Soluble Lactobacillus delbrueckii subsp. bulgaricus 92059 PrtB proteinase derivatives for production of bioactive peptide hydrolysates from casein.

The proteinase-encoding prtB gene of Lactobacillus (Lb.) delbrueckii (d.) subsp. bulgaricus 92059 was cloned and sequenced. Two soluble, secreted, C-terminally His-tagged derivatives were constructed and expressed in Lactococcus lactis by means of the NICE® Expression System. In both obtained derivatives PrtBb and PrtB2, the C-terminal, cell wall-binding domain was deleted. In addition, in derivative PrtB2, the C-terminal part of the B domain was deleted and the signal sequence was replaced by a lactococcal export signal. The affinity-purified derivatives were both proteolytically active. Peptide hydrolysates produced from casein with each of the derivatives showed identical peptide composition, as determined by liquid chromatography-mass spectrometry. Comparison of the peptides generated to those generated with living Lb. d. subsp. bulgaricus 92059 cells (Kliche et al. Appl Microbiol Biotechnol 101:7621-7633, 2017) showed that ß-casein was the casein fraction most susceptible to hydrolysis and that some significant differences were observed between the products obtained by either the derivatives or living Lb. d. subsp. bulgaricus 92059 cells. When tested for biological activity, the hydrolysate obtained with PrtBb showed 50% inhibition of angiotensin-converting enzyme at a concentration of 0.5 mg/ml and immunomodulation/anti-inflammation in an in vitro assay of TNF-α induced NFκB activation at concentrations of 5 and 2.5 mg/ml, respectively. The enzymatically obtained hydrolysate did not show any pro-inflammatory or cytotoxic activity.

Screening for proteolytically active lactic acid bacteria and bioactivity of peptide hydrolysates obtained with selected strains.

In a screening for proteolytically active lactic acid bacteria, three strains, Lactobacillus delbrueckii ssp. lactis 92202, Lactobacillus helveticus 92201, and Lactobacillus delbrueckii ssp. bulgaricus 92059, showed the highest activities following growth in milk. All three strains degraded α- and ß-casein, but did not hydrolyse κ-casein. HPLC analysis of skim milk fermentation revealed increasing amounts of peptides after 5 and 10 h with Lb. d. ssp. bulgaricus 92059. Hydrolysates obtained with Lb. d. ssp. lactis 92202 and Lb. d. ssp. bulgaricus 92059 revealed the highest angiotensin-converting enzyme-inhibitory effect. The effect was dose dependent. Almost no effect (<10%) was seen for Lb. helveticus 92201. For Lb. d. ssp. bulgaricus 92059, maximal inhibition of approx. 65% was reached after 25 h of fermentation. In an in vitro assay measuring potential immunomodulation, hydrolysates of the three strains yielded anti-inflammatory activities in the presence of TNF-α. However, the effects were more pronounced at lower hydrolysate concentrations. In the absence of TNF-α, slight pro-inflammatory effects were observed. The hydrolysate of Lb. d. ssp. bulgaricus 92059, when purified by means of solid-phase extraction, exhibited pro-inflammatory activity. Sour whey containing Lb. d. ssp. bulgaricus 92059 cells showed pro-inflammatory activity while cell-free sour whey was clearly anti-inflammatory. In the purified hydrolysate, 20 different α- and ß-casein (CN)-derived peptides could be identified by LC-MS. Most peptides originated from the central and C-terminal regions of ß-casein. Peptide length was between 9 (ß-CN(f 59-67)) and 22 amino acids (ß-CN(f 117-138)).

[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.

[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.

[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.

[Structures and quality assurance of preventive care and health promotion in Germany]. / Versorgungsstrukturen und Qualitätssicherung für Prävention und Gesundheitsförderung in Deutschland.

In order to identify requirements of quality assurance in this field, a general description of prevention, health promotion and education is outlined, based upon healthcare supply analyses and 158 interviews with experts. Prominent features are, among others, a distinctive heterogeneity and complexity of settings, suppliers, and interventions; supply of coverage is below public health criteria (needs); weak outcome evaluation; competition among suppliers, providers, and political agencies and decision makers; need for intra- and intersectoral coordination; the lack of evidence-based healthcare planning; and hurdles for quality assurance. A structural taxonomy of quality assurance systems is then developed, consisting of three dimensions: validity (quality of information), regularity, and degree of commitment and obligation. In terms of these dimensions, important systems of quality assurance in prevention, health promotion and education in Germany are analyzed. A number of different systems and approaches can be found. However, most of them share questionable validity, regularity, and degree of obligation. Increased commitment on behalf of providers, suppliers, and political institutions and decision makers for the quality of preventive interventions is inevitable in order to raise the performance of prevention and health promotion in Germany to their potential effectiveness.

[Health promotion effectiveness: developing and testing a system for routine evaluation in health education, workplace health promotion and setting approach supplied by the German statutory health insurance agencies]. / Gesundheitswirkungen der Prävention: Entwicklung und Erprobung eines Routine-Evaluationssystems für Primärprävention und Gesundheitsförderung der Krankenkassen in Settings, Betrieben und Gesundheitskursen.

The aim of the study was to develop and test a routine evaluation system for all health promotion and education activities funded by the German statutory health insurance companies. The system aims at measuring both individual health effects and the complex organisational effects of setting projects. Measurement instruments were developed synoptically and tested in three field tests (2003-2008). In order to assess the impact of individual health training, 212 courses of the health insurance companies were evaluated. To assess the setting approach, 56 schools participating in a health-promotion project were included, and for workplace health-promotion 6 projects of different health insurance companies were included. The research design was an observational study. Instead of control groups, individual data were compared to reference values for gender- and age-matched groups from national health surveys. The studies consisted of baseline and final assessment (T1/T2), complemented by a follow-up (T3), all adapted to the time of intervention (i. e., 3-24 months for T1/T2 and 3-18 months for T2/T3). The evaluation system provides multilevel-measurement based upon validated questionnaires for health-related structures and processes in institutions, and for the participating individual's subjective health, health problems, health-related quality of life, workplace and institutional satisfaction. Controlling for central confounders is also possible (input and dosage, age, gender, educational background). Thus, short but valid measurement instruments of high usability are available to evaluate the effectiveness of prevention, health promotion and education.

[Health promotion effectiveness: testing the German statutory health insurance agencies evaluation system in health promotion, and preliminary findings from 212 health training courses]. / Gesundheitswirkungen von Prävention: Erprobung des Evaluationssystems der Krankenkassen im Individualansatz und erste Befunde aus 212 Gesundheitskursen.

The purpose of this study was to develop a measurement system for the evaluation of health promotion training courses offered by German statutory health insurance companies. In a field test, N=1 671 participants from 212 youth and adult courses for the promotion of either physical activity, coping with stress or nutritional improvement were included. 80% were female. Participants were questioned in a pre-post-design with a three month follow-up. The questionnaires covered health behaviour and health status. Participants' compliance and psychometric quality of the measurement instruments were good. On average, the health insurance companies assigned participants to different interventions adequately according to the participant's individual health problems. The health promotion courses triggered improvements of high effect sizes for health behaviour patterns, of moderate effect sizes for physical complaints, subjective health ratings, and health-related quality of life. Effects decreased after the end of the intervention but remained significantly above the initial values. BMI values continued their improvement after the end of the training courses. Thus, health promotion training courses generated stable health improvements of practically relevant effect sizes. The interventions provided good support and health improvements for all subgroups of participants, regardless of age, gender and educational background. Thus, the health promotion curricula of the health insurance companies offer a ubiquitous and easily accessible but effective intervention for health promotion in Germany, although men are clearly underrepresented among the participants. The trainings may be recommended and used by other health-care suppliers. The evaluation toolkit provides practical and valid instruments for a routine evaluation of health promotion trainings. It should be applied within random sampling designs.

[Empowerment in prevention and health promotion--a critical conceptual evaluation of basic understanding, dimensions and assessment problems]. / Empowerment in Prävention und Gesundheitsförderung--Eine konzeptkritische Bestandsaufnahme von Grundverständnissen, Dimensionen und Erhebungsproblemen.

Empowerment is an important concept in health care, but despite its prevalence it seems to be more of a buzz word. Thus, a conceptual review on empowerment in prevention and health promotion was carried out. 62 German and international theoretical contributions, reviews and studies were incorporated, covering the fields of prevention, care and therapy, rehabilitation, health-care research, nursing and work-related stress. The analysis revealed eight main dimensions of empowerment: (1) shared decision-making, (2) self-efficacy, (3) social support and social capital, (4) skills and competences, (5) health care utilisation, (6) goal setting and attainment, (7) reflexive thought and (8) innovation. Their empirical assessment can be carried out on a micro-, meso-, or macro-level. Three distinct basic conceptual notions emerged from the analysis, each applying its own specific research questions and measurement instruments: clinical, organizational-professional and political understanding of "empowerment". Therefore, these three specific conceptual notions should each be developed and tested separately, in particular in reviews, and empirical studies should embrace all eight subdimensions.

[The development of evidence-based prevention. Health promotion and education as an approach to continuous quality improvement of health care]. / Evidenzbasierte Prävention und Gesundheitsförderung. Probleme und Lösungsansätze zur kontinuierlichen Qualitätsverbesserung der Versorgung.

Evidence-based health promotion and education relies on the systematic and critical discussion of the best available research on the effectiveness of interventions. In the last decade, evidence-based reviews provided decisive proof for the effectiveness of health promotion and education. The approach is also capable of identifying high-quality interventions and deficiencies. Nevertheless, there is an ongoing dispute concerning the transfer of evidence-based medicine to health promotion and education. Arguments concern databases, research strategies, validity and practical applicability of results. A discussion of these issues suggests that the methodology of evidence-based medicine is pertinent and informative. Some adaptations for health promotion and education would make sense, though: contexts and characteristics of interventions should be documented and published in rather more detail in order to reach better causal models. Pre-post studies which are of particular importance for health promotion and education should be elaborated according to the psychological multi-trait multi-method strategy (multiple measurements, modelling of process levels, multidimensional operationalization of complex outcomes). All relevant knowledge including qualitative studies should be integrated into cycles of theory formulation and evidence testing. Finally, a reappraisal of expert opinion is proposed relying on specific criteria for the transparency and plurality of consensus procedures ruling out conflicts of interest.

[Assessing the quality of structures, concepts, and processes in prevention, health promotion, and education. Requirements and solutions]. / Die Beurteilung der Struktur-, Konzept- und Prozessqualität von Prävention und Gesundheitsförderung. Anforderungen und Lösungen.

The effectiveness of health promotion is determined by the foundation of evidence, the targeting of health problems, and the adaptation of interventions to specific social and organizational contexts. Methods for the implementation of these objectives must be able to balance interacting intervention goals, to account for the suitability of interventions for specific target groups and settings, and to integrate complex and divergent data. The core methodology underlying these conditions is peer review assessment. A quality assurance system based on this approach is presented: Two inventories elicit detailed self-descriptions characterizing either actors or activities within health promotion and education. Two assessment instruments instruct experts in reviewing these data according to primary and partial dimensions of quality. Thus, systematically structured and quantifiable quality profiles of organizational units or specific activities are produced. On this basis, comparative indicators for benchmarking purposes can be calculated. Quality profiles containing the strengths and weaknesses of organizations or activities, including indicators, benchmarks, and reviewers' recommendations, are communicated to participating organizations in order to stimulate continuous quality improvement by feedback. Moreover, the system offers a database of comparative indicators for monitoring and optimizing health promotion and education.