Negishi Coupling of Pteridine-O-sulfonates

Negishi coupling of pteridine-O-sulfonate with Zn-aryls is reported. Hydrolysis of the protecting groups with 1M NH3 gave the 6-subustituted 2,4-diaminopteridine while hydrolysis with 1 M NaOH gave the 6-subsituted pterin.KEYWORDS Pteridine, pterin, Negishi coupling

Evaluation of the anti-mycobacterial, anti-oxidative and anti-proliferative activities of Rubia cordifolia ethanolic leaf extract sub-fractions in human lymphocytes and neutrophils

Background.  Rubia cordifolia has been used to treat various diseases and exhibits antimicrobial, anti-inflammatory, analgesic and antidiarrheal activities. The plant has not been investigated for its anti-mycobacterial activity against virulent tuberculosis strains as well as cytotoxic and anti-oxidant activities in mononuclear cells and neutrophils.Methods. Ethanolic and dichloromethane leaf extract fractions of Rubia cordifolia (0.2- 125μg/ml) were screened for anti-mycobacterial activity using a fluorescent microplate assay. The anti-oxidant activity of the fractions was tested using the radical scavenging assay, while their cytotoxicity to lymphocytes was measured using the WST-8 assay. Reactive oxygen species production by neutrophils exposed to fractions was tested using Cell Meter™ Fluorimetric ROS Assay kit.Results. The ethanolic leaf fractions exhibited overall superior anti-mycobacterial activity than the dichloromethane group and were further screened for anti-oxidant and cytotoxic activities. Ethanolic sub-fractions K2F-3.2, K2F-3.3 and K2F-3.4 showed significant antioxidant activities at concentration of 50 μg/ml to 200 μg/ml and higher in both the cell free-based radical scavenging activity and total reactive oxygen species production assays. For lymphocytes, the test agents showed anti-proliferative activity at 25 μg/ml to 200 μg/ml for sub-fraction K2F-3.3B and 50 μg/ml to 200 μg/ml for agents K2F-3.2 and K2F-3.4.Conclusion. The current study is the first to record the in vitro anti-mycobacterial, anti-oxidant and cytotoxic activities of Rubia cordifolia plant leaf extract sub-fractions using the given experimental setups and further research activities to identify the bioactive components are to be pursued.Keywords: Rubia cordifolia, DPPH, Mycobacteria, cell proliferation, antioxidant activity, RO

Substance use patterns in an adolescent psychiatric unit in Johannesburg, South Africa

Background: Substance use among adolescents carries a significant public health and socioeconomic burden with potential long-term consequences for the adolescent substance user (SU). Adolescents with mental health challenges are vulnerable to substance use and substance use worsens outcomes in this population. Aim: This study aimed to describe the substance use patterns among inpatients admitted to a specialised tertiary adolescent inpatient unit in Johannesburg over a 4-year period. Setting: This study was conducted at the Tara H. Moross Centre (Tara Hospital), in Johannesburg in the Gauteng province of South Africa. Methods: This was a retrospective comparative record review of all patients admitted to the adolescent unit over the 4 years. Results: A lifetime history of substance use was documented in 44.1% (n = 52) of the 118 patient’s records included in the final analysis. Cannabis was the most frequently used substance (n = 36, 69.2%). There were significant differences between the SU and substance nonuser groups regarding family structure (p = 0.012), family history of substance abuse (p = 0.046) and conflict within the family (p 0.001). Conclusion: The high prevalence of substance use in this sample demonstrates the dual burden of mental health disorders and substance use in an adolescent treatment programme in Johannesburg. Primary caregiver burden and relational difficulties within the family unit should be observed for planned multidisciplinary interventions. Contribution: The findings of this review provide an update on the pattern and prevalence of substance use among this adolescent mental healthcare user group, highlighting potential therapeutic targets

Assessment of capacity for Health Policy and Systems Research and Analysis in seven African universities: results from the CHEPSAA project

The importance of health policy and systems research and analysis (HPSR+A) is widely recognised. Universities are central to strengthening and sustaining the HPSR+A capacity as they teach the next generation of decision-makers and health professionals. However, little is known about the capacity of universities, specifically, to develop the field. In this paper we report results of capacity self-assessments by seven universities within five African countries, conducted through the Consortium for Health Policy and Systems Analysis in Africa (CHEPSAA). The capacity assessments focused on both capacity assets and needs, and covered the wider context, as well as organisational and individual capacity levels. Six thematic areas of capacity were examined: leadership and governance, organisation’s resources, scope of HPSR+A teaching and research, communication, networking and GRIPP, demand for HPRS+A, and resource environment. The self-assessments by each university used combinations of document reviews, semi-structured interviews and staff surveys, followed by comparative analysis. A Framework Approach, guided by the six thematic areas, was used to analyse data. We found that HPSR+A is an international priority, and an existing activity in Africa, though still neglected field with challenges including its reliance on unpredictable international funding. All universities have capacity assets, such as on-going HPSR+A teaching and research. There are, however, varying levels of assets (such as differences in staff numbers, group sizes and amount of HPSR+A teaching and research), which, combined with different capacity needs at all three levels (such as individual training, improvement in systems for quality assurance and fostering demand for HPSR+A work), can shape a future agenda for HPSR+A capacity strengthening. Capacity assets and needs at different levels appear related. Possible integrated strategies for strengthening universities’ capacity include: refining HPSR+A vision, mainstreaming the subject into under- and post-graduate teaching, developing emerging leaders and aligning HPSR+A capacity strengthening within the wider organisational development

Re-Generating Research Partnerships in Early Childhood Education: A Non-Idealized Vision

This chapter provides a challenge to positivist notions of partnership in early childhood education, and instead proposes a re-generative posthumanist perspective, based on relationality of partnerships. Specifically, the chapter addresses the troubles and struggles inherited in research partnerships through a non-idealized vision of research partnerships. It experiments with the notions of regenerating ‘change’ and regenerating ‘relationality’. It also addresses the multi-layered aspects of knowledge-in-the-making; non-innocent relations; difficulties of thinking change in research; and the potentialities of conflict and dissension. However, no certainties and closures about research partnerships are provided

Easy-To-Synthesize Spirocyclic Compounds Possess Remarkable in Vivo Activity against Mycobacterium tuberculosis

Society urgently needs new, effective medicines for the treatment of tuberculosis. To kick-start the required hit-to-lead campaigns, the libraries of pharmaceutical companies have recently been evaluated for starting points. The GlaxoSmithKline (GSK) library yielded many high-quality hits, and the associated data were placed in the public domain to stimulate engagement by the wider community. One such series, the spiro compounds, are described here. The compounds were explored by a combination of traditional in-house research and open source methods. The series benefits from a particularly simple structure and a short associated synthetic chemistry route. Many members of the series displayed striking potency and low toxicity, and highly promising in vivo activity in a mouse model was confirmed with one of the analogues. Ultimately the series was discontinued due to concerns over safety, but the associated data remain public domain, empowering others to resume the series if the perceived deficiencies can be overcome

The met and unmet health needs for HIV, hypertension, and diabetes in rural KwaZulu-Natal, South Africa: analysis of a cross-sectional multimorbidity survey

BACKGROUND: The convergence of infectious diseases and non-communicable diseases in South Africa is challenging to health systems. In this analysis, we assessed the multimorbidity health needs of individuals and communities in rural KwaZulu-Natal and established a framework to quantify met and unmet health needs for individuals living with infectious and non-communicable diseases. METHODS: We analysed data collected between May 25, 2018, and March 13, 2020, from participants of a large, community-based, cross-sectional multimorbidity survey (Vukuzazi) that offered community-based HIV, hypertension, and diabetes screening to all residents aged 15 years or older in a surveillance area in the uMkhanyakude district in KwaZulu-Natal, South Africa. Data from the Vukuzazi survey were linked with data from demographic and health surveillance surveys with a unique identifier common to both studies. Questionnaires were used to assess the diagnosed health conditions, treatment history, general health, and sociodemographic characteristics of an individual. For each condition (ie, HIV, hypertension, and diabetes), individuals were defined as having no health needs (absence of condition), met health needs (condition that is well controlled), or one or more unmet health needs (including diagnosis, engagement in care, or treatment optimisation). We analysed met and unmet health needs for individual and combined conditions and investigated their geospatial distribution. FINDINGS: Of 18 041 participants who completed the survey (12 229 [67·8%] were female and 5812 [32·2%] were male), 9898 (54·9%) had at least one of the three chronic diseases measured. 4942 (49·9%) of these 9898 individuals had at least one unmet health need (1802 [18·2%] of 9898 needed treatment optimisation, 1282 [13·0%] needed engagement in care, and 1858 [18·8%] needed a diagnosis). Unmet health needs varied by disease; 1617 (93·1%) of 1737 people who screened positive for diabetes, 2681 (58·2%) of 4603 people who screened positive for hypertension, and 1321 (21·7%) of 6096 people who screened positive for HIV had unmet health needs. Geospatially, met health needs for HIV were widely distributed and unmet health needs for all three conditions had specific sites of concentration; all three conditions had an overlapping geographical pattern for the need for diagnosis. INTERPRETATION: Although people living with HIV predominantly have a well controlled condition, there is a high burden of unmet health needs for people living with hypertension and diabetes. In South Africa, adapting current, widely available HIV care services to integrate non-communicable disease care is of high priority. FUNDING: Fogarty International Center and the National Institutes of Health, the Bill & Melinda Gates Foundation, the South African Department of Science and Innovation, the South African Medical Research Council, the South African Population Research Infrastructure Network, and the Wellcome Trust. TRANSLATION: For the isiZulu translation of the abstract see Supplementary Materials section