Transposable elements promote the evolution of genome streamlining

Eukaryotes and prokaryotes have distinct genome architectures, withmarked differences in genome size, the ratio of coding/non-coding DNA,and the abundance of transposable elements (TEs). As TEs replicate inde-pendently of their hosts, the proliferation of TEs is thought to have drivengenome expansion in eukaryotes. However, prokaryotes also have TEs inintergenic spaces, so why do prokaryotes have small, streamlined genomes?Using anin silicomodel describing the genomes of single-celled asexualorganisms that coevolve with TEs, we show that TEs acquired from theenvironment by horizontal gene transfer can promote the evolution ofgenome streamlining. The process depends on local interactions and isunderpinned by rock–paper–scissors dynamics in which populations ofcells with streamlined genomes beat TEs, which beat non-streamlinedgenomes, which beat streamlined genomes, in continuous and repeatingcycles. Streamlining is maladaptive to individual cells, but improves lineageviability by hindering the proliferation of TEs. Streamlining does not evolvein sexually reproducing populations because recombination partially freesTEs from the deleterious effects they cause.This article is part of the theme issue‘The secret lives of microbial mobilegenetic elements’

Therapies with CCL25 require controlled release via microparticles to avoid strong inflammatory reactions

Background: Chemokine therapy with C-C motif chemokine ligand 25 (CCL25) is currently under investigation as a promising approach to treat articular cartilage degeneration. We developed a delayed release mechanism based on Poly (lactic-co-glycolic acid) (PLGA) microparticle encapsulation for intraarticular injections to ensure prolonged release of therapeutic dosages. However, CCL25 plays an important role in immune cell regulation and inflammatory processes like T-cell homing and chronic tissue inflammation. Therefore, the potential of CCL25 to activate immune cells must be assessed more thoroughly before further translation into clinical practice. The aim of this study was to evaluate the reaction of different immune cell subsets upon stimulation with different dosages of CCL25 in comparison to CCL25 released from PLGA particles. Results: Immune cell subsets were treated for up to 5 days with CCL25 and subsequently analyzed regarding their cytokine secretion, surface marker expression, polarization, and migratory behavior. The CCL25 receptor C-C chemokine receptor type 9 (CCR9) was expressed to a different extent on all immune cell subsets. Direct stimulation of peripheral blood mononuclear cells (PBMCs) with high dosages of CCL25 resulted in strong increases in the secretion of monocyte chemoattractant protein-1 (MCP-1), interleukin-8 (IL-8), interleukin-1 beta (IL-1 beta), tumor-necrosis-factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma), upregulation of human leukocyte antigen-DR (HLA-DR) on monocytes and CD4(+) T-cells, as well as immune cell migration along a CCL25 gradient. Immune cell stimulation with the supernatants from CCL25 loaded PLGA microparticles caused moderate increases in MCP-1, IL-8, and IL-1 beta levels, but no changes in surface marker expression or migration. Both CCL25-loaded and unloaded PLGA microparticles induced an increase in IL-8 and MCP-1 release in PBMCs and macrophages, and a slight shift of the surface marker profile towards the direction of M2-macrophage polarization. Conclusions: While supernatants of CCL25 loaded PLGA microparticles did not provoke strong inflammatory reactions, direct stimulation with CCL25 shows the critical potential to induce global inflammatory activation of human leukocytes at certain concentrations. These findings underline the importance of a safe and reliable release system in a therapeutic setup. Failure of the delivery system could result in strong local and systemic inflammatory reactions that could potentially negate the benefits of chemokine therapy

Balancing equity and efficiency in the Dutch basic benefits package using the principle of proportional shortfall

Economic evaluations are increasingly used to inform decisions regarding the allocation of scarce health care resources. To systematically incorporate societal preferences into these evaluations, quality-adjusted life year gains could be weighted according to some equity principle, the most suitable of which is a matter of frequent debate. While many countries still struggle with equity concerns for priority setting in health care, the Netherlands has reached a broad consensus to use the concept of proportional shortfall. Our study evaluates the concept and its support in the Dutch health care context. We discuss arguments in the Netherlands for using proportional shortfall and difficulties in transitioning from principle to practice. In doing so, we address universal issues leading to a systematic consideration of equity concerns for priority setting in health care. The article thus has relevance to all countries struggling with the formalization of equity concerns for priority setting

Population ageing research: a family of disciplines

To study life course trajectories and ageing, scientific expertise is needed beyond epidemiology. More specifically, appropriate models of life course require a theoretical micro-foundation, need to incorporate multi-level context conditions and the interplay between them. It also requires the application of additional social scientific research methods that go beyond the application of statistical methods based on the multi-stage life table. These research theories and methods are available in disciplines like sociology, cultural anthropology, psychology, demography and economics. To effectively study healthy ageing of populations the individual approach of epidemiology has to be extended with the macro-population and socio-cultural approach of (social) demography and the institutional and network approaches of sociology

The Lifelines Cohort Study:a data source available for studying informal caregivers’ experiences and the outcomes of informal caregiving

Background Informal care is taking an increasingly important role in our health care system, and an improvement in our understanding of caregiving experiences and outcomes has become more relevant. The Lifelines informal care add-on study (Lifelines ICAS) was initiated within the Lifelines Cohort Study to cover the large heterogeneity in the caregiver population and to investigate the complex interplay among the characteristics of the caregiver, care recipient, and care situation and positive and negative caregiver outcomes. In this paper, we discuss the study design and data collection procedures of Lifelines ICAS, provide a detailed overview of its measures, and describe the caregiver study population. Methods Lifelines participants who participated in the 2nd Lifelines follow-up questionnaire were asked whether they provided informal care. Subsequently, they were invited to participate in Lifelines ICAS. Descriptive statistics were used to describe all informal caregivers in the 2nd Lifelines follow-up questionnaire and to describe the subsample of informal caregivers participating in Lifelines ICAS. Results A total of 11,651 Lifelines participants were self-identified as an informal caregiver and provided basic information about their care situation. A subsample of 965 informal caregivers participated in Lifelines ICAS and completed a comprehensive questionnaire about their care situation. In this subsample, the average age of caregivers was 53 years (SD 9.8), 75% were female, and 56% cared for a parent (in-law). Care recipients were on average 68 years old (SD 23.5), and 64% were female. Discussion Considering that informal caregivers are a huge resource for our health care system, Lifelines ICAS enables the study of differences among caregivers, care recipients, and care situations, as well as the study of common characteristics and features across caregiver groups. Notably, data from the Lifelines Cohort Study and Lifelines ICAS are available to all researchers on a fee-for-service basis, and Lifelines ICAS data may be enhanced by one or more follow-up measurements or linkages with other data sources

Health Seeking Behaviour and Utilization of Health Facilities for Schistosomiasis-Related Symptoms in Ghana

The World Health Organization recommends that long-term benefit of schistosomiasis control should include treatment in local health facilities. This means that patients should visit a hospital or clinic with their complaints. However, little is known about whether they do so. We conducted a study in three regions of Ghana and interviewed two thousand people about whether they recently had schistosomiasis-related symptoms such as blood in urine or blood in faeces, and what they had done about it. We included fever (mostly caused by malaria) for comparison. We found that 40% of patients with urinary symptoms sought care compared to 70% of those with intestinal symptoms and 90% with fever. Overall, only 20% of all schistosomiasis-related symptoms were reported to a hospital or clinic, compared to 30% for fever. Self-medication with allopathic (i.e., orthodox) medicines was the main alternative. Our study showed that the most important determinant for seeking health care or visiting a health facility is perceived severity of the symptom. Factors such as age, sex, socio-economic status and geographic region showed no impact or a clear pattern. We conclude that many schistosomiasis patients do not visit a health facility, the only place with effective drugs, necessitating additional control measures