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PurposeThe first aim of the trial is to study feasibility of combined programmed death protein ligand 1/cytotoxic T-lymphocyte-associated protein 4 inhibition concomitant to radiotherapy. In addition, efficacy of the entire treatment scheme consisting of induction chemoimmunotherapy followed by chemotherapy-free radioimmunotherapy (RIT) after intratumoral CD8 +immune cell-based patient selection will be analyzed.MethodsPatients with stage III–IVB head and neck squamous cell carcinoma were eligible for this multicenter phase II trial. Treatment consisted of a single cycle of cisplatin 30 mg/m² days 1–3, docetaxel 75 mg/m² day 1, durvalumab 1500 mg fix dose day 5 and tremelimumab 75 mg fix dose day 5. Patients with increased intratumoral CD8 +immune cell density or pathological complete response (pCR) in the rebiopsy entered RIT up to a total dose of 70 Gy. Patients received further three cycles of durvalumab/tremelimumab followed by eight cycles of durvalumab mono (every 4 weeks). The intended treatment for patients not meeting these criteria was standard radiochemotherapy outside the trial. Primary endpoint was a feasibility rate of patients entering RIT to receive treatment until at least cycle 6 of immunotherapy of ≥80%.ResultsBetween September 2018 and May 2020, 80 patients were enrolled (one excluded). Out of these, 23 patients had human papilloma virus (HPV)-positive oropharyngeal cancer. Median follow-up was 17.2 months. After induction chemoimmunotherapy 41 patients had pCR and 31 had increased intratumoral CD8 +immune cells. Of 60 patients entering RIT (primary endpoint cohort), 10 experienced imiting toxic (mainly hepatitis) and four discontinued for other reasons, resulting in a feasibility rate of 82%. The RIT cohort (n=60) had a progression-free survival (PFS) rate at one and 2 years of 78% and 72%, respectively, and an overall survival rate at one and 2 years of 90% and 84%, respectively. Patients with HPV-positive oropharyngeal cancers had greater benefit from RIT with a 2-year PFS rate of 94% compared with 64% for HPV-negative oropharyngeal cancers and other locations. In the entire study cohort (n=79) the 2-year PFS rate was 68% (91% for HPV-positive oropharynx vs 59% for others). Toxicity grade 3–4 mainly consisted of dysphagia (53%), leukopenia (52%) and infections (32%).ConclusionsThe trial met the primary endpoint feasibility of RIT. Induction chemo-immunotherapy followed by chemotherapy-free RIT after intratumoral CD8 +immune cell-based patient selection has promising PFS.Trial registration numberThe trial was registered with ClinicalTrials.gov (identifier: NCT03426657). The trial was conducted as investigator-sponsored trial (IST)., publishedVersion

The clinical psychiatric interview is the most important diagnostic tool for emergency physicians who are assessing patients with any kind of mental health issues. A sophisticated interview and observation of a patient can, most of the time, lead to a diagnosis and recommendations for most promising treatments. Unfortunately, most patients in acute crisis are not able or willing to participate in a full interview. The case presented in this chapter describes assessment and treatment of a patient who was clearly suicidal and not at all able to participate in her evaluation.

Generalized pustular psoriasis is a severe psoriatic subtype characterized by epidermal neutrophil infiltration. Although variants in IL36RN and MPO have been shown to affect immune cells, a systematic analysis of neutrophils and PBMC subsets and their differential gene expression dependent on MPO genotypes was not performed yet. We assessed the transcriptomes of MPO-deficient patients using single-cell RNA sequencing of PBMCs and RNA sequencing of neutrophils in a stable disease state. Cell-type annotation by multimodal reference mapping of single-cell RNA-sequencing data was verified by flow cytometry of surface and intracellular markers; the proportions of CD4

Background The predictive power of novel biological markers for treatment response to immune checkpoint inhibitors (ICI) is still not satisfactory for the majority of patients with cancer. One should identify valid predictive markers in the peripheral blood, as this is easily available before and during treatment. The current interim analysis of patients of the ST-ICI cohort therefore focuses on the development and validation of a liquid immune profile-based signature (LIPS) to predict response of patients with metastatic cancer to ICI targeting the programmed cell death protein 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) axis. Methods A total of 104 patients were prospectively enrolled. 54 immune cell subsets were prospectively analyzed in patients’ peripheral blood by multicolor flow cytometry before treatment with ICI (pre-ICI; n=89), and after the first application of ICI (n=65). Pre-ICI, patients were randomly allocated to a training (n=56) and a validation cohort (n=33). Univariate Cox proportional hazards regression analysis and least absolute shrinkage and selection operator Cox model were used to create a predictive immune signature, which was also checked after the first ICI, to consider the dynamics of changes in the immune status. Results Whole blood samples were provided by 89 patients pre-ICI and by 65 patients after the first ICI. We identified a LIPS which is based on five immune cell subtypes: CD14high monocytes, CD8+/PD-1+ T cells, plasmacytoid dendritic cells, neutrophils, and CD3+/CD56+/CD16+ natural killer (NK)T cells. The signature achieved a high accuracy (C-index 0.74 vs 0.71) for predicting overall survival (OS) benefit in both the training and the validation cohort. In both cohorts, the low-risk group had significantly longer OS than the high-risk group (HR 0.26, 95% CI 0.12 to 0.56, p=0.00025; HR 0.30, 95% CI 0.10 to 0.91, p=0.024, respectively). Regarding the whole cohort, LIPS also predicted progression-free survival (PFS). The identified LIPS was not affected by clinicopathological features with the exception of brain metastases. NKT cells and neutrophils of the LIPS can be used as dynamic predictive biomarkers for OS and PFS after first administration of the ICI. Conclusion Our study identified a predictive LIPS for survival of patients with cancer treated with PD-1/PD-L1 ICI, which is based on immune cell subsets in the peripheral whole blood. Trial registration number NCT03453892.

BackgroundTo determine safety and efficacy of single cycle induction treatment with cisplatin/docetaxel and durvalumab/tremelimumab in stage III-IVB head and neck cancer.MethodsPatients received a single cycle of cisplatin 30 mg/m² on days 1–3 and docetaxel 75 mg/m² on day 1 combined with durvalumab 1500 mg fix dose on day 5 and tremelimumab 75 mg fix dose on day 5. Patients with pathologic complete response (pCR) in the rebiopsy after induction treatment or at least 20% increase of intratumoral CD8+ cell density in the rebiopsy compared with baseline entered radioimmunotherapy with concomitant durvalumab/tremelimumab. The objective of this interim analysis was to analyze safety and efficacy of the chemoimmunotherapy-induction treatment before radioimmunotherapy.ResultsA total of 57 patients were enrolled, 56 were treated. Median pretreatment intratumoral CD8+ cell density was 342 cells/mm². After induction treatment, 27 patients (48%) had a pCR in the rebiopsy and further 25 patients (45%) had a relevant increase of intratumoral CD8+ cells (median increase by a factor of 3.0). Adverse event (AE) grade 3–4 appeared in 38 patients (68%) and mainly consisted of leukopenia (43%) and infections (29%). Six patients (11%) developed grade 3–4 immune-related AE. Univariate analysis computed p16 positivity, programmed death ligand 1 immune cell area and intratumoral CD8+ cell density as predictors of pCR. On multivariable analysis, intratumoral CD8+ cell density predicted pCR independently (OR 1.0012 per cell/mm², 95% CI 1.0001 to 1.0022, p=0.016). In peripheral blood CD8+ cells, the coexpression of programmed death protein 1 significantly increased especially in patients with pCR.ConclusionsSingle cycle induction treatment with cisplatin/docetaxel and durvalumab/tremelimumab is feasible and achieves a high biopsy-proven pCR rate.

The therapeutic index (TI) is a quantitative assessment of a drug safety proportional to its effectiveness. The estimation is intuitive when the engagement of the product with its target is dependent on stable chemistry and predictable pharmacokinetics as is the case for small molecules or antibodies. But for therapeutics with complex biodistribution and context-dependent potency such as adoptive cell therapy (ACT) products, TI estimations need to consider a broader array of factors. These include product-dependent variability such as functional fitness, unpredictable pharmacokinetics due to non-specific trapping, sequestration and extravasation into normal tissues and variable rates of in vivo expansion. In the case of solid malignancies, additional modifiers dependent on individual tumor immune biology may affect pharmacodynamics, including differential trafficking to benign compared with cancer tissue, hampered engagement with target cells, immune suppression and cellular dysfunction due to unfavorable metabolic conditions. Here, we propose a patient-specific assessment of factors affecting on-tumor from off-tumor activity in disparate immunologic environments that impact ACT’s clinical efficacy and may favorably balance the TI. for ACT products.

The bone is a complex organ that is dependent on a tight regulation between bone formation by osteoblasts (OBs) and bone resorption by osteoclasts (OCs). These processes can be influenced by environmental factors such as ionizing radiation (IR). In cancer therapy, IR is applied in high doses, leading to detrimental effects on bone, whereas radiation therapy with low doses of IR is applied for chronic degenerative and inflammatory diseases, with a positive impact especially on bone homeostasis. Moreover, the effects of IR are of particular interest in space travel, as astronauts suffer from bone loss due to space radiation and microgravity. This review summarizes the current state of knowledge on the effects of IR on bone with a special focus on the influence on OCs and OBs, as these cells are essential in bone remodeling. In addition, the influence of IR on the bone microenvironment is discussed. In summary, the effects of IR on bone and bone remodeling cells strongly depend on the applied radiation dose, as differential results are provided from in vivo as well as in vitro studies with varying doses of IR. Furthermore, the isolated effects of IR on a single cell type are difficult to determine, as the bone cells and bone microenvironment are building a tightly regulated network, influencing on one another. Therefore, future research is necessary in order to elucidate the influence of different bone cells on the overall radiation-induced effects on bone.

Recent biomarker research focuses on early immunological changes to predict treatment response to immune checkpoint inhibitors (ICI). Within this prospective ST-ICI trial, pre-planned biomarker analysis was performed and we developed a flow cytometry-based whole-blood prognostic immune signature (FCBPS) to predict overall survival (OS) benefit of cancer patients treated with ICI. For this, fifty-four immune cell subsets were analyzed in the patients’ peripheral blood before the second administration of the ICI. Patients were randomly allocated to a training and validation cohort. Univariate Cox proportional hazards regression analysis and LASSO Cox model were used to develop a predictive and prognostic signature. 104 patients were prospectively enrolled. 89 patients provided blood samples. The identified FCBPS signature bases on five immune cell subtypes: neutrophils, plasmacytoid dendritic cells (pDCs), natural killer (NK)T cells (CD56+/CD16+), monocytes (CD14high) and CD8+ T cells (PD-1+). This signature achieved a high accuracy (C-index 0.74 vs 0.71) for predicting OS benefit in the training and validation cohort. Both in the training and validation cohort, the low-risk group had significantly longer OS than the high-risk group (HR 0.26, 95% CI: 0.12-0.56, p=0.00025; HR 0.30, 95% CI: 0.10 −0.91, p=0.024,respectively). In the whole cohort, FCBPS is a predictor of OS (HROS=0.28, 95% CI: 0.15-0.52) and progression-free survival (HRPFS=0.22, 95% CI: 0.12-0.39) that remained independent in multivariate analyses and subgroup analyses after adjusting for clinical and pathological factors. The identified flow cytometry-based whole-blood prognostic signature (FCBPS) is a powerful predictor for metastatic cancer patients who benefit from ICI treatment.Trial registrationProspectively registered in ClinicalTrials.gov (NCT03453892) on January 24, 2018.

Supplementation of standard cancer therapies (radiotherapy, chemotherapy, surgery) with immunotherapies has revolutionized cancer treatment. In order to include recent improvements of multimodal therapies into clinical routine, knowledge about the immune status, the immune dynamics and the detailed composition and activation of patient's immune system is required. The here presented single-tube multicolor flow cytometry assay allows the discrimination of 20 clinically relevant immune cell subsets and their activation status in peripheral whole blood. It includes 15 different antibodies and can be established on a common 3 laser and 10 color flow-cytometer. Furthermore, this assay is easy to set-up and to perform as well as fast with only 40min of sample preparation time. Moreover, only 100μL of whole blood are sufficient for this precise determination of the individual immune status. It is already applied in translational programs of clinical studies and trials and can further be adapted for future ones.

Zusammenfassung Hintergrund Sitzendes Verhalten wird zunehmend als ein eigenständiger gesundheitlicher Risikofaktor eingeschätzt. Ein wesentliches Handlungsfeld für Interventionen zur Reduzierung sitzenden Verhaltens stellt deshalb der Büroarbeitsplatz dar. Dieses systematische Review untersucht, ob sitz- und/oder bewegungsspezifische Interventionen die Sitzzeiten von Büroangestellten am Arbeitsplatz reduzieren. Methoden Von April bis Mai 2016 wurde in den Datenbanken „PubMed“, „PsycINFO“ und „SPORTDiscus“ eine systematische Literaturrecherche durchgeführt. Insgesamt ließen sich 17 Studien identifizieren, welche die Sitzzeiten von Büroangestellten untersuchten. Die relevanten Studien wurden in einer „Best Evidence Synthesis“ zusammengefasst. Zusätzlich wurde eine Moderatoranalyse (u. a. Interventionsmethoden) durchgeführt. Ergebnisse Multikomponenten-Interventionen und Sitz-Steh-Arbeitsstationen sind vielversprechend zur Reduzierung der Sitzzeiten von Büroangestellten. In der Moderatoranalyse fiel der Anteil signifikant positiver Interventionsergebnisse für die Interventionsmethoden „Umweltveränderungen“, „Hinzufügen von Objekten zur Umgebung“ und „Anleitungen, um ein Verhalten auszuführen“ am höchsten aus. Interventionen mit spezifischem Fokus auf das Sitzen sowie Studien mit objektiver Messmethodik zur Erhebung der Sitzzeit zeigten sich erfolgversprechender. Schlussfolgerung Es existieren verschiedene erfolgversprechende Interventionen zur Reduzierung der Sitzzeiten am Büroarbeitsplatz. Hier sind Mehrkomponenten-Interventionen und die Installation von Sitz-Steh-Arbeitsstationen hervorzuheben. Wenig Evidenz liegt für die Langzeitwirkung vor. Die Heterogenität der Studien schränkt zudem allgemeingültige Wirksamkeitsaussagen ein. Zukünftige Studien sollten Interventionen stärker theoriebasiert planen und die Sitzzeiten mithilfe subjektiver und objektiver Messinstrumente erfassen.

The unicellular freshwater flagellate Euglena gracilis has a highly developed sensory system. The cells use different stimuli such as light and gravity to orient themselves in the surrounding medium to find areas for optimal growth. Due to the ability to produce oxygen and consume carbon dioxide, Euglena is a suitable candidate for life support systems. Participation in a long-term space experiment would allow for the analysis of changes and adaptations to the new environment, and this could bring new insights into the mechanism of perception of gravity and the associated signal transduction chain. For a molecular analysis of transcription patterns, an automated system is necessary, capable of performing all steps from taking a sample, processing it and generating data. One of the developmental steps is to find long-term stable reagents and materials and test them for stability at higher-than-recommended temperature conditions during extended storage time. We investigated the usability of magnetic beads in an Euglena specific lysis buffer after addition of the RNA stabilizer Dithiothreitol over 360 days and the lysis buffer with the stabilizer alone over 455 days at the expected storage temperature of 19 °C. We can claim that the stability is not impaired at all after an incubation period of over one year. This might be an interesting result for researchers who have to work under non-standard lab conditions, as in biological or medicinal fieldwork.

Supplementation of standard cancer therapies (radiotherapy, chemotherapy, surgery) with immunotherapies has revolutionized cancer treatment. In order to include recent improvements of multimodal therapies into clinical routine, knowledge about the immune status, the immune dynamics and the detailed composition and activation of patient's immune system is required. The here presented single-tube multicolor flow cytometry assay allows the discrimination of 20 clinically relevant immune cell subsets and their activation status in peripheral whole blood. It includes 15 different antibodies and can be established on a common 3 laser and 10 color flow-cytometer. Furthermore, this assay is easy to set-up and to perform as well as fast with only 40 min of sample preparation time. Moreover, only 100 μL of whole blood are sufficient for this precise determination of the individual immune status. It is already applied in translational programs of clinical studies and trials and can further be adapted for future ones.

Recent improvements in the flow cytometry technology allow the determination of the general immune status through the development of multicolor immunofluorescence panels. The one-tube multicolor flow cytometry assay (OTMA) that is presented here identifies 20 different, clinically relevant immune cell subsets and three common activation markers. Thereby, a comprehensive immune status that covers all major immune cells is easily obtained.The assay is suitable for every common three lasers and 10 color flow cytometer and includes the application of 15 different antibodies. Furthermore, the assay requires only 100 μL of EDTA-treated whole-blood and less than 40 min for sample preparation. By being easily adaptable to individual requirements and by additionally determining absolute cell counts, the assay is well-suited for translational research in clinical trials.

Recent improvements in the flow cytometry technology allow the determination of the general immune status through the development of multicolor immunofluorescence panels. The one-tube multicolor flow cytometry assay (OTMA) that is presented here identifies 20 different, clinically relevant immune cell subsets and three common activation markers. Thereby, a comprehensive immune status that covers all major immune cells is easily obtained.The assay is suitable for every common three lasers and 10 color flow cytometer and includes the application of 15 different antibodies. Furthermore, the assay requires only 100 μL of EDTA-treated whole-blood and less than 40 min for sample preparation. By being easily adaptable to individual requirements and by additionally determining absolute cell counts, the assay is well-suited for translational research in clinical trials.

Sustained pain relief following radon spa therapy in patients suffering from chronic painful diseases has been well described. But still, the underlying mechanisms are not fully understood. We conducted the prospective and explorative RAD-ON01 study which included 103 patients who suffered from chronic painful musculoskeletal disorders of the spine and/or joints and present here the data of the examination of pro- and anti-inflammatory cytokines in the serum of the patients before and at weeks 6, 12 and 30 after therapy. While TNFα, IL-1β, IFNγ, IL-1Ra and IL-10 were not altered, TGFβ was temporarily significantly (p = 0.013) elevated 6 weeks after therapy. Importantly, this elevation positively correlated with lowered pain sensitivity (r = 0.41). Further, the amount of IL-18 in the serum positively correlated with lowered pain sensitivity. Therefore, IL-18 can be considered as predictive marker for pain sensitivity of radon spa patients. We conclude that alterations in TGFβ and general IL-18 levels in serum have prognostic and predictive value in situations of lowered pain by exposure of patients to very low-doses of radiation as it is the case in radon spa.

Dormant states of organisms are easier to store than the living state because they tolerate larger variations in temperature, light, storage space etc., making them attractive for laboratory culture stocks and also for experiments under special circumstances, especially space flight experiments. Like several other organisms,Euglena gracilisis capable of forming desiccation tolerant resting states in order to survive periods of unfavourable environmental conditions. In earlier experiments it was found that dormantEuglenacells must not become completely desiccated. Some residual moisture is required to ensure recovery of the resting states. To analyse the water demand in recovery ofEuglenaresting states, cells were transferred to a defined amount of cotton wool (0.5 g). Subsequently different volumes of medium (1, 2, 3, 4, 5, 8, 10 and 20 ml) were added in order to supply humidity; a control was set up without additional liquid. Samples were sealed in transparent 50 ml falcon tubes and stored for 9 months under three different conditions:•Constant low light conditions in a culture chamber at 20°C,•In a black box, illuminated with short light emitting diode-light pulses provided by joule thieves and•In darkness in a black box.After 9 months, cells were transferred to fresh medium and cell number, photosynthetic efficiency and movement behavior was monitored over 3 weeks. It was found that cells recovered under all conditions except in the control, where no medium was supplied. Transcription levels of 21 genes were analysed with a Multiplex-polymerase chain reaction. One hour after rehydration five of these genes were found to be up-regulated: ubiquitin, heat shock proteins HSP70, HSP90, the calcium-sensor protein frequenin and a distinct protein kinase, which is involved in gravitaxis. The results indicate a transient general stress response of the cells.

Sedentary behaviour is a health risk factor independent of physical activity. Interventions that aim to reduce sitting at the workplace are particularly important as office workers spend a large proportion of their working hours sitting. This systematic review examines whether these interventions (SB or PA interventions during work time) reduce sitting time among office workers and which variables moderate intervention effects.A systematic literature search was conducted from April to May 2016 in the following databases: PubMed, PsycINFO and SPORTDiscus. In total, we identified 17 studies that assessed the time spent in sedentary behaviour at the office workplace. To summarize the study results, we applied a best-evidence synthesis. Additionally, we evaluated potential moderators, such as intervention strategies.Multi-component interventions and sit-stand workstations were most promising sedentary reduction interventions. The analysis of moderators highlighted that the proportion of positive intervention effects was higher in interventions based on the strategies "environmental restructuring", "adding objects to the environment" and "instructions on how to carry out the behaviour". Furthermore, interventions focusing on sedentary behaviour only and studies using objective measurement tools showed more often positive interventions effects.There are many promising interventions to reduce sitting time at the office workplace. However, there is insufficient evidence if the effects of these interventions are sustainable in the long term. Moreover, the considerable heterogeneity of included studies limits the validity of our findings. Future intervention studies should build on a theoretical planning approach and use subjective as well as objective evaluation measures.Sitzendes Verhalten wird zunehmend als ein eigenständiger gesundheitlicher Risikofaktor eingeschätzt. Ein wesentliches Handlungsfeld für Interventionen zur Reduzierung sitzenden Verhaltens stellt deshalb der Büroarbeitsplatz dar. Dieses systematische Review untersucht, ob sitz- und/oder bewegungsspezifische Interventionen die Sitzzeiten von Büroangestellten am Arbeitsplatz reduzieren.Von April bis Mai 2016 wurde in den Datenbanken „PubMed“, „PsycINFO“ und „SPORTDiscus“ eine systematische Literaturrecherche durchgeführt. Insgesamt ließen sich 17 Studien identifizieren, welche die Sitzzeiten von Büroangestellten untersuchten. Die relevanten Studien wurden in einer „Best Evidence Synthesis“ zusammengefasst. Zusätzlich wurde eine Moderatoranalyse (u. a. Interventionsmethoden) durchgeführt.Multikomponenten-Interventionen und Sitz-Steh-Arbeitsstationen sind vielversprechend zur Reduzierung der Sitzzeiten von Büroangestellten. In der Moderatoranalyse fiel der Anteil signifikant positiver Interventionsergebnisse für die Interventionsmethoden „Umweltveränderungen“, „Hinzufügen von Objekten zur Umgebung“ und „Anleitungen, um ein Verhalten auszuführen“ am höchsten aus. Interventionen mit spezifischem Fokus auf das Sitzen sowie Studien mit objektiver Messmethodik zur Erhebung der Sitzzeit zeigten sich erfolgversprechender.Es existieren verschiedene erfolgversprechende Interventionen zur Reduzierung der Sitzzeiten am Büroarbeitsplatz. Hier sind Mehrkomponenten-Interventionen und die Installation von Sitz-Steh-Arbeitsstationen hervorzuheben. Wenig Evidenz liegt für die Langzeitwirkung vor. Die Heterogenität der Studien schränkt zudem allgemeingültige Wirksamkeitsaussagen ein. Zukünftige Studien sollten Interventionen stärker theoriebasiert planen und die Sitzzeiten mithilfe subjektiver und objektiver Messinstrumente erfassen.

In recent times Euglena gracilis Z was employed as primary producer in closed environmental life-support system (CELSS), e.g. in space research. The photosynthetic unicellular flagellate is not capable of utilizing nitrate, nitrite, and urea as nitrogen source. Therefore, ammonium is supplied as an N-source in the lab (provided as diammonium-dihydrogenphosphate, (NH4)2HPO4) to E. gracilis cultures. While nitrate exerts low toxicity to organisms, ammonium is harmful for many aquatic organisms especially, at high pH-values, which causes the ionic NH4+ (low toxicity) to be partially transformed into the highly toxic ammonia, NH3. In earlier reports, Euglena gracilis was described to grow with various amino acids as sole N-source. Our aim was to investigate alternatives for (NH4)2HPO4 as N-source with lower toxicity for organisms co-cultivated with Euglena in a CELSS. The growth kinetics of Euglena gracilis cultures was determined in the presence of different amino acids (glycine, glutamine, glutamic acid, leucine, and threonine). In addition, uptake of those amino acids by the cells was measured. Cell growth in the presence of glycine and glutamine was quite comparable to the growth in (NH4)2HPO4 containing cultures while a delay in growth was observed in the presence of leucine and threonine. Unlike, aforementioned amino acids glutamate consumption was very poor. Cell density and glutamate concentration were almost unaltered throughout the experiment and the culture reached the stationary phase within 8 days. The data are compared with earlier studies in which utilization of amino acids in Euglena gracilis was investigated. All tested amino acids (glutamate with limitations) were found to have the potential of being an alternative N-source for Euglena gracilis. Hence, these amino acids can be used as a non-toxic surrogate for (NH4)2HPO4.

The German Aerospace Center (DLR) enabled German participation in the joint space campaign on the unmanned Shenzhou 8 spacecraft in November 2011. In this report, the effect of microgravity on Euglena gracilis cells is described. Custom-made dual compartment cell fixation units (containing cells in one chamber and fixative - RNA lysis buffer - in another one) were enclosed in a small container and placed in the Simbox incubator, which is an experiment support system. Cells were fixed by injecting them with fixative at different time intervals. In addition to stationary experiment slots, Simbox provides a 1 g reference centrifuge. Cell fixation units were mounted in microgravity and 1 g reference positions of Simbox. Two Simbox incubators were used, one for space flight and the other as ground reference. Cells were fixed soon after launch and shortly before return of the spaceship. Due to technical problems, only early in-flight samples (about 40 min after launch microgravity and corresponding 1 g reference) were fully mixed with fixative, therefore only data from those samples are presented. Transcription of several genes involved in signal transduction, oxidative stress defence, cell cycle regulation and heat shock responses was investigated with quantitative PCR. The data indicate that Euglena cells suffer stress upon short-term exposure to microgravity; various stress-induced genes were up-regulated. Of 32 tested genes, 18 were up-regulated, one down-regulated and the rest remained unaltered. These findings are in a good agreement with results from other research groups using other organisms.

In August 1939, at the 3rd International Neurological Congress in Copenhagen, Professor Lucio Bini reported on the first use of electricity to induce a seizure for therapeutic purposes in psychotic patients. At that time, the discovery of ECT amounted to a therapeutic revolution, helping millions of mentally ill patients and furthering the scientific understanding of several disorders. Although electricity had been used to treat several physical ailments and mental disorders, electricity, rather than the convulsive crisis, was considered therapeutic. In modern times von Meduna was the first to clearly recognize the therapeutic value of 'complete' seizures, but it was thanks to Cerletti's dedication to biological research and Bini's contribution that ECT became one of the most effective and safe treatments available. ECT remains a highly effective and safe treatment option and thousands of papers have been published on ECT since the original report by Bini. To celebrate this anniversary, we translated Prof. Bini's original report as an abstract presented in Copenhagen in 1939.

Die Weltwirtschaft ist in einem robusten Aufschwung. Das vom ifo Institut erhobene Weltwirtschaftsklima hat sich im Frühjahr 2006 zum dritten Mal in Folge verbessert; und liegt deutlich über dem langfristigen Durchschnitt. Die Expansion der Weltwirtschaft wird im Prognosezeitraum schwungvoll bleiben, sich jedoch schrittweise etwas abflachen. Die Konjunktur in Deutschland zeigt sich zur Jahresmitte 2006 gut in Form. Das hervorragende ifo Geschäftsklima indiziert, dass der Aufschwung der deutschen Wirtschaft beträchtlich an Breite gewonnen hat. Neben dem mit hoher Drehzahl laufenden Exportmotor ist nun auch die Binnenkonjunktur in Schwung gekommen. Die Investitionen in Ausrüstungen haben Tritt gefasst; die neuesten Zahlen des ifo Konjunkturtests signalisieren, dass nicht nur die im Sog des Exportbooms stehenden Unternehmen investieren, sondern nun auch die eher binnenwirtschaftlich orientierten Unternehmen. Selbst der private Konsum hat, nach dem Rückgang im Jahresendquartal 2005, zugelegt; zusätzliche Impulse werden in der zweiten Jahreshälfte von vorgezogenen Käufen ausgehen, mit denen die ab Januar kommenden Jahres geltende höhere Mehrwertsteuer kurzfristig noch eingespart werden kann. Ingesamt wird das reale Bruttoinlandsprodukt im laufenden Jahr um 1,8% expandieren; nach Ausschaltung der im Vergleich zu 2005 geringeren Zahl an Arbeitstagen um 2%. Im kommenden Jahr wird die Konjunktur durch die massive Erhöhung von Steuern und Abgaben zwar beträchtlich gedämpft; gleichwohl wird sich aber der Aufschwung fortsetzen. Diese Einschätzung stützt sich zu einem großen Teil auf die endogene Konjunkturdynamik der deutschen Wirtschaft. Nach einem "klassischen" Abschwung in den ersten Jahren dieses Jahrzehnts, der von einem Rückgang der Trendwachstumsrate begleitet war, wurde sowohl bei der gesamtwirtschaftlichen Produktion als auch bei den Ausrüstungsinvestitionen im Laufe des Jahres 2004 der untere Wendepunkt erreicht.