Delayed development of the protective IL-17A response following a Giardia muris infection in neonatal mice

Giardia is an intestinal protozoan parasite that has the ability to infect a wide range of hosts, which can result in the clinical condition 'giardiasis'. Over the years, experimental research has shown the crucial involvement of IL-17A to steer the protective immune response against Giardia. The development of the protective response, as reflected by a significant drop in cyst secretion, typically takes around 3 to 4 weeks. However, early-life infections often have a more chronic character lasting for several weeks or months. Therefore, the aim of the current study was to investigate the dynamics of a Giardia muris infection and the subsequent host immune response in neonatal mice infected 4 days after birth. The outcome of the study showed that a G. muris infection in pre-weaned mice failed to trigger a protective IL-17A response, which could explain the prolonged course of infection in comparison to older mice. Only after weaning, a protective intestinal immune response started to develop, characterized by an upregulation of IL-17A and Mb12 and the secretion of parasite-specific IgA

Mapping EQ-5D utilities to GBD 2010 and GBD 2013 disability weights : results of two pilot studies in Belgium

Background: Utilities and disability weights (DWs) are metrics used for calculating Quality-Adjusted Life Years and Disability-Adjusted Life Years (DALYs), respectively. Utilities can be obtained with multi-attribute instruments such as the EuroQol 5 dimensions questionnaire (EQ-5D). In 2010 and 2013, Salomon et al. proposed a set of DWs for 220 and 183 health states, respectively. The objective of this study is to develop an approach for mapping EQ-5D utilities to existing GBD 2010 and GBD 2013 DWs, allowing to predict new GBD 2010/2013 DWs based on EQ-5D utilities. Methods: We conducted two pilot studies including respectively four and twenty-seven health states selected from the 220 DWs of the GBD 2010 study. In the first study, each participant evaluated four health conditions using the standard written EQ-5D-5 L questionnaire. In the second study, each participant evaluated four health conditions randomly selected among the twenty-seven health states using a previously developed web-based EQ-5D-5 L questionnaire. The EQ-5D responses were translated into utilities using the model developed by Cleemput et al. A loess regression allowed to map EQ-5D utilities to logit transformed DWs. Results: Overall, 81 and 393 respondents completed the first and the second survey, respectively. In the first study, a monotonic relationship between derived utilities and predicted GBD 2010/2013 DWs was observed, but not in the second study. There were some important differences in ranking of health states based on utilities versus GBD 2010/2013 DWs. The participants of the current study attributed a relatively higher severity level to musculoskeletal disorders such as ‘Amputation of both legs’ and a relatively lower severity level to non-functional disorders such as ‘Headache migraine’ compared to the participants of the GBD 2010/2013 studies. Conclusion: This study suggests the possibility to translate any utility derived from EQ-5D scores into a DW, but also highlights important caveats. We observed a satisfactory result of this methodology when utilities were derived from a population of public health students, a written questionnaire and a small number of health states in the presence of a study leader. However the results were unsatisfactory when utilities were derived from a sample of the general population, using a web-based questionnaire. We recommend to repeat the study in a larger and more diverse sample to obtain a more representative distribution of educational level and age

Chimeric LysR-type transcriptional biosensors for customizing ligand specificity profiles toward flavonoids

Transcriptional biosensors enable key applications in both metabolic engineering and synthetic biology. Due to nature's immense variety of metabolites, these applications require biosensors with a ligand specificity profile customized to the researcher's needs. In this work, chimeric biosensors were created by introducing parts of a donor regulatory circuit from Sinorhizobium meliloti, delivering the desired luteolin-specific response, into a nonspecific biosensor chassis from Herbaspirillum seropedicae. Two strategies were evaluated for the development of chimeric LysR-type biosensors with customized ligand specificity profiles toward three closely related flavonoids, naringenin, apigenin, and luteolin. In the first strategy, chimeric promoter regions were constructed at the biosensor effector module, while in the second strategy, chimeric transcription factors were created at the biosensor detector module. Via both strategies, the biosensor repertoire was expanded with luteolin-specific chimeric biosensors demonstrating a variety of response curves and ligand specificity profiles. Starting from the nonspecific biosensor chassis, a shift from 27.5% to 95.3% luteolin specificity was achieved with the created chimeric biosensors. Both strategies provide a compelling, faster, and more accessible route for the customization of biosensor ligand specificity, compared to de novo design and construction of each biosensor circuit for every desired ligand specificity

Construction, start-up and operation of a continuously aerated laboratory-scale SHARON reactor in view of coupling with an Anammox reactor

In this study practical experiences during start-up and operation of a laboratory-scale SHARON reactor are discussed, along with the construction of the reactor. Special attention is given to the start-up in view of possible toxic effects of high nitrogen concentrations (up to 4 000 mgN(.)l(-1)) on the nitrifier population and because the reactor was inoculated with sludge from an SBR reactor operated under completely different conditions. Because of these considerations, the reactor was first operated as an SBR to prevent biomass washout and to allow the selection of a strong nitrifying population. A month after the inoculation the reactor was switched to normal chemostat operation. As a result the nitrite oxidisers were washed out and only the ammonium oxidisers persisted in the reactor. In this contribution also some practical considerations concerning the operation of a continuously aerated SHARON reactor, such as mixing, evaporation and wall growth are discussed. These considerations are not trivial, since the reactor will be used for kinetic characterisation and modelling studies. Finally the performance of the SHARON reactor under different conditions is discussed in view of its coupling with an Anammox unit. Full nitrification was proven to be feasible for nitrogen loads up to 1.5 gTAN-N(.)l(-1.)d(-1), indicating the possibility of the SHARON process to treat highly loaded nitrogen streams. Applying different influent concentrations led to different effluent characteristics indicating the need for proper control of the SHARON reactor

Welfare-adjusted life years (WALY) : a novel metric of animal welfare that combines the impacts of impaired welfare and abbreviated lifespan

Currently, separate measures are used to estimate the impact of animal diseases on mortality and animal welfare. This article introduces a novel metric, the Welfare-Adjusted Life Year (WALY), to estimate disease impact by combining welfare compromise and premature death components. Adapting the Disability-Adjusted Life Year approach used in human health audits, we propose WALY as the sum of a) the years lived with impaired welfare due to a particular cause and b) the years of life lost due to the premature death from the same cause. The years lived with impaired welfare are the product of the average duration of each welfare impediment, reflecting the actual condition that compromises animal welfare, the probability of an incident case developing and impaired welfare weights, representing the degree of impaired welfare. The years of life lost are calculated using the standard expected lifespan at the time of premature death. To demonstrate the concept, we estimated WALYs for 10 common canine diseases, namely mitral valve disease, dilated cardiomyopathy, chronic kidney disease, diabetes mellitus, atopic dermatitis, splenic haemangiosarcoma, appendicular osteosarcoma, cranial cruciate ligament disease, thoracolumbar intervertebral disc disease and cervical spondylomyelopathy. A survey of veterinarians (n = 61) was conducted to elicit impaired welfare weights for 35 welfare impediments. Paired comparison was the primary method to elicit weights, whereas visual analogue scale and time trade-off approaches rescaled these weights onto the desired scale, from 0 (the optimal welfare imaginable) to 1 (the worst welfare imaginable). WALYs for the 10 diseases were then estimated using the impaired welfare weights and published epidemiological data on disease impacts. Welfare impediment “amputation: one limb” and “respiratory distress” had the lowest and highest impaired welfare weights at 0.134 and 0.796, rescaled with a visual analogue scale, and 0.117 and 0.857, rescaled with time trade-off. Among the 10 diseases, thoracolumbar intervertebral disc disease and atopic dermatitis had the smallest and greatest adverse impact on dogs with WALYs at 2.83 (95% UI: 1.54–3.94) and 9.73 (95% uncertainty interval [UI]: 7.17–11.8), respectively. This study developed the WALY metric and demonstrated that it summarises welfare compromise as perceived by humans and total impact of diseases in individual animals. The WALY can potentially be used for prioritisation of disease eradication and control programs, quantification of population welfare and longitudinal surveillance of animal welfare in companion animals and may possibly be extended to production animals

Assessing disability weights based on the responses of 30,660 people from four European countries

Background: In calculations of burden of disease using disability-adjusted life years, disability weights are needed to quantify health losses relating to non-fatal outcomes, expressed as years lived with disability. In 2012 a new set of global disability weights was published for the Global Burden of Disease 2010 (GBD 2010) study. That study suggested that comparative assessments of different health outcomes are broadly similar across settings, but the significance of this conclusion has been debated. The aim of the present study was to estimate disability weights for Europe for a set of 255 health states, including 43 new health states, by replicating the GBD 2010 Disability Weights Measurement study among representative population samples from four European countries. Methods: For the assessment of disability weights for Europe we applied the GBD 2010 disability weights measurement approach in web-based sample surveys in Hungary, Italy, Netherlands, and Sweden. The survey included paired comparisons (PC) and population health equivalence questions (PHE) formulated as discrete choices. Probit regression analysis was used to estimate cardinal values from PC responses. To locate results onto the 0-to-1 disability weight scale, we assessed the feasibility of using the GBD 2010 scaling approach based on PHE questions, as well as an alternative approach using non-parametric regression. Results: In total, 30,660 respondents participated in the survey. Comparison of the probit regression results from the PC responses for each country indicated high linear correlations between countries. The PHE data had high levels of measurement error in these general population samples, which compromises the ability to infer ratio-scaled values from discrete choice responses. Using the non-parametric regression approach as an alternative rescaling procedure, the set of disability weights were bounded by distance vision mild impairment and anemia with the lowest weight (0.004) and severe multiple sclerosis with the highest weight (0.677). Conclusions: PC assessments of health outcomes in this study resulted in estimates that were highly correlated across four European countries. Assessment of the feasibility of rescaling based on a discrete choice formulation of the PHE question indicated that this approach may not be suitable for use in a web-based survey of the general population. Electronic supplementary material The online version of this article (doi:10.1186/s12963-015-0042-4) contains supplementary material, which is available to authorized users