Detection of sub-nmol amounts of the antiviral drug favipiravir in 19F MRI using photo-chemically induced dynamic nuclear polarization.

In biological tissues, 19F magnetic resonance (MR) enables the non-invasive, background-free detection of 19F-containing biomarkers. However, the signal-to-noise ratio (SNR) is usually low because biomarkers are typically present at low concentrations. Measurements at low magnetic fields further reduce the SNR. In a proof-of-principal study we applied LED-based photo-chemically induced dynamic nuclear polarization (photo-CIDNP) to amplify the 19F signal at 0.6 T. For the first time, 19F MR imaging (MRI) and spectroscopy (MRS) of a fully biocompatible model system containing the antiviral drug favipiravir has been successfully performed. This fluorinated drug has been used to treat Ebola and COVID-19. Since the partially cyclic reaction scheme for photo-CIDNP allows for multiple data acquisitions, averaging further improved the SNR. The mean signal gain factor for 19F has been estimated to be in the order of 103. An in-plane resolution of 0.39 × 0.39 mm2 enabled the analysis of spatially varying degrees of hyperpolarization. The minimal detectable amount of favipiravir per voxel was estimated to about 500 pmol. The results show that 19F photo-CIDNP is a promising method for the non-invasive detection of suitable 19F-containing drugs and other compounds with very low levels of the substance.

Distinct trajectories of HbA1c in newly diagnosed Type 2 diabetes from the DPV registry using a longitudinal group-based modelling approach.

AIM: To identify groups of heterogeneous HbA1c trajectories over time in newly diagnosed Type 2 diabetes. METHODS: The study comprised 6355 adults with newly diagnosed Type 2 diabetes (55% men, median age 62 years, baseline BMI 31 kg/m2 ) from the Diabetes Patienten Verlaufsdokumentation (DPV) prospective multicentre diabetes registry (Germany, Austria). Individuals were assessed during the first 5 years after diabetes diagnosis if they had ≥ 3 aggregated HbA1c measurements during follow-up. Latent class growth modelling was used to determine distinct subgroups that followed similar longitudinal HbA1c patterns (SAS: Proc Traj). Multinomial logistic regression models were used to investigate which variables were associated with the respective HbA1c trajectory groups. RESULTS: Four distinct longitudinal HbA1c trajectory (glycaemic control) groups were found. The largest group (56% of participants) maintained stable good glycaemic control (HbA1c 42-45 mmol/mol). Twenty-six percent maintained stable moderate glycaemic control (HbA1c 57-62 mmol/mol). A third group (12%) initially showed severe hyperglycaemia (HbA1c 97 mmol/mol) but reached good glycaemic control within 1 year. The smallest group (6%) showed stable poor glycaemic control (HbA1c 79-88 mmol/mol). Younger age at diabetes diagnosis, male sex, and higher BMI were associated with the stable moderate or poor glycaemic control groups. Insulin therapy was strongly associated with the highly improved glycaemic control group. CONCLUSIONS: Four subgroups with distinct HbA1c trajectories were determined in newly diagnosed Type 2 diabetes using a group-based modelling approach. Approximately one-third of people with newly diagnosed Type 2 diabetes need either better medication adherence or earlier intensification of glucose-lowering therapy.

SQUID-based detection of ultra-low-field multinuclear NMR of substances hyperpolarized using signal amplification by reversible exchange.

Ultra-low-field (ULF) nuclear magnetic resonance (NMR) is a promising spectroscopy method allowing for, e.g., the simultaneous detection of multiple nuclei. To overcome the low signal-to-noise ratio that usually hampers a wider application, we present here an alternative approach to ULF NMR, which makes use of the hyperpolarizing technique signal amplification by reversible exchange (SABRE). In contrast to standard parahydrogen hyperpolarization, SABRE can continuously hyperpolarize 1 H as well as other MR-active nuclei. For simultaneous measurements of 1 H and 19 F under SABRE conditions a superconducting quantum interference device (SQUID)-based NMR detection unit was adapted. We successfully hyperpolarized fluorinated pyridine derivatives with an up to 2000-fold signal enhancement in 19 F. The detected signals may be explained by two alternative reaction mechanisms. SABRE combined with simultaneous SQUID-based broadband multinuclear detection may enable the quantitative analysis of multinuclear processes.

[Changing structures--Integrating health]. / Strukturen ändern--Gesundheit integrieren.

Changes in (municipal) structures for the improvement of health are often required but, in contrast to behavioural measures, less frequently implemented and scientifically evaluated. Results on this subject for Germany are scarce. In recent years, municipal prevention and health promotion programmes received new impetus from the expansion of the German "Early Assistance" initiative. Early assistance programmes to help children grow up healthy initiated municipal processes such as the establishment of networks between health services and youth welfare services, prevention chains and nationwide initiatives. This has moved issues such as equal opportunities for health into the centre of politically driven structural development efforts. Neighbourhood management groups and municipal round tables on prevention-specific topics etc. have been established throughout Germany. Regarding this structural development, 6 projects from the field of prevention research give a good indication as to how the structure of municipal concepts can be effectively implemented.

[Strengthen the prevention and health promotion in a science-based way--Results and experience of the German National Prevention Research Initiative]. / Prävention und Gesundheitsförderung wissenschaftsbasiert stärken--Ergebnisse und Erfahrungen des BMBF-Förderschwerpunkts Präventionsforschung.

From 2004 to 2013, the German Ministry of Education and Research (BMBF) established its first funding programme for the promotion of prevention research. Objectives of this programme were the prevention of widespread health risks and diseases and to reinforce health promotion. Within this programme, 4 phases concentrated on socially disadvantaged target groups and on methodical and structural challenges relating to prevention/ health promotion. The projects covered evaluating the effectiveness of existing or newly-designed measures, developing and testing new concepts, programmes and access routes. Furthermore, the projects should contribute to the development of methods. The umbrella project "Kooperation für nachhaltige Präventionsforschung" (KNP-Cooperation for sustainable prevention research) was set up in 2009 to support the meaningful processing and application of key knowledge from this BMBF funding focus on prevention research and to promote networking between science, practice, and politics.

[From Adolescents to Old Age--To Design Preventive Activities Effectively]. / Von jungen Erwachsenen bis zum höheren Alter--Präventive Maßnahmen wirksam gestalten.

Same of the projects funded under the German Ministry of Education and Research's national prevention research initiative focusing explicit on adults. Those encompass because of increasing diversity different target groups. In this article the target groups are divided in adolescents, parents, persons in the working environment and elderly people in residential care homes. Accordingly, the foci of these projects are with regard to contents multifaceted, as well.

[Importance and Implementation of Prevention in Germany--A Nationwide Survey of Decision-makers in the GKV-Spitzenverband and Political Decision-makers]. / Stellenwert und Umsetzung der Prävention in Deutschland--Eine bundesweite Befragung von Entscheidungsträgern in GKV-Spitzenverband, Bund, Ländern und Kommunen.

Representatives of the statutory health insurance (n=46) and policy makers at the local, federal and state level (n=136) were interviewed in 2 nationwide online surveys about the significance and degree of implementation of prevention. The group comparison between the decision-makers shows significant differences in terms of attitudes towards health prevention. The political leaders are demanding an improvement of the GKV-benefit package and the obstacles require the cooperation of urgent attention.

[Memorandum on sustainable reinforcement of prevention and health promotion: challenges at the federal, state and local level]. / Memorandum--Prävention und Gesundheitsförderung nachhaltig stärken: Herausforderungen auf Bundes-, Landes- und kommunaler Ebene.

Research-based evidence and practice-based experience are core requirements for the effective implementation of preventive interventions. The knowledge gained in the Prevention Research Funding Initiative of the German Federal Ministry of Education and Research (2004-2013) was therefore amalgamated, reflected and consolidated in the Cooperation for Sustainable Prevention Research (KNP) meta-project. In annual strategy meetings, researchers and practitioners from the field and other experts developed 3 memoranda providing recommendations for the further development of research and practice in the field of prevention and health promotion. Memorandum III is primarily aimed at decision-makers in politics and administration at the federal, state and local level, in civil society and in the workplace. Its recommendations show that structuring efforts are urgently needed to achieve sustainable policy, particularly in the fields of health, education, employment and social affairs. Memorandum III brings together the knowledge extracted and problems identified in research projects. More so than its 2 predecessors, Memorandum III abstracts knowledge from the individual projects and attempts to derive guidance for action and decision-making, as shown by the 7 recommendations that appear to useful for consensus-building in practice and research. Value judgments are inevitable. Prevention and health promotion are an investment in the future: of social health, social capital and social peace. Improvement of the framework conditions is needed to achieve the harmonized awareness and the sustained effectiveness of these structure-building efforts in different policy areas, spheres of life, fields of action, and groups of actors. This includes the implementation of an overall national strategy as well as the expansion of sources of funding, extension of the legal framework, overarching coordination, and the establishment of a National Center of Excellence to develop and safeguard prevention and health promotion. The memorandum is intended to stimulate a discourse resulting in structure-building and stabilizing measures designed to ensure the sustainability of prevention and health promotion.

[Memorandum prevention research - research areas and methods]. / Memorandum zur Präventionsforschung - Themenfelder und Methoden (Langfassung).

From 2004 to 2012, the German Ministry of Education and Research (BMBF) established its first funding programme for the promotion of prevention research. 60 projects on primary prevention and health promotion and the meta-project entitled "Cooperation for Sustainable Prevention Research" (KNP) received BMBF grants under this programme during this period. The experience and knowledge gained and recommendations arising from the research funded under this programme are compiled in memorandum format. The "Memorandum on Prevention Research - Research Areas and Methods" highlights 5 research areas that are considered to be especially relevant from the perspective of the involved scientists and practice partners.The promotion of structural development and sustainability enhancement in disease prevention and health promotion are central areas that should branch out from existing nuclei of crystallization. Improving the health competence of the population and of specific subpopulations is another major area. Research in these areas should contribute to the development of theoretical concepts and to the empirical testing of these concepts. The transfer of knowledge for effective use of developed disease prevention and health promotion programmes and measures is still a scarcely researched area. Among other things, studies of the transfer of programmes from one context to another, analyses of the coop-eration between politics and science, and the continued theoretical and conceptual development of transfer research are needed. Long-term data on the effects of intervention studies are also needed for proper evaluation of sustainability. The latter dem-onstrates the importance of method development in disease prevention and health promotion research as an area that should receive separate funding and support. This research should include, in particular, studies of the efficacy of complex interventions, health economic analyses, and participative health research.

[Memorandum - research funding of prevention]. / Memorandum - Forschungsförderung Prävention.

The memorandum of the research funding of prevention has been devised within the framework of the Prevention Research Funding Programme of the Federal Ministry of Education and Research. It consists not only of the obtained findings of the research-practice co-operation but also of recommendations for the implementation of prospective, innovational, effective, practice-oriented and sustainable research. The respective knowledge has been acquired from quantitative surveys on the experiences of scientists and practice partners within the prevention research funding project as well as from extensive qualitative methods of structured group evaluation. A participatory co-operation between research and practice based on mutual respect, trust and recognition is seen as mandatory for the further development of both prevention and health promotion research. Research and practice partners are required to engage in an ab initio collaboration starting from the conception phase, whereby it is advisable to encourage and fortify the communication between research, practice and funding partners by systematic surveillance in form of a meta-project. In addition, the inclusion of the target population from the outset and on a collaborative basis is considered as beneficial in order to ensure the practical application of the research findings. Furthermore, innovatory research designs which are able to provide a framework for internal flexibility, continuous re-assessment and adjustment are fundamental for the implementation of practice-oriented research. Moreover, a dynamic co-operation between different groups of interest not only depends on sharing responsibility but also on sufficient funding for both research and practice, which is particularly important for the transfer and communication of the attained findings. With regard to the evaluation of both effectiveness and sustainability of interventions, a research funding project is required which makes long-term results possible through the utilization of regulated monitoring and guarantees quality and continuous effectiveness. Furthermore, in order to stimulate progress within the basic theories of prevention and health promotion, it is also essential for a funding project to focus on elementary concepts. Additionally, for the efficient and sustainable development of health within a population it is advisable to apply both self-contained research and the involvement of primary prevention and health promotion to research projects concerning health, social affairs, education, work and environment.

[Preventing burnout? A systematic review of effectiveness of individual and combined approaches]. / Burn-out wirksam prävenieren? Ein systematischer Review zur Effektivität individuumbezogener und kombinierter Ansätze.

Burnout has become an increasing topic of discussion in recent years. Against this background, it is important to evaluate the effectiveness of intervention programs aimed at preventing burnout. Using the databases Medline, PsycINFO, and PSYNDEX, we conducted a systematic search of burnout intervention studies from 1995-2011, completing this by a hand search. A total of 33 primary intervention studies (34 publications) were identified and reviewed. Twenty-four (71%) were person-centered interventions, while 10 (29%) were combined individual and organizational interventions. Of the interventions, 76% had a positive effect on burnout or its subcomponents; 16% of the studies were followed for periods ranging from more than 12 months to 3 years. In three of these studies, the intervention had a positive effect on burnout outcome measures. Burnout intervention programs tend to be effective, and their effects can be enhanced in refresher courses. Future research should focus on combined (person-centered and organization-based) intervention programs, include different risk groups, and provide long-term follow-up.

[Knowledge transfer methods in German disease prevention and health promotion. A survey of experts in the federal prevention research program]. / Transfermethoden der deutschen Prävention und Gesundheitsförderung. Eine Expertenbefragung im Förderschwerpunkt Präventionsforschung (BMBF).

AIM OF THE STUDY: This expert survey analyzed the application and perceived usefulness of knowledge transfer methods for disease prevention and health promotion research. METHODS: 302 experts from 70 administratively distinct projects sponsored under the German federal prevention research program received a questionnaire on transfer methods used for preparation, dissemination and implementation of their project results and the perceived expediency of these methods. 130 experts (43%) from 59 projects (84.3%) responded. 40% were cooperation partners from health care suppliers or practitioners, and 60% worked in research institutions. Descriptive statistics and ANOVA were used for data analysis. RESULTS: The experts had wide range of transfer methods at their disposal. The main implementation barriers were scarce funding and the complexity of disease prevention and health promotion programs. The predominant channels of dissemination were scientific media (congresses, journals) and the Internet. Manuals and handouts were the most common methods of processing of research results for facilitators. Regarding implementation, two-thirds of the projects conducted user training, integrated experts in program development, and co-operated with important institutions. Most of the transfer methods implemented were perceived as useful, but some rated as useful were rarely used, e. g. health economics and quality assurance in wide-scale rollout. There were no substantial rating differences between experts from research and user institutions. CONCLUSIONS: In view of the fundaments for the broad application of knowledge transfer technologies laid by prevention scientists, health care suppliers and decision-makers should support the transfer of prevention research, and precendence should be given to evidence-based programs with quality assurance in the implementation stages. Prevention researchers, in turn, should further develop health economics evidence and quality assurance for effective interventions. The rich skills available for knowledge transfer in disease prevention and health promotion can be systematically developed and disseminated in the future.

[Empowerment for the elderly]. / Empowerment bei Alteren.

Active management and controlling of one's social setting is an essential basis for physical and psychological well-being. A concept which aims at building abilities for an individual responsible and autonomous life is empowerment. Due to the demographic development, this concept will become more important for the elderly. In our productive and work-life related society, this age group is often considered as a burden. Their age group-specific potential is not sufficiently recognised and utilised, e.g., regarding its possible supportive role in interactions between a community's generations. This article illustrates different levels and strategies of empowerment for the elderly and analyses some concepts. One of these concepts is health literacy, which is defined as gaining competence, e.g., for the understanding of information or for acting on health-related issues. Studies of association between health literacy and health outcomes in the elderly are represented. Additionally, the promotion of empowerment is part of the prevention and health care, e.g., in terms of "active management" and "passive management". A further focus is improving the empowerment in elderly employees.

Purification and cloning of chloroplast 6-phosphogluconate dehydrogenase from spinach. Cyanobacterial genes for chloroplast and cytosolic isoenzymes encoded in eukaryotic chromosomes.

Previous attempts to purify chloroplast 6-phosphogluconate dehydrogenase (cp6PGDH), a key enzyme of the oxidative pentose phosphate pathway, have been unsuccessful due to rapid activity loss. An efficient purification protocol was developed and the enzyme from spinach leaves was purified 1000-fold to apparent homogeneity with a specific activity of 60 U.mg-1. The enzyme is a homodimer with subunits of 50 kDa. Antibodies raised against the purified cp6PGDH detected a 53-kDa protein from a crude extract, indicating alterations during purification. Purified cp6PGDH was microsequenced and the corresponding spinach cDNA was cloned using PCR techniques and degenerate primers. The cDNA for cytosolic 6PGDH from spinach was cloned for comparison. Phylogenetic analysis in the context of available homologues from eukaryotes and eubacteria revealed that animal and fungal cytosolic 6PGDH sequences are more similar to their homologues from gamma-proteobacteria, whereas plant 6PGDH is more similar to its cyanobacterial homologues. The ancestral gene for higher plant 6PGDH was acquired from the antecedent of plastids through endosymbiosis and gene transfer to the nucleus. A subsequent gene duplication gave rise to higher plant cytosolic 6PGDH, which assumed the function of its pre-existing cytosolic homologue through endosymbiotic gene replacement. The protein phylogeny of both 6PGDH and of the first enzyme of the oxidative pentose phosphate pathway, glucose-6-phosphate dehydrogenase, indicate a surprisingly close relationship between the plant and Trypanosoma brucei lineages, suggesting that T. brucei (a relative of Euglena gracilis) may be secondarily nonphotosynthetic.

Multiple recruitment of class-I aldolase to chloroplasts and eubacterial origin of eukaryotic class-II aldolases revealed by cDNAs from Euglena gracilis.

The photosynthetic protist Euglena gracilis is one of few organisms known to possess both class-I and class-II fructose-1,6-bisphosphate aldolases (FBA). We have isolated cDNA clones encoding the precursor of chloroplast class-I FBA and cytosolic class-II FBA from Euglena. Chloroplast class-I FBA is encoded as a single subunit rather than as a polyprotein, its deduced transit peptide of 139 amino acids possesses structural motifs neccessary for precursor import across Euglena's three outer chloroplast membranes. Evolutionary analyses reveal that the class-I FBA of Euglena was recruited to the chloroplast independently from the chloroplast class-I FBA of chlorophytes and may derive from the cytosolic homologue of the secondary chlorophytic endosymbiont. Two distinct subfamilies of class-II FBA genes are shown to exist in eubacteria, which can be traced to an ancient gene duplication which occurred in the common ancestor of contemporary gram-positive and proteobacterial lineages. Subsequent duplications involving eubacterial class-II FBA genes resulted in functional specialization of the encoded products for substrates other than fructose-1,6-bisphosphate. Class-II FBA genes of Euglena and ascomycetes are shown to be of eubacterial origin, having been acquired via endosymbiotic gene transfer, probably from the antecedants of mitochondria. The data provide evidence for the chimaeric nature of eukaryotic genomes.