Fat, carbohydrate and protein by oral gavage in the rat can be equally effective for satiation

This work was funded by the European Union Seventh Framework programme (Full4Health - grant number 266408) and the Scottish Government Rural and Environment Science and Analytical Services Division to the Rowett Institute. Funders had no role in the preparation of data or the manuscriptPeer reviewedPostprin

Potential Inhibitory Influence of miRNA 210 on Regulatory T Cells during Epicutaneous Chemical Sensitization

Toluene diisocyanate (TDI) is a potent low molecular weight chemical sensitizer and a leading cause of chemical-induced occupational asthma. The regulatory potential of microRNAs (miRNAs) has been recognized in a variety of disease states, including allergic disease; however, the roles of miRNAs in chemical sensitization are largely unknown. In a previous work, increased expression of multiple miRNAs during TDI sensitization was observed and several putative mRNA targets identified for these miRNAs were directly related to regulatory T-cell (Treg) differentiation and function including Foxp3 and Runx3. In this work, we show that miR-210 expression is increased in the mouse draining lymph node (dLN) and Treg subsets following dermal TDI sensitization. Alterations in dLN mRNA and protein expression of Treg related genes/putative miR-210 targets (foxp3, runx3, ctla4, and cd25) were observed at multiple time points following TDI exposure and in ex vivo systems. A Treg suppression assay, including a miR-210 mimic, was utilized to investigate the suppressive ability of Tregs. Cells derived from TDI sensitized mice treated with miR-210 mimic had less expression of miR-210 compared to the acetone control suggesting other factors, such as additional miRNAs, might be involved in the regulation of the functional capabilities of these cells. These novel findings indicate that miR-210 may have an inhibitory role in Treg function during TDI sensitization. Because the functional roles of miRNAs have not been previously elucidated in a model of chemical sensitization, these data contribute to the understanding of the potential immunologic mechanisms of chemical induced allergic disease

Body weight loss, effective satiation and absence of homeostatic neuropeptide compensation in male Sprague Dawley rats schedule fed a protein crosslinked diet

Acknowledgements This work was funded by the European Union Seventh Framework programme (Full4Health - grant number 266408) and the Scottish Government Rural and Environment Science and Analytical Services Division. We thank Danisco, Kettering, UK, for the gift of emulsifier. We thanks Dr Claus-Dieter Mayer of Biomathematics & Statistics Scotland for help with statistical analysis.Peer reviewedPostprin

The promiscuous public? Exploring public opinion and why it matters to political actors

Political actors often cite public opinion to provide support for public policy decisions. This process is made more challenging with diverse demands and perspectives of the public. How then do political actors decide which opinion gets heard? In this article, we go beyond the assumption that the practice of political representation is indistinguishable across various levels of political actors and ask, why do political actors value public opinion and how does it then influence the way in which they apply this information? Developing a multi-level approach, we employ semi-structured interviews with a wide range of political actors, including politicians, pollsters, and community activists. We find that motivations for defining and applying public opinion differs according to the hierarchy of political actors, demonstrating that the relationship between public and political actors is more nuanced and complex than what is often depicted. In particular, we find that minority views play just an important view in policymaking

Topical application of the anti-microbial chemical triclosan induces immunomodulatory responses through the S100A8/A9-TLR4 pathway

The anti-microbial compound triclosan is incorporated into numerous consumer products and is detectable in the urine of 75% of the general United States population. Recent epidemiological studies report positive associations with urinary triclosan levels and allergic disease. Although not sensitizing, earlier studies previously found that repeated topical application of triclosan augments the allergic response to ovalbumin (OVA) though a thymic stromal lymphopoietin (TSLP) pathway in mice. In the present study, early immunological effects following triclosan exposure were further evaluated following topical application in a murine model. These investigations revealed abundant expression of S100A8/A9, which reportedly acts as an endogenous ligand for Toll-like Receptor 4 (TLR4), in skin tissues and in infiltrating leukocytes during topical application of 0.75–3.0% triclosan. Expression of Tlr4 along with Tlr1, Tlr2 and Tlr6 increased in skin tissues over time with triclosan exposure; high levels of TLR4 were expressed on skin-infiltrating leukocytes. In vivo antibody blockade of the TLR4/MD-2 receptor complex impaired local inflammatory responses after four days, as evidenced by decreased Il6, Tnfα, S100a8, S100a9, Tlr1, Tlr2, Tlr4 and Tlr6 expression in the skin and decreased lymph node cellularity and production of IL-4 and IL-13 by lymph node T-cells. After nine days of triclosan exposure with TLR4/MD-2 blockade, impaired T-helper cell type 2 (TH2) cytokine responses were sustained, but other early effects on skin and lymph node cellularity were lost; this suggested alternative ligands/receptors compensated for the loss of TLR4 signaling. Taken together, these data suggest the S100A8/A9-TLR4 pathway plays an early role in augmenting immunomodulatory responses with triclosan exposure and support a role for the innate immune system in chemical adjuvancy

Genetic diversity of Trypanosoma cruzi infecting raccoons (Procyon lotor) in 2 metropolitan areas of southern Louisiana: implications for parasite transmission networks

Trypanosoma cruzi, the aetiological agent of Chagas disease, exists as an anthropozoonosis in Louisiana. Raccoons are an important reservoir, as they demonstrate high prevalence and maintain high parasitaemia longer than other mammals. Given the complex nature of parasite transmission networks and importance of raccoons as reservoirs that move between sylvatic and domestic environments, detailing the genetic diversity of T. cruzi in raccoons is crucial to assess risk to human health. Using a next-generation sequencing approach targeting the mini-exon, parasite diversity was assessed in 2 metropolitan areas of Louisiana. Sequences were analysed along with those previously identified in other mammals and vectors to determine if any association exists between ecoregion and parasite diversity. Parasites were identified from discrete typing units (DTUs) TcI, TcII, TcIV, TcV and TcVI. DTUs TcII, TcV and TcVI are previously unreported in raccoons in the United States (US). TcI was the most abundant DTU, comprising nearly 80% of all sequences. All but 1 raccoon harboured multiple haplotypes, some demonstrating mixed infections of different DTUs. Furthermore, there is significant association between DTU distribution and level III ecoregion in Louisiana. Finally, while certain sequences were distributed across multiple tissues, others appeared to have tissue-specific tropism. Taken together, these findings indicate that ongoing surveillance of T. cruzi in the US should be undertaken across ecoregions to fully assess risk to human health. Given potential connections between parasite diversity and clinical outcomes, deep sequencing technologies are crucial and interventions targeting raccoons may prove useful in mitigating human health risk

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Health impact, and economic value, of meeting housing quality standards: a retrospective longitudinal data linkage study

Background Poor-quality housing adversely affects residents’ health but there is a paucity of high-quality evidence to support this. Objective This research investigated the health impact of bringing housing to a national quality standard. Design A natural experiment of improvements to housing quality analysed using repeated measures of health-care utilisation and economic outcomes at an individual person level. Setting Carmarthenshire, UK. Participants A total of 32,009 residents registered for a minimum of 60 days at 8558 social homes that received housing improvements between January 2005 and March 2015. Interventions Multiple internal and external housing improvements, including wall and loft insulation, windows and doors, heating system upgrades, new kitchens and bathrooms, garden path safety improvements and electrical system upgrades (adding power sockets, and extractor fans in kitchens and bathrooms). Main outcome measures Emergency hospital admissions for cardiorespiratory conditions and injuries. Primary health-care utilisation for respiratory and common mental health disorders, emergency department injury attendances and health-care utilisation costs. Data sources Carmarthenshire County Council home address and intervention records were anonymously linked within the Secure Anonymous Information Linkage databank to demographic information from the Welsh Demographic Service data set; hospital admission data from the Patient Episode Dataset for Wales; primary care contacts and prescribed medications from general practice data; emergency department attendances from the Emergency Department Data Set; and deaths from the Office for National Statistics mortality register. Methods The study used a longitudinal panel design to examine changes in standard of eight housing cointervention from intervention records, and linked to individuals registered at intervention homes. Health outcomes were obtained retrospectively for each individual in a dynamic cohort and were captured for up to 123 consecutive months. An additional local authority region could not be utilised as a comparator owing to different reporting pressures resulting in the recording of a different intervention. The exposure group for each cointervention was compared with an internal reference group of people living in homes that did not receive the cointervention during their tenancy. A multilevel modelling approach was used to account for repeated observations for individuals living in intervention homes. Counts of health outcomes were analysed using negative binomial regression models to determine the effect of each cointervention that reached housing quality standards during an individual’s period of tenancy, compared with those living in properties that did not. We adjusted for potential confounding factors and for background trends in the regional general population. A cost–consequences analysis was conducted as part of the health economic evaluation. Results Residents aged ≥ 60 years living in homes in which electrical systems were upgraded were associated with 39% fewer admissions than those living in homes in which they were not [incidence rate ratio (IRR) 0.61, 95% confidence interval (CI) 0.53 to 0.72; p < 0.01]. Reduced admissions were also associated with windows and doors (IRR 0.71, 95% CI 0.63 to 0.81; p < 0.01), wall insulation (IRR 0.75, 95% CI 0.67 to 0.84; p < 0.01) and gardens and estates (IRR 0.73, 95% CI 0.64 to 0.83; p < 0.01) for those living in homes in which these cointervention were upgraded. There were no associations of change in emergency admissions with upgrading heating (IRR 0.91, 95% CI 0.82 to 1.01; p = 0.072), loft insulation (IRR 0.98, 95% CI 0.86 to 1.11; p = 0.695), kitchens (IRR 0.98, 95% CI 0.83 to 1.17; p = 0.843) or bathrooms (IRR 0.93, 95% CI 0.81 to 1.06; p = 0.287). Limitations There was no randomisation, there were incomplete data on the scale of the intervention for individual households and there were no estimates for the impact of the whole programme. Conclusions This complex interdisciplinary study found that hospital admissions could be avoided through improving housing quality standards