Radiation-Induced Leiomyosarcoma: Does Antimetabolite Chemotherapy Contribute? A Report of Three Cases

Purpose: Radiation therapy in low and high doses is known to be associated with the occurrence of late secondary sarcomas. The addition of chemotherapy has not been clearly demonstrated as a contributing factor. We describe three patients with radiation-associated leiomyosarcoma who had also received antimetabolite chemotherapy

Physical signatures of discontinuities of the time-dependent exchange-correlation potential

The exact exchange-correlation (XC) potential in time-dependent density-functional theory (TDDFT) is known to develop steps and discontinuities upon change of the particle number in spatially confined regions or isolated subsystems. We demonstrate that the self-interaction corrected adiabatic local-density approximation for the XC potential has this property, using the example of electron loss of a model quantum well system. We then study the influence of the XC potential discontinuity in a real-time simulation of a dissociation process of an asymmetric double quantum well system, and show that it dramatically affects the population of the resulting isolated single quantum wells. This indicates the importance of a proper account of the discontinuities in TDDFT descriptions of ionization, dissociation or charge transfer processes.Comment: 17 pages, 6 figure

Can vitamin D status influence the effect of stress on planning and problem-solving? A randomized control trial

Background: Nutritional interventions may serve as a stress resilience strategy with important implications for human health.Objective: The aim of this study was to investigate the effect of vitamin D supplementation throughout wintertime on problem-solving and planning abilities during stressful circumstances.Design: A total of 77 male inpatients with a mean age of 48 years (range 31–81) and stress-related mental health disorders were randomly assigned into a Vitamin D supplement group (daily intake of 40 μg) or a pla-cebo supplement group (Control) (daily intake of 120 mg olive oil). The intervention period was from January 2018 to May 2018. The means and standard deviations for vitamin D status (25-hydroxyvitamin D3, nmol/L), pre- and post-test, respectively, were 58(21) and 46(15) for the Control group, and 63(18) and 76(21) for the Vitamin D group. Problem-solving and planning abilities were measured by the Tower of London (ToL) task pre- (midwinter) and post- (spring) supplement intervention. The ToL task was performed during exposure to distracting noise.Results: The results revealed that vitamin D supplementation throughout the winter had a significant effect on number of correct responses on easier (1 and 2 move) ToL problems during stress; the Vitamin D group improved significantly from pre- to post-test, whereas the Control group did not. In addition, the Vitamin D group had significantly more correct responses than the Control group on post-test. The improved perfor-mance was not related to a speed-accuracy trade off effect; both groups showed significantly decreased plan-ning times from pre- to post-test. The intervention did not differentially affect task performance on the more difficult (3 to 5 move) ToL problems. For the more demanding problems, IQ seemed to explain most of the variance regarding accuracy. Age explained most of the variance associated with task planning time.Conclusion: Vitamin D supplementation seemed to improve resilience to stress, but it was limited to performance of easier tasks.publishedVersio

Vitamin D supplementation during winter: Effects on stress resilience in a randomized control trial

Vitamin D status may be important for stress resilience. This study investigated the effects of vitamin D supplements during winter on biological markers of stress resilience such as psychophysiological activity, serotonin, and cortisol in a placebo-controlled, randomized clinical trial. Eighty-six participants were randomly assigned to the Intervention (vitamin D) or Control (placebo) groups. Before and after the intervention participants were exposed to an experimental stress procedure. Psychophysiological activity was measured during three main conditions: baseline, stress, and recovery. Fasting blood samples were taken in the morning and saliva samples were collected at seven different time points across 24 h. Prior to intervention both groups had normal/sufficient vitamin D levels. Both groups showed a normal pattern of psychophysiological responses to the experimental stress procedure (i.e., increased psychophysiological responses from resting baseline to stress-condition, and decreased psychophysiological responses from stress-condition to recovery; all p < 0.009). Post-intervention, the Intervention group showed increased vitamin D levels (p < 0.001) and normal psychophysiological responses to the experimental stress procedure (p < 0.001). Importantly, the Control group demonstrated a classic nadir in vitamin D status post-intervention (spring) (p < 0.001) and did not show normal psychophysiological responses. Thus, physiologically the Control group showed a sustained stress response. No significant effects of vitamin D were found on serotonin and cortisol.publishedVersio

Von Fachlicher Risikoanalyse zu Politischer Risikobewertung: Die Vermittlung von Risikoanalysen im Bevölkerungsschutz in die Bundespolitik

In Deutschland werden seit 2010 im Auftrag des Bundesministeriums des Innern und für Heimat (bis 8. Dezember 2021 Bundesministerium des Innern, für Bau und Heimat), unter der Koordination des Bundesamtes für Bevölkerungsschutz und Katastrophenhilfe (BBK) regelmäßig Risikoanalysen zu unterschiedlichen Risiken erarbeitet und zur politischen Bewertung vor allem an den Innenausschuss des Deutschen Bundestages gesandt. Diese Studie untersucht explorativ die Rahmenbedingungen der politischen Arbeit von Abgeordneten des Deutschen Bundestages und geht der Frage nach, welche Gründe und Bedingungen die Wahrnehmung der Risikoanalysen beeinflussen und die Verwendung dieser für die Entscheidungsfindung und Politikgestaltung erschweren oder erleichtern. Zur Beantwortung dieser Frage wurden 15 leitfadengestützte Interviews mit aktiven und ehemaligen Bundestagsabgeordneten sowie zwei Gruppendiskussionen mit wissenschaftlichen Mitarbeitenden von Bundestagsabgeordneten durchgeführt. Auf der Grundlage eines heuristischen Modells erfolgte eine strukturierte qualitative Inhaltsanalyse des Materials entlang festgelegter Auswertungskategorien. Durch die Analyse konnten grundlegende Rahmenbedingungen für die Arbeits- und Verhaltensweisen der Abgeordneten herausgearbeitet und Gründe aufgezeigt werden, die eine politische Diskussion der Risikoanalysen in der Vergangenheit erschwert haben. Gleichzeitig erzielte die Analyse eine große Anzahl von Anhaltspunkten für direkte oder indirekte Verbesserungen in der kommunikativen Begleitung der Risikoanalysen sowie deren inhaltlicher und visueller Aufbereitung. Zusätzliche Aspekte hinsichtlich der politischen Wahrnehmung und Bewertung der Risikoanalysen konnten im Rahmen einer Analyse politischer Dokumente erarbeitet werden, die über das Dokumentations- und Informationssystem für Parlamentarische Vorgänge (DIP) abrufbar sind. Die Studie stellt abschließend Handlungsempfehlungen für einen erfolgreichen Transfer der Inhalte der Risikoanalysen in die Bundespolitik vor

Neuroprotective tissue adaptation induced by IL-12 attenuates CNS inflammation

IL-12 is a well-established driver of type 1 immune responses. Paradoxically, in several autoimmune conditions including neuroinflammation, IL-12 reduces pathology and exhibits regulatory properties. Yet, the mechanism and the involved cellular players behind this immune regulation remain elusive. To identify the IL-12-responsive elements which prevent immunopathology, we generated mouse models lacking a functional IL-12 receptor either in all cells or in specific populations within the immune or central nervous system (CNS) compartments, and induced experimental autoimmune encephalomyelitis (EAE), which models human Multiple Sclerosis (MS). This revealed that the CNS tissue-protective features of IL-12 are mediated by cells of the neuroectoderm, and not immune cells. Importantly, sections of brain from patients with MS show comparable patterns of expression, indicating parallel mechanisms in humans. By combining spectral flow cytometry, bulk and single-nucleus RNA sequencing, we uncovered an IL-12-induced neuroprotective adaption of the neuroectoderm critically involved in maintaining CNS tissue integrity during inflammation

Effect of Biodiversity Changes in Disease Risk: Exploring Disease Emergence in a Plant-Virus System

The effect of biodiversity on the ability of parasites to infect their host and cause disease (i.e. disease risk) is a major question in pathology, which is central to understand the emergence of infectious diseases, and to develop strategies for their management. Two hypotheses, which can be considered as extremes of a continuum, relate biodiversity to disease risk: One states that biodiversity is positively correlated with disease risk (Amplification Effect), and the second predicts a negative correlation between biodiversity and disease risk (Dilution Effect). Which of them applies better to different host-parasite systems is still a source of debate, due to limited experimental or empirical data. This is especially the case for viral diseases of plants. To address this subject, we have monitored for three years the prevalence of several viruses, and virus-associated symptoms, in populations of wild pepper (chiltepin) under different levels of human management. For each population, we also measured the habitat species diversity, host plant genetic diversity and host plant density. Results indicate that disease and infection risk increased with the level of human management, which was associated with decreased species diversity and host genetic diversity, and with increased host plant density. Importantly, species diversity of the habitat was the primary predictor of disease risk for wild chiltepin populations. This changed in managed populations where host genetic diversity was the primary predictor. Host density was generally a poorer predictor of disease and infection risk. These results support the dilution effect hypothesis, and underline the relevance of different ecological factors in determining disease/infection risk in host plant populations under different levels of anthropic influence. These results are relevant for managing plant diseases and for establishing conservation policies for endangered plant species

IL-12 sensing in neurons induces neuroprotective CNS tissue adaptation and attenuates neuroinflammation in mice

Interleukin-12 (IL-12) is a potent driver of type 1 immunity. Paradoxically, in autoimmune conditions, including of the CNS, IL-12 reduces inflammation. The underlying mechanism behind these opposing properties and the involved cellular players remain elusive. Here we map IL-12 receptor (IL-12R) expression to NK and T cells as well as neurons and oligodendrocytes. Conditionally ablating the IL-12R across these cell types in adult mice and assessing their susceptibility to experimental autoimmune encephalomyelitis revealed that the neuroprotective role of IL-12 is mediated by neuroectoderm-derived cells, specifically neurons, and not immune cells. In human brain tissue from donors with multiple sclerosis, we observe an IL-12R distribution comparable to mice, suggesting similar mechanisms in mice and humans. Combining flow cytometry, bulk and single-nucleus RNA sequencing, we reveal an IL-12-induced neuroprotective tissue adaption preventing early neurodegeneration and sustaining trophic factor release during neuroinflammation, thereby maintaining CNS integrity in mice