TGF-ßR inhibitor SB431542 restores immune suppression induced by regulatory B-T cell axis and decreases tumour burden in murine fibrosarcoma.

The contribution of immune cells in soft tissue sarcomas (STS) is not completely known and understanding their role is very essential for employing immunotherapy strategies. Here, we show that murine fibrosarcoma-conditioned medium promoted total spleen cell proliferation but inhibited T cell responses to mitogenic and allo-antigen-mediated stimulation. This increased proliferation was found to be in B cells resulting in generation of Breg further leading to Treg population. This was found to be the same in vitro and in vivo. The phenotype of these B cells was CD19+CD81+CD27+CD25+PD-L1hi and they secreted both IL-10 and TGF-ß. These tumor evoked Bregs (tBreg), when co-cultured with B depleted T cells, suppressed their proliferation in response to anti-CD3/CD28 stimulation. tBreg-induced suppression of T cell responses was not abrogated by the inhibition or neutralization of IL-10 but by the small molecule inhibitor of TGFß Receptor type I, SB431542. While SB531542 per se was not cytotoxic to tumor cells, administration of SB431542 in tumor-bearing mice (TBM) significantly reduced the tumor burden. In addition, the treatment significantly reduced Treg cells and rescued proliferation of T cells in response to mitogen and allo-antigen. Collectively, our results identify that tumor evoked Breg cells mediate T cell immune suppression through TGFß-mediated pathway and that targeting the Breg-Treg axis can be potentially used as an immunotherapy agent.

Proteomic analysis of radio-resistant breast cancer xenografts: Increased TGF-ß signaling and metabolism.

Our previous studies have shown that MCF-7 breast cancer cell line exposed to 6 Gy and allowed to recover for 7 days (D7-6G) developed radio-resistance. In this study, we have tested the ability of these cells to form tumors in severe combined immunodeficiency (SCID) mice and characterized these tumors by proteomic analyses. Untreated (MCF-C) and D7-6G cells (MCF-R) were injected s.c. in SCID mice and tumor growth monitored. On Day 18, the mice were killed and tumor tissues were fixed in formalin or RNA later. Expression of genes was assessed by reverse transcription-polymerase chain reaction and proteins by enzyme-linked immunosorbent assay/antibody labeling and flow cytometry. Label free proteomic analyses was carried out by liquid chromatography-mass spectrometry. Metabolic analysis was carried out using Seahorse analyzer. MCF-R cells had a shorter latency and formed larger tumors. These tumors were characterized by an increased expression of transforming growth factor ß (TGF-ß) isoforms; its downstream genes pSMAD3, Snail-1, Zeb-1, HMGA2; hybrid epithelial/mesenchymal phenotype; migration, enrichment of cancer stem cells and radioresistance following challenge dose of radiation. Proteomic analysis of MCF-7R tumors resulted in identification of a total of 649 differentially expressed proteins and pathway analyses using protein annotation through evolutionary relationship indicated enrichment of genes involved in metabolism. Data are available via ProteomeXchange with identifier PXD022506. Seahorse analyzer confirmed increased metabolism in these cells with increased oxidative phosphorylation as well as glycolysis. Increased uptake of 2-NBDG further confirmed increased glycolysis. In summary, we demonstrate that radioresistant breast cancer cells had an enrichment of TGF-ß signaling and increased metabolism.

Identifying 'win-win-win' futures from inequitable value chain trade-offs: A system dynamics approach.

CONTEXT: There is growing recognition that food systems must adapt to become more sustainable and equitable. Consequently, in developing country contexts, there is increasing momentum away from traditional producer-facing value chain upgrades towards efforts to increase both the availability and affordability of nutritious foods at the consumer level. However, such goals must navigate the inherent complexities of agricultural value chains, which involve multiple interactions, feedbacks and unintended consequences, including important but often surprising trade-offs between producers and consumers. OBJECTIVE AND METHODS: Based around the 'Loop' horticultural aggregation scheme of Digital Green in Bihar, India, we develop a system dynamics modelling framework to survey the value chain trade-offs emerging from upgrades that aim to improve the availability of fruits and vegetables in small retail-oriented markets. We model the processes of horticultural production, aggregation, marketing, and retailing - searching for futures that are 'win-win-win' for: (i) the availability of fruits and vegetables in small retail markets, (ii) the profits of farmers participating in aggregation, and (iii) the sustainability of the initial scheme for Digital Green as an organisation. We simulate two internal upgrades to aggregation and two upgrades to the wider enabling environment through a series of 5000 Monte Carlo trajectories - designed to explore the plausible future dynamics of the three outcome dimensions relative to the baseline. RESULTS: We find that 'win-win-win' futures cannot be achieved by internal changes to the aggregation scheme alone, emerging under a narrow range of scenarios that boost supplies to the small retail market whilst simultaneously supporting the financial takeaways of farmers. In contrast, undesirable producer versus consumer trade-offs emerge as unintended consequences of scaling-up aggregation and the introduction of market-based cold storage. SIGNIFICANCE: This approach furthers ongoing efforts to capture complex value chain processes, outcomes and upgrades within system dynamics modelling frameworks, before scanning the horizon of plausible external scenarios, internal dynamics and unintended trade-offs to identify 'win-win-win' futures for all.

Evidence on the magnitude of the economic, health and population effects of palm cooking oil consumption: an integrated modelling approach with Thailand as a case study.

BACKGROUND: Palm oil's high yields, consequent low cost and highly versatile properties as a cooking oil and food ingredient have resulted in its thorough infiltration of the food sector in some countries. Longitudinal studies have associated palm oil's high saturated fatty acid content with non-communicable disease, but neither the economic or disease burdens have been assessed previously. METHODS: This novel palm oil-focussed disease burden assessment employs a fully integrated health, macroeconomic and demographic Computable General Equilibrium Model for Thailand with nine regional (urban/rural) households. Nutritional changes from food consumption are endogenously translated into health (myocardial infarction (MI) and stroke) and population outcomes and are fed back into the macroeconomic model as health and caregiver-related productive labour supply effects and healthcare costs to generate holistic 2016-2035 burden estimates. Model scenarios mirror the replacement of palm cooking oil with other dietary oils and are compared with simulated total Thai health and macroeconomic burdens for MI and stroke. RESULTS: Replacing consumption of palm cooking oil with other dietary oils could reduce MI/stroke incident cases by 8280/2639 and cumulative deaths by 4683/894 over 20 years, removing approximately 0.5% of the total Thai burden of MI/stroke. This palm cooking oil replacement would reduce consumption shares of saturated/monounsaturated fatty acids in Thai household consumption by 6.5%/3% and increase polyunsaturated fatty acid consumption shares by 14%, yielding a 1.74% decrease in the population-wide total-to-HDL cholesterol ratio after 20 years. The macroeconomic burden that would be removed is US$308mn, approximately 0.44% of the total burden of MI/stroke on Thailand's economy or 0.003% of cumulative 20-year GDP. Bangkok and Central region households benefit most from removal of disease burdens. CONCLUSIONS: Simulations indicate that consumption of palm cooking oil, rather than other dietary oils, imposes a negative health burden (MI and stroke) and associated economic burden on a high consuming country, such as Thailand. Integrated sectoral model frameworks to assess these burdens are possible, and burden estimates from our simulated direct replacement of palm cooking oil indicate that using these frameworks both for broader analyses of dietary palm oil use and total burden analyses of other diseases may also be beneficial.

Analysing the policy space for the promotion of healthy, sustainable edible oil consumption in India.

OBJECTIVE: To identify opportunities and challenges for the promotion of healthy, sustainable oil consumption in India. DESIGN: We use a framework for policy space analysis which distinguishes between policy context, process and characteristics. SETTING: We focus on the Indian edible oils sector and on factors shaping the policy space at a national level. PARTICIPANTS: The study is based on the analysis of policy documents and semi-structured interviews with key experts and stakeholders in the edible oils sector. RESULTS: We find opportunities associated with the emergence of multisectoral policy frameworks for climate adaptation and non-communicable disease (NCD) prevention at a national level which explicitly include the oils sector, the existence of structures for sectoral policy coordination, some supportive factors for the translation of nutrition evidence into practice, and the possibility of integrating nutrition-sensitive approaches within current state-led agricultural interventions. However, the trade-offs perceived across sustainability, NCD prevention and food security objectives in the vegetable oils sector are considered a barrier for policy influence and implementation. Sustainability and nutrition advocates tend to focus on different segments of the value chain, missing potential synergies. Moreover, policy priorities are dominated by historical concerns for food security, understood as energy provision, as well as economic and strategic priorities. CONCLUSIONS: Systematic efforts towards identifying synergistic approaches, from agricultural production to distribution of edible oils, as well as increased involvement of nutrition advocates with upstream policies in the oils sector, could increase policy influence for advocates of both nutrition and sustainability.

Palm oil and dietary change: Application of an integrated macroeconomic, environmental, demographic, and health modelling framework for Thailand.

Palm oil is a cooking oil and food ingredient in widespread use in the global food system. However, as a highly saturated fat, palm oil consumption has been associated with negative effects on cardiovascular health, while large scale oil palm production has been linked to deforestation. We construct an innovative fully integrated Macroeconomic-Environmental-Demographic-health (MED-health) model to undertake integrated health, environmental, and economic analyses of palm oil consumption and oil palm production in Thailand over the coming 20 years (2016-2035). In order to put a health and fiscal food policy perspective on policy priorities of future palm oil consumption growth, we model the implications of a 54% product-specific sales tax to achieve a halving of future energy intakes from palm cooking oil consumption. Total patient incidence and premature mortality from myocardial infarction and stroke decline by 0.03-0.16% and rural-urban equity in health and welfare improves in most regions. However, contrary to accepted wisdom, reduced oil palm production would not be environmentally beneficial in the Thailand case, since, once established, oil palms have favourable carbon sequestration characteristics compared to alternative uses of Thai cropland. The increased sales tax also provokes mixed economic impacts: While real GDP increases in a second-best Thai tax policy environment, relative consumption-to-investment price changes may reduce household welfare over extended periods unless accompanied by non-distortionary government compensation payments. Overall, our holistic approach demonstrates that product-specific fiscal food policy taxes may involve important trade-offs between nutrition, health, the economy, and the environment.

TNF-α and IGF-1 differentially modulate ionizing radiation responses of lung cancer cell lines.

The mechanism by which tumor microenvironment derived cytokine network modulates therapy response is of great concern in lung cancer but is not completely understood. In this study, we evaluated the effects of tumor necrosis factor α (TNF-α) and insulin-like growth factor 1 (IGF-1) on response of lung cancer cell lines to ionizing radiation (IR). While TNF-α increased radio sensitivity and inhibited cell migration, treatment with IGF-1 promoted cell growth and increased migration. These effects of TNF- α were mediated by increased immediate activation of stress-activated protein kinases (SAPK)/jun amino-terminal kinases (JNK) and p38. IR induced DNA damage was increased by TNF- α and not altered by IGF-1. However, in IGF-1 treated cells, there was decreased γ- H2AX along with an increase in mitotic index, resulting in abnormal chromosomal segregation in the cells. Bio informatics analysis of 982 lung cancer patients revealed that higher expression of TNF- α was associated with low risk of cancer progression while overexpression of IGF-1 was correlated with high risk. Collectively, these results reveal that the cytokines in the tumor microenvironment differentially modulate radiation therapy through a variety of signaling mechanisms.

Significant alterations of the novel 15 gene signature identified from macrophage-tumor interactions in breast cancer.

BACKGROUND: Tumor microenvironment is composed of a largely altered extracellular matrix with different cell types. The complex interplay between macrophages and tumor cells through several soluble factors and signaling is an important factor in breast cancer progression. METHODS: We have extended our earlier studies on monocyte and macrophage conditioned medium (MϕCM) and have carried out proteomic analysis to identify its constituents as well as validation. The 8-gene signature identified through macrophage-breast cancer cell interactions was queried in cBioportal for bioinformatic analyses. RESULTS: Proteomic analysis (MALDI-TOF and LC-MS/MS) revealed integrin and matrix metalloproteinases in MϕCM which activated TGF-ß1, IL-6, TGF- ßRII and EGFR as well as its downstream STAT and SMAD signaling in breast cancer cells. Neutralization of pro-inflammatory cytokines (TNF-α. Il-1ß, IL-6) abrogated the MϕCM induced migration but invasion to lesser extent. The 8- gene signature identified by macrophage-tumor interactions (TNF-α, IL-1ß, IL-6, MMP1, MMP9, TGF-ß1, TGF-ßRII, EGFR) significantly co-occurred with TP53 mutation, WTAPP1 deletion and SLC12A5 amplification along with differential expression of PSAT1 and ESR1 at the mRNA level and TPD52and PRKCD at the protein level in TCGA (cBioportal). Together these genes form a novel 15 gene signature which is altered in 63.6% of TCGA (1105 samples) data and was associated with high risk and poor survival (p<0.05) in many breast cancer datasets (SurvExpress). CONCLUSIONS: These results highlight the importance of macrophage signaling in breast cancer and the prognostic role of the15-gene signature. GENERAL SIGNIFICANCE: Our study may facilitate novel prognostic markers based on tumor-macrophage interaction.

Policies for healthy and sustainable edible oil consumption: a stakeholder analysis for Thailand.

OBJECTIVE: Palm oil is a cheap and versatile edible oil in widespread use as a food ingredient that has been linked to negative health and environmental outcomes. The current study aimed to understand the prospects for future health-focused policy development to limit food use of palm oil and promote a greater diversity of oils in Thailand's food system. DESIGN: Eighteen semi-structured interviews were conducted with a range of stakeholders. The interviews probed views on the economic, health and environmental dimensions of the issue, the prospects for health-focused policy development and the policy development process. Transcripts were analysed using a health policy analytical framework. SETTING: Thailand. SUBJECTS: Stakeholders from a range of ministries, regulatory agencies, the private sector, non-governmental organizations and academia. RESULTS: There are several impediments to the emergence of strong regulation, including the primacy of economic considerations in setting policy, doubt and misperception about health implications and a complex regulatory environment with little space for health-related considerations. At the same time, some sections of the food industry producing food for domestic consumption are substituting palm with other oils on the basis of consumer health perceptions. CONCLUSIONS: Strong regulation to curb the growth of palm oil is unlikely to emerge soon. However, a long-term strategy can be envisaged that relies on greater policy support for other indigenous oils, strategic rebalancing towards the use of palm oil for biofuels and oleochemicals, and harnessing Thailand's food technology capabilities to promote substitution in food production in favour of oils with healthier fatty acid composition.

What Happens to Patterns of Food Consumption when Food Prices Change? Evidence from A Systematic Review and Meta-Analysis of Food Price Elasticities Globally.

Recent years have seen considerable interest in examining the impact of food prices on food consumption and subsequent health consequences. Fiscal policies targeting the relative price of unhealthy foods are frequently put forward as ways to address the obesity epidemic. Conversely, various food subsidy interventions are used in attempts to reduce levels of under-nutrition. Information on price elasticities is essential for understanding how such changes in food prices affect food consumption. It is crucial to know not only own-price elasticities but also cross-price elasticities, as food substitution patterns may have significant implications for policy recommendations. While own-price elasticities are common in analyses of the impact of food price changes on health, cross-price effects, even though generally acknowledged, are much less frequently included in analyses, especially in the public health literature. This article systematically reviews the global evidence on cross-price elasticities and provides combined estimates for seven food groups in low-income, middle-income and high-income countries alongside previously estimated own-price elasticities. Changes in food prices had the largest own-price effects in low-income countries. Cross-price effects were more varied and depending on country income level were found to be reinforcing, undermining or alleviating own-price effects.

PGE2 induced miR365/IL-6/STAT3 signaling mediates dendritic cell dysfunction in cancer.

AIM: To understand the mechanism of prostaglandin E2 (PGE2)-mediated immunosuppression in dendritic cells (DCs). MAIN METHODS: In vivo experiments were conducted on 4T1 tumor bearing mice (TBM). In vitro experiments were performed in bone marrow-derived DCs (BMDCs), or spleen cells. Cytokines were monitored by ELISA/ELIspot. Gene expression was monitored by RT-PCR/flow cytometry. KEY FINDINGS: In silico, in vitro, and in vivo experiments in 4T1 TBM revealed that PGE2 induced IL-6/pSTAT3 signaling through EP4 receptors in DCs, resulting in their dysfunction. These effects were reversed by EP4 antibody neutralization, EP4 antagonist, and STAT3 inhibitory peptides. PGE2 induced IL-6 was regulated by miR-365, as its mimic inhibited PGE2 induced IL-6 and the inhibitor increased lL-6 levels in DC. Bio-informatic analysis in human mammary cancers also revealed a strong compared co-relation between PGE2 and IL-6 (Correlation AnalyzeR) (R = 0.94). Mice bearing PTGS-2 KD 4T1 tumors had decreased tumor burden, PGE2, EP4, IL-6, and pSTAT3 signaling, along with improved DCs and T cell functions. Treatment of mice with a cyclooxygenase-2 (COX-2) inhibitor or EP4 antagonist decreased tumor burden, and this effect of EP4 antagonist was abrogated upon in vivo depletion of CD11c cells, indicating the crucial role of PGE2 signaling in DCs in tumor progression. SIGNIFICANCE: In summary, our data highlights the importance of dendritic cells in mediating PGE2-mediated immunosuppression and the use of EP4 or STAT3 inhibitors or miR365 mimics can restore immunogenicity in cancer.

The Extent, Range, and Nature of Quantitative Nutrition Research Engaging with Intersectional Inequalities: A Systematic Scoping Review.

Addressing malnutrition for all requires understanding inequalities in nutrition outcomes and how they intersect. Intersectionality is increasingly used as a theoretical tool for understanding how social characteristics intersect to shape inequalities in health outcomes. However, little is known about the extent, range, and nature of quantitative nutrition research engaging with intersectional inequalities. This systematic scoping review aimed to address this gap. Between 15 May 2021 and 15 May 2022, we searched 8 databases. Studies eligible for inclusion used any quantitative research methodology and aimed to investigate how social characteristics intersect to influence nutrition outcomes. In total, 55 studies were included, with 85% published since 2015. Studies spanned populations in 14 countries but were concentrated in the United States (n = 35) and India (n = 7), with just 1 in a low-income country (Mozambique). Race or ethnicity and gender were most commonly intersected (n = 20), and body mass index and overweight and/or obesity were the most common outcomes. No studies investigated indicators of infant and young child feeding or micronutrient status. Study designs were mostly cross-sectional (80%); no mixed-method or interventional research was identified. Regression with interaction terms was the most prevalent method (n = 26); 2 of 15 studies using nonlinear models took extra steps to assess interaction on the additive scale, as recommended for understanding intersectionality and assessing public health impacts. Nine studies investigated mechanisms that may explain why intersectional inequalities in nutrition outcomes exist, but intervention-relevant interpretations were mostly limited. We conclude that quantitative nutrition research engaging with intersectionality is gaining traction but is mostly limited to the United States and India. Future research must consider the intersectionality of a wider spectrum of public health nutrition challenges across diverse settings and use more robust and mixed-method research to identify specific interventions for addressing intersectional inequalities in nutrition outcomes. Data systems in nutrition must improve to facilitate this. This review was registered in PROSPERO as CRD42021253339.

Identifying value chain trade-offs from fruit and vegetable aggregation services in Bangladesh using a system dynamics approach.

Significant progress has been made in cereal production in Bangladesh due to an agricultural policy environment that prioritizes the productivity of staple crops over fruit and vegetables (F&V). However, many smallholder farmers remain poorly connected to markets, which may lead to a limited supply response of F&V that can reduce opportunities for sufficient intake in neglected, consumer-facing, smaller retail markets. To address this issue, aggregation schemes have been conceived that collect and transport F&Vs on behalf of multiple farmers. Given the volume of horticultural produce produced and the reliance on developed transport infrastructure, aggregation schemes tend to supply wholesale and urban markets rather than underdeveloped rural and isolated markets. To this end, we investigated how a particular aggregation intervention ('Loop') could potentially improve the distribution of F&V to smaller markets whilst improving farmer benefits. We used an innovative system dynamics modeling approach based on Loop`s aggregation services in Jashore, Bangladesh, and to identify the potential trade-offs between consumer outcomes in retail markets and farmer benefits. We find that combining aggregation with a quota at the smaller market, transport subsidy, and current price growth does not result in trade-offs between consumer purchases and farmers`benefits. However, combining aggregation with current price growth can increase demand without losing farmers`benefits. The findings emphasize that standalone and multiple market-oriented interventions generate broader win-win benefits to promote inclusive food systems.

Investigating market-based opportunities for the provision of nutritious and safe diets to prevent childhood stunting: a UKRI-GCRF action against stunting hub protocol paper.

BACKGROUND: Inadequate access to affordable, safe, desirable and convenient nutrient-dense food is one of the underlying causes of child stunting. While targeted nutrition-sensitive interventions (eg, backyard 'nutri-gardens') may increase dietary diversity within farming households, such interventions have limited scalability across the wider food system where markets remain underdeveloped. This research aims to develop and assess market-based interventions for key nutrient-dense foods to help improve the diets of women and children in the first 1000 days of life. METHODS: Data collection uses four parallel approaches in each of the three study countries (India, Indonesia and Senegal). (1) A novel food environment tool will be developed to characterise the accessibility and affordability of nutrient-dense foods in the study countries. The tool will be validated through pretesting using cognitive interviewing and piloting in purposively sampled households, 10 (cognitive interviewing) and 30 (piloting) households in each country; (2) stakeholder interviews (eg, with producers, intermediaries and retailers) will be conducted to map out nutrition-sensitive entry points of key value chains (eg, animal-sourced foods), before hotspots of potential food safety hazards will be identified from food samples collected along the chains; (3) the Optifood and Agrifood tools will be used to identify foods that can address food system nutrient gaps and engage key stakeholders to prioritise market interventions to improve nutrition outcomes. Optifood and Agrifood parameters will be informed by publicly available data, plus interviews and focus groups with value chain stakeholders; (4) informed by the previous three approaches and a campaign of participatory 'group model building', a novel system dynamics model will evaluate the impact of alternative market-based solutions on the availability and affordability of nutrient-dense foods over time. ETHICS AND DISSEMINATION: The study has received ethical approval in the United Kingdom, Senegal, Indonesia and India. Dissemination comprises peer-reviewed journals, international disciplinary conferences and multistakeholder dissemination workshops.

Cytokines from the tumor microenvironment modulate sirtinol cytotoxicity in A549 lung carcinoma cells.

Cytokines in tumor microenvironment play an important role in the success or failure of molecular targeted therapies. We have chosen tumor necrosis factor α (TNF-α), TNF related apoptosis inducing ligand (TRAIL), insulin-like growth factor 1 (IGF-1) and transforming growth factor ß (TGF-ß) as representative pro-inflammatory, pro-apoptotic, anti-apoptotic and anti-inflammatory tumor derived cytokines. Analysis of Oncomine database revealed the differential expression of these cytokines in a subset of cancer patients. The effects of these cytokines on cytotoxicity of FDA approved drugs - cisplatin and taxol and inhibitors of epidermal growth factor receptor - AG658, Janus kinase - AG490 and SIRT1 - sirtinol were assessed in A549 lung cancer cells. TRAIL augmented cytotoxicity of sirtinol and IGF-1 had a sparing effect. Since TRAIL and IGF-1 differentially modulated sirtinol cytotoxicity, further studies were carried out to identify the mechanisms. Sirtinol or knockdown of SIRT1 increased the expression of death receptors DR4 and DR5 and sensitized A549 cells to TRAIL. Increased cell death in presence of TRAIL and sirtinol was caspase independent and demonstrated classical features of necroptosis. Inhibition of iNOS increased caspase activity and switched the mode of cell death to caspase mediated apoptosis. Interestingly, sirtinol or SIRT1 knockdown did not increase IGF-1R expression. Instead, it abrogated ligand induced downregulation of IGF-1R and increased cell survival through PI3K-AKT pathway. In conclusion, these findings reveal that the tumor microenvironment contributes to modulation of cytotoxicity of drugs and that combination therapy, with agents that increase TRAIL signaling and suppress IGF-1 pathway may potentiate anticancer effect.

Fewer adults add salt at the table after initiation of a national salt campaign in the UK: a repeated cross-sectional analysis.

In 2003, the UK Food Standards Agency and the Department of Health began attempts to reduce national salt intakes via reformulation of processed foods and a consumer awareness campaign on the negative impacts of salt on health. The present study uses large nationally representative samples of households in England to assess whether discretionary salt use was affected by the national salt reduction campaign. Large cross-sectional datasets from the Health Survey for England were used to analyse trends in adults adding salt at the table between 1997 and 2007. Since 1997, there has been a steady decline in salt use at the table. Ordinal logistic regression analysis controlling for age, sex, total household income, region, ethnicity and background trends revealed that the reduction in salt use was significantly greater after the campaign (OR 0·58; 95% CI 0·54, 0·63). Women (OR 0·71; 95% CI 0·68, 0·74), non-white ethnic groups (OR 0·69; 95% CI 0·62, 0·77), high-income households (OR 0·75; 95% CI 0·69, 0·82), middle-income households (OR 0·79; 95% CI 0·75, 0·84) and households in central (OR 0·90; 95% CI 0·84, 0·98) or the south of England (OR 0·82; 95% CI 0·77, 0·88) were less likely to add salt at the table. The results extend previous evidence of a beneficial response to the salt campaign by demonstrating the effect on salt use at the table. Future programmatic and research efforts may benefit from targeting specific population groups and improving the evidence base for evaluating the impact of the campaign.

An evaluation of the UK Food Standards Agency's salt campaign.

Excessive salt intake is linked to cardiovascular disease and several other health problems around the world. The UK Food Standards Agency initiated a campaign at the end of 2004 to reduce salt intake in the population. There is disagreement over whether the campaign was effective in curbing salt intake or not. We provide fresh evidence on the impact of the campaign, by using data on spot urinary sodium readings and socio-demographic variables from the Health Survey for England over 2003-2007 and combining it with food price information from the Expenditure and Food Survey. Aggregating the data into a pseudo-panel, we estimate fixed effects models to examine the trend in salt intake over the period and to deduce the heterogeneous effects of the policy on the intake of socio-demographic groups. Our results are consistent with a previous hypothesis that the campaign reduced salt intakes by approximately 10%. The impact is shown to be stronger among women than among men. Older cohorts of men show a larger response to the salt campaign compared to younger cohorts, while among women, younger cohorts respond more strongly than older cohorts.

Rural-urban disparities in child nutrition in Bangladesh and Nepal.

BACKGROUND: The persistence of rural-urban disparities in child nutrition outcomes in developing countries alongside rapid urbanisation and increasing incidence of child malnutrition in urban areas raises an important health policy question - whether fundamentally different nutrition policies and interventions are required in rural and urban areas. Addressing this question requires an enhanced understanding of the main drivers of rural-urban disparities in child nutrition outcomes especially for the vulnerable segments of the population. This study applies recently developed statistical methods to quantify the contribution of different socio-economic determinants to rural-urban differences in child nutrition outcomes in two South Asian countries - Bangladesh and Nepal. METHODS: Using DHS data sets for Bangladesh and Nepal, we apply quantile regression-based counterfactual decomposition methods to quantify the contribution of (1) the differences in levels of socio-economic determinants (covariate effects) and (2) the differences in the strength of association between socio-economic determinants and child nutrition outcomes (co-efficient effects) to the observed rural-urban disparities in child HAZ scores. The methodology employed in the study allows the covariate and coefficient effects to vary across entire distribution of child nutrition outcomes. This is particularly useful in providing specific insights into factors influencing rural-urban disparities at the lower tails of child HAZ score distributions. It also helps assess the importance of individual determinants and how they vary across the distribution of HAZ scores. RESULTS: There are no fundamental differences in the characteristics that determine child nutrition outcomes in urban and rural areas. Differences in the levels of a limited number of socio-economic characteristics - maternal education, spouse's education and the wealth index (incorporating household asset ownership and access to drinking water and sanitation) contribute a major share of rural-urban disparities in the lowest quantiles of child nutrition outcomes. Differences in the strength of association between socio-economic characteristics and child nutrition outcomes account for less than a quarter of rural-urban disparities at the lower end of the HAZ score distribution. CONCLUSIONS: Public health interventions aimed at overcoming rural-urban disparities in child nutrition outcomes need to focus principally on bridging gaps in socio-economic endowments of rural and urban households and improving the quality of rural infrastructure. Improving child nutrition outcomes in developing countries does not call for fundamentally different approaches to public health interventions in rural and urban areas.

Agriculture for improved nutrition: the current research landscape.

BACKGROUND: Concern about food security and its effect on persistent undernutrition has increased interest in how agriculture could be used to improve nutritional outcomes in developing countries. Yet the evidence base for the impact of agricultural interventions targeted at improved nutrition is currently poor. OBJECTIVE: To map the extent and nature of current and planned research on agriculture for improved nutrition in order to identify gaps where more research might be useful. METHODS: The research, which was conducted from April to August 2012, involved developing a conceptual framework linking agriculture and nutrition, identifying relevant research projects and programs, devising and populating a "template" with details of the research projects in relation to the conceptual framework, classifying the projects, and conducting a gap analysis. RESULTS: The study identified a large number of research projects covering a broad range of themes and topics. There was a strong geographic focus on sub-Saharan Africa, and many studies were explicitly concerned with nutritional impacts on women and children. Although the study revealed a diverse and growing body of research, it also identified research gaps. Few projects consider the entire evidence chain linking agricultural input or practice to nutritional outcomes. There is comparatively little current research on indirect effects of agriculture on nutrition, or the effect of policies or governance, rather than technical interventions. Most research is focused on undernutrition and small farmer households, and few studies target consumers generally, urban populations, or nutrition-related non-communicable diseases. There is very little work on the cost-effectiveness of agricultural interventions. CONCLUSIONS: On the basis of these findings, we make suggestions for research investment and for broader engagement of researchers and disciplines in developing approaches to design and evaluate agricultural programs for improved nutrition.

Arabinogalactan G1-4A isolated from Tinospora cordifolia induces PKC/mTOR mediated direct activation of natural killer cells and through dendritic cell cross-talk.

BACKGROUND: Tinospora cordifolia polysaccharide G1-4A activates antigen-presenting cells, but its effect on natural killer (NK) cells is not known. The objective of this study is to assess the effect of G1-4A on NK cells; direct effects as well as through dendritic cell (DC) cross-talk. METHODS: NK cell phenotype and function were assessed in spleen cells treated in vitro with G1-4A or isolated from mice administered with G1-4A. Following treatment with G1-4A in vitro or in cells isolated from G1-4A treated mice (in vivo), activated NK cell phenotype was characterized as CD3-NKp46+CD69+ cells by flow cytometry; NK cell function was evaluated by IFN-γ secretion (ELISA) and cytotoxicity assay (calcein release by target cells in effector: target cells co-culture assay). RESULTS: Both in vitro as well as in vivoG1-4A treatment increased phenotypic and functional activation of NK cells. So, we wanted to determine if this was through NK-DC crosstalk or direct activation of NK cells. There was increased NK cell activation following co-culture with bone marrow derived DC matured withG1-4A in vitro or splenic DC isolated from G1-4A administered mice indicating crosstalk. G1-4A also increased activation of NK cells in (a) CD11c depleted splenic cells that was contact dependent and (b) purified NKp46+ cells that was abrogated by PKC/mTOR inhibitors indicating direct effects on NK cells. CONCLUSION: In summary, treatment with G1-4A results in phenotypic and functional activation of NK cells directly as well as through NK-DC cross talk and has the potential to be used as an immunotherapeutic agent.