Pump-probe capabilities at the SPB/SFX instrument of the European XFEL.

Pump-probe experiments at X-ray free-electron laser (XFEL) facilities are a powerful tool for studying dynamics at ultrafast and longer timescales. Observing the dynamics in diverse scientific cases requires optical laser systems with a wide range of wavelength, flexible pulse sequences and different pulse durations, especially in the pump source. Here, the pump-probe instrumentation available for measurements at the Single Particles, Clusters, and Biomolecules and Serial Femtosecond Crystallography (SPB/SFX) instrument of the European XFEL is reported. The temporal and spatial stability of this instrumentation is also presented.

Pump-probe laser system at the FXE and SPB/SFX instruments of the European X-ray Free-Electron Laser Facility.

User operation at the European X-ray Free-Electron Laser Facility started at the SASE1 undulator beamline in fall 2017. The majority of the experiments utilize optical lasers (mostly ultrafast) for pump-probe-type measurements in combination with X-ray pulses. This manuscript describes the purpose-developed pump-probe laser system as installed at SASE1, implemented features and plans for further upgrades.

Effect of the antioxidant idebenone on adverse events under mycophenolate mofetil therapy in a rat model.

BACKGROUND: Diarrhea and anemia are side effects of mycophenolic acid (MPA), but underlying mechanisms are not fully understood. Gene expression of major-alpha-hemoglobin and catalase was suppressed in livers of mycophenolate mofetil (MMF)-treated rats, suggesting MPA attenuates cellular defense against reactive oxygen species (ROS). We investigated whether the antioxidant idebenone might alleviate MPA-related side effects. METHODS: Rats were treated as follows: group 1: controls; group 2: idebenone; group 3: MMF; and group 4: MMF/idebenone. Blood was collected weekly to determine cell counts, hemoglobin, MPA, plasma albumin, total protein, creatinine, and urea concentrations. On day 28 RNA was extracted from liver, kidneys, and bone marrow (BM). Colon and jejunum were examined histologically. RESULTS: High-dose MMF-treated rats developed diarrhea, dehydration, and weight loss. After a week, a significant decrease (P=0.001) in erythrocyte count and hemoglobin concentration was observed that was not influenced by idebenone. Degenerative changes in the jejunum were slightly attenuated by idebenone. Idebenone did not influence MPA-induced suppression of catalase. A significant suppression of major-alpha-hemoglobin and the erythropoietin (EPO)-receptor in BM of MMF-treated groups and almost complete absence of hemopoietic progenitor cells were observed. EPO-mRNA was markedly upregulated in the MMF-group and even more in the MMF/idebenone-group. CONCLUSION: Idebenone showed minimal benefit on MMF-related diarrhea and anemia. BM of MMF-treated rats revealed erythroid aplasia as a possible reason for anemia. Marked upregulation of EPO-mRNA presumably reflects a compensatory mechanism. Because ROS have the potential to suppress EPO expression, it can be hypothesized that enhanced EPO-mRNA expression in MMF/idebenone-treated rats is caused by antagonism of ROS.

Flupenthixol in relapse prevention in schizophrenics with comorbid alcoholism: results from an open clinical study.

Substance use, especially alcoholism, has been recognized as a significant problem in schizophrenic patients, though only a few studies on the effects of pharmacotherapy in these patients have been conducted so far. The thioxanthene neuroleptic flupenthixol, which can be given intramuscularly (i.m.) for improving compliance, has been studied as a possible anti-craving drug both in animal models of alcoholism and some clinical studies. Pilot studies suggest that comorbid schizophrenics with substance use may benefit from treatment with flupenthixol. Efficacy of flupenthixol (10-60 mg i.m.) in reducing alcohol consumption of dual diagnosis patients was studied in an open 6-month clinical trial in 27 schizophrenics with comorbid alcoholism. Twenty-one patients entered the intention-to-treat analysis. Fourteen subjects were completers, 13 dropped out. Six patients completely abstained from alcohol during treatment. Alcohol consumption was significantly reduced compared to baseline (4 weeks before treatment as measured by timeline follow-back interview). In general, while patients showed a marked improvement concerning alcohol consumption, only a slight improvement in psychopathology was recorded. Overall tolerability was good. These data indicate a probable beneficial effect of flupenthixol in schizophrenic patients with comorbid alcoholism. Although the efficacy of flupenthixol as an anti-craving drug in dual diagnosis patients has to be explored in further studies, the drug may be considered a promising medication for these patients.

The Kraepelinian dichotomy: preliminary results of a 15-year follow-up study on functional psychoses: focus on negative symptoms.

In a 15-year follow-up study, we used a comparative approach to assess course and outcome for all functional psychoses. The presented results focus on negative symptoms and refer to a sample of 76 patients with schizophrenia, 38 patients with a schizoaffective disorder and 32 patients with an affective disorder according to ICD-9. These patients were assessed at their first psychiatric hospitalization and 15 years later. In summary, the findings indicate that the course and outcome of schizophrenia is less favorable than that of affective and schizoaffective disorders. Negative symptoms occurred in all functional psychoses, but were more frequent and prominent in the schizophrenic group than in the other two diagnostic groups at any time of assessment. Narrower concepts of negative symptoms, conceptualized as the deficit syndrome, seem to be specific for schizophrenia and appear quite rarely in patients with affective psychoses. Overall, our study supports Kraepelin's original hypothesis that bifurcated the psychoses into the affective psychoses and schizophrenia, whereby the latter have a more deleterious long-term course and outcome.