Evidence synthesis and translation for nutrition interventions to combat micronutrient deficiencies with particular focus on food fortification

Over two billion people suffer from micronutrient deficiencies. Food fortification is a prominent nutrition intervention to combat such deficiencies; however, its effectiveness, risks, and ethical implications vary depending on the contexts associated with the deficiency it is addressing and the circumstances with its implementation. The aim of this research was to analyse the profile of nutrition interventions for combating micronutrient deficiency with particular focus on food fortification reported in existing systematic reviews (SRs), guidelines and policy statements, and implementation actions for nutrition. A review of secondary data available from online databases of SRs, guidelines and policy statements, and implementation actions, categorised as either "nutrition-specific interventions" (NSpI) or "nutrition-sensitive interventions" (NSeI), was conducted. Currently, there is evidence available for a diversity of food fortification topics, and there has been much translation into action. Indeed, food fortification and micronutrient supplementation interventions and NSpI more broadly dominate the profile of interventions for which there were SRs, guidelines, and policy statements available. The findings demonstrate that, although there is a rational linear relationship between evidence synthesis and translation in formulating policy and actions to combat micronutrient deficiencies, the various nutrition interventions available to help combat micronutrient deficiencies are not equally represented in the evidence synthesis and translation processes. Effective and safe policies and actions to combat micronutrient deficiencies require decisions to be informed from a body of evidence that consists of evidence from a variety of interventions. Into the future, investment in making available a higher number of SRs, guidelines and policy statements, and actions of NSeI is indicated.

New prophylactic and therapeutic treatments to combat pathogenic Enterohaemorrhagic Escherichia coli

Bacterial diarrhoeal diseases have significant influence on global human health, and are a leading cause of preventable death in the developing world. Enterohaemorrhagic Escherichia coli (EHEC), pathogenic strains of E. coli that carry potent toxins, have been associated with a high number of large-scale outbreaks caused by contaminated food and water sources. This pathotype produces diarrhoea and haemorrhagic colitis in infected humans, and in some patients leads to the development of haemolytic uremic syndrome (HUS), which can result in mortality and chronic kidney disease. A major obstacle to the treatment of EHEC infections is the increased risk of HUS development that is associated with antibiotic treatment, and rehydration and renal support are often the only options available. New treatments designed to prevent or clear E. coli infections and reduce symptoms of illness would therefore have large public health and economic impacts. The three main aims of this thesis were: to explore mouse models for pre-clinical evaluation in vivo of small compounds that inhibit a major EHEC colonisation factor, to assess the production and role of two proteins considered promising candidates for a broad-spectrum vaccine against pathogenic E. coli, and to investigate a novel compound that has recently been identified as a potential inhibitor of EHEC toxin production. As EHEC cannot be safely tested in humans due to the risk of HUS development, appropriate small animal models are required for in vivo testing of new drugs. A number of different mouse models have been developed to replicate different features of EHEC pathogenesis, several of which we investigated with a focus on colonisation mediated by the Type III Secretion System (T3SS), a needle-like structure that translocates bacterial proteins into host cells, resulting in a tight, intimate attachment between pathogen and host, aiding colonisation of the gastrointestinal tract. As E. coli models were found not to depend significantly on the T3SS for colonisation, the Citrobacter rodentium model, a natural mouse pathogen closely related to E. coli, was deemed the most suitable mouse model currently available for in vivo testing of T3SS-targeting compounds. Two bacterial proteins, EaeH (an outer membrane adhesin) and YghJ (a putative secreted lipoprotein), highly conserved surface-associated proteins recently identified as III protective antigens against E. coli infection of mice, were explored in order to determine their suitability as candidates for a human vaccine against pathogenic E. coli. We focused on the expression and function of these proteins in the EHEC O157:H7 EDL933 strain and the adherent-invasive E. coli (AIEC) LF82 strain. Although expression of EaeH by other E. coli pathotypes has recently been shown to be upregulated upon contact with host intestinal cells, no evidence of this upregulation could be demonstrated in our strains. Additionally, while YghJ was produced by the AIEC strain, it was not secreted by bacteria under conditions that other YghJ-expressing E. coli pathotypes do, despite the AIEC strain carrying all the genes required to encode the secretion system it is associated with. While our findings indicate that a vaccine that raises antibodies against EaeH and YghJ may have limited effect on the EHEC and AIEC strains we used, recent studies into these proteins in different E. coli pathogens have suggested they are still excellent candidates for a broadly effective vaccine against E. coli. Finally, we characterised a small lead compound, identified by high-throughput screening as a possible inhibitor of Shiga toxin expression. Shiga toxin production causes both the symptoms of illness and development of HUS, and thus reduction of toxin production, release, or binding to host receptors could therefore be an effective way to treat infections and decrease the risk of HUS. Inhibition of Shiga toxin production by this compound was confirmed, and was shown to be caused by an inhibitory effect on activation of the bacterial SOS response rather than on the Shiga toxin genes themselves. The bacterial target of this compound was identified as RecA, a major regulator of the SOS response, and we hypothesise that the compound binds covalently to its target, preventing oligomerisation of RecA into an activated filament. Altogether, the results presented here provide an improved understanding of these different approaches to combating EHEC infection, which will aid the development of safe and effective vaccines and anti-virulence treatments against EHEC.

El rol de las redes de apoyo transnacional en la evolución del régimen de trata de personas en la región del mekong, 2004-2015

Con el fin de la unipolaridad no sólo se fortalecieron mecanismos de gobernanza global como los Regímenes Internacionales, sino también se fortalecieron actores no estatales. A pesar de la importancia que tomaron estos dos elementos aún no existe una teoría que explique exhaustivamente la relación que existe entre ellos. Es por lo anterior que, la investigación busca responder de qué manera el rol de las Redes de Apoyo Transnacional ha incidido en la evolución del régimen de tráfico de personas en la Región del Mekong. Asimismo tiene como objetivo comprender las relación entre el Régimen y las Redes de Apoyo Transnacional a través de la formulación de un caso de estudio basado en metodologías cualitativas, específicamente, en el análisis teórico-constructivista y el análisis de contenido de documentos producidos por actores estatales y no estatales.

Retos en la implementación de las normas internacionales al interior de los estados. estudio de caso: la región del Mekong y el protocolo de Palermo contra la trata de personas. (2007-2014)

El presente estudio de caso tiene como principal objetivo el de analizar la manera como las características sociopolíticas de los Estados del Mekong, específicamente en el caso de Camboya y Myanmar, dificultan la implementación de las normas enunciadas en el Protocolo de las Naciones Unidas para Prevenir, Reprimir y Sancionar la Trata de Personas, Especialmente Mujeres y Niños, también conocido como el Protocolo de Palermo. En este sentido, se parte de las características principales del Protocolo y de la manera como el tráfico de personas se presenta en el Mekong para posteriormente analizar la forma como la corrupción, la impunidad y la desigualdad de género representan retos sociopolíticos que obstruyen la implementación de los mandatos internacionales enmarcados en este instrumento

Consideration of problem formulation and option assessment (PFOA) for environmental risk assessment: Bt cotton in Vietnam.

2008