Heparin Isomeric Oligosaccharide Separation Using Volatile Salt Strong Anion Exchange Chromatography

The complexity of heparin and heparan sulfate saccharides makes their purification, including many isomeric structures, very challenging and is a bottleneck for structure–activity studies. High-resolution separations have been achieved by strong anion exchange (SAX) chromatography on Propac PA1 and cetyltrimethylammonium (CTA)-C18 silica columns; however, these entail subsequent desalting methodologies and consequent sample losses and are incompatible with orthogonal chromatography methodologies and, in particular, mass spectrometry. Here, we present the CTA-SAX purification of heparin oligosaccharides using volatile salt (VS) buffer. In VSCTA-SAX, the use of ammonium bicarbonate buffer for elution improves resolution through both weaker dissociation and conformational coordination of the ammonium across the sulfate groups. Using ion mobility mass spectrometry, we demonstrate that isomeric structures have different structural conformations, which makes chromatographic separation achievable. Resolution of such structures is improved compared to standard SAX methods, and in addition, VSCTA-SAX provides an orthogonal method to isolate saccharides with higher purity. Because ammonium bicarbonate is used, the samples can be evaporated rather than desalted, preventing substantial sample loss and allowing more effective subsequent analysis by electrospray mass spectrometry. We conclude that VSCTA-SAX is a powerful new tool that helps address the difficult challenge of heparin/heparan sulfate saccharide separation and will enhance structure–activity studies

The Implementation and Evaluation of a Media Literacy Intervention About PAES Use in Sport Science Students

With respect to both competitive and amateur/fitness sports, media may strongly influence young people’s opinions and behaviors concerning the use of PAES (Performance and Appearance Enhancing Substances). The present investigation addressed this topic by focusing on sport sciences students’ beliefs concerning the possible role of media related to the implementation and evaluation of a PAES-focus media literacy intervention conducted with sport science students. This study relied on a sample of 521 students (attrition rate 10.3%) (45.1% female, mean age = 22.6, SD = 2.20), which provided baseline data on students’ levels of media literacy concerning the use of PAES (i.e. “descriptive sample”), and a sample of 248 students, who participated in and provided data on the media literacy intervention. This latter sample included a group of 128 students (44.5% female, mean age = 23.03, SD = 3.76) who actively participated in the intervention (i.e. “intervention group”), and a group of 120 students who did not (i.e. “control group”, 53.3% female, mean age = 22.25, SD = 2.47). All students filled out media literacy questionnaires targeting students’ awareness of media influence, their views about the realism of media content, their sense of confidence in dealing with media messages, and their positive attitudes toward PAES use. Analyses of questionnaire data showed that students are relatively aware of media influence on people’s views and behaviors with respect to PAES use. At the same time, students also believed that young people do not consider media as “realistic sources” of information; nonetheless, they also did not consider themselves entirely capable of dealing effectively with media messages. With respect to the intervention, students overall appreciated and greatly welcomed the educational program on media literacy, and the analyses of intervention data across intervention and control groups showed that key media literacy variables changed over time, attesting to the overall effectiveness of the intervention.Ministry of Health, Italy CUPB86G17000660005 2017-

Enabling local public health adaptation to climate change

Local public health authorities often lack the capacity to adapt to climate change, despite being on the ‘front lines’ of climate impacts. Upper-level governments are well positioned to create an enabling environment for adaptation and build local public health authorities' capacity, yet adaptation literature has not specified how upper-level governments can build local-level adaptive capacity. In this paper we examine how federal and regional governments can contribute to enabling and supporting public health adaptation to climate change at the local level in federal systems. We outline the local level's self-assessed adaptive capacity for public health adaptation in Canadian and German comparative case studies, in terms of funding, knowledge and skills, organizations, and prioritization, drawing upon 30 semi-structured interviews. Based on interviewees' recommendations and complemented by scientific literature, we develop a set of practical measures that could enable or support local-level public health adaptation. We find that adaptive capacity varies widely between local public health authorities, but most report having insufficient funding and staff for adaptation activities. We propose 10 specific measures upper-level governments can take to build local public health authorities' capacity for adaptation, under the interrelated target areas of: building financial capital; developing and disseminating usable knowledge; collaborating and coordinating for shared knowledge; and claiming leadership. Federal and regional governments have an important role to play in enabling local-level public health adaptation, and have many instruments available to them to fulfill that role. Selecting and implementing measures to enable local public health authorities' adaptive capacity will require tailoring to, and consideration, of the local context and needs

What does the Paris Agreement mean for adaptation?

The Paris Agreement takes a significant step forward in strengthening the adaptation pillar of global climate policy. By widening the normative framing around adaptation, calling for stronger adaptation commitments from states, being explicit about the multilevel nature of adaptation governance, and outlining stronger transparency mechanisms for assessing adaptation progress, the Agreement is a milestone in ongoing efforts to make adaptation an equal priority with mitigation. Significant work remains to be done, however, to clarify how the long-term goal for adaptation set out in Article 7 will be meaningfully realized. The challenge for Parties in implementing the Paris Agreement will be to establish credible commitments from state and non-state actors with regard to adaptation planning, implementation, and financing

The Impact of the Human DNA Topoisomerase II C-Terminal Domain on Activity

Type II DNA topoisomerases (topos) are essential enzymes needed for the resolution of topological problems that occur during DNA metabolic processes. Topos carry out an ATP-dependent strand passage reaction whereby one double helix is passed through a transient break in another. Humans have two topoII isoforms, alpha and beta, which while enzymatically similar are differentially expressed and regulated, and are thought to have different cellular roles. The C-terminal domain (CTD) of the enzyme has the most diversity, and has been implicated in regulation. We sought to investigate the impact of the CTD domain on activity.We have investigated the role of the human topoII C-terminal domain by creating constructs encoding C-terminally truncated recombinant topoIIalpha and beta and topoIIalpha+beta-tail and topoIIbeta+alpha-tail chimeric proteins. We then investigated function in vivo in a yeast system, and in vitro in activity assays. We find that the C-terminal domain of human topoII isoforms is needed for in vivo function of the enzyme, but not needed for cleavage activity. C-terminally truncated enzymes had similar strand passage activity to full length enzymes, but the presence of the opposite C-terminal domain had a large effect, with the topoIIalpha-CTD increasing activity, and the topoIIbeta-CTD decreasing activity.In vivo complementation data show that the topoIIalpha C-terminal domain is needed for growth, but the topoIIbeta isoform is able to support low levels of growth without a C-terminal domain. This may indicate that topoIIbeta has an additional localisation signal. In vitro data suggest that, while the lack of any C-terminal domain has little effect on activity, the presence of either the topoIIalpha or beta C-terminal domain can affect strand passage activity. Data indicates that the topoIIbeta-CTD may be a negative regulator. This is the first report of in vitro data with chimeric human topoIIs

The effectiveness of public health interventions to reduce the health impact of climate change:a systematic review of systematic reviews

Climate change is likely to be one of the most important threats to public health in the coming years. Yet despite the large number of papers considering the health impact of climate change, few have considered what public health interventions may be of most value in reducing the disease burden. We aimed to evaluate the effectiveness of public health interventions to reduce the disease burden of high priority climate sensitive diseases

Examining the impact of 11 long-standing health conditions on health-related quality of life using the EQ-5D in a general population sample

Objectives Health-related quality of life (HRQoL) measures have been increasingly used in economic evaluations for policy guidance. We investigate the impact of 11 self-reported long-standing health conditions on HRQoL using the EQ-5D in a UK sample. Methods We used data from 13,955 patients in the South Yorkshire Cohort study collected between 2010 and 2012 containing the EQ-5D, a preference-based measure. Ordinary least squares (OLS), Tobit and two-part regression analyses were undertaken to estimate the impact of 11 long-standing health conditions on HRQoL at the individual level. Results The results varied significantly with the regression models employed. In the OLS and Tobit models, pain had the largest negative impact on HRQoL, followed by depression, osteoarthritis and anxiety/nerves, after controlling for all other conditions and sociodemographic characteristics. The magnitude of coefficients was higher in the Tobit model than in the OLS model. In the two-part model, these four long-standing health conditions were statistically significant, but the magnitude of coefficients decreased significantly compared to that in the OLS and Tobit models and was ranked from pain followed by depression, anxiety/nerves and osteoarthritis. Conclusions Pain, depression, osteoarthritis and anxiety/nerves are associated with the greatest losses of HRQoL in the UK population. The estimates presented in this article should be used to inform economic evaluations when assessing health care interventions, though improvements can be made in terms of diagnostic information and obtaining longitudinal data

Habituation and novelty detection fNIRS brain responses in 5 and 8 month old infants: The Gambia and UK

The first 1000 days of life are a critical window of vulnerability to exposure to socio-economic and health challenges (i.e. poverty/undernutrition). The Brain Imaging for Global Health (BRIGHT) project has been established to deliver longitudinal measures of brain development from 0-24 months in UK and Gambian infants and to assess the impact of early adversity. Here results from the Habituation-Novelty Detection functional near infrared spectroscopy (fNIRS) task at 5 and 8 months are presented (N = 62 UK; N = 115 Gambia). In the UK cohort distinct patterns of habituation and recovery of response to novelty are seen, becoming more robust from 5 to 8 months of age. This article is protected by copyright. All rights reserved. [Abstract copyright: This article is protected by copyright. All rights reserved.

Are local climate adaptation policies credible? A conceptual and operational assessment framework

After the Paris Agreement that put stronger emphasis on the development of climate change adaptation policies and on the definition of financing mechanisms, there is a patent need to track whether actual planning efforts are proving sufficient. This entails the development of assessment methods and metrics as plans are drafted and actions implemented. To this end, this paper explores the concept of credibility as a critical issue in climate policy and develops an Adaptation Policy Credibility (APC) conceptual and operational assessment framework for helping to allocate public funding and private investments, and for implementing and catalysing climate policy. Through a pilot testing in four early-adopting cities (Copenhagen, Durban, Quito and Vancouver), a clear potential for large-n tracking and assessment exercises of local climate adaptation plans is envisaged. The APC approach might also be useful to guide individual cities that aim to improve their adaptation planning and policy-making processes