Financial Capability and Asset Building in Social and Economic Development: Advancing the Sustainable Development Goals

The concern for economic well-being undergirds most of the United Nations Sustainable Development Goals. This Perspective articulates an agenda for advancing those goals in resource-constrained countries by leveraging financial capability and asset-building (FCAB) strategies. It also specifies a role for financial technology (commonly called “FinTech”) in this work. The authors conclude with a call for better integrating FCAB and FinTech into plans for advancing the SDGs

BIRC6 mediates imatinib resistance independently of Mcl-1

© 2017 Okumu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Baculoviral IAP repeat containing 6 (BIRC6) is a member of the inhibitors of apoptosis proteins (IAPs), a family of functionally and structurally related proteins that inhibit apoptosis. BIRC6 has been implicated in drug resistance in several different human cancers, however mechanisms regulating BIRC6 have not been extensively explored. Our phosphoproteomic analysis of an imatinib-resistant chronic myelogenous leukemia (CML) cell line (MYL-R) identified increased amounts of a BIRC6 peptide phosphorylated at S480, S482, and S486 compared to imatinib-sensitive CML cells (MYL). Thus we investigated the role of BIRC6 in mediating imatinib resistance and compared it to the well-characterized anti-apoptotic protein, Mcl-1. Both BIRC6 and Mcl-1 were elevated in MYL-R compared to MYL cells. Lentiviral shRNA knockdown of BIRC6 in MYL-R cells increased imatinib-stimulated caspase activation and resulted in a ~20-25-fold increase in imatinib sensitivity, without affecting Mcl-1. Treating MYL-R cells with CDK9 inhibitors decreased BIRC6 mRNA, but not BIRC6 protein levels. By contrast, while CDK9 inhibitors reduced Mcl-1 mRNA and protein, they did not affect imatinib sensitivity. Since the Src family kinase Lyn is highly expressed and active in MYL-R cells, we tested the effects of Lyn inhibition on BIRC6 and Mcl-1. RNAi-mediated knockdown or inhibition of Lyn (dasatinib/ponatinib) reduced BIRC6 protein stability and increased caspase activation. Inhibition of Lyn also increased formation of an N-terminal BIRC6 fragment in parallel with reduced amount of the BIRC6 phosphopeptide, suggesting that Lyn may regulate BIRC6 phosphorylation and stability. In summary, our data show that BIRC6 stability is dependent on Lyn, and that BIRC6 mediates imatinib sensitivity independently of Mcl-1 or CDK9. Hence, BIRC6 may be a novel target for the treatment of drugresistant CML where Mcl-1 or CDK9 inhibitors have failed

Developing an expanded vector control toolbox for malaria elimination

Vector control using long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) accounts for most of the malaria burden reductions achieved recently in low and middle-income countries (LMICs). LLINs and IRS are highly effective, but are insufficient to eliminate malaria transmission in many settings because of operational constraints, growing resistance to available insecticides and mosquitoes that behaviourally avoid contact with these interventions. However, a number of substantive opportunities now exist for rapidly developing and implementing more diverse, effective and sustainable malaria vector control strategies for LMICs. For example, mosquito control in high-income countries is predominantly achieved with a combination of mosquito-proofed housing and environmental management, supplemented with large-scale insecticide applications to larval habitats and outdoor spaces that kill off vector populations en masse, but all these interventions remain underused in LMICs. Programmatic development and evaluation of decentralised, locally managed systems for delivering these proactive mosquito population abatement practices in LMICs could therefore enable broader scale-up. Furthermore, a diverse range of emerging or repurposed technologies are becoming available for targeting mosquitoes when they enter houses, feed outdoors, attack livestock, feed on sugar or aggregate into mating swarms. Global policy must now be realigned to mobilise the political and financial support necessary to exploit these opportunities over the decade ahead, so that national malaria control and elimination programmes can access a much broader, more effective set of vector control interventions

A Push-Pull System to Reduce House Entry of Malaria Mosquitoes.

Mosquitoes are the dominant vectors of pathogens that cause infectious diseases such as malaria, dengue, yellow fever and filariasis. Current vector control strategies often rely on the use of pyrethroids against which mosquitoes are increasingly developing resistance. Here, a push-pull system is presented, that operates by the simultaneous use of repellent and attractive volatile odorants. Experiments were carried out in a semi-field set-up: a traditional house which was constructed inside a screenhouse. The release of different repellent compounds, para-menthane-3,8-diol (PMD), catnip oil e.o. and delta-undecalactone, from the four corners of the house resulted in significant reductions of 45% to 81.5% in house entry of host-seeking malaria mosquitoes. The highest reductions in house entry (up to 95.5%), were achieved by simultaneously repelling mosquitoes from the house (push) and removing them from the experimental set-up using attractant-baited traps (pull). The outcome of this study suggests that a push-pull system based on attractive and repellent volatiles may successfully be employed to target mosquito vectors of human disease. Reductions in house entry of malaria vectors, of the magnitude that was achieved in these experiments, would likely affect malaria transmission. The repellents used are non-toxic and can be used safely in a human environment. Delta-undecalactone is a novel repellent that showed higher effectiveness than the established repellent PMD. These results encourage further development of the system for practical implementation in the field

Field Testing of Different Chemical Combinations as Odour Baits for Trapping Wild Mosquitoes in The Gambia

Odour baited traps have potential use in population surveillance of insect vectors of disease, and in some cases for vector population reduction. Established attractants for human host-seeking mosquitoes include a combination of CO2 with L-lactic acid and ammonia, on top of which additional candidate compounds are being tested. In this field study in rural Gambia, using Latin square experiments with thorough randomization and replication, we tested nine different leading candidate combinations of chemical odorants for attractiveness to wild mosquitoes including anthropophilic malaria vectors, using modified Mosquito Magnet-X (MM-X) counterflow traps outside experimental huts containing male human sleepers. Highest catches of female mosquitoes, particularly of An. gambiae s.l. and Mansonia species, were obtained by incorporation of tetradecanoic acid. As additional carboxylic acids did not increase the trap catches further, this ‘reference blend’ (tetradecanoic acid with L-lactic acid, ammonia and CO2) was used in subsequent experiments. MM-X traps with this blend caught similar numbers of An. gambiae s.l. and slightly more Mansonia and Culex mosquitoes than a standard CDC light trap, and these numbers were not significantly affected by the presence or absence of human sleepers in the huts. Experiments with CO2 produced from overnight yeast cultures showed that this organic source was effective in enabling trap attractiveness for all mosquito species, although at a slightly lower efficiency than obtained with use of CO2 gas cylinders. Although further studies are needed to discover additional chemicals that increase attractiveness, as well as to optimise trap design and CO2 source for broader practical use, the odour-baited traps described here are safe and effective for sampling host-seeking mosquitoes outdoors and can be incorporated into studies of malaria vector ecology

HIV Testing Experience and Risk Behavior Among Sexually Active Black Young Adults: A CBPR-Based Study Using Respondent-Driven Sampling in Durham, North Carolina

African Americans are disproportionately affected by the HIV epidemic inclusive of men who have sex with men, heterosexual men, and women. As part of a community-based participatory research study we assessed HIV testing experience among sexually active 18 to 30 year old Black men and women in Durham, North Carolina. Of 508 participants, 173 (74%) men and 236 (86%; p=.0008) women reported ever being tested. Barriers to testing (e.g., perceived risk and stigma) were the same for men and women, but men fell behind mainly because a primary facilitator of testing---routine screening in clinical settings---was more effective at reaching women. Structural and behavioral risk factors associated with HIV infection were prevalent but did not predict HIV testing experience. Reduced access to health care services for low income Black young adults may exacerbate HIV testing barriers that already exist for men and undermine previous success rates in reaching women

Disclosure of HSV-2 serological test results in the context of an adolescent HIV prevention trial in Kenya

HSV-2 biomarkers are often used in adolescent sub-Saharan HIV prevention studies, but evaluations of test performance and disclosure outcomes are rare in the published literature. Therefore, we investigated the proportion of ELISA-positive and indeterminant samples confirmed by Western blot (WB); the psychosocial response to disclosure; and whether reports of sexual behavior and HSV-2 symptoms are consistent with WB confirmatory results among adolescent orphans in Kenya

Fine-scale spatial and temporal variations in insecticide resistance in Culex pipiens complex mosquitoes in rural south-eastern Tanzania.

BACKGROUND: Culex mosquitoes cause considerable biting nuisance and sporadic transmission of arboviral and filarial diseases. METHODS: Using standard World Health Organization procedures, insecticide resistance profiles and underlying mechanisms were investigated during dry and wet seasons of 2015 and 2016 in Culex pipiens complex from three neighbouring administrative wards in Ulanga District, Tanzania. Synergist tests with piperonyl butoxide, diethyl maleate, and triphenyl phosphate, were employed to investigate mechanisms of the observed resistance phenotypes. Proportional biting densities of Culex species, relative to other taxa, were determined from indoor surveillance data collected in 2012, 2013, and 2015. RESULTS: Insecticide resistance varied significantly between wards and seasons. For example, female mosquitoes in one ward were susceptible to bendiocarb and fenitrothion in the wet season, but resistant during the dry season, while in neighbouring ward, the mosquitoes were fully susceptible to these pesticides in both seasons. Similar variations occurred against bendiocarb, DDT, deltamethrin, and lambda-cyhalothrin. Surprisingly, with the exception of one ward in the wet season, the Culex populations were susceptible to permethrin, commonly used on bednets in the area. No insecticide resistance was observed against the organophosphates, pirimiphos-methyl and malathion, except for one incident of reduced susceptibility in the dry season. Synergist assays revealed possible involvement of monooxygenases, esterases, and glutathione S-transferase in pyrethroid and DDT resistance. Morphology-based identification and molecular assays of adult Culex revealed that 94% were Cx. pipiens complex, of which 81% were Cx. quinquefasciatus, 2% Cx. pipiens, and 3% hybrids. About 14% of the specimens were non-amplified during molecular identifications. Female adults collected indoors were 100% Cx. pipiens complex, and constituted 79% of the overall biting risk. CONCLUSIONS: The Cx. pipiens complex constituted the greatest biting nuisance inside people's houses, and showed resistance to most public health insecticides possible. Resistance varied at a fine geographical scale, between adjacent wards, and seasons, which warrants some modifications to current insecticide resistance monitoring strategies. Resistance phenotypes are partly mediated by metabolic mechanisms, but require further evaluation through biochemical and molecular techniques. The high densities and resistance in Culex could negatively influence the acceptability of other interventions such as those used against malaria mosquitoes

malERA: An updated research agenda for malaria elimination and eradication

Achieving a malaria-free world presents exciting scientific challenges as well as overwhelming health, equity, and economic benefits. WHO and countries are setting ambitious goals for reducing the burden and eliminating malaria through the “Global Technical Strategy” and 21 countries are aiming to eliminate malaria by 2020. The commitment to achieve these targets should be celebrated. However, the need for innovation to achieve these goals, sustain elimination, and free the world of malaria is greater than ever. Over 180 experts across multiple disciplines are engaged in the Malaria Eradication Research Agenda (malERA) Refresh process to address problems that need to be solved. The result is a research and development agenda to accelerate malaria elimination and, in the longer term, transform the malaria community’s ability to eradicate it globally