is sponsored by the Office of Health, Infectious Diseases and Nutrition Bureau for Global Health

The guidelines were prepared b

Greywater irrigation as a source of organic micro-pollutants to shallow groundwater and nearby surface water

Increased water demands due to population growth and increased urbanisation have driven adoption of various water reuse practices. The irrigation of greywater (water from all household uses, except toilets) has been proposed as one potential sustainable practice. Research has clearly identified environmental harm from the presence of micro-pollutants in soils, groundwater and surface water. Greywater contains a range of micro pollutants yet very little is known about their potential environmental fate when greywater is irrigated to soil. Therefore, this study assessed whether organic micro-pollutants in irrigated greywater were transferred to shallow groundwater and an adjacent surface waterway. A total of 22 organic micro-pollutants were detected in greywater. Six of these (acesulfame, caffeine, DEET, paracetamol, salicylic acid and triclosan) were selected as potential tracers of greywater contamination. Three of these chemicals (acesulfame, caffeine, DEET) were detected in the groundwater, while salicylic acid was also detected in adjacent surface water. Caffeine and DEET in surface water were directly attributable to greywater irrigation. Thus the practice of greywater irrigation can act as a source of organic micro-pollutants to shallow groundwater and nearby surface water. The full list of micro-pollutants that could be introduced via greywater and the risk they pose to aquatic ecosystems is not yet known

Clinical signs and symptoms in a joint model of four disease activity parameters in juvenile dermatomyositis: a prospective, longitudinal, multicenter cohort study

BACKGROUND: It is currently impossible to predict the prognosis of patients with juvenile dermatomyositis (JDM). The aim of this study was to find clinical features most strongly associated with outcome variables in JDM as a first step towards tailor-made treatment. METHODS: In a large, prospectively followed, multicenter cohort study of 340 patients with JDM, each contributing multiple visits, a Bayesian model of disease activity was developed, using the four continuous outcome variables creatine kinase (CK), childhood myositis assessment score (CMAS), manual muscle testing of 8 muscle groups (MMT8) and the physician's global assessment of disease activity (PGA). Covariates were clinical signs and symptoms. Correlations among visits of the same patient were resolved by introducing subject-specific random effects. RESULTS: Myalgia and dysphonia were associated with worse disease activity according to all outcome variables. Periorbital rash, rash on the trunk, rash over large joints, nail fold changes and facial swelling were associated with higher PGA. Notably, periorbital rash was also associated with higher CK and lower CMAS and nail fold changes with lower CMAS. Contractures were associated with lower CMAS and MMT8 and higher PGA. Patients with higher CMAS exhibited a higher MMT8 as well. PGA had the highest probability among the four outcome variables of being abnormal even if the other three outcome variables were normal. CONCLUSIONS: The signs and symptoms associated with disease activity could be used to stratify patients and adapt treatment plans to disease activity. The correlation between CMAS and MMT8 and the unique information captured by PGA implied that PGA should be maintained as an outcome variable, whereas CMAS and MMT8 might be simplified

Selective deletion of PPARβ/δ in fibroblasts causes dermal fibrosis by attenuated LRG1 expression.

Connective tissue diseases of the skin are characterized by excessive collagen deposition in the skin and internal organs. Fibroblasts play a pivotal role in the clinical presentation of these conditions. Nuclear receptor peroxisome-proliferator activated receptors (PPARs) are therapeutic targets for dermal fibrosis, but the contribution of the different PPAR subtypes are poorly understood. Particularly, the role of fibroblast PPARβ/δ in dermal fibrosis has not been elucidated. Thus, we generated a mouse strain with selective deletion of PPARβ/δ in the fibroblast (FSPCre- <i>Pparb/d</i> <sup>-/-</sup> ) and interrogated its epidermal and dermal transcriptome profiles. We uncovered a downregulated gene, leucine-rich alpha-2-glycoprotein-1 ( <i>Lrg1</i> ), of previously unknown function in skin development and architecture. Our findings suggest that the regulation of <i>Lrg1</i> by PPARβ/δ in fibroblasts is an important signaling conduit integrating PPARβ/δ and TGFβ1-signaling networks in skin health and disease. Thus, the FSPCre- <i>Pparb/d</i> <sup>-/-</sup> mouse model could serve as a novel tool in the current gunnery of animal models to better understand dermal fibrosis

Cluster-randomised controlled trial of community mobilisation in Mumbai slums to improve care during pregnancy, delivery, postpartum and for the newborn

Background: The United Nations Millennium Development Goals look to substantial improvements in child and maternal survival. Morbidity and mortality during pregnancy, delivery and the postnatal period are prime obstacles to achieving these goals. Given the increasing importance of urban health to global prospects, Mumbai's City Initiative for Newborn Health aims to improve maternal and neonatal health in vulnerable urban slum communities, through a combination of health service quality improvement and community participation. The protocol describes a trial of community intervention aimed at improving prevention, care seeking and outcomes.Objective: To test an intervention that supports local women as facilitators in mobilising communities for better health care. Community women's groups will build an understanding of their potential to improve maternal and infant health, and develop and implement strategies to do so.Design: Cluster-randomized controlled trial.Methods: The intervention will employ local community-based female facilitators to convene groups and help them to explore maternal and neonatal health issues. Groups will meet fortnightly through a seven-phase process of sharing experiences, discussion of the issues raised, discovery of potential community strengths, building of a vision for action, design and implementation of community strategies, and evaluation.The unit of allocation will be an urban slum cluster of 1000-1500 households. 48 clusters have been randomly selected after stratification by ward. 24 clusters have been randomly allocated to receive the community intervention. 24 clusters will act as control groups, but will benefit from health service quality improvement. Indicators of effect will be measured through a surveillance system implemented by the project. Key distal outcome indicators will be neonatal mortality and maternal and neonatal morbidity. Key proximate outcome indicators will be home care practices, uptake of antenatal, delivery and postnatal care, and care for maternal and neonatal illness.Data will be collected through a vital registration system for births and deaths in the 48 study clusters. Structured interviews with families will be conducted at about 6 weeks after index deliveries. We will also collect both quantitative and qualitative data to support a process evaluation.Trial registration: Current controlled trials ISRCTN9625679

Bioprocessing strategies to enhance the challenging isolation of neuro-regenerative cells from olfactory mucosa

Olfactory ensheathing cells (OECs) are a promising potential cell therapy to aid regeneration. However, there are significant challenges in isolating and characterizing them. In the current study, we have explored methods to enhance the recovery of cells expressing OEC marker p75NTR from rat mucosa. With the addition of a 24-hour differential adhesion step, the expression of p75NTR was significantly increased to 73 ± 5% and 46 ± 18% on PDL and laminin matrices respectively. Additionally, the introduction of neurotrophic factor NT-3 and the decrease in serum concentration to 2% FBS resulted in enrichment of OECs, with p75NTR at nearly 100% (100 ± 0% and 98 ± 2% on PDL and laminin respectively), and candidate fibroblast marker Thy1.1 decreased to zero. Culturing OECs at physiologically relevant oxygen tension (2–8%) had a negative impact on p75NTR expression and overall cell survival. Regarding cell potency, co-culture of OECs with NG108-15 neurons resulted in more neuronal growth and potential migration at atmospheric oxygen. Moreover, OECs behaved similarly to a Schwann cell line positive control. In conclusion, this work identified key bioprocessing fundamentals that will underpin future development of OEC-based cell therapies for potential use in spinal cord injury repair. However, there is still much work to do to create optimized isolation methods

Educational initiatives and training for paediatric rheumatology in Europe

The Paediatric Rheumatology European Society (PReS) has over many years, developed a portfolio of educational activities to address increasing educational needs of workforce and support young clinicians to acquire skills to develop new knowledge and deliver clinical care in the future. These educational activities aim to facilitate growth of paediatric rheumatology and ultimately improve the clinical care for children and families. This article describes the current portfolio of PReS educational activities and their relevance to the international paediatric rheumatology community