Formation and Tandem Mass Spectrometry of Doubly Charged Lipid-Metal Ion Complexes.

Phospholipids are major components of most eukaryotic cell membranes. Changes in metabolic states are often accompanied by phospholipid structure variations. The structural changes of phospholipids are the hallmark of disease states, or specific lipid structures have been associated with distinct organisms. Prime examples are microorganisms that synthesize phospholipids with, for example, different branched chain fatty acids. Assignment and relative quantitation of structural isomers of phospholipids that arise from attachment of different fatty acids to the glycerophospholipid backbone are difficult with routine tandem mass spectrometry or with liquid chromatography without authentic standards. In this work, we report on the observation that all investigated phospholipid classes form doubly charged lipid-metal ion complexes during electrospray ionization (ESI) and show that these complexes can be used to assign lipid classes and fatty acid moieties, distinguish isomers of branched chain fatty acids, and relatively quantify these isomers in positive-ion mode. Use of water free methanol and addition of divalent metal salts (100 mol %) to ESI spray solutions afford highly abundant doubly charged lipid-metal ion complexes (up to 70 times of protonated compounds). Higher-energy collisional dissociation and collision-induced dissociation of doubly charged complexes yield a diverse set of lipid class-dependent fragment ions. In common for all lipid classes is the liberation of fatty acid-metal adducts that yield fragment ions from the fatty acid hydrocarbon chain upon activation. This ability is used to pinpoint sites of branching in saturated fatty acids and is showcased for free fatty acids as well as glycerophospholipids. The analytical utility of doubly charged phospholipid-metal ion complexes is demonstrated by distinguishing fatty acid branching-site isomers in phospholipid mixtures and relatively quantifying the corresponding isomeric compounds.

Radiotherapy of the Hepatocellular Carcinoma in Mice Has a Time-Of-Day-Dependent Impact on the Mouse Hippocampus.

Chronic liver diseases including hepatocellular carcinoma (HCC) create a state of chronic inflammation that affects the brain via the liver-brain axis leading to an alteration of neurotransmission and cognition. However, little is known about the effects of HCC on the hippocampus, the key brain region for learning and memory. Moreover, radiotherapy used to treat HCC has severe side effects that impair patients' life quality. Thus, designing optimal strategies, such as chronotherapy, to enhance the efficacy and reduce the side effects of HCC treatment is critically important. We addressed the effects of HCC and the timed administration of radiotherapy in mice on the expression of pro-inflammatory cytokines, clock genes, markers for glial activation, oxidative stress, neuronal activity and proliferation in the hippocampal neurogenic niche. Our data showed that HCC induced the upregulation of genes encoding for pro-inflammatory cytokines, altered clock gene expressions and reduced proliferation in the hippocampus. Radiotherapy, in particular when applied during the light/inactive phase enhanced all these effects in addition to glial activation, increased oxidative stress, decreased neuronal activity and increased levels of phospho(p)-ERK. Our results suggested an interaction of the circadian molecular clockwork and the brain's innate immune system as key players in liver-brain crosstalk in HCC and that radiotherapy when applied during the light/inactive phase induced the most profound alterations in the hippocampus.

Expert consensus-based clinical recommendation for an integrative anthroposophic treatment of acute bronchitis in children: A Delphi survey.

BACKGROUND: Acute bronchitis is one of the most common pediatric diseases. In addition to conventional therapies, a frequent use of complementary and alternative medicine (CAM) has been stated. Anthroposophic medicine (AM) is one of the most practiced complementary and integrative medicine (CIM) approaches in Central Europe but hitherto no consensus-based clinical recommendations or guidelines are available. Therefore, a consensus-based recommendation leading to an informed and reasonable use of AM in the treatment of acute bronchitis in pediatrics was developed. METHODS: A total of 61 physicians in Germany with expertise in the field of anthroposophic pediatrics was invited to complete an online multistep Delphi process. Two independent reviewers quantitatively and qualitatively evaluated the results. The survey was completed when >75 % consensus was achieved. RESULTS: The clinical recommendation comprises 15 subitems related to treatment as well as clinical and psychosocial aspects. All items reached strong consensus (>90 %; N = 9) or consensus (75-90 %; N = 6). CONCLUSION: The comprehensive clinical recommendation creates a scientific base for the anthroposophic integrative treatment of acute bronchitis in children in Germany. It will make the anthroposophic approach more applicable, understandable and comparable to a wider public of physicians and other health professionals in Germany.

Innovation and Integrity in Intervention Research: Conceptual Issues, Methodology, and Knowledge Translation.

In this article, we introduce the special issue entitled Innovation and Integrity in Intervention Science. Its focus is on essential problems and prospects for intervention research examining two related topics, i.e., methodological issues and research integrity, and challenges in the transfer of research knowledge into practice and policy. The main aims are to identify how to advance methodology in order to improve research quality, examine scientific integrity in the field of intervention science, and discuss future steps to enhance the transfer of knowledge about evidence-based intervention principles into sustained practice, routine activities, and policy decisions. Themes of the special issue are twofold. The first includes questions about research methodology in intervention science, both in terms of research design and methods, as well as data analyses and the reporting of findings. Second, the issue tackles questions surrounding the types of knowledge translation frameworks that might be beneficial to mobilize the transfer of research-based knowledge into practice and public policies. The issue argues that innovations in methodology and thoughtful approaches to knowledge translation can enable transparency, quality, and sustainability of intervention research.

Innovation and Integrity: Desiderata and Future Directions for Prevention and Intervention Science.

This article summarizes essential implications of the papers within this special issue and discusses directions for future prevention and intervention research on conceptual issues, methodological and transfer-related challenges and opportunities. We identify a need to move from programs to principles in intervention research and encourage the implementation of research on potential mechanisms underlying intervention effectiveness. In addition, current methodological issues in intervention research are highlighted, including advancements in methodology and statistical procedures, extended outcome assessments, replication studies, and a thorough examination of potential biases. We further discuss transfer-related issues, for example the need for more research on the flexibility and adaptability of programs and intervention approaches as well as more general problems in knowledge translation reasoning the need for enhanced communication between practitioners, policy makers, and researchers. Finally, we briefly touch on the need to discuss the relation between single intervention programs, the mental health system, and changes of contextual conditions at the macro level.

Toward Dynamic Adaptation of Psychological Interventions for Child and Adolescent Development and Mental Health.

Children's and adolescents' mental health needs emphasize the necessity of a new era of translational research to enhance development and yield better lives for children, families, and communities. Developmental, clinical, and translational research serves as a powerful tool for managing the inevitable complexities in pursuit of these goals. This article proposes key ideas that will strengthen current evidence-based intervention practices by creating stronger links between research, practice, and complex systems contexts, with the potential of extending applicability, replicability, and impact. As exemplified in some of the articles throughout this special issue, new research and innovative implementation models will likely contribute to better ways of assessing and dynamically adapting structure and intervention practice within mental health systems. We contend that future models for effective interventions with children and adolescents will involve increased attention to (a) the connection of research on the developmental needs of children and adolescents to practice models; (b) consideration of informed contextual and cultural adaptation in implementation; and (c) a rational model of evidence-based planning, using a dynamic, inclusive approach with high support for adaptation, flexibility, and implementation fidelity. We discuss future directions for translational research for researchers, practitioners, and administrators in the field to continue and transform these ideas and their illustrations.

Good Enough? Interventions for Child Mental Health: From Adoption to Adaptation-From Programs to Systems.

This special issue examines essential challenges and successes for developing, implementing, and disseminating evidence-based psychological interventions for child and adolescent development and mental health. The main aims are to identify what evidence is "good enough" for roll-out, if and how interventions need to be adapted to developmental diversity and contextual variation, and how they relate to complex systemic contexts. Themes of the special issue are twofold and first include questions about adoption versus adaptation, in terms of both developmental tailoring and cultural adaptation of existing intervention programs. Second, the issue tackles questions about what systems of support are needed to ensure the system readiness for child and adolescent mental health interventions. We argue that moving from simple adoption to dynamic adaptation and from programs to collaborative systems offers new perspectives for developing and implementing flexible protocols and strategies that allow adapted intervention. The special issue raises broader questions of whether current intervention programs and practices are good enough in moving us from mere adoption to innovation in system readiness, or whether we need to do more before we can claim that interventions are good enough for roll-out.