Molecular basis of selective amyloid-ß degrading enzymes in Alzheimer's disease.

The accumulation of the small 42-residue long peptide amyloid-ß (Aß) has been proposed as a major trigger for the development of Alzheimer's disease (AD). Within the brain, the concentration of Aß peptide is tightly controlled through production and clearance mechanisms. Substantial experimental evidence now shows that reduced levels of Aß clearance are present in individuals living with AD. This accumulation of Aß can lead to the formation of large aggregated amyloid plaques-one of two detectable hallmarks of the disease. Aß-degrading enzymes (ADEs) are major players in the clearance of Aß. Stimulating ADE activity or expression, in order to compensate for the decreased clearance in the AD phenotype, provides a promising therapeutic target. It has been reported in mice that upregulation of ADEs can reduce the levels of Aß peptide and amyloid plaques-in some cases, this led to improved cognitive function. Among several known ADEs, neprilysin (NEP), endothelin-converting enzyme-1 (ECE-1), insulin degrading enzyme (IDE) and angiotensin-1 converting enzyme (ACE) from the zinc metalloprotease family have been identified as important. These ADEs have the capacity to digest soluble Aß which, in turn, cannot form the toxic oligomeric species. While they are known for their amyloid degradation, they exhibit complexity through promiscuous nature and a broad range of substrates that they can degrade. This review highlights current structural and functional understanding of these key ADEs, giving some insight into the molecular interactions that leads to the hydrolysis of peptide substrates, the crucial tasks performed by them and the potential for therapeutic use in the future.

Sustainable Urban Mobility Plans: implementation process and indicators to evaluate effects on physical activity.

BACKGROUND: Active mobility and public transport increase physical activity (PA) levels. With varying intensity and effectiveness, European cities implement Sustainable Urban Mobility Plans (SUMPs) to spur transport-related PA. Therefore, we aim to examine drivers and barriers to SUMP implementation and assess its influence on PA across European cities. METHODS: We screened policy reports to gain insights into SUMP implementation in one Danish, two German and two Polish cities. Further, we conducted semi-structured interviews with SUMP stakeholders in these cities to explore their experiences with SUMP implementation. Thematic analysis of interview transcripts was applied to identify similarities and differences across cities. To assess the effect of SUMP implementation on PA, we searched for data on indicators of transport-related PA. RESULTS: All investigated cities are committed to sustainable mobility. Nonetheless, complex institutional structures, the dominant role of motorized traffic as well as complex regional and local policy integration hamper SUMP implementation. Danish, German and Polish cities face different contexts in terms of financing, national guidelines and the prominence of sustainability as a policy objective. Each city adopts unique indicators for monitoring the effects of SUMPs on transport-related PA. The variety of indicators and limited data availability impede a comparative evaluation across cities. Constrained by this restriction, we identified motorization rate, modal split and public transport ridership as suitable indicators. CONCLUSIONS: Local idiosyncrasies need to be accounted for when assessing the implementation of SUMPs. Nonetheless, consistent indicators and data transparency are essential for comparing the effectiveness of SUMPs and their impact on PA.

Dietary behaviour and physical activity policies in Europe: learnings from the Policy Evaluation Network (PEN).

The European Policy Evaluation Network (PEN), initiated in autumn 2018, aimed at advancing the evidence base for public policies impacting dietary behaviour, physical activity and sedentary behaviours in Europe. This is needed because non-communicable diseases-the leading cause of global mortality-are substantially caused by physical inactivity and unhealthy dietary behaviours, which in turn are driven by upstream factors that have not yet been addressed effectively by prevention approaches. Thus, successful policy interventions are required that target entire populations and tackle the 'causes of the causes'. To advance our knowledge on the effective implementation of policies and their impact in terms of improving health behaviours, PEN focused on five research tasks: (i) Adaptation and implementation of a Food Environment Policy Index (Food-EPI) and development of a Physical Activity Environment Policy Index (PA-EPI); (ii) Mapping of health-related indicators needed for policy evaluation and facilitating a harmonized pan-European approach for surveillance to assess the impact of policy interventions; (iii) Refining quantitative methods to evaluate the impact of public policies; (iv) Identifying key barriers and facilitators of implementation of policies; and (v) Advance understanding the equity impact of the development, implementation and evaluation of policies aimed at promoting physical activity and a healthy diet. Finally, and in order to provide concrete evidence for policymaking, existing exemplary policies, namely sugar-sweetened beverages taxation, active transport policies and school policies on nutrition and physical activity were assessed in consideration of these five tasks. At the end of the PEN project's formal runtime, considerable advancements have been made. Here, we present an overview of the most important learnings and outputs.

The impact of mass-media campaigns on physical activity: a review of reviews through a policy lens.

BACKGROUND: This review of reviews aimed to: (1) summarize the evidence from published reviews on the effectiveness of mass-media campaigns to promote physical activity (PA) or PA-related determinants (intermediate psychological and proximal outcomes) and (2) to identify policy-relevant recommendations related to successful PA campaigns. METHODS: An extensive literature search was performed on 1 March 2021. Reviews that evaluated the impact of campaigns on distal (e.g. PA) and/or proximal outcomes of PA (awareness, knowledge, etc.) and that targeted the general population or subsets were included. Quality of reviews was assessed using the AMSTAR-2 tool. Policy-relevant recommendations were systematically derived and synthesized and formulated as good practice statements. A protocol was registered beforehand (ID: CRD42021249184). RESULTS: A total of 1915 studies were identified, of which 22 reviews were included. The most consistent evidence was found for the effectiveness of mass-media campaigns on proximal outcomes, while the evidence for distal outcomes was mixed. Good practice statements were derived: (1) to achieve behaviour change, mass-media is an important component of larger, multilevel and multicomponent strategies; (2) mass-media strategies should be coordinated and aligned at local- and national-level and be sustained, monitored and resourced at these levels and (3) media should be tailored to reduce socioeconomic inequalities. CONCLUSIONS: Mass-media can play an important role in the promotion of PA. In general, evidence was more inconsistent for effectiveness on distal outcomes than for proximal outcomes. Policy-relevant recommendations include that mass-media strategies should be resourced, coordinated, aligned, sustained, monitored and evaluated on the local and national level.

The Physical Activity Environment Policy Index for monitoring government policies and actions to improve physical activity.

BACKGROUND: A multifaceted response, including government action, is essential to improve population levels of physical activity (PA). This article describes the development process of the 'Physical Activity Environment Policy Index' (PA-EPI) monitoring framework, a tool to assess government policies and actions for creating a healthy PA environment. METHODS: An iterative process was undertaken. This involved a review of policy documents from authoritative organizations, a PA policy audit of four European countries, and a systematic review of scientific literature. This was followed by an online consultation with academic experts (N = 101; 20 countries, 72% response rate), and policymakers (N = 40, 4 EU countries). During this process, consensus workshops were conducted, where quantitative and qualitative data, alongside theoretical and pragmatic considerations, were used to inform PA-EPI development. RESULTS: The PA-EPI is conceptualized as a two-component 'policy' and 'infrastructure support' framework. The two-components comprise eight policy and seven infrastructure support domains. The policy domains are education, transport, urban design, healthcare, public education (including mass media), sport-for-all, workplaces and community. The infrastructure support domains are leadership, governance, monitoring and intelligence, funding and resources, platforms for interaction, workforce development and health-in-all-policies. Forty-five 'good practice statements' or indicators of ideal good practice within each domain conclude the PA-EPI. A potential eight-step process for conducting the PA-EPI is described. CONCLUSIONS: Once pre-tested and piloted in several countries of various sizes and income levels, the PA-EPI good practice statements will evolve into benchmarks established by governments at the forefront of creating and implementing policies to address inactivity.

Health Enhancing Physical Activity Policies in Poland: Findings from the HEPA PAT Survey.

Insufficient physical activity (PA) is one of major risk factors for serious diseases and premature mortality worldwide. Public policies to enhance PA across society are recognized as an effective tool against the problem. This paper presents the results of a comprehensive assessment of national-level PA policy approach in Poland. A standardized survey of Word Health Organization named the Health-Enhancing Physical Activity Policy Audit Tool (HEPA PAT) was used for data collection. Content analysis and strengths, weaknesses, opportunities, and threats analysis (SWOT) were used to characterize various PA policy aspects, to appraise the current situation, and accommodate organizational and environmental factors that it is influenced by. The results show that the national PA policy approach has been constantly developing in Poland, but there is room for improvement in a number of areas. The most important weaknesses are the lack of clear leadership, no mechanisms in place to coordinate efforts undertaken at different levels, and lack of collaboration across different levels of government and across different sectors of economy. Providing an umbrella covering all PA promotion policies and activities is, therefore, a key issue to be addressed. The country should seize the opportunity coming from an increasing awareness of a healthy lifestyle among Polish society.

The added value of using the HEPA PAT for physical activity policy monitoring: a four-country comparison.

BACKGROUND: Public policy is increasingly recognized as an important component of physical activity promotion. This paper reports on the current status of physical activity policy development and implementation in four European countries based on the Health-Enhancing Physical Activity Policy Audit Tool (HEPA PAT) developed by WHO. It compares the findings to previous studies and discusses the general utility of this tool and its unique features in relation to other instruments. METHODS: The study was conducted as part of the Policy Evaluation Network ( www.jpi-pen.eu ) in Germany, Ireland, the Netherlands and Poland. Data collection built upon information obtained via the EU Physical Activity Monitoring Framework survey, additional desk research and expert opinion. Data analysis employed Howlett's policy cycle framework to map and compare national physical activity policies in the four countries. RESULTS: In all countries under study, policy agenda-setting is influenced by prevalence data from national health monitoring systems, and the sport and/or health sector takes the lead in policy formulation. Key policy documents were located mainly in the health sector but also in sport, urban design and transport. Physical activity programmes implemented to meet policy objectives usually cover a broad range of target groups, but currently only a small selection of major policies are evaluated for effectiveness. National experts made several suggestions to other countries wishing to establish physical activity policies, e.g. regarding cross-sectoral support and coordination, comprehensive national action plans, and monitoring/surveillance. CONCLUSIONS: This study provides a detailed overview of physical activity policies in the four countries. Results show that national governments are already very active in the field but that there is room for improvement in a number of areas, e.g. regarding the contribution of sectors beyond sport and health. Using the HEPA PAT simultaneously in four countries also showed that procedures and timelines have to be adapted to national contexts. Overall, the instrument can make an important contribution to understanding and informing physical activity policy, especially when used as an add-on to regular monitoring tools like the EU HEPA Monitoring Framework.

The evidence for the impact of policy on physical activity outcomes within the school setting: A systematic review.

BACKGROUND: Despite the well-established health benefits of physical activity (PA) for young people (aged 4-19 years), most do not meet PA guidelines. Policies that support PA in schools may be promising, but their impact on PA behavior is poorly understood. The aim of this systematic review was to ascertain the level and type of evidence reported in the international scientific literature for policies within the school setting that contribute directly or indirectly to increasing PA. METHODS: This systematic review is compliant with Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. Six databases were searched using key concepts of policy, school, evaluation, and PA. Following title and abstract screening of 2323 studies, 25 progressed to data synthesis. Methodological quality was assessed using standardized tools, and the strength of the evidence of policy impact was described based on pre-determined codes: positive, negative, inconclusive, or untested statistically. RESULTS: Evidence emerged for 9 policy areas that had a direct or indirect effect on PA within the school setting. These were whole school PA policy, physical education, sport/extracurricular PA, classroom-based PA, active breaks/recess, physical environment, shared use agreements, active school transport, and surveillance. The bulk of the evidence was significantly positive (54%), 27% was inconclusive, 9% was significantly negative, and 11% was untested (due to rounding, some numbers add to 99% or 101%). Frequency of evidence was highest in the primary setting (41%), 34% in the secondary setting, and 24% in primary/secondary combined school settings. By policy area, frequency of evidence was highest for sport/extracurricular PA (35%), 17% for physical education, and 12% for whole school PA policy, with evidence for shared use agreements between schools and local communities rarely reported (2%). Comparing relative strength of evidence, the evidence for shared use agreements, though sparse, was 100% positive, while 60% of the evidence for whole school PA policy, 59% of the evidence for sport/extracurricular PA, 57% of the evidence for physical education, 50% of the evidence for PA in classroom, and 50% of the evidence for active breaks/recess were positive. CONCLUSION: The current evidence base supports the effectiveness of PA policy actions within the school setting but cautions against a "one-size-fits-all" approach and emphasizes the need to examine policy implementation to maximize translation into practice. Greater clarity regarding terminology, measurement, and methods for evaluation of policy interventions is needed.

Policy Evaluation Network (PEN): Protocol for systematic literature reviews examining the evidence for impact of policies on physical activity across seven different policy domains.

Introduction: Over 40 million deaths annually are due to noncommunicable diseases, 15 million of these are premature deaths and physical inactivity contributes an estimated 9% to this figure. Global responses have included the Sustainable Development Goals (SDGs) and the Global Action Plan on Physical Activity (GAPPA). Both point to policy action on physical activity (PA) to address change, yet the impact of policy on PA outcomes is unknown.  The protocol described outlines the methodology for systematic literature reviews that will be undertaken by the Policy Evaluation Network (PEN) to address this knowledge gap. Methods: The seven best investments for promotion of population PA identified in the Toronto Charter highlighted seven policy domains (schools, transport, urban design, primary health care systems, public education, community-wide programmes and sport) which will form the basis of these PEN reviews. Seven individual scientific literature searches across six electronic databases will be conducted. Each will use the key concepts of policy, PA, evaluation and a distinct concept for each of the seven policy domains. This will be supplemented with a search of the reference list of included articles. Methodological quality will be assessed and overall effectiveness for each included study will be described according to pre-determined criteria. Conclusions: Each review will provide policy makers with a list of policy statements and corresponding actions which the evidence has determined impact on PA directly or indirectly. By collating the evidence, and demonstrating the depth of the science base which informs these policy recommendations, each review will provide guidance to policymakers to use evidence-based or evidence-informed policies to achieve the 15% relative reduction in physical inactivity as defined by GAPPA. Registration:  PROSPERO CRD42020156630 (10/07/2020).

Polish Experience of Implementing Vision Zero.

PURPOSE OF REVIEW: The aim of this study is to present an outline and the principles of Poland's road safety strategic programming as it has developed over the last 25 years since the first Integrated Road Safety System with a strong focus on Sweden's "Vision Zero". RECENT FINDINGS: Countries that have successfully improved road safety have done so by following strategies centred around the idea that people are not infallible and will make mistakes. The human body can only take a limited amount of energy upon impact, so roads, vehicles and road safety programmes must be designed to address this. SUMMARY: The article gives a summary of Poland's experience of programming preventative measures that have "Vision Zero" as their basis. It evaluates the effectiveness of relevant programmes.

Self-organizing maps classification of epidemiological data and toenail selenium content monitored on cancer and healthy patients from Poland.

This paper deals with epidemiological multivariate statistical analysis of cancer and health patients from Pomeranian and Lubuskie Voivodships, Poland. The anthropometric and epidemiologic data include 8 parameters: toenail selenium concentration, sex, age, body mass index (BMI), smoking status, taking of Se supplements, health state, and family history of cancer. The self-organizing maps (SOM) are used for simultaneous classification of parameters and patients with relation to cancer diagnosis. Three different patterns (groups) of patients with cancer diagnosis are outlined: (i) older, smoking men with low toenail selenium concentration; (ii) older smoking women with family relation to cancer and toenail selenium deficiency; (iii) middle, aged nonsmokers with high level of selenium toenail concentration. The simultaneous classification of parameters and patients makes it possible to determine discriminating parameters for each pattern and relations between parameters. The relation of each parameter to cancer disease is discussed as special attention is paid to toenail selenium deficiency. More than 80% of patients with cancer diagnosis possess toenail selenium deficiency, accompanied by old age and smoking.