentation products similar to those of the photoexcitation measurements are observed. Furthermore, the cluster sizes 10 and 12 are observed regardless of the investigated precursor size, together with clusters of the precursor size reduced by 10 and 12. This is a first hint for a fission process of doubly negatively charged lead clusters into two singly charged products. In a following measurement, doubly charged lead clusters are produced and photoexcited. The observed abundance spectra confirm this assumption.
Introduction: Antiseptics are used for the prophylaxis of infections of acute wounds and for the treatment of critically colonized chronic wounds as well as localized infections of acute and chronic wounds. If an antiseptic with too much tissue toxicity and/or too little efficacy is used, the wound healing can be delayed.
Objective: The aim was to compare the irritation potency of frequently used wound antiseptics by using the hen's egg test on the chorioallantoic membrane (HET-CAM). Additionally, the influence of antiphlogistic active additives which might increase the tolerability was examined. To allow a more extensive comparison, antiseptics classified as obsolete such as hydrogen peroxide, creams on PVP- iodine base, silver sulfadiazine, chlorhexidine and nitrofural as well as the non-antiseptic wound treatment agents dexpanthenol and hemoglobin spray were also examined.
Method: The HET-CAM was used as a semi-in-vivo method to test the tolerability of wound antiseptics to tissues by observing the reactions that occur in the blood vessels of the highly vascularized CAM such as hemorrhage, lysis and coagulation. The irritation score (IS) was calculated and differentiated in 4 ranges according to Spielmann (1991).
Results: The vascular injuries of the CAM were considered as an indirect indicator of the tolerability. It is accepted that agents with no or low irritation potential on the CAM are to be preferred in the clinical practice if they are clinically effective.
Severe CAM reaction was observed after short-term application of octenidine based wound gel (active ingredient octenidine 0.05%) (IS: 10.3) and chlorhexidine digluconate 0.5% solution (IS: 9.5). Moderate reaction was observed for the combination of octenidine 0.05% in aqueous solution with panthenol 1.34% and allantoin 0.2% (IS: 8.7), hydrogen peroxide 1.5% in aqueous solution (IS: 6.1) and hydrogen peroxide 0.5% solution (IS: 5.5). Slight reaction was observed for hydrogen peroxide 1.5% solution in combination with sodium thiocyanate 0.698% (IS: 2.6), sodium thiocyanate 0.698% solution (IS: 2.1) and Dermacyn® (active ingredient NaOCl/HOCl each 0.004) (IS: 1.2). Polihexanide 0.04% in Ringer solution (IS: 0.9), Polihexanide 0.05% in Lipofundin, Granulox® (active agent hemoglobin 10%) (IS: 0) and dexpanthenol 5% solution (IS: 0) showed no reaction. In the long-term observation (24 hours after application), Dermacyn® showed the best results (59% of irritation remained alive after 24 hours). The addition of dexpanthenol and allantoin reduced the irritability only slightly, whereas the decrease of IS of hydrogen peroxide by addition of sodium thiocyanate was almost significant (p 0.0596).
Conclusion: It is suggested that agents with no or low irritation potential on the CAM are to be preferred in the clinical practice if they are clinically effective. It is suggested that further in vivo and in vitro studies are to be undertaken with these agents.
Solely regarding local tolerability, polihexanide and hypochlorite are the antiseptic agents of choice of the tested preparations. The wound oxygenizer hemoglobin spray is tolerated without irritation as well as the negative control 0.9% NaCl solution. Because of their other disadvantages in conjunction with their irritability, the outdated cream formulations on basis of silver sulfadiazine, PVP- iodine, chlorhexidine and nitrofural cannot be recommended for wound antisepsis.
Akute traumatische Wunden sind mit Bakterien kontaminiert und haben ein Infektionsrisiko von etwa 6 %. Daher wird die antiseptische Wundspülung vor chirurgischer Versorgung kontaminierter Wunden empfohlen. Hierfür werden unterschiedliche Antiseptika eingesetzt. Das Ziel dieser retrospektiven, nicht randomisierten Längskohorten-Studie bestand darin, den präventiven Effekt von vier verschiedenen Spüllösungen vor chirurgischer Behandlung auf die SSI-Rate bei traumatischen Weichteilwunden zu ermitteln.
Über einen Zeitraum von drei Jahrzehnten wurde die prophylaktische Wundspülung bei Patienten mit kontaminierten traumatischen Wunden untersucht, die eine chirurgische Behandlung mit oder ohne primären Wundverschluss benötigten. Von 1974-1983 wurde entweder PHMB, PVP-I, 4 % Wasserstoffperoxid, oder unverdünnte Ringerlösung verwendet. Von 1984-1996 wurden nur PHMB oder PVP-I angewendet. Von 1997 bis Ende der Studie 2005 wurde nur noch PHMB angewendet.
Die kombinierte Rate von oberflächlichen und tiefen Wundinfekten betrug 1,7% in der PHMB-Gruppe, 4,8% in der PVP-I-Gruppe, 5,9% in der Ringer-Gruppe, und 11,7% in der Wasserstoffperoxid-Gruppe. Verglichen mit allen anderen Behandlungsgruppen zeigte PHMB die höchste Effizienz, um Infektionen in traumatischen Weichteilwunden vorzubeugen. Bei Riss-Quetsch-Wunden war der Unterschied verglichen mit PVP-I nur für die tiefen Wundinfektionen signifikant. Bei Schnittwunden wurden sowohl A1- als auch A2-SSI signifikant in der Häufigkeit reduziert.
Auf Grund des Stichprobenumfangs ist trotz des retrospektiven Studiendesigns kein Zweifel an der infektionspräventiven Überlegenheit von PHMB zur Spülung bei traumatischen Weichteilwunden gegeben. Die Infektionsraten der retrospektiven Studie können als Basis für die Fallzahlkalkulation für eine dringend benötigte prospektive klinische Studie zugrunde gelegt werden.
Hintergrund: Medizinische Untersuchungs- und Operationshandschuhe dienen dazu, bei minimaler Bewegungseinschränkung das Kontaminationsrisiko sowohl des Trägers als auch des Patienten zu reduzieren. Aufgrund der Möglichkeit von Latexallergien wird zurzeit verstärkt nach Alternativen zum Naturprodukt Latex gesucht. Aus diesem Grund werden verstärkt synthetische Materialien wie Nitril im Gesundheitswesen eingesetzt. Derzeit ist jedoch nicht bekannt, ob die unterschiedlichen physikalischen Eigenschaften der verschiedenen Materialien im Fall einer manipulationsbedingten Mikroperforation einen Einfluss auf die bakterielle Barrieretransmigration haben. Deshalb sollten Untersuchungshandschuhe aus unterschiedlichen Materialien einer vergleichenden Überprüfung der Barrierefunktion nach experimenteller Perforation unterzogen werden. Methoden: Es wurden Untersuchungshandschuhe aus Latex (3 Modelle), aus Nitril (4 Modelle) und Neopren(komposit) (2 Modelle) von verschiedenen Herstellern geprüft.Des Weiteren wurden jeweils ein Operationshandschuh aus Latex mit und ohne CHG sowie ein synthetischer Operationshandschuh getestet. Die Materialien wurden unter standardisierten Verfahren perforiert und anschließend die Flüssigkeitsretention sowie die tatsächliche bakterielle Transmigration in Abhängigkeit von einer standardisierten dynamischen mechanischen Dehnung gemessen. Zusätzlich wurden die Handschuhmodelle auf ihre Elastizität untersucht. Ergebnisse: Im Fall einer Perforation zeigte sich, dass Untersuchungshandschuhe aus Nitril und reinem Neopren gegenüber denen aus Latex und Neoprenkomposit in der Regel ein schlechteres Rückhaltevermögen für Bakterien sowie für Flüssigkeiten besitzen. Ebenfalls benötigten die Nitrilhandschuhe für die Elongation die meiste Kraft und zeigten die geringste maximal mögliche Dehnung. Aufgrund signifikanter Unterschiede der Modelle innerhalb eines Materialtyps ist jedoch die genaue Betrachtung eines spezifischen Modells wichtig. Allgemein besaßen die untersuchten Operationshandschuhe ein hohes bakterielles Rückhaltevermögen. Vor allem das Modell aus thermoplastischem Elastomer war allen anderen Modellen auch bezüglich Elastizität und maximaler Dehnung überlegen. Fazit: Aus den Daten lässt sich ableiten, dass die bakterielle Barrieretransmigration mit der Steifigkeit oder Elastizität des Handschuhmaterials korreliert. Aus diesem Grund haben in der Regel aus Latex hergestellte Handschuhe im Fall einer Perforation eine höhere Schutzwirkung. In letzter Konsequenz sollte aufgrund einer im Krankenhausalltag möglichen manipulationsbedingten Mikroperforation immer eine Abwägung zwischen der Gefahr einer Latexallergie und dem erforderlichen Schutz vor Infektionen durchgeführt werden.
Die Antiseptika-Forschung ist ein wichtiges Gebiet, aber die Testmethoden sind nur bis zur Prüfstufe des Suspensionstests einheitlich geregelt. Daher sind die Ergebnisse sich in der Testhierarchie anschließender Studien schwierig zu vergleichen und zwingen den Praktiker, Therapieentscheidungen oft auf Basis empirischer Erfahrungen zu treffen. In der vorliegenden Arbeit wurde das Verhalten verschiedener in der klinischen Praxis gebräuchlicher Antiseptika in einem Prüfkörpertest untersucht, der an die Wirksamkeit höhere Anforderungen als der klassische Suspensionstest stellt. Dabei sollte auf dem Prüfkörper zugleich eine für Wunden realitätsnahe Belastung eingesetzt werden. Für die Testung wurden Metallträger mit verschiedenen Erregersuspensionen und Belastungen kontaminiert, angetrocknet und die Wirksamkeit von PVP-Iod und Chlorhexidindigluconat bei verschiedenen Einwirkungszeiten ermittelt. Das erfolgte mit der Zielsetzung festzustellen, ob sich einer der beiden Wirkstoffe als Referenz für künftige Prüfkörpertests eignet. PVP-Iod zeigte in allen Versuchen unabhängig vom Testorganismus (S. aureus, P. aeruginosa und E. faecium) und von der verwendeten Belastung (ohne, MEM + 10 % FBS, 10 bzw. 30 % Vollblut) eine rasch einsetzende, stabile und ausreichende antiseptische Wirkung (ohne Belastung RF > 5, mit Belastung RF > 3 [Pitten et al. 2003]). Das bildete einen deutlichen Kontrast zu den mit Chlorhexidindigluconat erzielten Ergebnissen. Die mit PVP-Iod und Chlorhexidindigluconat gewonnenen Ergebnisse wurden mit den Ergebnissen einer vorangegangenen Studie [Brautferger 2010] zu Octenidindihydrochlorid und Polihexanid verglichen. Auch als Schlussfolgerung dieses Vergleiches kann PVP-Iod als Referenzsubstanz für die Antiseptikatestung empfohlen werden. Obwohl PVP-Iod in Fragen von Verträglichkeit, Remanenz etc. von den neueren Antiseptika übertroffen wird, zeigte kein anderer Wirkstoff in unseren Testungen ein vergleichbar stabiles Wirkungsverhalten. In Verbindung mit der jahrzehntelangen Erfahrung im Einsatz von PVP-Iod kann daher PVP-Iod als Referenzsubstanz für die Antiseptikatestung empfohlen werden.