Survey of Nematode-Destroying Fungi from Selected Vegetable-Growing Areas in Kenya

Plant-parasitic nematodes cause severe damage to a wide range of economic crops, causing upto 5% yield losses globally. In Kenya, vegetables are affected, among other pests, by parasitic nematodes, causing upto 80% loss in yield. Nematode control is very difficult and relies heavily on use of chemical nematicides. Use of these chemical nematicides leads to biological magnification, and elimination of natural enemies of other pathogens, thus creating a need for greater application of pesticides, increased production costs, and development of insecticide-resistance. These factors have led to a growing interest in search for alternate management strategies. The objective of this study was, therefore, to document nematode-destroying fungi in selected, major vegetable-growing areas in Kenya as a step towards developing a self-sustaining system for management of plant-parasitic nematodes. Soil samples were collected from five vegetable-production zones, viz., Kinare, Kabete, Athi-river, Machakos and Kibwezi, and transported to the laboratory for extraction of nematode-destroying fungi. The soil-sprinkle technique described by Jaffee et al (1996) was used for isolating the nematode-destroying fungi from soil, while, their identification was done using identification keys described by Soto Barrientos et al (2001). From this study, a total of 171 fungal isolates were identified as nematodedestroying. The highest population was recorded in Kabete, at 33.9% of the total, followed by Machakos, Kibwezi, Athi-river, with the least in Kinare, at 24.6, 22.2, 11.7 and 7.6% of the total population, in that order. Arthrobotrys was the most frequent genus, with mean occurrence of 7.3, followed by Monacrosporium with 6 and Stylophage with 5.2. A. dactyloides was significantly (P=0.002) affected by the agro-ecological zone, with the highest occurrence recorded in Kabete, and the least in Athi-river. Kibwezi recorded highest diversity index, with a mean of 1.017, while, Athi-river recorded the least, with a mean of 0.333. Kibwezi had the highest species richness, recording a mean of 3.4, while, the least mean of 1.6 was recorded in Athi-river. Mean species richness of 2.2 was recorded for both Kabete and Machakos, and 1.8 for Kinare. From the three genera recorded, Arthrobotrys was more effective at trapping nematodes compared to Monocrosporium and Stylopage. The genus Arthrobotrys had the highest number of trapped nematodes, with a total population of 57, followed by Monacrosporium, the least being Stylopage, with 45 and 36, respectively, in a period of 104 hours. From the study, it is evident that agricultural practices affect occurrence and diversity of nematodedestroying fungi, and, Arthrobotrys can be used as a bio-control agent for managing plant-parasitic nematodes

A system dynamics-based scenario analysis of residential solid waste management in Kisumu, Kenya

The problem of solid waste management presents an issue of increasing importance in many low-income settings, including the progressively urbanised context of Kenya. Kisumu County is one such setting with an estimated 500 t of waste generated per day and with less than half of it regularly collected. The open burning and natural decay of solid waste is an important source of greenhouse gas (GHG) emissions and atmospheric pollutants with adverse health consequences. In this paper, we use system dynamics modelling to investigate the expected impact on GHG and PM_{2.5} emissions of (i) a waste-to-biogas initiative and (ii) a regulatory ban on the open burning of waste in landfill. We use life tables to estimate the impact on mortality of the reduction in PM_{2.5} exposure. Our results indicate that combining these two interventions can generate over 1.1 million tonnes of cumulative savings in GHG emissions by 2035, of which the largest contribution (42%) results from the biogas produced replacing unclean fuels in household cooking. Combining the two interventions is expected to reduce PM_{2.5} emissions from the waste and residential sectors by over 30% compared to our baseline scenario by 2035, resulting in at least around 1150 cumulative life years saved over 2021–2035. The contribution and novelty of this study lies in the quantification of a potential waste-to-biogas scenario and its environmental and health impact in Kisumu for the first time

The wicked problem of waste management: An attention-based analysis of stakeholder behaviours

Copyright © 2021 The Authors. Surging amounts of waste are reported globally and especially in lower-income countries, with negative consequences for health and the environment. Increasing concern has been raised for the limited progress achieved in practice by diverse sets of policies and programmes. Waste management is a wicked problem characterised by multilayered interdependencies, complex social dynamics and webs of stakeholders. Interactions among these generate unpredictable outcomes that can be missed by decision makers through their understanding and framing of their context. This article aims to identify possible sources of persistent problems by focussing on what captures, shapes and limits the attention of stakeholders and decision-makers, drawing on the attention-based view from organisation theory. The theory describes the process through which issues and opportunities are noticed and how these are translated into actions, by focussing on the influencers at the individual, organisational and context scale. Views on issues and opportunities for waste management were collected in a series of fieldwork activities from 60 participants representing seven main types of stakeholders in the typical lower-middle income Kenyan city of Kisumu. Through a thematic analysis guided by the attention-based view, we identified patterns and misalignment of views, especially between government, community-based organisations and residents, which may contribute to persistent waste problems in Kisumu. Some point to detrimental waste handling practices, from separation to collection and treatment, as the main cause of issues. For others, these practices are due to a poor control of such practices and enforcement of the law. This study's major theoretical contribution is extending the application of attention theory to multi-stakeholder problems and to non-formalized organisations, namely residents and to the new field of waste management. This novel lens contributes a greater understanding of waste issues and their management in Africa that is relevant to policy and future research. By revealing the “wickedness” of the waste problem, we point to the need for a holistic and systems-based policy approach to limit further unintended consequences.Wellcome Trust (CUSSH project, ref. no. 209387/Z/17/Z); U.K. Natural Environment Research Council (CAMELLIA project, ref. no. NE/S003495/1)

Developing a programme theory for a transdisciplinary research collaboration: Complex Urban Systems for Sustainability and Health [version 1; peer review: 2 approved]

Background: Environmental improvement is a priority for urban sustainability and health and achieving it requires transformative change in cities. An approach to achieving such change is to bring together researchers, decision-makers, and public groups in the creation of research and use of scientific evidence. / Methods: This article describes the development of a programme theory for Complex Urban Systems for Sustainability and Health (CUSSH), a four-year Wellcome-funded research collaboration which aims to improve capacity to guide transformational health and environmental changes in cities. / Results: Drawing on ideas about complex systems, programme evaluation, and transdisciplinary learning, we describe how the programme is understood to “work” in terms of its anticipated processes and resulting changes. The programme theory describes a chain of outputs that ultimately leads to improvement in city sustainability and health (described in an ‘action model’), and the kinds of changes that we expect CUSSH should lead to in people, processes, policies, practices, and research (described in a ‘change model’). / Conclusions: Our paper adds to a growing body of research on the process of developing a comprehensive understanding of a transdisciplinary, multiagency, multi-context programme. The programme theory was developed collaboratively over two years. It involved a participatory process to ensure that a broad range of perspectives were included, to contribute to shared understanding across a multidisciplinary team. Examining our approach allowed an appreciation of the benefits and challenges of developing a programme theory for a complex, transdisciplinary research collaboration. Benefits included the development of teamworking and shared understanding and the use of programme theory in guiding evaluation. Challenges included changing membership within a large group, reaching agreement on what the theory would be ‘about’, and the inherent unpredictability of complex initiatives

Inhibition of all-TRANS-retinoic acid metabolism by R116010 induces antitumour activity

All-trans-retinoic acid is a potent inhibitor of cell proliferation and inducer of differentiation. However, the clinical use of all-trans-retinoic acid in the treatment of cancer is significantly hampered by its toxicity and the prompt emergence of resistance, believed to be caused by increased all-trans-retinoic acid metabolism. Inhibitors of all-trans-retinoic acid metabolism may therefore prove valuable in the treatment of cancer. In this study, we characterize R116010 as a new anticancer drug that is a potent inhibitor of all-trans-retinoic acid metabolism. In vitro, R116010 potently inhibits all-trans-retinoic acid metabolism in intact T47D cells with an IC50-value of 8.7 nM. In addition, R116010 is a selective inhibitor as indicated by its inhibition profile for several other cytochrome P450-mediated reactions. In T47D cell proliferation assays, R116010 by itself has no effect on cell proliferation. However, in combination with all-trans-retinoic acid, R116010 enhances the all-trans-retinoic acid-mediated antiproliferative activity in a concentration-dependent manner. In vivo, the growth of murine oestrogen-independent TA3-Ha mammary tumours is significantly inhibited by R116010 at doses as low as 0.16 mg kg−1. In conclusion, R116010 is a highly potent and selective inhibitor of all-trans-retinoic acid metabolism, which is able to enhance the biological activity of all-trans-retinoic acid, thereby exhibiting antitumour activity. R116010 represents a novel and promising anticancer drug with an unique mechanism of action

Molecular targeting of retinoic acid metabolism in neuroblastoma: the role of the CYP26 inhibitor R116010 in vitro and in vivo

Isomerisation to all-trans-retinoic acid (ATRA) is widely accepted as the key mechanism underlying the favourable clinical properties of 13-cis-retinoic acid (13cisRA). As intracellular metabolism of ATRA by CYP26 may result in clinical resistance to 13cisRA, an increase in efficacy may be achieved through modulation of this metabolic pathway. We have evaluated the effect of the CYP26 inhibitor R116010 on retinoid metabolism in neuroblastoma cell lines and a xenograft model. In neuroblastoma cells, which showed a high level of CYP26 induction in response to ATRA, R116010 selectively inhibited ATRA metabolism. In addition, siRNA-mediated knockdown of CYP26 selectively increased ATRA levels and the expression of retinoid-responsive marker genes was potentiated by R116010. Treatment of mice bearing SH-SY5Y xenografts with 13cisRA (100 mg kg−1) revealed substantial levels (16%) of intratumoral ATRA after 6 h, despite plasma ATRA levels representing only 1% total retinoids under these conditions. Co-administration of R116010 with 13cisRA in this mouse model resulted in significant increases in plasma ATRA and 13cisRA concentrations. Furthermore, R116010 induced significant decreases in levels of 4-oxo metabolites in hepatic tissue after co-administration with either ATRA or 13cisRA. These data suggest considerable potential for CYP26 inhibitors in the future treatment of neuroblastoma with 13cisRA

Pharmacokinetics and metabolism of 13-cis-retinoic acid (isotretinoin) in children with high-risk neuroblastoma – a study of the United Kingdom Children's Cancer Study Group

The administration of 13-cis-retinoic acid (13-cisRA), following myeloablative therapy improves 3-year event-free survival rates in children with high-risk neuroblastoma. This study aimed to determine the degree of inter-patient pharmacokinetic variation and extent of metabolism in children treated with 13-cisRA. 13-cis-retinoic acid (80 mg m−2 b.d.) was administered orally and plasma concentrations of parent drug and metabolites determined on days 1 and 14 of courses 2, 4 and 6 of treatment. Twenty-eight children were studied. The pharmacokinetics of 13-cisRA were best described by a modified one-compartment, zero-order absorption model combined with lag time. Mean population pharmacokinetic parameters included an apparent clearance of 15.9 l h−1, apparent volume of distribution of 85 l and absorption lag time of 40 min with a large inter-individual variability associated with all parameters (coefficients of variation greater than 50%). Day 1 peak 13-cisRA levels and exposure (AUC) were correlated with method of administration (P<0.02), with 2.44- and 1.95-fold higher parameter values respectively, when 13-cisRA capsules were swallowed as opposed to being opened and the contents mixed with food before administration. Extensive accumulation of 4-oxo-13-cisRA occurred during each course of treatment with plasma concentrations (mean±s.d. 4.67±3.17 μM) higher than those of 13-cisRA (2.83±1.44 μM) in 16 out of 23 patients on day 14 of course 2. Extensive metabolism to 4-oxo-13-cisRA may influence pharmacological activity of 13-cisRA

Increasing the intracellular availability of all-trans retinoic acid in neuroblastoma cells

Recent data indicate that isomerisation to all-trans retinoic acid (ATRA) is the key mechanism underlying the favourable clinical properties of 13-cis retinoic acid (13cisRA) in the treatment of neuroblastoma. Retinoic acid (RA) metabolism is thought to contribute to resistance, and strategies to modulate this may increase the clinical efficacy of 13cisRA. The aim of this study was to test the hypothesis that retinoids, such as acitretin, which bind preferentially to cellular retinoic acid binding proteins (CRABPs), or specific inhibitors of the RA hydroxylase CYP26, such as R116010, can increase the intracellular availability of ATRA. Incubation of SH-SY5Y cells with acitretin (50 μM) or R116010 (1 or 10 μM) in combination with either 10 μM ATRA or 13cisRA induced a selective increase in intracellular levels of ATRA, while 13cisRA levels were unaffected. CRABP was induced in SH-SY5Y cells in response to RA. In contrast, acitretin had no significant effect on intracellular retinoid concentrations in those neuroblastoma cell lines that showed little or no induction of CRABP after RA treatment. Both ATRA and 13cisRA dramatically induced the expression of CYP26A1 in SH-SY5Y cells, and treatment with R116010, but not acitretin, potentiated the RA-induced expression of a reporter gene and CYP26A1. The response of neuroblastoma cells to R116010 was consistent with inhibition of CYP26, indicating that inhibition of RA metabolism may further optimise retinoid treatment in neuroblastoma