Abstract
Human and animal cross-sectional studies have shown that maternal levels of the inflammatory cytokine interleukin-6 (IL-6) may compromise brain phenotypes assessed at single time points. ...However, how maternal IL-6 associates with the trajectory of brain development remains unclear. We investigated whether maternal IL-6 levels during pregnancy relate to offspring amygdala volume development and anxiety-like behavior in Japanese macaques. Magnetic resonance imaging (MRI) was administered to 39 Japanese macaque offspring (Female: 18), providing at least one or more time points at 4, 11, 21, and 36 months of age with a behavioral assessment at 11 months of age. Increased maternal third trimester plasma IL-6 levels were associated with offspring’s smaller left amygdala volume at 4 months, but with more rapid amygdala growth from 4 to 36 months. Maternal IL-6 predicted offspring anxiety-like behavior at 11 months, which was mediated by reduced amygdala volumes in the model’s intercept (i.e., 4 months). The results increase our understanding of the role of maternal inflammation in the development of neurobehavioral disorders by detailing the associations of a commonly examined inflammatory indicator, IL-6, on amygdala volume growth over time, and anxiety-like behavior.
Respiratory syncytial virus (RSV) is associated with wheezing and childhood asthma. We previously reported that RSV infection prolongs methacholine-induced airway hyperresponsiveness in ovalbumin ...(OVA)-sensitized mice. In addition, allergically sensitized RSV-infected (OVA/RSV) mice had more abundant airway epithelial mucus production compared with OVA mice 14 days after infection, whereas there was almost no mucus in mice that were only RSV infected. We hypothesized that this increased mucus was associated with mucosal expression of Muc5ac, a mucus gene expression in airways, and gob-5, a member of the Ca(2)(+)-activated chloride channel family. By histochemical analysis, we found that there was significantly increased staining for gob-5 and Muc5ac in the airways of OVA/RSV mice compared with either OVA mice or allergically sensitized mice that were challenged with inactivated RSV, and virtually no detectable staining in the RSV group. These findings were confirmed by Western blot analysis. The increased mucus expression in the OVA/RSV group was associated with increased lung levels of interleukin-17, a factor known to stimulate airway mucin gene expression. The impact of virus infection combined with allergic inflammation on mucus production may partially explain the more severe disease and airway hyperresponsiveness associated with RSV in the setting of atopy.
We conducted a randomized trial to assess the effectiveness of F-18-fluorodeoxyglucose (FDG) positron emission tomography (PET)-assisted management in patients with severe ventricular dysfunction and ...suspected coronary disease.
Such patients may benefit from revascularization, but have significant perioperative morbidity and mortality. F-18-fluorodeoxyglucose PET can detect viable myocardium that might recover after revascularization.
Included were patients with severe left ventricular (LV) dysfunction and suspected coronary disease being considered for revascularization, heart failure, or transplantation work-ups or in whom PET was considered potentially useful. Patients were stratified according to recent angiography or not, then randomized to management assisted by FDG PET (n = 218) or standard care (n = 212). The primary outcome was the composite of cardiac death, myocardial infarction, or recurrent hospital stay for cardiac cause, within 1 year.
At 1 year, the cumulative proportion of patients who had experienced the composite event was 30% (PET arm) versus 36% (standard arm) (relative risk 0.82, 95% confidence interval CI 0.59 to 1.14; p = 0.16). The hazard ratio (HR) for the composite outcome, PET versus standard care, was 0.78 (95% CI 0.58 to 1.1; p = 0.15); for patients that adhered to PET recommendations for revascularization, revascularization work-up, or neither, HR = 0.62 (95% CI 0.42 to 0.93; p = 0.019); in those without recent angiography, for cardiac death, HR = 0.4 (95% CI 0.17 to 0.96; p = 0.035).
This study did not demonstrate a significant reduction in cardiac events in patients with LV dysfunction and suspected coronary disease for FDG PET-assisted management versus standard care. In those who adhered to PET recommendations and in patients without recent angiography, significant benefits were observed. The utility of FDG PET is best realized in this subpopulation and when adherence to recommendations can be achieved.
ObjectiveTo determine the feasibility of a definitive trial of metformin to prevent type 2 diabetes in the postnatal period in women with gestational diabetes.DesignA multicentre, placebo-controlled, ...double-blind randomised feasibility trial with qualitative evaluation.SettingThree inner-city UK National Health Service hospitals in London.ParticipantsPregnant women with gestational diabetes treated with medication.Interventions2 g of metformin (intervention) or placebo (control) from delivery until 1 year postnatally.Primary outcome measuresRates of recruitment, randomisation, follow-up, attrition and adherence to the intervention.Secondary outcome measuresPreliminary estimates of glycaemic effects, qualitative exploration, acceptability of the intervention and costs.ResultsOut of 302 eligible women, 57.9% (175/302) were recruited. We randomised 82.3% (144/175) of those recruited, with 71 women in the metformin group and 73 women in the placebo group. Of the participants remaining in the study and providing any adherence information, 54.1% (59/109) took at least 75% of the target intervention dose; the overall mean adherence was 64% (SD 33.6). Study procedures were found to be acceptable to women and healthcare professionals. An increased perceived risk of developing type 2 diabetes, or a positive experience of taking metformin during pregnancy, encouraged participation and adherence to the intervention. Barriers to adherence included disruption to the medication schedule caused by the washout periods ahead of each study visit or having insufficient daily reminders.ConclusionsIt is feasible to run a full-scale definitive trial on the effectiveness of metformin to prevent type 2 diabetes in women with gestational diabetes, during the early postnatal period. Adherence and engagement with the study could be improved with more regular reminders and potentially the addition of ongoing educational or peer support to reinforce messages around type 2 diabetes prevention.Trial registration numberISRCTN20930880.
Expert opinion was canvassed to identify crucial knowledge gaps in current understanding of climate change impacts on coral reef fishes. Scientists that had published three or more papers on the ...effects of climate and environmental factors on reef fishes were invited to submit five questions that, if addressed, would improve our understanding of climate change effects on coral reef fishes. Thirty-three scientists provided 155 questions, and 32 scientists scored these questions in terms of: (i) identifying a knowledge gap, (ii) achievability, (iii) applicability to a broad spectrum of species and reef habitats, and (iv) priority. Forty-two per cent of the questions related to habitat associations and community dynamics of fish, reflecting the established effects and immediate concern relating to climate-induced coral loss and habitat degradation. However, there were also questions on fish demographics, physiology, behaviour and management, all of which could be potentially affected by climate change. Irrespective of their individual expertise and background, scientists scored questions from different topics similarly, suggesting limited bias and recognition of a need for greater interdisciplinary and collaborative research. Presented here are the 53 highest-scoring unique questions. These questions should act as a guide for future research, providing a basis for better assessment and management of climate change impacts on coral reefs and associated fish communities.
•Leaching is affected by the microstructure of organic coating.•Inhibitor particles encapsulated with defect-free polymeric binder do not leach out of coating.•Clusters of inhibitor pigments directly ...connected to the environment leach out without any restriction.•Leaching continues until the cluster of connected inhibitor pigments becomes depleted from inhibitive species.
Active anti-corrosion pigments, such as strontium chromate, are essential components of many corrosion protective organic coatings, since these leach out to provide active inhibition to the metallic substrate at the defective areas of the coatings arising during service from mechanical and/or environmental damages. Currently, formulators use empirical tests to determine effective inhibitor concentration, because the factors that determine leaching behaviour are poorly understood. In this study, we present insights into leaching mechanisms by correlating the microstructure of model coatings pigmented with strontium aluminium polyphosphate hydrate (SAPH) to the transport of different species.
It is found that diffusion and transport of active species through the polymeric matrix does not significantly contribute to the leaching kinetics. Thus, leaching starts when inhibitor pigments are in direct contact with the environment via surface-breaking defects in the coating, and continues as long as the cluster of connected inhibitor pigments is in direct contact with the environment, until 3-dimensional connectivity is lost. Therefore, the extent, shape and size of the clusters of connected inhibitor pigments, as well as the solubility and dissolution rates of individual pigments, play important roles in the leaching process. Additionally, the 3-dimensional percolation threshold (Pc) for pigment connectivity is proposed as a critical parameter that has significant influence on the leaching rate as well as the barrier properties of corrosion protective coatings.
Respiratory syncytial virus (RSV) is an important cause of respiratory infection in people of all ages, and is the leading cause of hospitalization in infants. Although commercially available ...monoclonal antibody is available for passive prophylaxis of neonates at risk of severe disease, there is no available vaccine to prevent RSV. Measurement of neutralizing activity will be a key endpoint for vaccine evaluation. Assessment of neutralizing antibody against RSV has been limited to traditional plaque reduction, which is time-consuming and inherently operator dependent and highly variable. Here, we describe a flow cytometry-based RSV-specific neutralization assay which is more rapid than traditional methods, highly sensitive and highly reproducible.
The CD103
subset of lung-migratory dendritic cells (DCs) plays an important role in the generation of CD8
T cell responses following respiratory infection. Here, we demonstrate that the dependence on ...CD103
DCs for stimulation of RSV-specific T cells is both epitope and age-dependent. CD103
DCs in neonatal mice develop two phenotypically and functionally distinct populations following respiratory infection. Neonatal CD103
DCs expressing low levels of CD103 (CD103lo DCs) and other lineage and maturation markers including costimulatory molecules are phenotypically immature and functionally limited. CD103lo DCs sorted from infected neonates were unable to stimulate cells of the K
M2
specificity, which are potently stimulated by CD103hi DCs sorted from the same animals. These data suggest that the delayed maturation of CD103
DCs in the neonate limits the K
M2
-specific response and explain the distinct CD8
T cell response hierarchy displayed in neonatal mice that differs from the hierarchy seen in adult mice. These findings have implications for the development of early-life vaccines, where the promotion of responses with less age bias may prove advantageous. Alternately, specific approaches may be used to enhance the maturation and function of the CD103lo DC population in neonates to promote more adult-like T cell responses.
The purpose of this brief communication is to highlight emerging evidence to existing guidelines regarding potential benefits of supporting early, rather than delayed, peanut introduction during the ...period of complementary food introduction in infants. This document should be considered as interim guidance based on consensus among the following organizations: American Academy of Allergy, Asthma & Immunology, American Academy of Pediatrics, American College of Allergy, Asthma & Immunology, Australasian Society of Clinical Immunology and Allergy, Canadian Society of Allergy and Clinical Immunology, European Academy of Allergy and Clinical Immunology, Israel Association of Allergy and Clinical Immunology, Japanese Society for Allergology, Society for Pediatric Dermatology, and World Allergy Organization. More formal guidelines regarding early-life, complementary feeding practices and the risk of allergy development will follow in the next year from the National Institute of Allergy and Infectious Diseases-sponsored Working Group and the European Academy of Allergy and Clinical Immunology.
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