The B subunit of Escherichia coli heat-labile toxin alters the development and antigen-presenting capacity of dendritic cells

Escherichia coli’s heat-labile enterotoxin (Etx) and its non-toxic B subunit (EtxB) have been characterized as adjuvants capable of enhancing T cell responses to co-administered antigen. Here, we investigate the direct effect of intravenously administered EtxB on the size of the dendritic and mye-loid cell populations in spleen. EtxB treatment appears to enhance the development and turnover of dendritic and myeloid cells from precursors within the spleen. EtxB treatment also gives a dendritic cell (DC) population with higher viability and lower activation status based on the reduced expression of MHC-II, CD80 and CD86. In this respect, the in vivo effect of EtxB differs from that of the highly inflammatory mediator lipopolysaccharide. In in vi-tro bone marrow cultures, EtxB treatment was also found to enhance the development of DC from precursors dependent on Flt3L. In terms of the in vivo effect of EtxB on CD4 and CD8 T cell responses in mice, the interaction of EtxB directly with DC was demonstrated following conditional deple-tion of CD11c+ DC. In summary, all results are consistent with EtxB displaying adjuvant ability by enhancing the turnover of DC in spleen, leading to newly mature myeloid and DC in spleen, thereby increasing DC capacity to perform as antigen-presenting cells on encounter with T cells

Readability, presentation and quality of allergy-related patient information leaflets: a cross sectional and longitudinal study

Objective: Patient information leaflets (PILs) are widely used to reinforce or illustrate health information and to complement verbal consultation. The objectives of the study were to assess the readability and presentation of PILs published by Allergy UK, and to conduct a longitudinal assessment to evaluate the impact of leaflet amendment and revision on readability. Methods: Readability of Allergy UK leaflets available in 2013 was assessed using Simple Measure of Gobbledegook (SMOG) and Flesch-Kincaid Reading Grade Formula. Leaflet presentation was evaluated using the Clear Print Guidelines of the Royal National Institute of Blind People (RNIB) and the Patient Information Appraisal System developed by the British Medical Association (BMA). Changes in the leaflets’ readability scores over five years were investigated. Results: 108 leaflets, covering a wide range of allergic conditions and treatment options, were assessed. The leaflets had average SMOG and Flesch-Kincaid scores of 13.9 (range 11-18, SD 1.2) and 10.9 (range 5-17, SD 2.1) respectively. All leaflets met the RNIB Clear Print guidelines, with the exception of font size which was universally inadequate. The leaflets scored on average 10 (median 10, range 7-15) out of a maximum of 27 on the BMA checklist. The overall average SMOG score of 31 leaflets available in both 2008 and 2013 had not changed significantly. The process of leaflet revision resulted in 1% change in readability scores overall, with a predominantly upward trend with six leaflets increasing their readability score by >10% and only three decreasing by >10%. Conclusion: Allergy-related patient information leaflets are well presented but have readability levels that are higher than those recommended for health information. Involving service users in the process of leaflet design, together with systematic pre-publication screening of readability would enhance the accessibility and comprehensibility of written information for people with allergy and their careers

Digital communication between clinician and patient in General Practice and the impact on marginalised groups : a realist review

Background Increasingly, the NHS is embracing the use of digital communication technology for communication between clinicians and patients. Policymakers deem digital clinical communication as presenting a solution to the capacity issues currently faced by general practice. There is some concern that these technologies may exacerbate existing inequalities in accessing health care. It is not known what impact they may have on groups who are already marginalised in their ability to access general practice. Aim To assess the potential impact of the availability of digital clinician–patient communication on marginalised groups’ access to general practice in the UK. Design and setting Realist review in general practice. Method A four-step realist review process was used: to define the scope of the review; to search for and scrutinise evidence; to extract and synthesise evidence; and to develop a narrative, including hypotheses. Results Digital communication has the potential to overcome the following barriers for marginalised groups: practical access issues, previous negative experiences with healthcare service/staff, and stigmatising reactions from staff and other patients. It may reduce patient-related barriers by offering anonymity and offers advantages to patients who require an interpreter. It does not impact on inability to communicate with healthcare professionals or on a lack of candidacy. It is likely to work best in the context of a pre-existing clinician–patient relationship. Conclusion Digital communication technology offers increased opportunities for marginalised groups to access health care. However, it cannot remove all barriers to care for these groups. It is likely that they will remain disadvantaged relative to other population groups after their introduction

Proteomic Analysis of a Noninvasive Human Model of Acute Inflammation and Its Resolution: The Twenty-one Day Gingivitis Model

The 21-day experimental gingivitis model, an established noninvasive model of inflammation in response to increasing bacterial accumulation in humans, is designed to enable the study of both the induction and resolution of inflammation. Here, we have analyzed gingival crevicular fluid, an oral fluid comprising a serum transudate and tissue exudates, by LC−MS/MS using Fourier transform ion cyclotron resonance mass spectrometry and iTRAQ isobaric mass tags, to establish meta-proteomic profiles of inflammation-induced changes in proteins in healthy young volunteers. Across the course of experimentally induced gingivitis, we identified 16 bacterial and 186 human proteins. Although abundances of the bacterial proteins identified did not vary temporally, Fusobacterium outer membrane proteins were detected. Fusobacterium species have previously been associated with periodontal health or disease. The human proteins identified spanned a wide range of compartments (both extracellular and intracellular) and functions, including serum proteins, proteins displaying antibacterial properties, and proteins with functions associated with cellular transcription, DNA binding, the cytoskeleton, cell adhesion, and cilia. PolySNAP3 clustering software was used in a multilayered analytical approach. Clusters of proteins that associated with changes to the clinical parameters included neuronal and synapse associated proteins

Protocol for a randomised controlled trial investigating the effectiveness of an online e health application for the prevention of Generalised Anxiety Disorder

BACKGROUND Generalised Anxiety Disorder (GAD) is a highly prevalent psychiatric disorder. Effective prevention in young adulthood has the potential to reduce the prevalence of the disorder, to reduce disability and lower the costs of the disorder to the community. The present trial (the WebGAD trial) aims to evaluate the effectiveness of an evidence-based online prevention website for GAD. METHODS/DESIGN The principal clinical question under investigation is the effectiveness of an online GAD intervention (E-couch) using a community-based sample. We examine whether the effect of the intervention can be maximised by either human support, in the form of telephone calls, or by automated support through emails. The primary outcome will be a reduction in symptoms on the GAD-7 in the active arms relative to the non active intervention arms. DISCUSSION The WebGAD trial will be the first to evaluate the use of an internet-based cognitive behavioural therapy (CBT) program contrasted with a credible control condition for the prevention of GAD and the first formal RCT evaluation of a web-based program for GAD using community recruitment. In general, internet-based CBT programs have been shown to be effective for the treatment of other anxiety disorders such as Post Traumatic Stress Disorder, Social Phobia, Panic Disorder and stress in clinical trials; however there is no evidence for the use of internet CBT in the prevention of GAD. Given the severe shortage of therapists identified in Australia and overseas, and the low rates of treatment seeking in those with a mental illness, the successful implementation of this protocol has important practical outcomes. If found to be effective, WebGAD will provide those experiencing GAD with an easily accessible, free, evidence-based prevention tool which can be promoted and disseminated immediately

Native liquid extraction surface analysis mass spectrometry : analysis of noncovalent protein complexes directly from dried substrates

Liquid extraction surface analysis (LESA) mass spectrometry is a promising tool for the analysis of intact proteins from biological substrates. Here, we demonstrate native LESA mass spectrometry of noncovalent protein complexes of myoglobin and hemoglobin from a range of surfaces. Holomyoglobin, in which apomyoglobin is noncovalently bound to the prosthetic heme group, was observed following LESA mass spectrometry of myoglobin dried onto glass and polyvinylidene fluoride surfaces. Tetrameric hemoglobin [(αβ)(2)(4H)] was observed following LESA mass spectrometry of hemoglobin dried onto glass and polyvinylidene fluoride (PVDF) surfaces, and from dried blood spots (DBS) on filter paper. Heme-bound dimers and monomers were also observed. The ‘contact’ LESA approach was particularly suitable for the analysis of hemoglobin tetramers from DBS. [Figure: see text

Does metabolic reprogramming underpin age-associated changes in T cell phenotype and function?

T cells are required for an effective adaptive immune response. The principal function of T cells is to promote efficient removal of foreign material by identifying and mounting a specific response to nonself. A decline in T cell function in aging is thought to contribute to reduced response to infection and vaccination and an increase in autoimmunity. This may in part be due to the age-related decrease in naïve CD4+ T cells and increase in antigen-experienced CD4+ T cells, loss of redox homeostasis, and impaired metabolic switching. Switching between subsets is triggered by the integration of extracellular signals sensed through surface receptors and the activation of discrete intracellular metabolic pathways. This article explores how metabolic programming and loss of redox homeostasis during aging may contribute to age-associated changes in T cell phenotype and function. © 2014 Elsevier Inc

The ANU WellBeing study: a protocol for a quasi-factorial randomised controlled trial of the effectiveness of an Internet support group and an automated Internet intervention for depression

BACKGROUND Recent projections suggest that by the year 2030 depression will be the primary cause of disease burden among developed countries. Delivery of accessible consumer-focused evidenced-based services may be an important element in reducing this burden. Many consumers report a preference for self-help modes of delivery. The Internet offers a promising modality for delivering such services and there is now evidence that automated professionally developed self-help psychological interventions can be effective. By contrast, despite their popularity, there is little evidence as to the effectiveness of Internet support groups which provide peer-to-peer mutual support. METHODS/DESIGN Members of the community with elevated psychological distress were randomised to receive one of the following: (1) Internet Support Group (ISG) intervention, (2) a multi-module automated psychoeducational and skills Internet Training Program (ITP), (3) a combination of the ISG and ITP, or (4) an Internet Attention Control website (IAC) comprising health and wellbeing information and question and answer modules. Each intervention was 12 weeks long. Assessments were conducted at baseline, post-intervention, 6 and 12 months to examine depressive symptoms, social support, self-esteem, quality of life, depression literacy, stigma and help-seeking for depression. Participants were recruited through a screening postal survey sent to 70,000 Australians aged 18 to 65 years randomly selected from four rural and four metropolitan regions in Australia. DISCUSSION To our knowledge this study is the first randomised controlled trial of the effectiveness of a depression ISG. TRIAL REGISTRATION Current Controlled Trials ISRCTN65657330.This study was funded by a National Health and Medical Research Council Project Grant 471435 to KG, HC and AM. KG is supported by NHMRC Fellowship No. 525413 and HC is supported by Fellowship No. 525411

Systemic reduction in glutathione levels occurs in patients with primary open-angle glaucoma

PURPOSE. To assess the level of plasma glutathione in patients with untreated primary open-angle glaucoma. METHODS. Twenty-one patients with newly diagnosed primary open-angle glaucoma and 34 age- and gender-matched control subjects were subjected to a blood analysis to detect the level of circulating glutathione in its reduced and oxidized forms. The effect of age, gender, and systemic blood pressure on circulating glutathione levels was also analyzed. RESULTS. Age had a negative effect on the level of both reduced and total glutathione (P = 0.002, r = -0.52 and P = 0.002, r = -0.52, respectively) in control subjects but not in patients with glaucoma (P > 0.05, r = 0.27, and P > 0.05, r = 0.22, respectively). In the control group, men demonstrated higher levels of both reduced and total glutathione than did women (P = 0.024 and P = 0.032, respectively). After correction for age and gender influences on blood glutathione levels, patients with glaucoma exhibited significantly lower levels of reduced and total glutathione than did control subjects (P = 0.010, F = 7.24 and P = 0.006, F = 8.38, respectively). No differences between study groups were observed in either oxidized glutathione levels or redox index (P > 0.05, F = 0.50; and P > 0.05, F = 0.30, respectively). CONCLUSIONS. Patients with glaucoma exhibit low levels of circulating glutathione, suggesting a general compromise of the antioxidative defense. Copyright © Association for Research in Vision and Ophthalmology