Do hypoxia/normoxia culturing conditions change the neuroregulatory profile of Wharton Jelly mesenchymal stem cells secretome?

Introduction: The use of human umbilical cord Wharton Jelly-derived mesenchymal stem cells (hWJ-MSCs) has been considered a new potential source for future safe applications in regenerative medicine. Indeed, the application of hWJ-MSCs into different animal models of disease, including those from the central nervous system, has shown remarkable therapeutic benefits mostly associated with their secretome. Conventionally, hWJ-MSCs are cultured and characterized under normoxic conditions (21 % oxygen tension), although the oxygen levels within tissues are typically much lower (hypoxic) than these standard culture conditions. Therefore, oxygen tension represents an important environmental factor that may affect the performance of mesenchymal stem cells in vivo. However, the impact of hypoxic conditions on distinct mesenchymal stem cell characteristics, such as the secretome, still remains unclear. Methods: In the present study, we have examined the effects of normoxic (21 % O2) and hypoxic (5 % O2) conditions on the hWJ-MSC secretome. Subsequently, we address the impact of the distinct secretome in the neuronal cell survival and differentiation of human neural progenitor cells. Results: The present data indicate that the hWJ-MSC secretome collected from normoxic and hypoxic conditions displayed similar effects in supporting neuronal differentiation of human neural progenitor cells in vitro. However, proteomic analysis revealed that the use of hypoxic preconditioning led to the upregulation of several proteins within the hWJ-MSC secretome. Conclusions: Our results suggest that the optimization of parameters such as hypoxia may lead to the development of strategies that enhance the therapeutic effects of the secretome for future regenerative medicine studies and applications. © 2015 Teixeira et al.Portuguese Foundation for Science and Technology (FCT) (Ciência 2007 program and IF Development Grant (AJS); and pre-doctoral fellowships to FGT (SFRH/69637/ 2010) and SIA (SFRH/BD/81495/2011); Canada Research Chairs (LAB) and a SSE Postdoctoral Fellowship (KMP); The National Mass Spectrometry Network (RNEM) (REDE/1506/REM/2005); co-funded by Programa Operacional Regional do Norte (ON.2 – O Novo Norte), ao abrigo do Quadro de Referência Estratégico Nacional (QREN), através do Fundo Europeu de Desenvolvimento Regional (FEDER).info:eu-repo/semantics/publishedVersio

Development and psychometric properties of the PROMIS® pediatric fatigue item banks

PURPOSE: This paper reports on the development and psychometric properties of self-reported pediatric fatigue item banks as part of the Patient Reported Outcomes Measurement Information System (PROMIS). METHODS: Candidate items were developed by using PROMIS qualitative methodology. The resulting 39 items (25 tiredness- and 14 energy-related) were field tested in a sample that included 3,048 participants aged 8–17 years. We used confirmatory factor analysis (CFA) to evaluate dimensionality, differential item functioning (DIF) analysis to evaluate parameter stability between genders and by age; we examined residual correlations to evaluate local dependence (LD) among items, and estimated the parameters of item response theory (IRT) models. RESULTS: Of 3,048 participants, 48% were males, 60% were white and 23% had at least one chronic condition. CFA results suggest two moderately correlated factors. Two items were removed due to high LD, and three due to gender-based DIF. Two item banks were calibrated separately using IRT: Tired and (Lack of) Energy, which consisted of 23 and 11 items, respectively; ten- and 8-item short-forms were created. CONCLUSION: The PROMIS assessment of self-reported fatigue in pediatrics includes two item banks: Tired and (Lack of) Energy. Both demonstrated satisfactory psychometric properties and can be used for research settings

Deaths and Medical Visits Attributable to Environmental Pollution in the United Arab Emirates

<div><p>Background</p><p>This study estimates the potential health gains achievable in the United Arab Emirates (UAE) with improved controls on environmental pollution. The UAE is an emerging economy in which population health risks have shifted rapidly from infectious diseases to chronic conditions observed in developed nations. The UAE government commissioned this work as part of an environmental health strategic planning project intended to address this shift in the nature of the country’s disease burden.</p> <p>Methods and Findings</p><p>We assessed the burden of disease attributable to six environmental exposure routes outdoor air, indoor air, drinking water, coastal water, occupational environments, and climate change. For every exposure route, we integrated UAE environmental monitoring and public health data in a spatially resolved Monte Carlo simulation model to estimate the annual disease burden attributable to selected pollutants. The assessment included the entire UAE population (4.5 million for the year of analysis). The study found that outdoor air pollution was the leading contributor to mortality, with 651 attributable deaths (95% confidence interval [CI] 143–1,440), or 7.3% of all deaths. Indoor air pollution and occupational exposures were the second and third leading contributors to mortality, with 153 (95% CI 85–216) and 46 attributable deaths (95% CI 26–72), respectively. The leading contributor to health-care facility visits was drinking water pollution, to which 46,600 (95% CI 15,300–61,400) health-care facility visits were attributed (about 15% of the visits for all the diseases considered in this study). Major study limitations included (1) a lack of information needed to translate health-care facility visits to quality-adjusted-life-year estimates and (2) insufficient spatial coverage of environmental data.</p> <p>Conclusions</p><p>Based on international comparisons, the UAE’s environmental disease burden is low for all factors except outdoor air pollution. From a public health perspective, reducing pollutant emissions to outdoor air should be a high priority for the UAE’s environmental agencies.</p> </div