A Regional Initiative to Reduce Skin Infections amongst Aboriginal Children Living in Remote Communities of the Northern Territory, Australia

Skin infections are endemic in many in remote Australian Aboriginal communities and have been linked to very high rates of chronic heart and kidney disease in this population. We report the results of a regional collaboration that aimed to reduce skin infections amongst children aged less than 15 years in five remote communities. The program included annual mass scabies treatment days offered to all residents and routine screening/follow-up of children. Trained community workers helped conduct over 6000 skin assessments on 2329 children over a three year period. Of every 100 children seen at the commencement of the study, 47 were found to have skin sores and many had multiple sores. We demonstrate a reduction both in the number of children with skin sores and in the severity of those sores. On average, of every 100 children seen per month, there were 14 fewer children with skin sores and seven fewer children with multiple sores. Overall improvement in treatment uptake was a critical factor. We found no discernible impact against scabies. While the burden of skin infections remains unacceptably high, we believe the results presented here are a good news story for local action to address a serious public health problem

Australian and New Zealand Pulmonary Rehabilitation Guidelines

Background and objective: The aim of the Pulmonary Rehabilitation Guidelines (Guidelines) is to provide evidence-based recommendations for the practice of pulmonary rehabilitation (PR) specific to Australian and New Zealand healthcare contexts. Methods: The Guideline methodology adhered to the Appraisal of Guidelines for Research and Evaluation (AGREE) II criteria. Nine key questions were constructed in accordance with the PICO (Population, Intervention, Comparator, Outcome) format and reviewed by a COPD consumer group for appropriateness. Systematic reviews were undertaken for each question and recommendations made with the strength of each recommendation based on the GRADE (Gradings of Recommendations, Assessment, Development and Evaluation) criteria. The Guidelines were externally reviewed by a panel of experts. Results: The Guideline panel recommended that patients with mild-to-severe COPD should undergo PR to improve quality of life and exercise capacity and to reduce hospital admissions; that PR could be offered in hospital gyms, community centres or at home and could be provided irrespective of the availability of a structured education programme; that PR should be offered to patients with bronchiectasis, interstitial lung disease and pulmonary hypertension, with the latter in specialized centres. The Guideline panel was unable to make recommendations relating to PR programme length beyond 8 weeks, the optimal model for maintenance after PR, or the use of supplemental oxygen during exercise training. The strength of each recommendation and the quality of the evidence are presented in the summary. Conclusion: The Australian and New Zealand Pulmonary Rehabilitation Guidelines present an evaluation of the evidence for nine PICO questions, with recommendations to provide guidance for clinicians and policymakers

Strand Transfer and Elongation of HIV-1 Reverse Transcription Is Facilitated by Cell Factors In Vitro

Recent work suggests a role for multiple host factors in facilitating HIV-1 reverse transcription. Previously, we identified a cellular activity which increases the efficiency of HIV-1 reverse transcription in vitro. Here, we describe aspects of the activity which shed light on its function. The cellular factor did not affect synthesis of strong-stop DNA but did improve downstream DNA synthesis. The stimulatory activity was isolated by gel filtration in a single fraction of the exclusion volume. Velocity-gradient purified HIV-1, which was free of detectable RNase activity, showed poor reverse transcription efficiency but was strongly stimulated by partially purified cell proteins. Hence, the cell factor(s) did not inactivate an RNase activity that might degrade the viral genomic RNA and block completion of reverse transcription. Instead, the cell factor(s) enhanced first strand transfer and synthesis of late reverse transcription suggesting it stabilized the reverse transcription complex. The factor did not affect lysis of HIV-1 by Triton X-100 in the endogenous reverse transcription (ERT) system, and ERT reactions with HIV-1 containing capsid mutations, which varied the biochemical stability of viral core structures and impeded reverse transcription in cells, showed no difference in the ability to be stimulated by the cell factor(s) suggesting a lack of involvement of the capsid in the in vitro assay. In addition, reverse transcription products were found to be resistant to exogenous DNase I activity when the active fraction was present in the ERT assay. These results indicate that the cell factor(s) may improve reverse transcription by facilitating DNA strand transfer and DNA synthesis. It also had a protective function for the reverse transcription products, but it is unclear if this is related to improved DNA synthesis

Human CD141+ (BDCA-3)+ dendritic cells (DCs) represent a unique myeloid DC subset that cross-presents necrotic cell antigens

The characterization of human dendritic cell (DC) subsets is essential for the design of new vaccines. We report the first detailed functional analysis of the human CD141+ DC subset. CD141+ DCs are found in human lymph nodes, bone marrow, tonsil, and blood, and the latter proved to be the best source of highly purified cells for functional analysis. They are characterized by high expression of toll-like receptor 3, production of IL-12p70 and IFN-β, and superior capacity to induce T helper 1 cell responses, when compared with the more commonly studied CD1c+ DC subset. Polyinosine-polycytidylic acid (poly I:C)–activated CD141+ DCs have a superior capacity to cross-present soluble protein antigen (Ag) to CD8+ cytotoxic T lymphocytes than poly I:C–activated CD1c+ DCs. Importantly, CD141+ DCs, but not CD1c+ DCs, were endowed with the capacity to cross-present viral Ag after their uptake of necrotic virus-infected cells. These findings establish the CD141+ DC subset as an important functionally distinct human DC subtype with characteristics similar to those of the mouse CD8α+ DC subset. The data demonstrate a role for CD141+ DCs in the induction of cytotoxic T lymphocyte responses and suggest that they may be the most relevant targets for vaccination against cancers, viruses, and other pathogens

A randomised controlled trial of supplemental oxygen versus medical air during exercise training in people with chronic obstructive pulmonary disease: Supplemental oxygen in pulmonary rehabilitation trial (SuppORT) (Protocol)

© 2016 Alison et al. Background: Oxygen desaturation during exercise is common in people with chronic obstructive pulmonary disease (COPD). The aim of the study is to determine, in people with COPD who desaturate during exercise, whether supplemental oxygen during an eight-week exercise training program is more effective than medical air (sham intervention) in improving exercise capacity and health-related quality of life both at the completion of training and at six-month follow up. Methods/Design: This is a multi-centre randomised controlled trial with concealed allocation, blinding of participants, exercise trainers and assessors, and intention-to-treat analysis. 110 people with chronic obstructive pulmonary disease who demonstrate oxygen desaturation lower than 90 % during the six-minute walk test will be recruited from pulmonary rehabilitation programs in seven teaching hospitals in Australia. People with chronic obstructive pulmonary disease on long term oxygen therapy will be excluded. After confirmation of eligibility and baseline assessment, participants will be randomised to receive either supplemental oxygen or medical air during an eight-week supervised treadmill and cycle exercise training program, three times per week for eight weeks, in hospital outpatient settings. Primary outcome measures will be endurance walking capacity assessed by the endurance shuttle walk test and health-related quality of life assessed by the Chronic Respiratory Disease Questionnaire. Secondary outcomes will include peak walking capacity measured by the incremental shuttle walk test, dyspnoea via the Dyspnoea-12 questionnaire and physical activity levels measured over seven days using an activity monitor. All outcomes will be measured at baseline, completion of training and at six-month follow up. Discussion: Exercise training is an essential component of pulmonary rehabilitation for people with COPD. This study will determine whether supplemental oxygen during exercise training is more effective than medical air in improving exercise capacity and health-related quality of life in people with COPD who desaturate during exercise. Trial registration: Australian New Zealand Clinical Trials Registry ACTRN12612000395831 , 5th Jan,201

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children