An influenza virus inspired polymer system for the timed release of siRNA

Small interfering RNA silences specific genes by interfering with mRNA translation, and acts to modulate or inhibit specific biological pathways; a therapy that holds great promise in the cure of many diseases. However, the naked small interfering RNA is susceptible to degradation by plasma and tissue nucleases and due to its negative charge unable to cross the cell membrane. Here we report a new polymer carrier designed to mimic the influenza virus escape mechanism from the endosome, followed by a timed release of the small interfering RNA in the cytosol through a self-catalyzed polymer degradation process. Our polymer changes to a negatively charged and non-toxic polymer after the release of small interfering RNA, presenting potential for multiple repeat doses and long-term treatment of diseases.

Polymer nanocarrier system for endosome escape and timed release of siRNA with complete gene silencing and cell death in cancer cells

An influenza virus-inspired polymer mimic nanocarrier was used to deliver siRNA for specific and near complete gene knockdown of an osteoscarcom cell line (U-2SO). The polymer was synthesized by single-electron transfer living radical polymerization (SET-LRP) at room temperature to avoid complexities of transfer to monomer or polymer. It was the only LRP method that allowed good block copolymer formation with a narrow molecular weight distribution. At nitrogen to phosphorus (N/P) ratios of equal to or greater than 20 (greater than a polymer concentration of 13.8 μg/mL) with polo-like kinase 1 (PLK1) siRNA gave specific and near complete (>98%) cell death. The polymer further degrades to a benign polymer that showed no toxicity even at polymer concentrations of 200 μg/mL (or N/P ratio of 300), suggesting that our polymer nanocarrier can be used as a very effective siRNA delivery system and in a multiple dose administration. This work demonstrates that with a well-designed delivery device, siRNA can specifically kill cells without the inclusion of an additional clinically used highly toxic cochemotherapeutic agent. Our work also showed that this excellent delivery is sensitive for the study of off-target knockdown of siRNA.

A dominant-negative mutation in the TRESK potassium channel is linked to familial migraine with aura

Migraine with aura is a common, debilitating, recurrent headache disorder associated with transient and reversible focal neurological symptoms. A role has been suggested for the two-pore domain (K2P) potassium channel, TWIK-related spinal cord potassium channel (TRESK, encoded by KCNK18), in pain pathways and general anaesthesia. We therefore examined whether TRESK is involved in migraine by screening the KCNK18 gene in subjects diagnosed with migraine. Here we report a frameshift mutation, F139WfsX24, which segregates perfectly with typical migraine with aura in a large pedigree. We also identified prominent TRESK expression in migraine-salient areas such as the trigeminal ganglion. Functional characterization of this mutation demonstrates that it causes a complete loss of TRESK function and that the mutant subunit suppresses wild-type channel function through a dominant-negative effect, thus explaining the dominant penetrance of this allele. These results therefore support a role for TRESK in the pathogenesis of typical migraine with aura and further support the role of this channel as a potential therapeutic target.

Monitoring the price and affordability of foods and diets globally

Food prices and food affordability are important determinants of food choices, obesity and non-communicable diseases. As governments around the world consider policies to promote the consumption of healthier foods, data on the relative price and affordability of foods, with a particular focus on the difference between ‘less healthy’ and ‘healthy’ foods and diets, are urgently needed. This paper briefly reviews past and current approaches to monitoring food prices, and identifies key issues affecting the development of practical tools and methods for food price data collection, analysis and reporting. A step-wise monitoring framework, including measurement indicators, is proposed. ‘Minimal’ data collection will assess the differential price of ‘healthy’ and ‘less healthy’ foods; ‘expanded’ monitoring will assess the differential price of ‘healthy’ and ‘less healthy’ diets; and the ‘optimal’ approach will also monitor food affordability, by taking into account household income. The monitoring of the price and affordability of ‘healthy’ and ‘less healthy’ foods and diets globally will provide robust data and benchmarks to inform economic and fiscal policy responses. Given the range of methodological, cultural and logistical challenges in this area, it is imperative that all aspects of the proposed monitoring framework are tested rigorously before implementation.

INFORMAS (International Network for Food and Obesity/non-communicable diseases Research, Monitoring and Action Support) : overview and key principles

Non-communicable diseases (NCDs) dominate disease burdens globally and poor nutrition increasingly contributes to this global burden. Comprehensive monitoring of food environments, and evaluation of the impact of public and private sector policies on food environments is needed to strengthen accountability systems to reduce NCDs. The International Network for Food and Obesity/NCDs Research, Monitoring and Action Support (INFORMAS) is a global network of public-interest organizations and researchers that aims to monitor, benchmark and support public and private sector actions to create healthy food environments and reduce obesity, NCDs and their related inequalities. The INFORMAS framework includes two ‘process’ modules, that monitor the policies and actions of the public and private sectors, seven ‘impact’ modules that monitor the key characteristics of food environments and three ‘outcome’ modules that monitor dietary quality, risk factors and NCD morbidity and mortality. Monitoring frameworks and indicators have been developed for 10 modules to provide consistency, but allowing for stepwise approaches (‘minimal’, ‘expanded’, ‘optimal’) to data collection and analysis. INFORMAS data will enable benchmarking of food environments between countries, and monitoring of progress over time within countries. Through monitoring and benchmarking, INFORMAS will strengthen the accountability systems needed to help reduce the burden of obesity, NCDs and their related inequalities.

Monitoring policy and actions on food environments : rationale and outline of the INFORMAS policy engagement and communication strategies

The International Network for Food and Obesity/non-communicable diseases Research, Monitoring and Action Support (INFORMAS) proposes to collect performance indicators on food policies, actions and environments related to obesity and non-communicable diseases. This paper reviews existing communications strategies used for performance indicators and proposes the approach to be taken for INFORMAS. Twenty-seven scoring and rating tools were identified in various fields of public health including alcohol, tobacco, physical activity, infant feeding and food environments. These were compared based on the types of indicators used and how they were quantified, scoring methods, presentation and the communication and reporting strategies used. There are several implications of these analyses for INFORMAS: the ratings/benchmarking approach is very commonly used, presumably because it is an effective way to communicate progress and stimulate action, although this has not been formally evaluated; the tools used must be trustworthy, pragmatic and policy-relevant; multiple channels of communication will be needed; communications need to be tailored and targeted to decision-makers; data and methods should be freely accessible. The proposed communications strategy for INFORMAS has been built around these lessons to ensure that INFORMAS's outputs have the greatest chance of being used to improve food environments.

Monitoring and benchmarking government policies and actions to improve the healthiness of food environments : a proposed Government Healthy Food Environment Policy Index

Government action is essential to increase the healthiness of food environments and reduce obesity, diet-related non-communicable diseases (NCDs), and their related inequalities. This paper proposes a monitoring framework to assess government policies and actions for creating healthy food environments. Recommendations from relevant authoritative organizations and expert advisory groups for reducing obesity and NCDs were examined, and pertinent components were incorporated into a comprehensive framework for monitoring government policies and actions. A Government Healthy Food Environment Policy Index (Food-EPI) was developed, which comprises a ‘policy’ component with seven domains on specific aspects of food environments, and an ‘infrastructure support’ component with seven domains to strengthen systems to prevent obesity and NCDs. These were revised through a week-long consultation process with international experts. Examples of good practice statements are proposed within each domain, and these will evolve into benchmarks established by governments at the forefront of creating and implementing food policies for good health. A rating process is proposed to assess a government's level of policy implementation towards good practice. The Food-EPI will be pre-tested and piloted in countries of varying size and income levels. The benchmarking of government policy implementation has the potential to catalyse greater action to reduce obesity and NCDs.

A proposed approach to monitor private-sector policies and practices related to food environments, obesity and non-communicable disease prevention

Private-sector organizations play a critical role in shaping the food environments of individuals and populations. However, there is currently very limited independent monitoring of private-sector actions related to food environments. This paper reviews previous efforts to monitor the private sector in this area, and outlines a proposed approach to monitor private-sector policies and practices related to food environments, and their influence on obesity and non-communicable disease (NCD) prevention. A step-wise approach to data collection is recommended, in which the first (‘minimal’) step is the collation of publicly available food and nutrition-related policies of selected private-sector organizations. The second (‘expanded’) step assesses the nutritional composition of each organization's products, their promotions to children, their labelling practices, and the accessibility, availability and affordability of their products. The third (‘optimal’) step includes data on other commercial activities that may influence food environments, such as political lobbying and corporate philanthropy. The proposed approach will be further developed and piloted in countries of varying size and income levels. There is potential for this approach to enable national and international benchmarking of private-sector policies and practices, and to inform efforts to hold the private sector to account for their role in obesity and NCD prevention.

Monitoring the levels of important nutrients in the food supply

A food supply that delivers energy-dense products with high levels of salt, saturated fats and trans fats, in large portion sizes, is a major cause of non-communicable diseases (NCDs). The highly processed foods produced by large food corporations are primary drivers of increases in consumption of these adverse nutrients. The objective of this paper is to present an approach to monitoring food composition that can both document the extent of the problem and underpin novel actions to address it. The monitoring approach seeks to systematically collect information on high-level contextual factors influencing food composition and assess the energy density, salt, saturated fat, trans fats and portion sizes of highly processed foods for sale in retail outlets (with a focus on supermarkets and quick-service restaurants). Regular surveys of food composition are proposed across geographies and over time using a pragmatic, standardized methodology. Surveys have already been undertaken in several high- and middle-income countries, and the trends have been valuable in informing policy approaches. The purpose of collecting data is not to exhaustively document the composition of all foods in the food supply in each country, but rather to provide information to support governments, industry and communities to develop and enact strategies to curb food-related NCDs.

Monitoring food and non-alcoholic beverage promotions to children

Food and non-alcoholic beverage marketing is recognized as an important factor influencing food choices related to non-communicable diseases. The monitoring of populations' exposure to food and non-alcoholic beverage promotions, and the content of these promotions, is necessary to generate evidence to understand the extent of the problem, and to determine appropriate and effective policy responses. A review of studies measuring the nature and extent of exposure to food promotions was conducted to identify approaches to monitoring food promotions via dominant media platforms. A step-wise approach, comprising ‘minimal’, ‘expanded’ and ‘optimal’ monitoring activities, was designed. This approach can be used to assess the frequency and level of exposure of population groups (especially children) to food promotions, the persuasive power of techniques used in promotional communications (power of promotions) and the nutritional composition of promoted food products. Detailed procedures for data sampling, data collection and data analysis for a range of media types are presented, as well as quantifiable measurement indicators for assessing exposure to and power of food and non-alcoholic beverage promotions. The proposed framework supports the development of a consistent system for monitoring food and non-alcoholic beverage promotions for comparison between countries and over time.

Monitoring the health-related labelling of foods and non-alcoholic beverages in retail settings

Food labelling on food packaging has the potential to have both positive and negative effects on diets. Monitoring different aspects of food labelling would help to identify priority policy options to help people make healthier food choices. A taxonomy of the elements of health-related food labelling is proposed. A systematic review of studies that assessed the nature and extent of health-related food labelling has been conducted to identify approaches to monitoring food labelling. A step-wise approach has been developed for independently assessing the nature and extent of health-related food labelling in different countries and over time. Procedures for sampling the food supply, and collecting and analysing data are proposed, as well as quantifiable measurement indicators and benchmarks for health-related food labelling.

Monitoring foods and beverages provided and sold in public sector settings

This paper outlines a step-wise framework for monitoring foods and beverages provided or sold in publicly funded institutions. The focus is on foods in schools, but the framework can also be applied to foods provided or sold in other publicly funded institutions. Data collection and evaluation within this monitoring framework will consist of two components. In component I, information on existing food or nutrition policies and/or programmes within settings would be compiled. Currently, nutrition standards and voluntary guidelines associated with such policies/programmes vary widely globally. This paper, which provides a comprehensive review of such standards and guidelines, will facilitate institutional learnings for those jurisdictions that have not yet established them or are undergoing review of existing ones. In component II, the quality of foods provided or sold in public sector settings is evaluated relative to existing national or sub-national nutrition standards or voluntary guidelines. Where there are no (or only poor) standards or guidelines available, the nutritional quality of foods can be evaluated relative to standards of a similar jurisdiction or other appropriate standards. Measurement indicators are proposed (within ‘minimal’, ‘expanded’ and ‘optimal’ approaches) that can be used to monitor progress over time in meeting policy objectives, and facilitate comparisons between countries.

Monitoring the impacts of trade agreements on food environments

The liberalization of international trade and foreign direct investment through multilateral, regional and bilateral agreements has had profound implications for the structure and nature of food systems, and therefore, for the availability, nutritional quality, accessibility, price and promotion of foods in different locations. Public health attention has only relatively recently turned to the links between trade and investment agreements, diets and health, and there is currently no systematic monitoring of this area. This paper reviews the available evidence on the links between trade agreements, food environments and diets from an obesity and non-communicable disease (NCD) perspective. Based on the key issues identified through the review, the paper outlines an approach for monitoring the potential impact of trade agreements on food environments and obesity/NCD risks. The proposed monitoring approach encompasses a set of guiding principles, recommended procedures for data collection and analysis, and quantifiable ‘minimal’, ‘expanded’ and ‘optimal’ measurement indicators to be tailored to national priorities, capacity and resources. Formal risk assessment processes of existing and evolving trade and investment agreements, which focus on their impacts on food environments will help inform the development of healthy trade policy, strengthen domestic nutrition and health policy space and ultimately protect population nutrition.