Experimentelle Endotoxämie beim Menschen: Geschlechterunterschiede in der inflammatorischen und neuro-endokrinen Reaktion

In der vorliegenden Arbeit wurden Geschlechterunterschiede in der inflammatorischen und neuroendokrinen Reaktion auf eine experimentelle Endotoxämie beim Menschen untersucht. Hierzu wurde eine akute systemische Immunreaktion mithilfe von niedrig dosiertem Endotoxin (Lipopolysacharid (LPS), 0,4 ng/ kg Körpergewicht) in gesunden Männern und Frauen induziert. Es konnte gezeigt werden, dass der weibliche Organismus in vivo während einer akuten systemischen Entzündungsreaktion mit einer stärker ausgeprägten Freisetzung der pro-inflammatorischen Zytokine Tumornekrosefaktor-α (TNF-α) und Interleukin-6 (IL-6) reagiert. Als Folge auf die intravenöse Injektion von LPS kam es zu einer Zunahme der Zustandsangst, zu einer negativen Verschiebung der Stimmungsparameter sowie zu einer Zunahme der Symptome des Sickness Behaviors, jedoch ohne signifikante Geschlechterunterschiede. Nichtsdestotrotz konnten signifikante Unterschiede in der neuroendokrinen Reaktion nachgewiesen werden. So reagierten die weiblichen Probanden mit einer höheren Sezernierung von Cortisol und Prolaktin als die männlichen. Der Noradrenalin und der Dehydroepiandrosteron (DHEA) Spiegel veränderte sich hingegen in beiden Geschlechtern ohne signifikante Unterschiede. Die Hypothese, dass die erhöhte pro-inflammatorische Immunantwort zeitgleich mit einem stärker ausgeprägten Sickness Behavior einhergeht, konnte nicht bestätigt werden. Auch die nachgewiesenen geschlechterspezifischen Unterschiede in der neuroendokrinen Immunantwort lieferten keine eindeutige Erklärung für die unterschiedlich verlaufende inflammatorische Immunantwort oder die fehlenden Unterschiede in der neuropsychologischen Reaktion. Ferner zeigte die ex vivo Untersuchung der Immunzellen auf geschlechtsspezifische Unterschiede in der Sensitivität gegenüber glukokortikoiden und adrenergen Rezeptor-Agonisten keine signifikanten Unterschiede. Zusammenfassend stellen die Befunde dieser Arbeit dar, dass es gravierende Geschlechterunterschiede in der akuten inflammatorischen und neuroendokrinen Immunantwort gibt. Diese spiegeln sich jedoch nicht in den neuropsychologischen Reaktionen wieder. Die Daten deuten darauf hin, dass der weibliche Organismus über kompensatorische Mechanismen verfügt, die der stärkeren inflammatorischen Immunantwort entgegenwirken und so Unterschiede in den neuropsychologischen Reaktionen unterbinden

Nanoscale transient polarization gratings

We present the generation of transient polarization gratings at the nanoscale, achieved using a tailored accelerator configuration of the FERMI free electron laser. We demonstrate the capabilities of such a transient polarization grating by comparing its induced dynamics with the ones triggered by a more conventional intensity grating on a thin film ferrimagnetic alloy. While the signal of the intensity grating is dominated by the thermoelastic response of the system, such a contribution is suppressed in the case of the polarization grating. This exposes helicity-dependent magnetization dynamics that have so-far remained hidden under the large thermally driven response. We anticipate nanoscale transient polarization gratings to become useful for the study of any physical, chemical and biological systems possessing chiral symmetry

A new method for measuring angle-resolved phases in photoemission

Quantum mechanically, photoionization can be fully described by the complex photoionization amplitudes that describe the transition between the ground state and the continuum state. Knowledge of the value of the phase of these amplitudes has been a central interest in photoionization studies and newly developing attosecond science, since the phase can reveal important information about phenomena such as electron correlation. We present a new attosecond-precision interferometric method of angle-resolved measurement for the phase of the photoionization amplitudes, using two phase-locked Extreme Ultraviolet pulses of frequency $\omega$ and $2\omega$, from a Free-Electron Laser. Phase differences $\Delta \tilde \eta$ between one- and two-photon ionization channels, averaged over multiple wave packets, are extracted for neon $2p$ electrons as a function of emission angle at photoelectron energies 7.9, 10.2, and 16.6 eV. $\Delta \tilde \eta$ is nearly constant for emission parallel to the electric vector but increases at 10.2 eV for emission perpendicular to the electric vector. We model our observations with both perturbation and \textit{ab initio} theory, and find excellent agreement. In the existing method for attosecond measurement, Reconstruction of Attosecond Beating By Interference of Two-photon Transitions (RABBITT), a phase difference between two-photon pathways involving absorption and emission of an infrared photon is extracted. Our method can be used for extraction of a phase difference between single-photon and two-photon pathways and provides a new tool for attosecond science, which is complementary to RABBITT

A detailed investigation of single-photon laser enabled Auger decay in neon

Single-photon laser enabled Auger decay (spLEAD) is an electronic de-excitation process which was recently predicted and observed in Ne. We have investigated it using bichromatic phase-locked free electron laser radiation and extensive angle-resolved photoelectron measurements, supported by a detailed theoretical model. We first used separately the fundamental wavelength resonant with the Ne+ 2s?2p transition, 46.17 nm, and its second harmonic, 23.08 nm, then their phase-locked bichromatic combination. In the latter case the phase difference between the two wavelengths was scanned, and interference effects were observed, confirming that the spLEAD process was occurring. The detailed theoretical model we developed qualitatively predicts all observations: branching ratios between the final Auger states, their amplitudes of oscillation as a function of phase, the phase lag between the oscillations of different final states, and partial cancellation of the oscillations under certain conditions

Positive treatment expectations shape perceived medication efficacy in a translational placebo paradigm for the gut-brain axis

Placebo research has established the pivotal role of treatment expectations in shaping symptom experience and patient-reported treatment outcomes. Perceived treatment efficacy constitutes a relevant yet understudied aspect, especially in the context of the gut-brain axis with visceral pain as key symptom. Using a clinically relevant experimental model of visceral pain, we elucidated effects of pre-treatment expectations on post-treatment perceived treatment efficacy as an indicator of treatment satisfaction in a translational placebo intervention. We implemented positive suggestions regarding intravenous treatment with a spasmolytic drug (in reality saline), herein applied in combination with two series of individually calibrated rectal distensions in healthy volunteers. The first series used distension pressures inducing pain (pain phase). In the second series, pressures were surreptitiously reduced, modeling pain relief (pain relief phase). Using visual analog scales (VAS), expected and perceived treatment efficacy were assessed, along with perceived pain intensity. Manipulation checks supported that the induction of positive pre-treatment expectations and the modeling of pain relief were successful. Generalized Linear Models (GLM) were implemented to assess the role of inter-individual variability in positive pre-treatment expectations in perceived treatment efficacy and pain perception. GLM indicated no association between pre-treatment expectations and perceived treatment efficacy or perceived pain for the pain phase. For the relief phase, pre-treatment expectations ($\it p$ = 0.024) as well as efficacy ratings assessed after the preceding pain phase ($\it p$ < 0.001) were significantly associated with treatment efficacy assessed after the relief phase, together explaining 54% of the variance in perceived treatment efficacy. The association between pre-treatment expectations and perceived pain approached significance ($\it p$ = 0.057) in the relief phase. Our data from an experimental translational placebo intervention in visceral pain support that reported post-treatment medication efficacy is shaped by pre-treatment expectations. The observation that individuals with higher positive expectations reported less pain and higher treatment satisfaction after pain relief may provide first evidence that perceived symptom improvement may facilitate treatment satisfaction. The immediate experience of symptoms within a given psychosocial treatment context may dynamically change perceptions about treatment, with implications for treatment satisfaction, compliance and adherence of patients with conditions of the gut-brain axis