Glycomics Analysis of Mammalian Heparan Sulfates Modified by the Human Extracellular Sulfatase HSulf2

The Sulfs are a family of endosulfatases that selectively modify the 6O-sulfation state of cell-surface heparan sulfate (HS) molecules. Sulfs serve as modulators of cell-signaling events because the changes they induce alter the cell surface co-receptor functions of HS chains. A variety of studies have been aimed at understanding how Sulfs modify HS structure, and many of these studies utilize Sulf knockout cell lines as the source for the HS used in the experiments. However, genetic manipulation of Sulfs has been shown to alter the expression levels of HS biosynthetic enzymes, and in these cases an assessment of the fine structural changes induced solely by Sulf enzymatic activity is not possible. Therefore, the present work aims to extend the understanding of substrate specificities of HSulf2 using in vitro experiments to compare HSulf2 activities on HS from different organ tissues.To further the understanding of Sulf enzymatic activity, we conducted in vitro experiments where a variety of mammalian HS substrates were modified by recombinant human Sulf2 (HSulf2). Subsequent to treatment with HSulf2, the HS samples were exhaustively depolymerized and analyzed using size-exclusion liquid chromatography-mass spectrometry (SEC-LC/MS). We found that HSulf2 activity was highly dependent on the structural features of the HS substrate. Additionally, we characterized, for the first time, the activity of HSulf2 on the non-reducing end (NRE) of HS chains. The results indicate that the action pattern of HSulf2 at the NRE is different compared to internally within the HS chain.The results of the present study indicate that the activity of Sulfs is dependent on the unique structural features of the HS populations that they edit. The activity of HSulf2 at HS NREs implicates the Sulfs as key regulators of this region of the chains, and concomitantly, the protein-binding events that occur there

Leadership, action, learning and accountability to deliver quality care for women, newborns and children

Recognizing the need for action, the national governments of Bangladesh, Côte d’Ivoire, Ethiopia, Ghana, India, Malawi, Nigeria, Uganda and United Republic of Tanzania, together with WHO, the United Nations Children’s Fund (UNICEF), the United Nations Population Fund (UNFPA), implementation partners and other stakeholders, have established the Network for Improving Quality of Care for Maternal Newborn and Child Health care.10 The network has agreed to pursue the ambitious goals of halving maternal and newborn deaths and stillbirths and improving experience of care in participating health facilities within five years of implementation. Under the leadership of the participating countries’ health ministries, the network will support the implementation of national frameworks for quality improvement by pursuing four strategic objectives: (i) leadership by building and strengthening national institutions and processes for improving quality of care; (ii) action by accelerating and sustaining implementation of quality-of-care improvement packages through operationalizing a standards-based approach to quality improvement; (iii) learning by promoting joint learning and generating evidence on quality planning, improvement and control of health services; and (iv) accountability by developing, strengthening and sustaining institutions and mechanisms for accountability of quality maternal, neonatal and child health services that are equitable and dignified

National learning systems to sustain and scale up delivery of quality healthcare: a conceptual framework

All around the world, health systems fail to provide good quality of care (QoC). By developing learning systems, health systems are able to better identify good practices and to explain how to sustain and scale these good practices. To facilitate the operationalisation of national learning systems, the Network for Improving Quality of Care for Maternal Newborn and Child Health (the Network) developed a conceptual framework for national learning systems to support QoC at scale. The Network facilitated an iterative process to reach consensus on a conceptual framework for national learning systems to sustain and scale up delivery of quality healthcare. Following a landscape analysis, the Network Secretariat and WHO convened two consultative meetings with country partners, technical experts and stakeholders. Based on these inputs, we developed a conceptual framework for national learning systems to support QoC at scale. National learning systems use a variety of approaches to identify practices that have improved QoC at the patient and provider levels. They also facilitate scale up and sustain strategies used successfully to support quality improvement. Despite growing consensus on the importance of learning for QoC, no one has yet detailed how this learning should be operationalised nationally. Our conceptual framework is the first to facilitate the operationalisation of national learning systems so that health systems can begin to develop, adapt and implement mechanisms to learn about what works or fails and to scale up and sustain this learning for QoC