New insights into the kinetics and variability of egg excretion in controlled human hookworm infections

Four healthy volunteers were infected with 50 Necator americanus infective larvae (L3) in a controlled human hookworm infection trial and followed for 52 weeks. The kinetics of fecal egg counts in volunteers was assessed with Bayesian multilevel analysis, which revealed an increase between weeks 7 and 13, followed by an egg density plateau of about 1000 eggs/g of feces. Variation in egg counts was minimal between same-day measurements but varied considerably between days, particularly during the plateau phase. These analyses pave the way for the controlled human hookworm model to accelerate drug and vaccine efficacy studies

Early Induction of Human Regulatory Dermal Antigen Presenting Cells by Skin-Penetrating Schistosoma Mansoni Cercariae

Host-parasite interactio

Early Induction of Human Regulatory Dermal Antigen Presenting Cells by Skin-Penetrating Schistosoma Mansoni Cercariae

Following initial invasion of Schistosoma mansoni cercariae, schistosomula reside in the skin for several days during which they can interact with the dermal immune system. While murine experiments have indicated that exposure to radiation-attenuated (RA) cercariae can generate protective immunity which is initiated in the skin stage, contrasting non-attenuated cercariae, such data is missing for the human model. Since murine skin does not form a reliable marker for immune responses in human skin, we used human skin explants to study the interaction with non-attenuated and RA cercariae with dermal innate antigen presenting cells (APCs) and the subsequent immunological responses. We exposed human skin explants to cercariae and visualized their invasion in real time (initial 30 min) using novel imaging technologies. Subsequently, we studied dermal immune responses and found an enhanced production of regulatory cytokine interleukin (IL)-10, pro-inflammatory cytokine IL-6 and macrophage inflammatory protein (MIP)-1α within 3 days of exposure. Analysis of dermal dendritic cells (DDCs) for their phenotype revealed an increased expression of immune modulators programmed death ligand (PD-L) 1 and 2, and increased IL-10 production. Ex vivo primed DDCs suppress Th1 polarization of naïve T-cells and increase T-cell IL-10 production, indicating their regulatory potential. These immune responses were absent or decreased after exposure to RA parasites. Using transwells, we show that direct contact between APCs and cercariae is required to induce their regulatory phenotype. To the best of our knowledge this is the first study that attempts to provide insight in the human dermal S. mansoni cercariae invasion and subsequent immune responses comparing non-attenuated with RA parasites. We reveal that cercariae induce a predominantly regulatory immune response whereas RA cercariae fail to achieve this. This initial understanding of the dermal immune suppressive capacity of S. mansoni cercariae in humans provides a first step toward the development of an effective schistosome vaccine

Aandacht voor veiligheid

De komende decennia worden er tussen de 500.000 en 1.500.000 woningen gebouwd waarvan een groot deel in laag Nederland. Deze studie laat zien dat door deze woningen overstromingsbestendig te bouwen schadereductie mogelijk is. Het schaderisico wordt dan nog eens een factor 2 minder als naast een Business as Usual variant nieuwbouwwoningen worden opgehoogd tot +5 m NAP. De kosten van opgehoogde nieuwbouwhuizen zijn hoger en variëren tussen de 0,4 en 1.7 miljard euro/jaar, hetgeen overeenkomt met 0,1-0,5% van het BNP. Dijkversterking levert de hoogste reductie op in het schaderisico bij de gehanteerde scenario’s. Gevolgbeperkende maatregelen in de ruimtelijk ordening als additionele oplossingsrichting zijn echter goed mogelijk als er ook een economische perspectief is bijvoorbeeld door middel van multifunctioneel ruimtegebruik

The Influence of Personal Health Data on the Health Coaching Process

Tracking health data, for example, through wearable devices or health apps, is increasingly commonplace. Consequently, health coaches (e.g., personal trainers, dieticians) are facing growing numbers of clients who bring their data to the clinic. These data potentially add value to the coaching process, for example, by showing more objective and specific information on clients' behaviors. However, in practice, it turns out to be hard to effectively utilize health data in a coaching setting, and it is not yet fully understood how data affect the coaching process and the coach-client communication. We organized a workshop (12 coaches, 3 clients) and a field study (5 coaches, 6 clients), where we observed coach-client interactions enriched with data. By including both familiar and unfamiliar coach-client pairs, as well as alternating the timing of the data presented (i.e., at the beginning, or halfway through the session), we acquired a variety of data-driven coaching interactions and analyzed this using a mixture of qualitative and quantitative methods. Our results show that data are not “plug-and-play.” There is an extensive process of interpreting and contextualizing data, in which the client has a key role, which is essential to gain relevant and actionable insights from the data useful to the coaching process. We also observed that data affect the coach-client communication on both content and relationship levels. We will reflect on these insights in terms of design recommendations for wearable tracking devices and e-health technology to effectively support health coaches and their interactions with their clients

INFRAPATELLAR FAT PAD FROM LATE OSTEOARTHRITIS PATIENTS HAS AN ANABOLIC PHENOTYPE

Clinical epidemiolog

Peroxisome proliferator activated receptor alpha activation decreases inflammatory and destructive responses in osteoarthritic cartilage

SummaryObjectivePeroxisome proliferator activated receptor α (PPARα) agonists are used in clinical practice as lipid-lowering drugs and are also known to exert anti-inflammatory effects on various tissues. We hypothesized that PPARα activation leads to anti-inflammatory and anti-destructive effects in human OA cartilage.MethodsCartilage explants obtained from six OA patients were cultured for 48h with 10ng/ml interleukin (IL)1β as a pro-inflammatory stimulus. 100μM Wy-14643, a potent and selective PPARα agonist, was added to the cultures and gene expression of matrix metalloproteinase (MMP)1, MMP3, MMP13, collagen type II (COL2A1), aggrecan and PPARα in cartilage explants and the release of glycosaminoglycans (GAGs), nitric oxide (NO) and prostaglandin E2 (PGE2) in the culture media were analyzed and compared to the control without Wy-14643.ResultsAddition of Wy-14643 decreased mRNA expression of MMP1, MMP3 and MMP13 in cartilage explants that responded to IL1β, whereas Wy-14643 did not affect gene expression of COL2A1 and aggrecan. Wy-14643 also decreased secretion of inflammatory marker NO in the culture medium of cartilage explants responding to IL1β. Wy-14643 inhibited the release of GAGs by cartilage explants in culture media.ConclusionPPARα agonist Wy-14643 inhibited the inflammatory and destructive responses in human OA cartilage explants and did not have an effect on COL2A1 or aggrecan mRNA expression. These effects of PPARα agonists on osteoarthritic cartilage warrant further investigation of these drugs as a potential therapeutic strategy for osteoarthritis (OA)