CD39 abrogates platelet-derived factors induced IL-1β expression in the human placenta

Tissue insults in response to inflammation, hypoxia and ischemia are accompanied by the release of ATP into the extracellular space. There, ATP modulates several pathological processes, including chemotaxis, inflammasome induction and platelet activation. ATP hydrolysis is significantly enhanced in human pregnancy, suggesting that increased conversion of extracellular ATP is an important anti-inflammatory process in preventing exaggerated inflammation, platelet activation and hemostasis in gestation. Extracellular ATP is converted into AMP, and subsequently into adenosine by the two major nucleotide-metabolizing enzymes CD39 and CD73. Here, we aimed to elucidate developmental changes of placental CD39 and CD73 over gestation, compared their expression in placental tissue from patients with preeclampsia and healthy controls, and analyzed their regulation in response to platelet-derived factors and different oxygen conditions in placental explants as well as the trophoblast cell line BeWo. Linear regression analysis showed a significant increase in placental CD39 expression, while at the same time CD73 levels declined at term of pregnancy. Neither maternal smoking during first trimester, fetal sex, maternal age, nor maternal BMI revealed any effects on placental CD39 and CD73 expression. Immunohistochemistry detected both, CD39 and CD73, predominantly in the syncytiotrophoblast layer. Placental CD39 and CD73 expression were significantly increased in pregnancies complicated with preeclampsia, when compared to controls. Cultivation of placental explants under different oxygen conditions had no effect on the ectonucleotidases, whereas presence of platelet releasate from pregnant women led to deregulated CD39 expression. Overexpression of recombinant human CD39 in BeWo cells decreased extracellular ATP levels after culture in presence of platelet-derived factors. Moreover, platelet-derived factors-induced upregulation of the pro-inflammatory cytokine, interleukin-1β, was abolished by CD39 overexpression. Our study shows that placental CD39 is upregulated in preeclampsia, suggesting an increasing demand for extracellular ATP hydrolysis at the utero-placental interface. Increased placental CD39 in response to platelet-derived factors may lead to enhanced conversion of extracellular ATP levels, which in turn could represent an important anti-coagulant defense mechanism of the placenta

Effective practices of international volunteering for health : perspectives from partner organizations

Abstract: The demand for international volunteer experiences to promote global health and nutrition is increasing and numerous studies have documented the experiences of the international volunteers who travel abroad; however, little is known about effective practices from the perspective of partner organizations. This study aims to understand how variables such as the skill-level of volunteers, the duration of service, cultural and language training, and other key variables affect partner organizations’ perceptions of volunteer effectiveness at promoting healthcare and nutrition..

Electives in undergraduate medical education: AMEE Guide No. 88

This Guide outlines the scope and potential roles an elective can contribute to undergraduate medical training and identifies ways to maximize learning opportunities, including within global health. The types of educational activity available for electives range from meeting individual educational need through to exploration of potential career pathways, with many factors influencing choice. Key areas of organization underpinning a successful elective before, during and after the placement include developing clarity of the intended educational outcomes as well as addressing practicalities such as travel and accommodation. Risk management including the implications for the participating schools as well as the student and their elective supervisors is crucial. This Guide would not be complete without some discussion around ethics and professional conduct during an elective, with consideration of the impact of elective placements, particularly in low-middle income countries

Extent, nature and consequences of performing outside scope of training in global health

Background Globalization has made it possible for global health professionals and trainees to participate in short-term training and professional experiences in a variety of clinical- and non-clinical activities across borders. Consequently, greater numbers of healthcare professionals and trainees from high-income countries (HICs) are working or volunteering abroad and participating in short-term experiences in low- and middle-income countries (LMICs). How effective these activities are in advancing global health and in addressing the crisis of human resources for health remains controversial. What is known, however, is that during these short-term experiences in global health (STEGH), health professionals and those in training often face substantive ethical challenges. A common dilemma described is that of acting outside of one’s scope of training. However, the frequency, nature, circumstances, and consequences of performing outside scope of training (POST) have not been well-explored or quantified. Methods The authors conducted an online survey of HIC health professionals and trainees working or volunteering in LMICs about their experiences with POST, within the last 5 years. Results A total of 223 survey responses were included in the final analysis. Half (49%) of respondents reported having been asked to perform outside their scope of training; of these, 61% reported POST. Trainees were nearly twice as likely as licensed professionals to report POST. Common reasons cited for POST were a mismatch of skills with host expectations, suboptimal supervision at host sites, inadequate preparation to decline POST, a perceived lack of alternative options and emergency situations. Many of the respondents who reported POST expressed moral distress that persisted over time. Conclusions Given that POST is ethically problematic and legally impermissible, the high rates of being asked, and deciding to do so, were notable. Based on these findings, the authors suggest that additional efforts are needed to reduce the incidence of POST during STEGH, including pre-departure training to navigate dilemmas concerning POST, clear communication regarding expectations, and greater attention to the moral distress experienced by those contending with POST

Power, potential, and pitfalls in global health academic partnerships: review and reflections on an approach in Nepal

ABSTRACT Background:: Global health academic partnerships are centered around a core tension: they often mirror or reproduce the very cross-national inequities they seek to alleviate. On the one hand, they risk worsening power dynamics that perpetuate health disparities; on the other, they form an essential response to the need for healthcare resources to reach marginalized populations across the globe. Objectives:: This study characterizes the broader landscape of global health academic partnerships, including challenges to developing ethical, equitable, and sustainable models. It then lays out guiding principles of the specific partnership approach, and considers how lessons learned might be applied in other resource-limited settings. Methods:: The experience of a partnership between the Ministry of Health in Nepal, the non-profit healthcare provider Possible, and the Health Equity Action and Leadership Initiative at the University of California, San Francisco School of Medicine was reviewed. The quality and effectiveness of the partnership was assessed using the Tropical Health and Education Trust Principles of Partnership framework. Results:: Various strategies can be taken by partnerships to better align the perspectives of patients and public sector providers with those of expatriate physicians. Actions can also be taken to bring greater equity to the wealth and power gaps inherent within global health academic partnerships. Conclusions:: This study provides recommendations gleaned from the analysis, with an aim towards both future refinement of the partnership and broader applications of its lessons and principles. It specifically highlights the importance of targeted engagements with academic medical centers and the need for efficient organizational work-flow practices. It considers how to both prioritize national and host institution goals, and meet the career development needs of global health clinicians