Multi-omics delineation of cytokine-induced endothelial inflammatory states.

Vascular endothelial cells (ECs) form a dynamic interface between blood and tissue and play a crucial role in the progression of vascular inflammation. Here, we aim to dissect the system-wide molecular mechanisms of inflammatory endothelial-cytokine responses. Applying an unbiased cytokine library, we determined that TNFα and IFNγ induced the largest EC response resulting in distinct proteomic inflammatory signatures. Notably, combined TNFα + IFNγ stimulation induced an additional synergetic inflammatory signature. We employed a multi-omics approach to dissect these inflammatory states, combining (phospho-) proteome, transcriptome and secretome and found, depending on the stimulus, a wide-array of altered immune-modulating processes, including complement proteins, MHC complexes and distinct secretory cytokines. Synergy resulted in cooperative activation of transcript induction. This resource describes the intricate molecular mechanisms that are at the basis of endothelial inflammation and supports the adaptive immunomodulatory role of the endothelium in host defense and vascular inflammation.

The Effects of Sampling and Storage Conditions on the Metabolite Profile of the Marine Sponge Geodia barretti.

Geodia barretti is a deep-sea marine sponge common in the north Atlantic and waters outside of Norway and Sweden. The sampling and subsequent treatment as well as storage of sponges for metabolomics analyses can be performed in different ways, the most commonly used being freezing (directly upon collection or later) or by storage in solvent, commonly ethanol, followed by freeze-drying. In this study we therefore investigated different sampling protocols and their effects on the detected metabolite profiles in liquid chromatography-mass spectrometry (LC-MS) using an untargeted metabolomics approach. Sponges (G. barretti) were collected outside the Swedish west coast and pieces from three sponge specimens were either flash frozen in liquid nitrogen, frozen later after the collection cruise, stored in ethanol or stored in methanol. The storage solvents as well as the actual sponge pieces were analyzed, all samples were analyzed with hydrophilic interaction liquid chromatography as well as reversed phase liquid chromatography with high resolution mass spectrometry using full-scan in positive and negative ionization mode. The data were evaluated using multivariate data analysis. The highest metabolite intensities were found in the frozen samples (flash frozen and frozen after sampling cruise) as well as in the storage solvents (methanol and ethanol). Metabolites extracted from the sponge pieces that had been stored in solvent were found in very low intensity, since the majority of metabolites were extracted to the solvents to a high degree. The exception being larger peptides and some lipids. The lowest variation between replicates were found in the flash frozen samples. In conclusion, the preferred method for sampling of sponges for metabolomics was found to be immediate freezing in liquid nitrogen. However, freezing the sponge samples after some time proved to be a reliable method as well, albeit with higher variation between the replicates. The study highlights the importance of saving ethanol extracts after preservation of specimens for biology studies; these valuable extracts could be further used in studies of natural products, chemosystematics or metabolomics.

How to recruit inactive residents for lifestyle interventions: participants' characteristics based on various recruitment strategies.

Care Sport Connectors (CSCs) have been appointed to create a connection between primary care and physical activity (PA) sectors to stimulate inactive residents into becoming physically active. Adequate recruitment strategies are necessary to reach the intended target group in order to foster the sustainability of lifestyle interventions. The objective of this study is to explore PA behavior and health characteristics of the target group reached by CSCs and if these characteristics differ between participants when grouped based on how they were recruited. Participants from lifestyle interventions were included between September 2014 and April 2016 using a purposive sampling method. Participants were recruited through CSCs via public relations (n = 135), a personal letter (n = 136), or a referral (n = 98) and compared based on their PA level, health-related quality of life, motivation, self-efficacy, morbidity and health-related fitness. Scores were analyzed with a multi-level (mixed model) analysis measured before the intervention. The three groups were different in PA level (p = 0.002). The outcomes regarding health-related quality of life, motivation, and number of somatic disorders were also significantly different for the three groups, except for the categories of mental health (p = 0.145) and self-efficacy (p = 0.464). For all dimensions, the referral group scored the least favorable. The investment in time and money for an active recruitment strategy like referrals is worthwhile because it provides CSCs the opportunity to reach people who are inactive and at risk of chronic disease. Future studies are necessary to reveal the effect on PA levels and health in the long-term.

Personalized Care Management for Persons with Parkinson's Disease.

There is a growing awareness that delivery of integrated and personalized care is necessary to meet the needs of persons living with Parkinson's disease. In other chronic diseases than Parkinson's disease, care management models have been deployed to deliver integrated and personalized care, yielding positive effects on patients' health outcomes, quality of life and health care utilization. However, care management models have been highly heterogeneous, as there is currently no clear operationalization of its core elements. In addition, most care management models are disease-specific and not tailored to the individual needs and preferences of a patient. In this viewpoint we present an integrated and personalized care management model for persons with Parkinson's disease costing of five core elements: (1) care coordination, (2) patient navigation, (3) information provision, (4) early detection of signs and symptoms through proactive monitoring and (5) process monitoring. Following the description of each core element, implications for implementing the model into practice are discussed. Finally, we provide clinical and methodological considerations on the evaluation of care management models.

Perceptions of Care Sport Connectors' Tasks for Strengthening the Connection Between Primary Care, Sports and Physical Activity: A Delphi Study.

INTRODUCTION: Care sport connectors stimulate physical activity and facilitate collaboration between the primary care and physical activity sectors in the Netherlands. To strengthen intersectoral collaboration between the primary care and sports sectors, it is necessary to study which tasks a care sport connector must fulfil according to their own and other professionals' perceptions. METHODS: A Delphi study was conducted with 182 professionals from the primary care, public health and physical activity sectors. Rounds 1 and 2 included questions about task perception, willingness to collaborate and expectations of care sport connectors. Rounds 3 and 4 were used to reach consensus. RESULTS: All professions acknowledged physical activity promotion tasks, but they are not all willing to collaborate. They expect a broad range of roles from care sport connectors: informative, executive, guiding and intermediate. Care sport connectors reached consensus on two roles: informative and intermediate. DISCUSSION: Care sport connectors have an important role in strengthening intersectoral collaboration. All the professions acknowledged a task concerning physical activity promotion and accepted a broker role. Thus, a public health mind-set seems to be present to some extent. However, challenges remain, such as the lack of willingness to collaborate among primary care professionals and sports policies not (yet) supporting intersectoral collaboration.

Exploring the impact of the care sport connector in the Netherlands.

BACKGROUND: Regular physical activity (PA) is deemed to contribute to the primary and secondary prevention of several chronic diseases, like diabetes mellitus, cancer, cardiovascular diseases, and osteoporosis. In 2012, Care Sport Connectors (CSC), to whom a broker has been ascribed, were introduced in the Netherlands to stimulate PA and guide primary care patients towards local sport facilities. The aim of this study was to explore which structural embedding is the most promising for CSCs' work. METHODS: In three rounds of interviews, 13 CSCs were followed for 2 years in their work. In these interviews, a network survey was used to identify organisations in the CSCs' network, whether they collaborated with these organisations, and the role of the organisations in the connection. Data from the network survey were analysed using the RE-AIM framework and disaggregated into how CSCs were structurally embedded (Type A: only PA sector; Type B: different sectors; Type C: partnership). A related samples Wilcoxon signed rank test was performed to study how the CSCs' network developed between 2014 and 2016. RESULTS: All CSCs established a connection between the primary care and the PA sector in which the average number of organisations with which CSCs collaborated increased significantly between 2014 (8.3) and 2016 (19.8) (p = 0.002). However, differences were identified in the way CSCs were structurally embedded and in the way they established the connection. Type A CSCs established the connection mostly around their own activities, supported PA organisations with their activities, and collaborated with primary care and welfare professionals around their own activities. Type B and Type C CSCs established the connection by organising, supporting, and implementing different kinds of activities targeting different kinds of audiences, and collaborated mostly with primary care professionals around the referral of professionals' patients. CONCLUSIONS: The results of this study suggest that adopting an integral approach (Type B and C) for the structural embedding of the CSC is more promising for reaching the desired outcomes. Whether CSCs really improve the target groups' PA level and health needs to be further studied. TRIAL REGISTRATION: Dutch Trial Register NTR4986 . Registered 14 December 2014.

The connection between the primary care and the physical activity sector: professionals' perceptions.

BACKGROUND: To stimulate physical activity (PA) and guide primary care patients towards local PA facilities, Care Sport Connectors (CSC), to whom a broker role has been ascribed, were introduced in 2012 in the Netherlands. The aim of this study is to assess perceptions of primary care, welfare, and sport professionals towards the CSC role and the connection between the primary care and the PA sector. METHODS: Nine focus groups were held with primary care, welfare and sport professionals within the CSC network. In these focus groups the CSC role and the connection between the sectors were discussed. Both top-down and bottom-up codes were used to analyse the focus groups. RESULTS: Professionals ascribed three roles to the CSC: 1) broker role, 2) referral, 3) facilitator. Professionals were enthusiastic about how the current connection was established. However, barriers relating to their own sector were currently hindering the connection: primary care professionals' lack of time, money and knowledge, and the lack of suitable PA activities and instructors for the target group. CONCLUSIONS: This study provides further insight into the CSC role and the connection between the sectors from the point of view of primary care, welfare, and sport professionals. Professionals found the CSC role promising, but barriers are currently hindering the collaboration between both sectors. More time for the CSC and changes in the way the primary care and PA sector are organized seem to be necessary to overcome the identified barriers and to make a success of the connection. TRIAL REGISTRATION: Dutch Trial register NTR4986 . Registered 14 December 2014.