Synthesis of optically-labelled vanadyl complexes and their evaluation as protein tyrosine phosphatase inhibitors and intracellular probes

Cysteine based phosphatases (CBPs) are a diverse family of enzymes that act to remove the phosphate group from proteins, phosphatidylinositols and other biomolecules, thereby counteracting the effects of kinases. Due to the wide range of roles they play in the cell, the CBPs are implicated in many diseases such as cancer, diabetes and neurodegenerative disorders, and therefore it is of interest to develop compounds to study these enzymes. Within our group, vanadium compounds have been shown to inhibit the CBPs with a potency and selectivity that can be tuned by varying the ligand and the oxidation state of the vanadium centre. One subset of interest is the vanadium complexes of 3-hydroxypicolinic acid which have an inhibition range against phosphatases of low nanomolar to high micromolar depending on the oxidation state of vanadium and the enzyme studied. A small selection of novel fluorescent vanadyl complexes based on the hydroxypicolinic acid motif have been synthesised as novel phosphatase inhibitors. Incorporation of an amine-functionalised spacer between the picolinate ligands provided a handle for incorporation of a fluorescent group away from the picolinate-vanadyl core. These compounds were then tested against a range of phosphatases to determine their potency and selectivity as inhibitors of CBPs. The complexes showed good inhibition properties against the CBPs investigated in a range similar to that of free vanadyl. The fluorophore was used to study the interaction of the vanadyl complexes with the enzymes, and to investigate cell uptake. Fluorescence quenching and anisotropy assays were carried out to look at the stability of complexes in assay conditions. From the data obtained it appears that the vanadyl complexes are stable in the presence of the enzymes and under assay conditions. Preliminary data also indicate that the complexes are taken up into cells and therefore can be investigated as intracellular probes.Open Acces

Offerings of women in the transformation of African higher education : a retrospective overview

Abstract: This article presents an unusual concrete insight to African higher education transformation. The purpose is to examine the roles of African women mainly Charlotte Maxeke, a South African, in the transformation of higher education and to identify the legacy these transformation offerings translate into for women. It is organized as follows: first, the origin of transformation in higher education systems to global massification of education in the background section is traced. Second, in an attempt to understand as a means of examining the roles of women in the transformation of higher education, existing literature as evidence is engaged. Two crucial issues— challenges for African higher education transformation and women’s role in higher education development in Africa—were reviewed analytically toward transformation of higher education. Third, empowerment theory, as suitable theory for the reasonable accomplishment of the purpose of this article, is presented. Last, the theory was applied to the discussions justifying the conclusion. The methodology used is both descriptive and exploratory. The article divulges that women had always being fanatical about empowerment of themselves and others because women had at some points in history contributed to developmental alterations of African higher education given..

Collaborative engagement for sustainability in the Asia Pacific region: call for papers

The formation of strategic alliances between companies for mutual commercial benefit is a widely used approach by contemporary business. The development of such alliances with non-commercial organisations, such as government agencies and voluntary associations, to deliver social and environmental outcomes, is a more recent phenomenon. In the past decade such cross-sectoral strategic alliances have become a key mechanism for pursuing corporate sustainability and responsibility. By bringing together their respective competencies and resources for the greater good, people in governments, business, civil society and multilateral agencies have sought innovative ways to respond to many contemporary sustainable development challenges: climate change; human security; the prevention and treatment of major diseases; ethics, governance and responsible investment; entrepreneurship and employment; pension and superannuation funds management; and, sustainable financing for development. Globally, the appetite for such strategic alliances and stakeholder engagement appears strong. Over 90% of corporate executives responding to a World Economic Forum survey felt that in future ‘partnerships between business, government, and civil society would play either a major role or some role in addressing key development challenges.’ This interest is paralleled by an expanding literature on inter-organisational relations in management, organisation and international development studies, among other disciplines

Clinical learning environment and supervision: satisfaction levels of University of Rwanda Students

Background: Nursing and midwifery students need to learn theoretical knowledge and practical skills. Students are satisfied with a clinical education program when the environment is conducive to acquiring the knowledge, skills and professional attitude essential for their career.Objective: To assess the level of satisfaction with the clinical learning environment among nursing and midwifery students at the University of Rwanda.Methods: A descriptive cross-sectional study design was used to assess 280 undergraduate nursing and midwifery students. The study used the instrument entitled, the ‘Clinical Learning Environment Supervision and Nurse Teacher Tool’ (CLES+T). Data analysis used descriptive statistics.Results: The majority of participants were highly satisfied with the clinical learning environment (58%), ward atmosphere (54%), the leadership of ward manager (58%) and supervisory relationship (62%). Chi-square results showed a significant association between class level (p=0.001) and last clinical placement (p=0.000). Some students (7%) were dissatisfied with the supervisory relationship.Conclusion: Most nursing and midwifery students were satisfied with the clinical learning environment. However, the reported levels of dissatisfaction showed that improvements are needed to attain a quality education and meet the Sustainable Development Goal (SDG) Four: to ensure inclusive and equitable quality education and promote lifelong learning opportunities for all.Keywords: Clinical placement, learning,student, satisfaction, nursing, midwifer

Birth, expansion, and death of VCY -containing palindromes on the human Y chromosome

Abstract: Background: Large palindromes (inverted repeats) make up substantial proportions of mammalian sex chromosomes, often contain genes, and have high rates of structural variation arising via ectopic recombination. As a result, they underlie many genomic disorders. Maintenance of the palindromic structure by gene conversion between the arms has been documented, but over longer time periods, palindromes are remarkably labile. Mechanisms of origin and loss of palindromes have, however, received little attention. Results: Here, we use fiber-FISH, 10x Genomics Linked-Read sequencing, and breakpoint PCR sequencing to characterize the structural variation of the P8 palindrome on the human Y chromosome, which contains two copies of the VCY (Variable Charge Y) gene. We find a deletion of almost an entire arm of the palindrome, leading to death of the palindrome, a size increase by recruitment of adjacent sequence, and other complex changes including the formation of an entire new palindrome nearby. Together, these changes are found in ~ 1% of men, and we can assign likely molecular mechanisms to these mutational events. As a result, healthy men can have 1–4 copies of VCY. Conclusions: Gross changes, especially duplications, in palindrome structure can be relatively frequent and facilitate the evolution of sex chromosomes in humans, and potentially also in other mammalian species

The 4 youth by youth HIV self-testing crowdsourcing contest: A qualitative evaluation.

INTRODUCTION: Crowdsourcing, a participatory approach to solicit ideas from a large group of diverse individuals, provides an opportunity to nurture youth participation in HIV self-testing service design. The objective of this study was to describe the responses to a crowdsourcing contest aimed at soliciting ideas on how to promote HIV self-testing (HIVST) among young people in Nigeria. METHODS: The "4 Youth by Youth" HIV Self-Testing Crowdsourcing contest was an online and off-line contest that asked Nigerian youth (10-24 years old) for ideas in response to the following: How might we promote HIVST among young people in Nigeria? All data were collected and analyzed between October 2018, and June 2019. Ideas and perceptions generated from the crowdsourcing contest were qualitatively analyzed using thematic content analysis. Specifically, four reviewers analyzed whether the ideas generated were desirable (appealing to young people), feasible (easy to implement) and impactful (will significantly influence HIVST uptake among young people). RESULTS: A total of 903 entries were received in response to the contest prompt. Participants submitted entries in various forms: online form (39.7%), offline Dropbox (44.6%), email (6.1%) and WhatsApp (9.7%). Of the total entries, 85% (n = 769/903) entries were eligible and were scored as having either high, moderate or low level of feasibility, impact and desirability, on a 3-point Likert scale. A significant portion of the entries were given a score of 3 for feasibility (4.9%), desirability (7.1%), impact (3.0%) or a total overall score of 7 or more (8.2%). The three main themes that emerged from the entries include:1) Peer-to-peer distribution and leveraging on existing infrastructures 2) Youth-Oriented Branding of the HIVST Kit 3) Mobile platforms and social media technology. CONCLUSION: The "4 Youth by Youth" Self-Testing contest engaged a broad audience of young people to generate ideas and perspectives on how to promote HIVST. This process informed the development of youth innovated implementation strategies to increase uptake of HIVST among adolescents and youth at risk for HIV

Risk prediction tools for cancer in primary care.

Numerous risk tools are now available, which predict either current or future risk of a cancer diagnosis. In theory, these tools have the potential to improve patient outcomes through enhancing the consistency and quality of clinical decision-making, facilitating equitable and cost-effective distribution of finite resources such as screening tests or preventive interventions, and encouraging behaviour change. These potential uses have been recognised by the National Cancer Institute as an 'area of extraordinary opportunity' and an increasing number of risk prediction models continue to be developed. The data on predictive utility (discrimination and calibration) of these models suggest that some have potential for clinical application; however, the focus on implementation and impact is much more recent and there remains considerable uncertainty about their clinical utility and how to implement them in order to maximise benefits and minimise harms such as over-medicalisation, anxiety and false reassurance. If the potential benefits of risk prediction models are to be realised in clinical practice, further validation of the underlying risk models and research to assess the acceptability, clinical impact and economic implications of incorporating them in practice are needed.This is the final version of the article. It was first available from NPG via http://dx.doi.org/10.1038/bjc.2015.40

Maintaining quality of health services after abolition of user fees: A Uganda case study

<p>Abstract</p> <p>Background</p> <p>It has been argued that quality improvements that result from user charges reduce their negative impact on utilization especially of the poor. In Uganda, because there was no concrete evidence for improvements in quality of care following the introduction of user charges, the government abolished user fees in all public health units on 1^stMarch 2001. This gave us the opportunity to prospectively study how different aspects of quality of care change, as a country changes its health financing options from user charges to free services, in a developing country setting. The outcome of the study may then provide insights into policy actions to maintain quality of care following removal of user fees.</p> <p>Methods</p> <p>A population cohort and representative health facilities were studied longitudinally over 3 years after the abolition of user fees. Quantitative and qualitative methods were used to obtain data. Parameters evaluated in relation to quality of care included availability of drugs and supplies and; health worker variables.</p> <p>Results</p> <p>Different quality variables assessed showed that interventions that were put in place were able to maintain, or improve the technical quality of services. There were significant increases in utilization of services, average drug quantities and stock out days improved, and communities reported health workers to be hardworking, good and dedicated to their work to mention but a few. Communities were more appreciative of the services, though expectations were lower. However, health workers felt they were not adequately motivated given the increased workload.</p> <p>Conclusion</p> <p>The levels of technical quality of care attained in a system with user fees can be maintained, or even improved without the fees through adoption of basic, sustainable system modifications that are within the reach of developing countries. However, a trade-off between residual perceptions of reduced service quality, and the welfare gains from removal of user fees should guide such a policy change.</p

Young people's preferences for HIV self-testing services in Nigeria: a qualitative analysis.

BACKGROUND: HIV self-testing (HIVST) provides young people with a convenient, discreet, and empowering way to know their HIV status. However, there is limited knowledge of young people's preferences for HIVST services and potential factors that may influence the uptake of HIVST among this population. The purpose of this research was to use qualitative methods to examine HIVST preferences among Nigerian youth. METHODS: Semi-structured in-depth interviews with a purposive sample of young people 14-24 years old were conducted in Lagos, Nigeria. Data were analyzed thematically to identify themes and domains related to preferences and factors influencing the use of HIV self-testing. RESULTS: A total of 65 youth with mean age of 21 years, were interviewed, and the majority were females (56%). Four themes emerged as the most important characteristics that may influence young people's preferences for HIV self-testing: 1) Cost (i.e. majority of participants noted that they would pay between NGN500 to NGN1,500 naira (USD1.38-USD4.16) for oral HIV self-testing kits); 2) Testing method (i.e. although blood-based sample kits were more popular than oral-based self-testing kits, most preferred the oral-based option due to its perceived benefits and for some, phobia of needles); 3) Access location (i.e. participants suggested they preferred to obtain the HIVST kits from youth-friendly centers, pharmacies, private health facilities, and online stores); and 4) Continuing care and support (i.e. participants highlighted the importance of linkage to care with trained youth health workers for positive or negative test results or toll-free helpline). CONCLUSION: HIV self-testing preferences among Nigerian youth appear to be influenced by several factors including lower cost, less invasive testing method, location of testing, and linkage to care and support post testing. Findings underscore the need to address young people's HIV self-testing preferences as a foundation for implementing programs and research to increase the uptake of HIVST