The transcriptional response of Caenorhabditis elegans to ivermectin exposure identifies novel genes involved in the response to reduced food intake

We have examined the transcriptional response of Caenorhabditis elegans following exposure to the anthelmintic drug ivermectin (IVM) using whole genome microarrays and real-time QPCR. Our original aim was to identify candidate molecules involved in IVM metabolism and/or excretion. For this reason the IVM tolerant strain, DA1316, was used to minimise transcriptomic changes related to the phenotype of drug exposure. However, unlike equivalent work with benzimidazole drugs, very few of the induced genes were members of xenobiotic metabolising enzyme families. Instead, the transcriptional response was dominated by genes associated with fat mobilization and fatty acid metabolism including catalase, esterase, and fatty acid CoA synthetase genes. This is consistent with the reduction in pharyngeal pumping, and consequential reduction in food intake, upon exposure of DA1316 worms to IVM. Genes with the highest fold change in response to IVM exposure, cyp-37B1, mtl-1 and scl-2, were comparably up-regulated in response to short–term food withdrawal (4 hr) independent of IVM exposure, and GFP reporter constructs confirm their expression in tissues associated with fat storage (intestine and hypodermis). These experiments have serendipitously identified novel genes involved in an early response of C. elegans to reduced food intake and may provide insight into similar processes in higher organisms

A Research Agenda for Helminth Diseases of Humans: Towards Control and Elimination

Human helminthiases are of considerable public health importance in sub-Saharan Africa, Asia, and Latin America. The acknowledgement of the disease burden due to helminth infections, the availability of donated or affordable drugs that are mostly safe and moderately efficacious, and the implementation of viable mass drug administration (MDA) interventions have prompted the establishment of various large-scale control and elimination programmes. These programmes have benefited from improved epidemiological mapping of the infections, better understanding of the scope and limitations of currently available diagnostics and of the relationship between infection and morbidity, feasibility of community-directed or school-based interventions, and advances in the design of monitoring and evaluation (M&E) protocols. Considerable success has been achieved in reducing morbidity or suppressing transmission in a number of settings, whilst challenges remain in many others. Some of the obstacles include the lack of diagnostic tools appropriate to the changing requirements of ongoing interventions and elimination settings; the reliance on a handful of drugs about which not enough is known regarding modes of action, modes of resistance, and optimal dosage singly or in combination; the difficulties in sustaining adequate coverage and compliance in prolonged and/or integrated programmes; an incomplete understanding of the social, behavioural, and environmental determinants of infection; and last, but not least, very little investment in research and development (R&D). The Disease Reference Group on Helminth Infections (DRG4), established in 2009 by the Special Programme for Research and Training in Tropical Diseases (TDR), was given the mandate to undertake a comprehensive review of recent advances in helminthiases research, identify research gaps, and rank priorities for an R&D agenda for the control and elimination of these infections. This review presents the processes undertaken to identify and rank ten top research priorities; discusses the implications of realising these priorities in terms of their potential for improving global health and achieving the Millennium Development Goals (MDGs); outlines salient research funding needs; and introduces the series of reviews that follow in this PLoS Neglected Tropical Diseases collection, “A Research Agenda for Helminth Diseases of Humans.

Mobilidade, acidentes de trânsito e fatores associados entre estudantes universitários da Guatemala

El objetivo fue identificar y cuantificar la asociación entre la intensidad de exposición (km/año recorridos), la accidentalidad y sus factores asociados en universitarios de Guatemala. Se realizó un estudio trasversal durante el curso 2010-2011, sobre una muestra de 1.016 conductores, quienes cumplimentaron un cuestionario autoadministrado que valoraba: patrones de movilidad, uso de dispositivos de seguridad, estilos de conducción y accidentalidad. Se obtuvieron asociaciones positivas entre la intensidad de exposición y la mayor implicación en circunstancias de riesgo al volante (coeficiente de regresión ajustado de 3,25, IC95%: 2,23-4,27, para las mayores exposiciones). Tanto una mayor implicación en tales circunstancias, como una mayor edad, fueron las variables más fuertemente asociadas con la mayor accidentalidad. Pese a que la intensidad de exposición se asocia positivamente con una mayor accidentalidad, se constató que la mayor parte de dicha asociación está mediada por una mayor implicación en circunstancias de riesgo al volante.The aim of this study was to identify and quantify the association between the amount of driving (km/year), traffic accidents, and other factors among university students in Guatemala. A cross-sectional study was performed during the 2010-2011 school year in a sample of 1,016 drivers who completed a self-administered questionnaire that assessed mobility patterns, use of safety accessories, driving style, and automobile crashes. The results showed a positive association between amount of driving and greater involvement in risky driving (adjusted regression coefficient 3.25, 95%CI: 2.23-4.27, for the highest level of exposure). More frequent involvement in risky driving and older age showed the strongest associations with traffic accidents. Although the amount of driving was positively associated with a higher accident rate, most of this association was found to be mediated by involvement in risky driving practices.O objetivo foi identificar e quantificar a associação entre a intensidade de exposição (km/anos percorridos), a acidentalidade e os seus fatores em universitários da Guatemala. Realizou-se um estudo transversal durante o curso 2010-2011 sobre uma amostra de 1.016 condutores de veículos, que responderam a um questionário autoadministrado que valorizava: padrões de mobilidade, uso de dispositivos de segurança, maneira de condução e acidentalidade. Obtiveram-se associações positivas entre intensidade de exposição e maior implicância em circunstâncias de risco ao conduzir (coeficiente de regressão ajustado a 3,25; IC95%: 2,23-4,27, para as maiores exposições). Tanto a maior implicância em ditas circunstâncias como uma maioridade foram as variáveis mais fortemente associadas com a maior acidentalidade. Apesar de a intensidade de exposição ser associada positivamente com uma maior acidentalidade, estabelecemos que a maior parte da dita associação está mediada pela maior implicância em circunstâncias de risco ao conduzir