Controlled interfacial assembly of 2D curved colloidal crystals and jammed shells

Assembly of colloidal particles on fluid interfaces is a promising technique for synthesizing two-dimensional micro-crystalline materials useful in fields as diverse as biomedicine1, materials science2, mineral flotation3 and food processing4. Current approaches rely on bulk emulsification methods, require further chemical and thermal treatments, and are restrictive with respect to the materials employed5-9. The development of methods that exploit the great potential of interfacial assembly for producing tailored materials have been hampered by the lack of understanding of the assembly process. Here we report a microfluidic method that allows direct visualization and understanding of the dynamics of colloidal crystal growth on curved interfaces. The crystals are periodically ejected to form stable jammed shells, which we refer to as colloidal armour. We propose that the energetic barriers to interfacial crystal growth and organization can be overcome by targeted delivery of colloidal particles through hydrodynamic flows. Our method allows an unprecedented degree of control over armour composition, size and stability.Comment: 18 pages, 5 figure

Defibrinated bovine plasma inhibits retroviral transcription by blocking p52 activation of the NFkappaB element in the long terminal repeat.

Bovine leukemia virus (BLV) induces a persistent but latent infection in cattle. Viral latency is invoked by a protein known as plasma blocking factor (PBF) that is found in both bovine and human plasma. We report here on pathways that mediate latency in the presence of PBF. Reporter-gene constructs driven by the promoters of 6 retroviruses were used to measure the production of chloramphenicol acetyl transferase (CAT) in cell lines cultured with or without defibrinated bovine plasma. Plasma inhibited CAT production only in constructs containing an NFκB-binding element proximal to the initiation site (BLV, human immunodeficiency virus, and human T-cell leukemia virus). The promoters of Bovine immunodeficiency virus, Feline immunodeficiency virus, or Feline leukemia virus were not inhibited in the presence of bovine plasma. Using gel mobility shift assays, we demonstrated that activation of viral transcription upon stimulation with phorbol esters and ionomycin was mediated through the NFκB element and that this was abrogated in the presence of plasma. Furthermore, analysis of individual NFκB proteins in nuclear extracts of mononuclear cells or Jurkat cells showed that all 5 members of the NFκB family were upregulated in response to stimulation, but only p52 was significantly downregulated in the presence of bovine plasma. Thus, we infer that plasma effects are mediated through interference with either p52 translocation to the nucleus or p52 synthesis

Microbial ligand costimulation drives neutrophilic steroid-refractory asthma

Funding: The authors thank the Wellcome Trust (102705) and the Universities of Aberdeen and Cape Town for funding. This research was also supported, in part, by National Institutes of Health GM53522 and GM083016 to DLW. KF and BNL are funded by the Fonds Wetenschappelijk Onderzoek, BNL is the recipient of an European Research Commission consolidator grant and participates in the European Union FP7 programs EUBIOPRED and MedALL. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

A mixed-method study exploring barriers and facilitators to midwives’ mental health in Ontario

Background: There is a paucity of information regarding the mental health of midwives working in Ontario, Canada. Many studies have investigated midwives’ mental health around the world, but little is known about how the model of midwifery care in Ontario contributes to or negatively impacts midwives’ mental health. The aim of the study was to gain a deeper understanding of factors that contribute to and negatively impact Ontario midwives’ mental health. Methods: We employed a mixed-methods, sequential, exploratory design, which utilized focus groups and individual interviews, followed by an online survey. All midwives in Ontario who had actively practiced within the previous 15 months were eligible to participate. Findings: We conducted 6 focus groups and 3 individual interviews, with 24 midwives, and 275 midwives subsequently completed the online survey. We identified four broad factors that impacted midwives’ mental health: (1) the nature of midwifery work, (2) the remuneration model, (3) the culture of the profession, and (4) external factors. Discussion: Based on our findings and the existing literature, we have five broad recommendations for improving Ontario midwives’ mental health: (1) provide a variety of work options for midwives; (2) address the impacts of trauma on midwives; (3) make mental health services tailored for midwives accessible; (4) support healthy midwife-to-midwife relationships; and (5) support improved respect and understanding of midwifery. Conclusion: As one of the first comprehensive investigations into midwives’ mental health in Ontario, this study highlights factors that contribute negatively to midwives’ mental health and offers recommendations for how midwives’ mental health can be improved systemically

Unintended pregnancy: magnitude and correlates in six urban sites in Senegal

BACKGROUND: In Senegal, unintended pregnancy has become a growing concern in public health circles. It has often been described through the press as a sensational subject with emphasis on the multiple infanticide cases as a main consequence, especially among young unmarried girls. Less scientific evidence is known on this topic, as fertility issues are rarely discussed within couples. In a context where urbanization is strong, economic insecurity is persistent and the population is globalizing, it is important to assess the magnitude of unintended pregnancy among urban women and to identify its main determinants. METHODS: Data were collected in 2011 from a representative sample of 9614 women aged 15–49 years in six urban sites in Senegal. For this analysis, we include 5769 women who have ever been pregnant or were pregnant at the time of the survey. These women were asked if their last pregnancy in the last two years was ‘wanted ’then’, ‘wanted later’ or ‘not wanted’. Pregnancy was considered as unintended if the woman responded ‘wanted later’ or ‘not wanted’. Descriptive analyses were performed to measure the magnitude of unintended pregnancies, while multinomial logistic regression models were used to identify factors associated with the occurrence of unintended pregnancy. The analyses were performed using Stata version 12. All results were weighted. RESULTS: The results show that 14.3% of ever pregnant women reported having a recent unintended pregnancy. The study demonstrates important distinctions between women whose last pregnancy was intended and those whose last pregnancy was unintended. Indeed, this last group is more likely to be poor, from a young age (< 25 years) and multiparous. In addition, it appears that low participation of married women in decision-making within the couple (management of financial resources) and the lack of discussion on family planning issues are associated with greater experience of unintended pregnancy. CONCLUSION: This study suggests a need to implement more targeted programs that guarantee access to family planning for all women in need. In urban areas that are characterized by economic insecurity, as in Senegal, it is important to consider strategies for promoting communication within couples on fertility issues

Cigarette smoke exposure facilitates allergic sensitization in mice

BACKGROUND: Active and passive smoking are considered as risk factors for asthma development. The mechanisms involved are currently unexplained. OBJECTIVE: The aim of this study was to determine if cigarette smoke exposure could facilitate primary allergic sensitization. METHODS: BALB/c mice were exposed to aerosolized ovalbumin (OVA) combined with air or tobacco smoke (4 exposures/day) daily for three weeks. Serology, lung cytopathology, cytokine profiles in bronchoalveolar lavage fluid (BALF) and on mediastinal lymph node cultures as well as lung function tests were performed after the last exposure. The natural history and the immune memory of allergic sensitization were studied with in vivo recall experiments. RESULTS: Exposure to OVA induced a small increase in OVA-specific serum IgE as compared with exposure to PBS (P < 0.05), while no inflammatory reaction was observed in the airways. Exposure to cigarette smoke did not induce IgE, but was characterized by a small but significant neutrophilic inflammatory reaction. Combining OVA with cigarette smoke not only induced a significant increase in OVA-specific IgE but also a distinct eosinophil and goblet cell enriched airway inflammation albeit that airway hyperresponsiveness was not evidenced. FACS analysis showed in these mice increases in dendritic cells (DC) and CD4(+ )T-lymphocytes along with a marked increase in IL-5 measured in the supernatant of lymph node cell cultures. Immune memory experiments evidenced the transient nature of these phenomena. CONCLUSION: In this study we show that mainstream cigarette smoke temporary disrupts the normal lung homeostatic tolerance to innocuous inhaled allergens, thereby inducing primary allergic sensitization. This is characterized not only by the development of persistent IgE, but also by the emergence of an eosinophil rich pulmonary inflammatory reaction

Modeling Susceptibility versus Resistance in Allergic Airway Disease Reveals Regulation by Tec Kinase Itk

Murine models of allergic asthma have been used to understand the mechanisms of development and pathology in this disease. In addition, knockout mice have contributed significantly to our understanding of the roles of specific molecules and cytokines in these models. However, results can vary significantly depending on the mouse strain used in the model, and in particularly in understanding the effect of specific knockouts. For example, it can be equivocal as to whether specific gene knockouts affect the susceptibility of the mice to developing the disease, or lead to resistance. Here we used a house dust mite model of allergic airway inflammation to examine the response of two strains of mice (C57BL/6 and BALB/c) which differ in their responses in allergic airway inflammation. We demonstrate an algorithm that can facilitate the understanding of the behavior of these models with regards to susceptibility (to allergic airway inflammation) (Saai) or resistance (Raai) in this model. We verify that both C57BL/6 and BALB/c develop disease, but BALB/c mice have higher Saai for development. We then use this approach to show that the absence of the Tec family kinase Itk, which regulates the production of Th2 cytokines, leads to Raai in the C57BL/6 background, but decreases Saai on the BALB/c background. We suggest that the use of such approaches could clarify the behavior of various knockout mice in modeling allergic asthma

An intranasal selective antisense oligonucleotide impairs lung cyclooxygenase-2 production and improves inflammation, but worsens airway function, in house dust mite sensitive mice

<p>Abstract</p> <p>Background</p> <p>Despite its reported pro-inflammatory activity, cyclooxygenase (COX)-2 has been proposed to play a protective role in asthma. Accordingly, COX-2 might be down-regulated in the airway cells of asthmatics. This, together with results of experiments to assess the impact of COX-2 blockade in ovalbumin (OVA)-sensitized mice in vivo, led us to propose a novel experimental approach using house dust mite (HDM)-sensitized mice in which we mimicked altered regulation of COX-2.</p> <p>Methods</p> <p>Allergic inflammation was induced in BALBc mice by intranasal exposure to HDM for 10 consecutive days. This model reproduces spontaneous exposure to aeroallergens by asthmatic patients. In order to impair, but not fully block, COX-2 production in the airways, some of the animals received an intranasal antisense oligonucleotide. Lung COX-2 expression and activity were measured along with bronchovascular inflammation, airway reactivity, and prostaglandin production.</p> <p>Results</p> <p>We observed impaired COX-2 mRNA and protein expression in the lung tissue of selective oligonucleotide-treated sensitized mice. This was accompanied by diminished production of mPGE synthase and PGE₂in the airways. In sensitized mice, the oligonucleotide induced increased airway hyperreactivity (AHR) to methacholine, but a substantially reduced bronchovascular inflammation. Finally, mRNA levels of hPGD synthase remained unchanged.</p> <p>Conclusion</p> <p>Intranasal antisense therapy against COX-2 in vivo mimicked the reported impairment of COX-2 regulation in the airway cells of asthmatic patients. This strategy revealed an unexpected novel dual effect: inflammation was improved but AHR worsened. This approach will provide insights into the differential regulation of inflammation and lung function in asthma, and will help identify pharmacological targets within the COX-2/PG system.</p

Allergen Uptake, Activation, and IL-23 Production by Pulmonary Myeloid DCs Drives Airway Hyperresponsiveness in Asthma-Susceptible Mice

Maladaptive, Th2-polarized inflammatory responses are integral to the pathogenesis of allergic asthma. As regulators of T cell activation, dendritic cells (DCs) are important mediators of allergic asthma, yet the precise signals which render endogenous DCs “pro-asthmatic”, and the extent to which these signals are regulated by the pulmonary environment and host genetics, remains unclear. Comparative phenotypic and functional analysis of pulmonary DC populations in mice susceptible (A/J), or resistant (C3H) to experimental asthma, revealed that susceptibility to airway hyperresponsiveness is associated with preferential myeloid DC (mDC) allergen uptake, and production of Th17-skewing cytokines (IL-6, IL-23), whereas resistance is associated with increased allergen uptake by plasmacytoid DCs. Surprisingly, adoptive transfer of syngeneic HDM-pulsed bone marrow derived mDCs (BMDCs) to the lungs of C3H mice markedly enhanced lung IL-17A production, and rendered them susceptible to allergen-driven airway hyperresponsiveness. Characterization of these BMDCs revealed levels of antigen uptake, and Th17 promoting cytokine production similar to that observed in pulmonary mDCs from susceptible A/J mice. Collectively these data demonstrate that the lung environment present in asthma-resistant mice promotes robust pDC allergen uptake, activation, and limits Th17-skewing cytokine production responsible for driving pathologic T cell responses central to the development of allergen-induced airway hyperresponsiveness