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Molecular functionalization of porphyrins opens countless new opportunities in tailoring their physicochemical properties for light-harvesting applications. However, the immense materials space spanned by a vast number of substituent ligands and chelating metal ions prohibits high-throughput screening of combinatorial libraries. In this work, machine-learning algorithms equipped with the domain knowledge of chemical graph theory were employed for predicting the energy gaps of >12 000 porphyrins from the Computational Materials Repository. Among a variety of graph-based molecular descriptors, the electrotopological-state index, which encodes electronic and topological structure information, captures the energy gaps of porphyrins with a prediction RMSE < 0.06 eV. Importantly, feature sensitivity analysis suggests that the carbon structural motif in methine bridges connected to the anchor group predominantly influences the energy gaps of porphyrins, consistent with the spatial distribution of their frontier molecular orbitals from quantum-chemical calculations.

Geometry-based reactivity descriptors, e.g., regular, generalized, and orbitalwise coordination numbers, were used for unraveling intrinsic size effects of Au nanocatalysts towards CO oxidation. For an ensemble of Au nanoparticles with varying sizes and shapes, s-orbital coordination numbers (CN s ) linearly correlate with *CO and *O adsorption energies at the on-top and hollow sites, respectively, outperforming their regular (CN) and generalized (C[combining macron]N[combining macron]) counterparts attributed to an explicit consideration of interatomic interactions. To take into account the geometric strain of surface atoms, the embedded-atom method (EAM) potential trained with ab initio energies of the bulk, nanoclusters, and extended surfaces at the GGA-PBE level was used for optimizing the Wulff-shaped, free-standing Au nanoparticles up to 7.2 nm. Microkinetic analysis of CO oxidation on extended {111}, {100}, {211}, and {532} surfaces, along with a facile and accurate prediction of *CO and *O adsorption energies at nanoparticles using the herein developed structure-reactivity relationships, captures experimentally measured activity trends of supported Au nanoparticles of varying sizes on a wide variety of metal oxides and illustrates the importance of under-coordinated atoms and insensitivity of surface strains in Au-catalyzed CO oxidation.

Objective: To examine the associations among household food insecurity (FI), academic performance, and weight status in urban primary schoolchildren., Design: Cross-sectional study., Setting: Primary schools in Tehran, Iran., Participants: A total of 803 students (419 boys and 384 girls), aged 10-12 years, were recruited from 43 primary schools., Main Outcome Measures: Levels of FI were measured using a locally validated, 18-item household food security survey module. Academic performance was assessed by 152 teachers through a specifically designed, 20-scale questionnaire. Standard anthropometric measurements were also taken., Analysis: Linear and multinomial regressions were conducted., Results: At the household level, FI was associated with poorer grades in all subjects studied (except for social science in FI without hunger) (P < .05). At the child level, a significant association was observed between low food security and poorer grades in all subjects studied, whereas for very low food security, this relationship was significant only for mathematics, reading, and science (P < .05). Food insecurity without hunger (odds ratio = 2.56; 95% confidence interval, 1.05-6.23) and low food security (odds ratio = 4.41; 95% confidence interval, 1.58-12.23) were associated with overweight only in girls., Conclusions and Implications: The findings confirm the need for policies and programs to improve students' dietary quality and food security to improve their health as well as educational attainment. Future research is needed to explore further the association between food security and academic performance., (Copyright © 2017 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Conflict of Interests The authors thank the participants of this study.

Objective: Food choice is a process through which people think, feel, and eat food. It does not only influence individuals' health and well-being, families and communities, but also it has an effect on regional, national, and global levels. This qualitative study was conducted to explore perceptions and lived experiences of Tehran adult residents on psychological, social and cultural determinants of food choice. Method: In this qualitative design, we recruited 33 adults aged 30 to 64 years from various districts of Tehran, capital of Iran, and we explored how people make decisions about food choice in practice and shape their perception, attitude, and eating practices. An individual in-depth semi-structured interview guide included major questions with follow-up probes was used to explore participants' current and past eating habits from childhood to adulthood, dietary change at different life courses, and effective psychological state on food selection in different seasons. Results: This study revealed that food choice in the studied adults (30-64 years old) was widely influenced by psychological, social, and cultural determinants, which can be categorized into 5 main themes: cultural context and patterns; social Structure and norms; information resources and media; household and family structure; and nutrition transition. Conclusion: The findings clarified the importance of social and cultural contexts, which influence the food choice of adults in a metropolis like Tehran. Many of these concepts are contextualized from childhood. These findings could serve as guideline to design socio-culturally appropriate strategies and improve dietary behaviors of Iranians.

Background: Well-informed interventions are needed if school-based health promotion is to be effective. Among other aims, the Iranian Health Promoting School (IHPS) program that was launched in 2011, has an important aim of promoting dietary behaviors of adolescents. The present study, therefore, aimed to investigate the factors affecting unhealthy snacking of adolescents and provide evidence for a more effective IHPS program., Methods: In a cross-sectional study design, 1320 students from 40 schools in Kerman city were selected using a proportional stratified random sampling method. A modified qualitative Food Frequency Questionnaire (FFQ) was used to gather data about unhealthy snacking behavior. Data about intrapersonal and environmental factors were obtained using a validated and reliable questionnaire. A mixed-effects negative-binomial regression model was used to analyze the data., Results: Taste and sensory perception (prevalence rate ratio [PRR]=1.18; 95% CI: 1.09-1.27), being a male (PRR=1.20; 95% CI: 1.05-1.38) and lower nutritional knowledge (PRR=0.96; 95% CI: 0.91-0.99) were associated with higher weekly unhealthy snaking. Perceived self-efficacy (PRR=0.95; 95% CI: 0.91-1.00) negatively influenced the frequency of unhealthy snaking, with this approaching significance (P<.06). In case of environmental factors, high socio-economic status (SES) level (PRR=1.45; 95% CI: 1.26-1.67), single-parent family (PRR=1.14; 95% CI: 1.01-1.30), more social norms pressure (PRR=1.08; 95% CI: 1.01-1.17), pocket money allowance (PRR=1.21; 95% CI: 1.09-1.34), easy accessibility (PRR=1.06; 95% CI:1.01-1.11), and less perceived parental control (PRR=0.96; 95% CI: 0.92-0.99) all had a role in higher consumption of unhealthy snacks. Interestingly, larger school size was associated with less unhealthy snacking (PRR=0.79; 95% CI: 0.68-0.92)., Conclusion: Unhealthy snacking behavior is influenced by individual, socio-cultural and physical-environmental influences, namely by factors relating to poor parenting practices, high SES level, family characteristics, improper social norms pressure, and less knowledge and self-efficacy of students. This evidence can be used to inform a more evidencebased IHPS program through focusing on supportive strategies at the home, school, and local community levels., (© 2017 The Author(s); Published by Kerman University of Medical Sciences. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Background: This study aimed to investigate food experts' views on important nutrition and food systems knowledge issues for education purposes at schools in Iran., Methods: In 2012, semi-structured, face-to-face or telephone interviews were conducted with twenty-eight acknowledged Iranian experts in food and nutrition fields. Participants were selected from four major provinces in Iran (Tehran, Isfahan, Fars and Gilan). Open-ended interview questions were used to identify nutrition and food systems knowledge issues, which experts considered as important to be included in school education programs. Qualitative interviews were analyzed thematically using NVivo., Results: A framework of knowledge that would assist Iranian students and school-leavers to make informed decisions in food-related areas was developed, comprising five major clusters and several sub-clusters. Major knowledge clusters included nutrition basics; food production; every day food-related practices; prevalent nutritional health problems in Iran and improvement of students' ethical attitudes in the food domain., Conclusion: These findings provide a guide to curriculum developers and policy makers to assess current education curricula in order to optimize students' knowledge of nutrition and food systems., Competing Interests: Conflict of Interests The authors declare that there is no conflict of interest.

Background: Food and nutrition literacy is an emerging term which is increasingly used in policy and research. Though research in this area is growing, progression is limited by the lack of an accepted method to measure food and nutrition literacy. The aim of this study is to develop a valid and reliable questionnaire to assess food and nutrition literacy in elementary school children in the city of Tehran., Methods: The study was conducted in three phases. To develop Food and Nutrition Literacy (FNLIT) questionnaire, a comprehensive literature review and a qualitative study were initially performed to identify food and nutrition literacy dimensions and its components. Content and face validity of the questionnaire were evaluated by an expert panel as well as students. In the second phase, construct validity of the scale was evaluated using Explanatory Factor Analyses (EFA) and Confirmatory Factor Analyses (CFA). In the last phase (confirmatory phase), the final version of the questionnaire was evaluated on 400 students., Results: Findings show Content Validity Ratio (CVR) and Content Validity Index (CVI) of the 62-item questionnaire at acceptable levels of 0.87 and 0.92, respectively. EFA suggested a six-factor construct, namely, understanding food and nutrition information, knowledge, functional, interactive, food choice, and critical. The results of CFA indicated acceptable fit indices for the proposed models. All subscales demonstrated satisfactory internal consistency (Cronbach's alpha≥0.70), except for critical skill subscale (0.48). The intraclass correlation coefficient (ICC = 0.90, CI: 0.83-0.94) indicated that Food and Nutrition Literacy (FNLIT) scale had satisfactory stability. Each phase of development progressively improved the questionnaire, which resulted in a 46-item (42 likert-type items and 4 true-false items) Food and Nutrition Literacy (FNLIT) scale. The questionnaire measured two domains with 6 subscales, including: 1) cognitive domain: understanding and knowledge; 2) skill domain: functional, food choice, interactive, and critical skills., Conclusion: The developed food and nutrition literacy scale is a valid and reliable instrument to measure food and nutrition literacy in children. This measure lays a solid empirical and theoretical foundation for future research and tailored interventions to promote food and nutrition literacy in this age group.

Addressing the global burden of cancer, understanding its diverse biology, and promoting appropriate prevention and treatment strategies around the world has become a priority for the United Nations and International Atomic Energy Agency (IAEA), the WHO, and International Agency for Research on Cancer (IARC). The IAEA sponsored an international prospective cohort study to better understand biology, treatment response, and outcomes of diffuse large B-cell lymphoma (DLBCL) in low and middle-income countries across five UN-defined geographical regions. We report an analysis of biological variation in DLBCL across seven ethnic and environmentally diverse populations. In this cohort of 136 patients treated to a common protocol, we demonstrate significant biological differences between countries, characterized by a validated prognostic gene expression score (p < .0001), but International Prognostic Index (IPI)-adjusted survivals in all participating countries were similar. We conclude that DLBCL treatment outcomes in these populations can be benchmarked to international standards, despite biological heterogeneity.

Introduction: Childhood malnutrition is a major public health issue. Multidisciplinary approach for Improvement of Nutritional Status of Children in Iran was implemented in order to reduce malnutrition among children., Objective: This study aimed to evaluate the implementation aspect of the program and to explore key informants' perceptions and experience regarding the factors affected its implementation., Methods: Data were collected through the review of secondary data and semistructured interviews at national, province, and local levels. Four layers of key informants were selected purposefully for interviewing, including policymakers, senior nutrition officers, head of Hygiene, Remedy and Insurance Affairs in Imam Khomeini Relief Foundation, and community health workers. Qualitative content analysis was carried out based on Supporting the Use of Research Evidence framework and Tailored Implementation for Chronic Diseases' checklist to interpret the viewpoints of the study participants., Results: Results showed that the program had successes in improving mother's knowledge on health, nutrition, and child care through health system and increased families' access to food, but there were some aspects that affected program's implementation. Some of these factors are the lack of clarity in the program's protocol and indicators, human shortage and inadequate financial resources, poor facilities, inattention to staff motivation, insufficient commitment among different sections, poor communication and supervision among different executive sections, and program protocols designing regardless of practical condition., Conclusion: Based on the results, top-down approach in policymaking and inadequate financial and human resources were responsible for most of the challenges encountered in the implementation.

As a part of an international study on the molecular analysis of Diffuse Large B-cell Lymphoma (DLBCL), a robust protocol for gene expression analysis from RNA extraction to qRT-PCR using Formalin Fixed Paraffin Embedded tissues was developed. Here a study was conducted to define a strategy to validate the previously reported 6-gene (LMO2, BCL6, FN1, CCND2, SCYA3 and BCL2) model as predictor of prognosis in DLBCL. To avoid variation, all samples were tested in a single centre and single platform. This study comprised 8 countries (Brazil, Chile, Hungary, India, Philippines, S. Korea, Thailand and Turkey). Using the Kaplan-Meier and log rank test on patients (n=162) and two mortality risk groups (with those above and below the mean representing high and low risk groups) confirmed that the 6-gene predictor score correlates significantly with overall survival (OS, p<0.01) but not with event free survival (EFS, p=0.18). Adding the International Prognostic Index (IPI) shows that the 6-gene predictor score correlates significantly with high IPI scores for OS (p<0.05), whereas those with low IPI scores show a trend not reaching significance (p=0.08). This study defined an effective and economical qRT-PCR strategy and validated the 6-gene score as a predictor of OS in an international setting.

Objective: To identify major dietary patterns and their association with socio-economic status (SES) and food insecurity in two major ethnic groups living in Urmia, north-west Iran., Design: A cross-sectional study., Setting: All four geographical zones of Urmia city., Subjects: Participants (n 723; 427 women and 296 men), aged 20-64 years, from two ethnic groups (445 Azeri Turks and 278 Kurds)., Results: Three major dietary patterns were extracted: 'Traditional High SES' (THS), 'Traditional Low SES' (TLS) and 'Transitional'. After adjusting for confounders, the THS pattern was positively associated with education level and negatively associated with moderate or severe food insecurity in Azeri Turks; whereas, among Kurds, it was more common in women and positively associated with age. The TLS pattern was more common among men and negatively associated with educational level and all levels of food insecurity in Azeris; while, among Kurds, it was more common among men, positively associated with being married and negatively associated with household income/capita. The 'Transitional' pattern was positively associated with being employed and negatively associated with age and all levels of food insecurity in Azeris; while, among Kurds, it was more common among men and negatively associated with age, being married and physical activity level., Conclusions: Findings suggest that household SES and food insecurity are associated with detrimental dietary patterns and that this effect may be stronger than cultural and ethnic background. These patterns differ by age and gender. Therefore, such characteristics should be considered in planning and formulating diet-related policies and programmes.

Background: The research to date does not present an articulated approach to ensure nutrition and food systems education is systematically implemented within schools. This paper aimed to investigate food experts' views of the best strategies to improve school-leavers' knowledge of nutrition and food systems., Methods: In this qualitative study, 28 Iranian food and nutrition experts from four major provinces (Tehran, Fars, Isfahan, and Gilan) were selected and agreed to be interviewed. Required data were collected through in-depth, semi-structured, face-to-face, or telephone interviews and were analyzed thematically using NVivo., Results: The experts' suggested strategies to improve Iranian school-leavers' knowledge of nutrition and food systems fell into three key themes: Policy, education processes, and supportive environments. Together they formed an overarching theme of a multileveled system approach for transferring knowledge., Conclusions: Development of a scaffolded education program could assist curriculum developers and policy makers to assess and update current nutrition and food systems education programs in schools. Insights gained about education initiatives in one country such as Iran can provide an important impetus to support nutrition and food system education more widely.

Background: Food aid programs are strategies that aim to improve nutritional status and to tackle food insecurity. This study aimed to evaluate the effect of a National Food Supplementary Program for Children on households' food security., Methods: The study sample included 359 mothers of children aged 6-72 months under the coverage of the program in two provinces of Iran. Demographic and socioeconomic characteristics of the households and percentage of supplementary food items consumed by target child were assessed by a questionnaire and checklist. Data on household food security were collected by locally adapted Household Food Insecurity Access Scale at the baseline of the study and 6 months thereafter., Results: At the baseline, only 4.7% of families were food secure, while 43.5% were severely food insecure, and these proportions were changed to 7.9% and 38%, respectively ( P < 0.001), at the end of the study. Odds of having worse food insecurity in households with medium and high wealth index was 65% and 87% lower than those with low wealth index, respectively (odds ratio [OR] = 0.35, 95% confidence interval [CI]: 0.2-0.61, and OR = 0.23, 95% CI: 0.12-0.43). Food sharing was common among more than 95% of the studied households. Mean maternal body mass index (BMI) increased significantly after 6 months ( P < 0.001). However, there was no significant association between mother's BMI and household food security in the baseline and at the end of the study ( P > 0.05)., Conclusions: Findings show that the food supplementary program for children can also improve the household food security status. Further research is needed to assess other factors that affect the effectiveness of this kind of programs.

Background: Obesity is investigated as a health concern due to high prevalence in the world. Nowadays, researchers are looking for an indirect method to measure weight and height. Self-reported Body Mass Index (BMI) is ever more served as an alternative method for direct weight and height measurement. Misreporting is a usual concern in self-reported BMI, thus, this study set explored the association and degree of agreement of self-reported BMI with weight perception, Self-Rated Health (SRH), and appearance satisfaction in people living in Tehran, Iran., Methods: 722 men and women (268 men and 454 women) aged 30-64 years were selected using Cluster Multi-stage Sampling with the Probability Proportional to Size (PPS) method from each area. The questionnaire included demographic and socioeconomic variables and self-reported weight and height and questions related to weight and health perception, and appearance satisfaction. Independent samples T-test compared the mean of scales and differences in characteristics between BMI categories, analyzed using chi-square test. The Cohen's kappa coefficient examined the association between self-reported BMI and weight perception, SRH, and appearance satisfaction., Results: The mean self-reported weight was 80.79 ± 12.87 in men and 68.33 ± 11.53 in women. The results of the agreement analysis for weight perception were Kappa = 0.38 with p < 0.0001 for women and Kappa = 0.23 with p <0.0001 for men. This measure of agreement, while statistically significant, is fair agreement. SRH and appearance satisfaction were not significantly correlated with self-reported BMI., Conclusion: The measurements of height and weight can cause significant imprecisions in calculation of BMI, which is used as a guide for identifying persons at risk of disease. Direct measurement of height and weight should be performed whenever possible for optimal measurements in clinical practice and clinically oriented researches.

This research reports the encapsulation of dexamethasone (Dex) within the chitosan microspheres (CSMs) embedded in a fibrous structure of poly(ɛ-caprolactone) (PCL) to provide a platform for osteogenic differentiation of human mesenchymal stem cells (hMSCs). Dex loaded CSMs were prepared by spray drying a mixture of chitosan and Dex. Then, they were electrospun with PCL solution to create a bilayer fibrous scaffold (PCL/CSMs-Dex). The CSMs act as good depots for sustained release of Dex over a period of 14 days, without noticeable burst release. This is mainly attributed to the core-shell structure of the final PCL/CSMs-Dex-matrix, which could prolong the release and eliminate the initial burst. The water contact angle of PCL scaffolds decreased from 141.4 ± 3.8 to 118.4 ± 7.6 in the presence of CSMs. Improved proliferation of hMSCs cultured on PCL/CSMs-Dex scaffolds was also evidenced. Furthermore, osteogenic assays showed an increase in alkaline phosphatase activity and mineral deposits. The expression of bone-specific genes also confirmed the osteogenic differentiation of cells cultured on these Dex-loaded core-shell structures. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1657-1667, 2016., (© 2016 Wiley Periodicals, Inc.)

Background: Emerging evidence suggests that neighborhood characteristics can have direct and indirect effects on the weight status of the residents., Objectives: To assess the relationship between general and central obesity and the neighborhood environment in two ethnic groups (Azeri Turks and Kurds) living in Urmia city, Northwestern Iran., Patients and Methods: In this cross-sectional study, 723 participants (427 women and 296 men) aged 20 - 64 years from two ethnic groups (Azeri Turks, n = 445; Kurds, n = 278) were selected from 38 neighborhoods using a combination of cluster, random, and systematic sampling methods. Neighborhood characteristics were obtained by a validated 22-item neighborhood and a health observational checklist. General and central obesity were measured and evaluated using standard methods. Principal component analysis (PCA) was used to define the dominant neighborhood environment. The association of neighborhood characteristics with general and central obesity was analyzed by a logistic regression model., Results: Three common neighborhood environments were identified: 1) modern-affluent, 2) central-high access and 3) marginal. These three factors explained 73.2% of the total variance. Overall, the participants living in a higher tertile of the central-high access neighborhoods had an increased chance of central obesity (OR = 1.63, 95% CI: 1.13 - 2.34). Azeri Turks living in the highest tertile of the modern-affluent neighborhoods had a significantly higher likelihood of having general obesity (OR = 2.49, 95% CI: 1.37 - 4.01). Adjustment for age, gender, marital status, socioeconomic status (SES), energy intake, and physical activity did not change the results. However, after adjustment for educational level, the association was not significant., Conclusions: The findings point to a relationship between neighborhood characteristics and obesity only in the Azeri Turks. However, educational level was more important than neighborhood quality in predicting the risk of obesity.

Objectives: This study was performed to examine the association between household food insecurity, self-efficacy and infant feeding styles in mothers with children under 2 years old in Varamin, Iran., Methods: In this cross-sectional study, 423 mothers aged 17-40 years from different areas of Varamin were selected by a multistage sampling methods from October 2013 to February 2014. The questionnaires consisted of three valid instruments, including: Household Food Insecurity Access Scale, Comprehensive Feeding Practices Questionnaire and Mother's Self-Efficacy Questionnaire. Data were analyzed using Chi-square, t tests, ANOVA, Pearson correlations and multiple linear regressions. Structural equation modeling was also used., Results: Mild and moderate-severe food insecurity was observed in 39.5 and 12.8 % of the households respectively. Mean score of mother's self-efficacy in food secure households was 32.5 ± 3.7; while in mild food insecure and moderate-severe food insecure households were 31.9 ± 3.1 and 28.4 ± 4.0, respectively (P = 0.001). There was a significant negative correlation between household food insecurity and mother's self-efficacy (r = -0.297, P < 0.01). Significant correlation was seen between mother's self-efficacy and the maternal infant feeding styles. Household food insecurity and mother's self-efficacy had significant relationship with mother-infant feeding styles: control of home food access [β (SE)] = [-0.015(0.004), P = 0.001]; restriction for weight control [β = 0.038(0.013), P = 0.003]; restriction for health [β = 0.019(0.008), P = 0.027] and encouragement [=0.018(0.006), P = 0.001]. The model had sufficient fitness with data of the research (CFI = 0.927, RMSEA = 0.076)., Conclusions: Our findings suggest that performing interventions in order to enhance mother's self-efficacy in food insecure households can lead to improve positive maternal feeding behaviors.

Background: In spite of the recent discovery of genetic mutations in most myelodysplasic (MDS) patients, the pathophysiology of these disorders still remains poorly understood, and only few in vivo models are available to help unravel the disease., Methods: We performed global specific gene expression profiling and functional pathway analysis in purified Sca1+ cells of two MDS transgenic mouse models that mimic human high-risk MDS (HR-MDS) and acute myeloid leukemia (AML) post MDS, with NRASD12 and BCL2 transgenes under the control of different promoters MRP8NRASD12/tethBCL-2 or MRP8[NRASD12/hBCL-2], respectively., Results: Analysis of dysregulated genes that were unique to the diseased HR-MDS and AML post MDS mice and not their founder mice pointed first to pathways that had previously been reported in MDS patients, including DNA replication/damage/repair, cell cycle, apoptosis, immune responses, and canonical Wnt pathways, further validating these models at the gene expression level. Interestingly, pathways not previously reported in MDS were discovered. These included dysregulated genes of noncanonical Wnt pathways and energy and lipid metabolisms. These dysregulated genes were not only confirmed in a different independent set of BM and spleen Sca1+ cells from the MDS mice but also in MDS CD34+ BM patient samples., Conclusions: These two MDS models may thus provide useful preclinical models to target pathways previously identified in MDS patients and to unravel novel pathways highlighted by this study.

Objective: To study the association of weight status with food insecurity (FI) and socio-economic status (SES) in Azeri and Kurd ethnic groups living in Urmia city, North-Western Iran., Design: In this cross-sectional study, 723 participants (427 women and 296 men) aged 20-64 years old, from two ethnic groups (445 Azeri and 278 Kurd), were selected through a combination of cluster, random and systematic sampling methods. Demographic and socio-economic characteristics were assessed by a valid questionnaire, and household food security status was analyzed using an adapted household food insecurity access scale through face-to-face interviews at homes. General and central obesities were measured and evaluated using standard methods., Results: Based on the findings, moderate-to-severe FI, as well as low SES, was more dominant in Kurds, compared to Azeris. After adjusting for confounders, being female (OR = 4.33, CI 95%: 2.35-7.97) and moderate-to-severe FI (OR = 2.00, CI 95%: 1.01-3.97) in Azeris and being female (OR = 5.39, CI 95%: 2.28-12.23) and higher total cost of household/capita (OR = 1.005, CI 95%: 1.002-1.009) in Kurds were related to higher odds of general obesity while low (OR = 0.41, CI 95%: 0.18-0.91) and moderate (OR = 0.13, CI 95%: 0.02-0.60) education levels were linked to lower chance of general obesity. Furthermore, the chance of central obesity was lower in Azeris with high educational levels (OR = 0.64, CI 95%: 0.21-0.94), females (OR = 0.72, CI 95%: 0.34-0.86), home owners (OR = 0.56, CI 95%: 0.31-0.91) and females Kurds (OR = 0.60, CI 95%: 0.37-0.97) with moderate-to-severe FI and higher total income per capita. In contrast, the chance of central obesity increased in Kurds with increased age (OR = 1.06, CI 95%: 1.02-1.10) and total cost of household per capita (OR = 1.004, CI 95%: 1.000-1.008)., Conclusion: These findings show that the association between moderate-to-severe FI and risk of general/central obesity varies in Azeris, compared to Kurds. However, better SES decreased the chance of general/central obesity in both ethnic groups.

We have previously shown that a specific promyelocytic leukemia-retinoic acid receptor alpha (PML-RARA) DNA vaccine combined with all-trans retinoic acid (ATRA) increases the number of long term survivors with enhanced immune responses in a mouse model of acute promyelocytic leukemia (APL). This study reports the efficacy of a non-specific DNA vaccine, pVAX14Flipper (pVAX14), in both APL and high risk myelodysplastic syndrome (HR-MDS) models. PVAX14 is comprised of novel immunogenic DNA sequences inserted into the pVAX1 therapeutic plasmid. APL mice treated with pVAX14 combined with ATRA had increased survival comparable to that obtained with a specific PML-RARA vaccine. Moreover, the survival advantage correlated with decreased PML-RARA transcript levels and increase in anti-RARA antibody production. In HR-MDS mice, pVAX14 significantly improved survival and reduced biomarkers of leukemic transformation such as phosphorylated mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) 1. In both preclinical models, pVAX14 vaccine significantly increased interferon gamma (IFNγ) production, memory T-cells (memT), reduced the number of colony forming units (CFU) and increased expression of the adapter molecule signalling to NF-κB, MyD88. These results demonstrate the adjuvant properties of pVAX14 providing thus new approaches to improve clinical outcome in two different models of myeloid malignancies, which may have potential for a broader applicability in other cancers.

Background: Health consequences of food insecurity among infants and toddlers have not been fully examined. The purpose of this study was to assess the relationship between household food insecurity, mother's infant feeding practices and iron status of 6-24 months children., Methods: In this cross-sectional study, 423 mother-child pairs were randomly selected by multistage sampling method. Children blood samples were analyzed for hemoglobin and serum ferritin concentrations. Household food security was evaluated using a validated Household Food Insecurity Access Scale. The mother's feeding practices were evaluated using Infant and Young Child Feeding practice variables including: The duration of breastfeeding and the time of introducing of complementary feeding., Results: Based on the results, of the studied households only 47.7% were food secure. Mild and moderate-severe household food insecurity was 39.5% and 12.8%, respectively. Anemia, iron deficiency (ID), and iron deficiency anemia were seen in 29.1%, 12.2%, and 4.8% of children, respectively. There was no significant association between household food insecurity; mother's feeding practices and child ID with or without anemia., Conclusions: We found no association between household food insecurity and the occurrence of anemia in the 6-24 months children. However, these findings do not rule out the possibility of other micronutrient deficiencies among the food-insecure household children.

Iran has been active in human nutrition training for the past five decades, but the existing curricular programs do not equip the graduates with the knowledge and skills required for solving food security and nutritional problems of the country. Given this, the Nutrition Department (ND) of Iran's Ministry of Health and Medical Education (MOHME) initiated a curricular reform to develop responsive graduate programs in key areas of nutrition that fill the existing gaps in nutrition training with the goal of improving nutrition policy-making and program development, implementation and evaluation. ND called for a request for proposals for a project entitled "Graduate Level Training in Nutrition". Specifically, with technical assistance from leading academic institutions in Asia, North America and UK, seven new graduate programs were housed in three separate institutions, but coordinated so that together they form a broad multidisciplinary resource for graduate education and research. These seven-degree programs are MSc and PhD in Molecular/Cellular Nutrition, MSc and PhD in Nutritional Epidemiology, MSc and PhD in Food Policy and Nutrition Intervention, and MSc in Community Nutrition. The programs were prepared in collaboration and active participation of selected faculty members of the three Iranian universities, International Union of Nutritional Sciences and the University of Philippines at Los Baños. The development of these programs was made possible through a loan from the World Bank, under the Second Primary Health and Nutrition Project in the MOHME.

Objective: To assess key experts' opinion regarding essential competencies required for effective public health nutrition practice within the health-care system of Iran., Design: Qualitative study using the modified Delphi technique through an email-delivered questionnaire., Setting: Iran., Subjects: Fifty-five experts were contacted through email. The inclusion criterion for the study panel was being in a relevant senior-level position in nutrition science or public health nutrition in Iran., Results: In the first round, forty-two out of fifty-five experts responded to the questionnaire (response rate=76 %). A sixty-five-item questionnaire was designed with nine competency areas, including 'nutrition science', 'planning and implementing nutritional interventions', 'health and nutrition services', 'advocacy and communication', 'assessment and analysis', 'evaluation', 'cultural, social and political aspects', 'using technology' and 'leadership and management'. All experts who had participated in the first round completed a modified version of the questionnaire with seventy-seven items in the second round. The experts scored 'nutrition science' as the most essential competency area, while more applied areas such as 'management and leadership' were less emphasized. In both rounds, the mean difference between the opinions of the necessity of each area was 5.6 %., Conclusions: The Iranian experts had general agreement on most of the core competency areas of public health nutritionists. The results indicated the need for capacity building and revisions to educational curricula for public health nutritionist programmes, with more emphasis on skill-based competency development.

Background: Adequate calcium intake may have a crucial role with regards to prevention of many chronic diseases, including hypertension, hypercholesterolemia, different types of cancer, obesity and osteoporosis. In children, sufficient calcium intake is especially important to support the accelerated growth spurt during the preteen and teenage years and to increase bone mineral mass to lay the foundation for older age., Objectives: This study aimed to assess daily calcium intake in school-age children to ensure whether they fulfill the FGP dairy serving recommendations, the recommended levels of daily calcium intake and to assess the relationship between dietary calcium intake and major bone health indicators., Patients and Methods: A total of 501 Iranian school-age children were randomly selected. Calcium intake was assessed using a semi-quantitative food frequency questionnaire. Bone health indicators were also assessed., Results: Dairy products contributed to 69.3% of the total calcium intake of the children. Daily adequate intake of calcium was achieved by 17.8% of children. Only 29.8% met the Food guide pyramid recommendations for dairy intake. Dietary calcium intake was not significantly correlated with serum calcium and other selected biochemical indicators of bone health., Conclusions: The need for planning appropriate nutrition strategies for overcoming inadequate calcium intake in school age children in the city of Tehran is inevitable.

Background: Advertisements can influence children's health related behaviors. Television advertisements are the main avenues directing commercials at children in Iran. This study aimed to explore the content of food advertisement during children's television programs in 2007-8 and to compare it with those reported in 2000., Methods: All advertisements broadcasted before, during, and after children's programs aired on two major Iran national television networks were videotaped for a period of 4 weeks during 2007-8. For each advertisement, type of product(s) and mode of presentation (s) were coded., Results: A total of 229 television advertisements were broadcasted. Food commercials were the most frequent group (31%) across the two channels. Among the food products advertised, calorie dense foods, including chocolate, soft drinks, extruded cereals, ice cream, cookies and candies were the most frequent. The appeal mainly used in television food advertisements was "stimulation of hunger/thirst" (38.5%). The advertisements were mostly presented as animations (54%) and the messages used were mainly directed to good taste., Conclusion: Although the total number of food advertisements during children's television programs has decreased but the consumption of high fat, high sugar, low nutrient dense foods continues to be promoted. Policies to address the issue should be scrutinized.

Objective: Reduced appetite and low food intake are often a concern in preschool children, since it can lead to malnutrition, a leading cause of impaired growth and mortality in childhood. It is occasionally considered that folic acid has a positive effect on appetite enhancement and consequently growth in children. The aim of this study was to assess the effect of folic acid on the appetite of preschool children 3 to 6 y old., Methods: The study sample included 127 children ages 3 to 6 who were randomly selected from 20 preschools in the city of Tehran in 2011. Since appetite was measured by linguistic terms, a fuzzy logistic regression was applied for modeling. The obtained results were compared with a statistical ordinal logistic model., Results: After controlling for the potential confounders, in a statistical ordinal logistic model, serum folate showed a significantly positive effect on appetite. A small but positive effect of folate was detected by fuzzy logistic regression. Based on fuzzy regression, the risk for poor appetite in preschool children was related to the employment status of their mothers., Conclusions: In this study, a positive association was detected between the levels of serum folate and improved appetite. For further investigation, a randomized controlled, double-blind clinical trial could be helpful to address causality., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Myelodysplastic syndrome (MDS) transforms into an acute myelogenous leukemia (AML) with associated increased bone marrow (BM) blast infiltration. Using a transgenic mouse model, MRP8[NRASD12/hBCL-2], in which the NRAS:BCL-2 complex at the mitochondria induces MDS progressing to AML with dysplastic features, we studied the therapeutic potential of a BCL-2 homology domain 3 mimetic inhibitor, ABT-737. Treatment significantly extended lifespan, increased survival of lethally irradiated secondary recipients transplanted with cells from treated mice compared with cells from untreated mice, with a reduction of BM blasts, Lin-/Sca-1(+)/c-Kit(+), and progenitor populations by increased apoptosis of infiltrating blasts of diseased mice assessed in vivo by technicium-labeled annexin V single photon emission computed tomography and ex vivo by annexin V/7-amino actinomycin D flow cytometry, terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling, caspase 3 cleavage, and re-localization of the NRAS:BCL-2 complex from mitochondria to plasma membrane. Phosphoprotein analysis showed restoration of wild-type (WT) AKT or protein kinase B, extracellular signal-regulated kinase 1/2 and mitogen-activated protein kinase patterns in spleen cells after treatment, which showed reduced mitochondrial membrane potential. Exon specific gene expression profiling corroborates the reduction of leukemic cells, with an increase in expression of genes coding for stem cell development and maintenance, myeloid differentiation, and apoptosis. Myelodysplastic features persist underscoring targeting of BCL-2-mediated effects on MDS-AML transformation and survival of leukemic cells.

The study determined the prevalence of food insecurity and its sociodemographic determinants among Afghan immigrants in two major cities of Iran. This cross-sectional study was conducted on a sample of 310 adult females from immigrant Afghan households in Tehran (n=155) and Mashhad (n=155), who were recruited through multistage sampling. Data were collected through face-to-face interviews, using a questionnaire. Food security was measured by a locally-adapted Household Food Insecurity Access Scale. More than 60% suffered from moderate-to-severe food insecurity, 37% were mildly food-insecure while about 23% were food-secure. Food insecurity was significantly more prevalent in female-headed households, households whose head and spouse had lower level of education, belonged to the Sunni sect, and those with illegal residential status, unemployment/low job status, not owning their house, low socioeconomic status (SES), and living in Mashhad. Prevalence of food insecurity was relatively high among Afghan immigrants in Iran. This calls for the need to develop community food security strategies for ensuring their short- and long-term health.

Background: Despite reports on association between overweight/obesity among women and household food insecurity (FI) in developed countries, such association is not evident in developing countries. This study aimed to assess the association between household FI and weight status in adult females in Tehran, Iran., Methods: In this cross-sectional study, 418 households were selected through systematic cluster sampling from 6 districts of Tehran. Height and weight were measured and body mass index (BMI) was calculated. Socio-economic status of the household was assessed by a questionnaire. Three consecutive 24-hour diet recalls were completed. FI was measured using adapted Household Food Insecurity Access Scale. Logistic regression was used to test the effects of SES and food security on weight status, simultaneously. Using Structural Equation Modeling (SEM) potential causal relationships between FI and weight status was explored., Results: Only 1.0% of women were underweight, while 40.3% were overweight and 33% were obese, respectively. Severe, moderate, and mild food insecurity was observed in 11.5, 14.7, and 17.8%, respectively. Among women in moderately food insecure households, the possibility of overweight was lower than those of food secure households (OR 0.41; CI95%:0.17-0.99), while in severely food insecure households, the risk of abdominal obesity for women was 2.82 times higher than food secures (CI95%:1.12-7.08) (P<0.05). SEM detected no causal relationship between FI and weight status., Conclusion: Association of severe food insecurity with abdominal obesity in adult females of households may indicate their vulnerability and the need for tailoring programs to prevent further health problems in this group.

We have previously demonstrated that two prognostic features of myelodysplastic syndromes (MDS) and acute myelogenous leukemia (AML), mutant NRAS and over-expressing BCL-2, cooperate physically and functionally in vivo. Screening of MDS patient bone marrow (BM) identified NRAS:BCL-2 co-localization in 64% cases, correlating with percentage BM blasts, apoptotic features and disease status (p<0.0001). Localization of the complex at the plasma membrane or the mitochondria correlated with disease and apoptosis features in MDS patients, whilst caspase-9 mediated mechanism was elucidated in vivo and in vitro. The intensity and localization of the RAS:BCL-2 complex merits further evaluation as a novel biomarker of MDS., (Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.)

Acute promyelocytic leukemia is characterized by a chromosomal translocation involving the retinoic acid receptor alpha gene. To identify co-operating pathways to leukemogenesis, we crossed MRP8-PML/RARA transgenic mice with BXH-2 mice which harbor an endogenous murine leukemia virus that causes acute myeloid leukemia. Approximately half of the leukemias that arose in this cross showed features of acute promyelocytic leukemia. We identified 22 proviral insertion sites in acute promyelocytic-like leukemias and focused our analysis on insertion at Sox4, a HMG box transcription factor. Using a transplant model, co-operation between PML-RARα and Sox4 was confirmed with increased penetrance and reduced latency of disease. Interestingly, karyotypic analysis revealed cytogenetic changes suggesting that the factors combined to initiate but not complete leukemic transformation. The cooperation between these transcription factors is consistent with the paradigm of multiple routes to the disease and reinforces the concept that transcription factor networks are important therapeutic targets in myeloid leukemias.

Purpose: The evidence for the effectiveness of theory of planned behavior (TPB)-based interventions is mixed. There is also mixed evidence on the effectiveness of adding implementation intentions to TPB-based interventions. In this study we assessed and compared the short-term effects of TPB-only intervention and TPB plus implementation intentions intervention on snacking behavior and intention to consume unhealthy snacks in Iranian adolescent girls., Design: Three-arm cluster randomized controlled trial., Setting: Ten middle schools in Tehran (Iran)., Subjects: A total of 29 classes included 739 female adolescents (age range: 12-15 years). Intervention. Two brief interventions including TPB-only intervention and TPB plus implementation intentions intervention., Measures: Food frequency questionnaire and intentions at baseline, 10 days, and 3 months measuring snacking behavior and cognitions about unhealthy snack consumption, respectively., Analysis: Hierarchical linear modeling to assess the interventions' effects., Results: Both interventions successfully decreased intention to consume and consumption of unhealthy snacks at postintervention. Calculation of the effect sizes revealed that the TPB plus implementation intentions intervention was more effective than the TPB-only intervention. The effects remained significant at 3-month follow-up in the TPB plus implementation intentions intervention group only, although the effect size decreased., Conclusion: Overall, the study suggests that adding implementation intentions on top of TPB-based persuasive messages improves effectiveness and sustainability of desirable changes.

Objective: Nutrition has long been considered one of the most important environmental factors affecting human intelligence. Although carbohydrates are the most widely studied nutrient for their possible effects on cognition, limited data are available linking usual refined carbohydrate intake and intelligence. The present study was conducted to examine the relationship between long-term refined carbohydrate intake and non-verbal intelligence among schoolchildren., Design: Cross-sectional study., Setting: Tehran, Iran., Subjects: In this cross-sectional study, 245 students aged 6-7 years were selected from 129 elementary schools in two western regions of Tehran. Anthropometric measurements were carried out. Non-verbal intelligence and refined carbohydrate consumption were determined using Raven's Standard Progressive Matrices test and a modified sixty-seven-item FFQ, respectively. Data about potential confounding variables were collected. Linear regression analysis was applied to examine the relationship between non-verbal intelligence scores and refined carbohydrate consumption., Results: Individuals in top tertile of refined carbohydrate intake had lower mean non-verbal intelligence scores in the crude model (P < 0.038). This association remained significant after controlling for age, gender, birth date, birth order and breast-feeding pattern (P = 0.045). However, further adjustments for mother's age, mother's education, father's education, parental occupation and BMI made the association statistically non-significant. We found a significant inverse association between refined carbohydrate consumption and non-verbal intelligence scores in regression models (β = -11.359, P < 0.001). This relationship remained significant in multivariate analysis after controlling for potential confounders (β = -8.495, P = 0.038)., Conclusions: The study provides evidence indicating an inverse relationship between refined carbohydrate consumption and non-verbal intelligence among Tehrani children aged 6-7 years. Prospective studies are needed to confirm our findings.

Background: Dietary Guidelines are considered as a useful tool for the promotion of healthy dietary behaviors. In Iran, despite the development of the latest National Food-Based Dietary Guidelines, in 2006, it has not been introduced at the community level yet. The present study aims to evaluate the effectiveness of an intervention program to promote Iran's Food-Based Dietary Guidelines (IFBDGs) in urban adult women., Methods: A sample of 435 healthy women, aged 26 to 54 years, was randomly assigned to the intervention or control groups. The intervention group was designed based on the Health Belief Model (HBM). Each subject in the intervention group received three sessions of group education on IFBDGs and the food guide pyramid and participated in a healthy cooking class. Dietary intake, cognitive outcomes related to the constructs of the HBM, physical activity, and the BMI were measured in both groups before, immediately, and one month after the intervention. The outcome measures were compared with the analysis of covariance (ANCOVA), by adjusting for baseline values., Results: The intervention group had a significantly lower total daily energy intake than the control group after the intervention (P=.000). The adjusted differences in the changes of body mass index from the baseline were significant in both post intervention measurements in the intervention group compared to the controls., Conclusions: The intervention designed based on the Health Belief Model was effective in improving the adherence to FBDGs and could serve as a basic model for the promotion of healthy nutrition behavior among women in the primary health care setting.

Objective: To assess the vitamin D status of 9-12-year-old primary-school children in Tehran during autumn and winter 2007-2008., Design: A descriptive cross-sectional study., Setting: Primary schools of Tehran city, Iran., Subjects: A total of 1111 children aged 9-12 years (573 boys and 538 girls) from sixty primary schools were enrolled in the study. Weight, height, BMI and serum levels of Ca, P, Mg, 25-hydroxyvitamin D (25(OH)D), intact parathyroid hormone (iPTH), osteocalcin and bone-specific alkaline phosphatase of all the participants were assessed. Dietary Ca intake was also evaluated using a quantitative FFQ for a subsample of the study population (n 503). Vitamin D sufficiency was defined on the basis of serum levels of 25(OH)D as either ≥37 nmol/l (criterion 1) or ≥50 nmol/l (criterion 2)., Results: Daily intake of Ca did not differ significantly between boys and girls (929·6 (sd 436·7) mg and 909·5 (sd 465·5) mg, respectively). However, on the basis of the first criterion, approximately 86 % of the children had vitamin D deficiency, with 38·3 % being severely deficient (25(OH)D < 12·5 nmol/l). According to the second criterion, prevalence of vitamin D deficiency rose to 91·7 %. Prevalence of vitamin D deficiency was higher in girls than in boys by either criterion. Serum levels of 25(OH)D inversely correlated with iPTH (r = -0·154, P < 0·001) and BMI (r = -0·092, P = 0·002) but directly correlated with duration of sun exposure (r = 0·115, P < 0·001)., Conclusions: The high prevalence of vitamin D deficiency among schoolchildren (especially among girls) warrants immediate interventions for proper nutritional support.

Background: This study's aim was to design and validate a semi-quantitative food frequency questionnaire (FFQ) for assessment of fruits and vegetables (FV) consumption in adults of Isfahan by comparing the FFQ with dietary reference method and blood plasma levels of beta-carotene, vitamin C, and retinol., Methods: This validation study was performed on 123 healthy adults of Isfahan. FV intake was assessed using a 110-item FFQ. Data collection was performed during two different time periods to control for seasonal effects, fall/winter (cold season) and spring/summer (warm season). In each phase a FFQ and 1 day recall, and 2 days of food records as the dietary reference method were completed and plasma vitamin C, beta-carotene and retinol were measured. Data was analyzed by Pearson or Spearman and intraclass correlations., Results: Serum Lipids, sex, age, body mass index (BMI) and educational level adjusted Pearson correlation coefficient of FV with plasma vitamin C, beta-carotene and retinol were 0.55, 0.47 and 0.28 in the cold season (p < 0.05) and 0.52, 0.45 and 0.35 in the warm season (p < 0.001), respectively. Energy and fat intake, sex, age, BMI and educational level adjusted Pearson correlation coefficient for FV with dietary reference method in the cold and warm seasons were 0.62 and 0.60, respectively (p < 0.001). Intraclass correlation for reproducibility of FFQ in FV was 0.65 (p<0.001)., Conclusions: The designed FFQ had a good criterion validity and reproducibility for assessment of FV intake. Thus, it can serve as a valid tool in epidemiological studies to assess fruit and vegetable intake.

Introduction: It is postulated that breast cancer stem cells (bCSCs) mediate disease recurrence and drive formation of distant metastases - the principal cause of mortality in breast cancer patients. Therapeutic targeting of bCSCs, however, is hampered by their heterogeneity and resistance to existing therapeutics. In order to identify strategies to selectively remove bCSCs from breast cancers, irrespective of their clinical subtype, we sought an apoptosis mechanism that would target bCSCs yet would not kill normal cells. Suppression of the apoptosis inhibitor cellular FLICE-Like Inhibitory Protein (c-FLIP) partially sensitizes breast cancer cells to the anti-cancer agent Tumour Necrosis Factor-Related Apoptosis Inducing Ligand (TRAIL). Here we demonstrate in breast cancer cell lines that bCSCs are exquisitely sensitive to the de-repression of this pro-apoptotic pathway, resulting in a dramatic reduction in experimental metastases and the loss of bCSC self-renewal., Methods: Suppression c-FLIP was performed by siRNA (FLIPi) in four breast cancer cell lines and by conditional gene-knockout in murine mammary glands. Sensitivity of these cells to TRAIL was determined by complementary cell apoptosis assays, including a novel heterotypic cell assay, while tumour-initiating potential of cancer stem cell subpopulations was determined by mammosphere cultures, aldefluor assay and in vivo transplantation., Results: Genetic suppression of c-FLIP resulted in the partial sensitization of TRAIL-resistant cancer lines to the pro-apoptotic effects of TRAIL, irrespective of their cellular phenotype, yet normal mammary epithelial cells remained refractory to killing. While 10% to 30% of the cancer cell populations remained viable after TRAIL/FLIPi treatment, subsequent mammosphere and aldefluor assays demonstrated that this pro-apoptotic stimulus selectively targeted the functional bCSC pool, eliminating stem cell renewal. This culminated in an 80% reduction in primary tumours and a 98% reduction in metastases following transplantation. The recurrence of residual tumour initiating capacity was consistent with the observation that post-treated adherent cultures re-acquired bCSC-like properties in vitro. Importantly however this recurrent bCSC activity was attenuated following repeated TRAIL/FLIPi treatment., Conclusions: We describe an apoptotic mechanism that selectively and repeatedly removes bCSC activity from breast cancer cell lines and suggest that a combined TRAIL/FLIPi therapy could prevent metastatic disease progression in a broad range of breast cancer subtypes.

It is well established that lysosomes play an active role during the execution of cell death. A range of stimuli can lead to lysosomal membrane permeabilization (LMP), thus inducing programmed cell death without involvement of the classical apoptotic programme. However, these lysosomal pathways of cell death have mostly been described in vitro or under pathological conditions. Here we show that the physiological process of post-lactational regression of the mammary gland is accomplished through a non-classical, lysosomal-mediated pathway of cell death. We found that, during involution, lysosomes in the mammary epithelium undergo widespread LMP. Furthermore, although cell death through LMP is independent of executioner caspases 3, 6 and 7, it requires Stat3, which upregulates the expression of lysosomal proteases cathepsin B and L, while downregulating their endogenous inhibitor Spi2A (ref. 8). Our findings report a previously unknown, Stat3-regulated lysosomal-mediated pathway of cell death under physiological circumstances. We anticipate that these findings will be of major importance in the design of treatments for cancers such as breast, colon and liver, where cathepsins and Stat3 are commonly overexpressed and/or hyperactivated respectively., (© 2011 Macmillan Publishers Limited. All rights reserved.)

Objectives: To detect major dietary patterns and their relation with demographic, socioeconomic, and lifestyle factors in adult women living in Tehran, Iran., Methods: In a cross-sectional study, 460 women 20-50 y of age were selected by a stratified random-sampling method. Factor analysis was conducted to ascertain the major dietary patterns, and analysis of covariance was fitted to assess the relation between demographic, socioeconomic, and lifestyle variables and adherence to major dietary patterns., Results: Two major dietary patterns were extracted: healthy and unhealthy. After adjustment for confounders, age (b=0.31, P<0.01), university degree (b=0.85, P<0.01), housing size >20 m(2)/head (b=0.30, P<0.01), total family income US >$500/mo (b=0.25, P<0.05), physical activity (b=0.01, P<0.05), and history of hypertension (b=0.36, P<0.05) were positively associated and duration of residence in Tehran (b=-0.01, P<0.05) was negatively associated with a healthy dietary pattern. Conversely, ethnicity (Turk versus Fars; b=0.30, P<0.01) and smoking (b=0.64, P<0.01) were positively associated and age (b=-0.33, P<0.01) was negatively associated with an unhealthy dietary pattern., Conclusion: Our findings support the association between demographic, socioeconomic, lifestyle factors and dietary patterns of the studied women. Therefore, it is suggested these factors should be considered in future studies on the association between dietary patterns and disease., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

Background/aim: The high prevalence of non-communicable diseases and their risk factors among the general urban population of Tehran necessitates an urgent implementation of nutritional interventional programs to curtail these risk factors. This study aimed to provide preliminary data on the knowledge, attitude and practices of urban Tehranian adults regarding nutrition and their relation to major non-communicable disease risk factors and to assess the need for educational interventions., Methods: This cross-sectional study was performed within the framework of the second phase of the Tehran Lipid and Glucose Study (TLGS). Subjects were 826 individuals, 369 men and 457 women, aged 20-70 years old, selected randomly from among 15,005 participants in the TLGS. Knowledge, attitude and practices of subjects were assessed by a 'knowledge, attitude and practice' questionnaire; height, weight, waist and hip circumferences were measured, and BMI and waist to hip ratio were calculated. Biochemical data including fasting blood glucose, cholesterol, triglycerides and HDL-cholesterol were measured, based on standard protocols, and LDL-cholesterol was calculated. Associations between nutritional knowledge, attitude, practice, sex, age and educational level, and between knowledge, attitude and practice and BMI, waist to hip ratio and levels of lipid and lipoproteins, were determined., Results: For knowledge 26.5, 52.7 and 20.8%, for attitude, 27.6, 48.9 and 23.5% and for practice, 27.4, 51.7 and 20.9% of individuals had desirable, moderate and weak knowledge scores, respectively. With increases in educational levels, knowledge scores increased (p < 0.001). Attitudes of illiterate and poorly literate groups were weaker than those of other groups (p < 0.001). However, illiterate and poorly literate groups had higher practice scores as compared to middle school and high school graduates (p < 0.001). Mean practice scores of university graduates were higher than high school graduates (p < 0.05). Those aged 30-50 years had higher knowledge scores than older individuals (p < 0.001). LDL- and total cholesterol were correlated to practice scores (p < 0.001, r = 0.23). Subjects with borderline triglyceride levels had better practice scores than normal individuals (p < 0.001)., Conclusions: The findings revealed that age, educational level and gender are factors that can influence knowledge, attitude and practices, regarding nutrition. It is vital to develop approaches and implement programs to improve the nutritional practices of the population., ((c) 2010 S. Karger AG, Basel.)

Recent studies in breast cancer cell lines have shown that oncostatin M (OSM) not only inhibits proliferation but also promotes cell detachment and enhances cell motility. In this study, we have looked at the role of OSM signaling in nontransformed mouse mammary epithelial cells in vitro using the KIM-2 mammary epithelial cell line and in vivo using OSM receptor (OSMR)-deficient mice. OSM and its receptor were up-regulated approximately 2 d after the onset of postlactational mammary regression, in response to leukemia inhibitory factor (LIF)-induced signal transducer and activator of transcription-3 (STAT3). This resulted in sustained STAT3 activity, increased epithelial apoptosis, and enhanced clearance of epithelial structures during the remodeling phase of mammary involution. Concurrently, OSM signaling precipitated the dephosphorylation of STAT5 and repressed expression of the milk protein genes beta-casein and whey acidic protein (WAP). Similarly, during pregnancy, OSM signaling suppressed beta-casein and WAP gene expression. In vitro, OSM but not LIF persistently down-regulated phosphorylated (p)-STAT5, even in the continued presence of prolactin. OSM also promoted the expression of metalloproteinases MMP3, MMP12, and MMP14, which, in vitro, were responsible for OSM-specific apoptosis. Thus, the sequential activation of IL-6-related cytokines during mammary involution culminates in an OSM-dependent repression of epithelial-specific gene expression and the potentiation of epithelial cell extinction mediated, at least in part, by the reciprocal regulation of p-STAT5 and p-STAT3.

Myelodysplastic syndromes (MDS) are clonal stem cell hematologic disorders that evolve to acute myeloid leukemia (AML) and thus model multistep leukemogenesis. Activating RAS mutations and overexpression of BCL-2 are prognostic features of MDS/AML transformation. Using NRASD12 and BCL-2, we created two distinct models of MDS and AML, where human (h)BCL-2 is conditionally or constitutively expressed. Our novel transplantable in vivo models show that expression of hBCL-2 in a primitive compartment by mouse mammary tumor virus-long terminal repeat results in a disease resembling human MDS, whereas the myeloid MRP8 promoter induces a disease with characteristics of human AML. Expanded leukemic stem cell (Lin(-)/Sca-1(+)/c-Kit(+)) populations and hBCL-2 in the increased RAS-GTP complex within the expanded Sca-1(+) compartment are described in both MDS/AML-like diseases. Furthermore, the oncogenic compartmentalizations provide the proapoptotic versus antiapoptotic mechanisms, by activating extracellular signal-regulated kinase and AKT signaling, in determination of the neoplastic phenotype. When hBCL-2 is switched off with doxycycline in the MDS mice, partial reversal of the phenotype was observed with persistence of bone marrow blasts and tissue infiltration as RAS recruits endogenous mouse (m)BCL-2 to remain active, thus demonstrating the role of the complex in the disease. This represents the first in vivo progression model of MDS/AML dependent on the formation of a BCL-2:RAS-GTP complex. The colocalization of BCL-2 and RAS in the bone marrow of MDS/AML patients offers targeting either oncogene as a therapeutic strategy.

Myelodysplastic syndromes (MDS) comprise a heterogeneous group of disorders characterized by ineffective hematopoiesis, with an increased propensity to develop acute myelogenous leukemia (AML). The molecular basis for MDS progression is unknown, but a key element in MDS disease progression is loss of chromosomal material (genomic instability). Using our two-step mouse model for myeloid leukemic disease progression involving overexpression of human mutant NRAS and BCL2 genes, we show that there is a stepwise increase in the frequency of DNA damage leading to an increased frequency of error-prone repair of double-strand breaks (DSB) by nonhomologous end-joining. There is a concomitant increase in reactive oxygen species (ROS) in these transgenic mice with disease progression. Importantly, RAC1, an essential component of the ROS-producing NADPH oxidase, is downstream of RAS, and we show that ROS production in NRAS/BCL2 mice is in part dependent on RAC1 activity. DNA damage and error-prone repair can be decreased or reversed in vivo by N-acetyl cysteine antioxidant treatment. Our data link gene abnormalities to constitutive DNA damage and increased DSB repair errors in vivo and provide a mechanism for an increase in the error rate of DNA repair with MDS disease progression. These data suggest treatment strategies that target RAS/RAC pathways and ROS production in human MDS/AML.

Histone deacetylase inhibitors (HDI) increase gene expression through induction of histone acetylation. However, it remains unclear whether increases in specific gene expression events determine the apoptotic response following HDI administration. Herein, we show that a variety of HDI trigger in hematopoietic cells not only widespread histone acetylation and DNA damage responses but also actual DNA damage, which is significantly increased in leukemic cells compared with normal cells. Thus, increase in H2AX and ataxia telangiectasia mutated (ATM) phosphorylation, early markers of DNA damage, occurs rapidly following HDI administration. Activation of the DNA damage and repair response following HDI treatment is further emphasized by localizing DNA repair proteins to regions of DNA damage. These events are followed by subsequent apoptosis of neoplastic cells but not normal cells. Our data indicate that induction of apoptosis by HDI may result predominantly through accumulation of excessive DNA damage in leukemia cells, leading to activation of apoptosis.

Hyperactivation of Ras is one of the most common abnormalities in acute myeloid leukemia. In experimental models, Ras inhibits myeloid differentiation, which is characteristic of leukemia; however, the mechanism through which it disrupts hematopoiesis is poorly understood. In multipotent FDCP-mix cells, Ras inhibits terminal neutrophil differentiation, thereby indefinitely extending their proliferative potential. Ras also strongly promotes the sensitivity of these cells to granulocyte-macrophage colony-stimulating factor (GM-CSF). Using this model, we have dissected the signaling elements downstream of Ras to determine their relative contribution to the dysregulation of hematopoiesis. Cells expressing Ras mutants selectively activating Raf (Ras*T35S) or phosphatidylinositol 3-kinase (Ras*Y40C) did not significantly affect differentiation or proliferative capacity, whereas Ras*E37G (which selectively activates RalGEFs) perpetuated proliferation and blocked neutrophil development in a manner similar to that of Ras. Correspondingly, expression of constitutively active versions of these effectors confirmed the overriding importance of Ral guanine nucleotide exchange factors. Cells expressing Ras demonstrated hyperactivation of Ral, which itself was able to exactly mimic the phenotype of Ras, including hypersensitivity to GM-CSF. Conversely, dominant negative Ral promoted spontaneous neutrophil development. Ral, in turn, appears to influence differentiation through multiple effectors. These data show, for the first time, the importance of Ral in regulating differentiation and self-renewal in hematopoietic cells.

NK cell-mediated cytotoxicity of target cells is the result of a balance between the activating and inhibitory signals provided by their respective ligand-receptor interactions. In our current study, we have investigated the significance of CD59 on human target cells in modulating this process. A range of CD59 site-specific Abs were used in NK cytotoxicity blocking studies against the CD59-expressing K562 target cell line. Significantly reduced cytotoxicity was observed in the presence of Abs previously shown to lack blocking capacity for C-mediated lysis. We investigated the consequences for alternative membrane attachment modalities, namely bis-myristoylated-peptidyl (BiMP) and GPI anchoring, on CD59-negative U937 cells. Expression of GPI-anchored CD59 either via transfection or incorporation rendered U937 targets more susceptible to NK cytotoxicity, whereas incorporation of CD59 via a BiMP anchor to similar levels did not alter susceptibility to NK cytotoxicity. Localization of both BiMP- and GPI-anchored CD59 proteins was shown to be within the lipid raft microdomain. A role for the GPI anchor and independence from glycosylation status was confirmed by expression of transmembrane-anchored CD59 or unglycosylated CD59 and by testing in NK cytotoxicity assays. To investigate mechanisms, we compared the signaling capacity of the various forms of expressed and incorporated CD59 following Ab cross-linking in calcium flux assays. GPI-anchored CD59, with or without glycosylation, mediated activation events, whereas CD59 forms lacking the GPI anchor did not. The data show that the increased susceptibility of target cells expressing CD59 to NK cytotoxicity requires GPI anchor-mediating signaling events, likely mediated by interactions between GPI-anchored CD59 on targets and NK receptors.

CD59 blocks formation of the membrane attack complex of complement by inhibiting binding of C9 to the C5b-8 complex. To investigate a role for CD59 in promoting T cell responses, we compared T cell activation in CD59a-deficient (Cd59a-/-) and wild-type (WT) mice after in vitro stimulation and after infection with rVV. Virus-specific CD4+ T cell responses were significantly enhanced in Cd59a-/- mice compared with WT mice. Similarly, Cd59a-/- T cells responded more vigorously to in vitro stimulation with CD3-specific Abs compared with WT mice. This effect of CD59a on T cell proliferation was found to be complement-independent. Collectively, these results demonstrate that CD59a down-modulates CD4+ T cell activity in vitro and in vivo, thereby revealing another link between complement regulators and T cell activation.

There is compelling evidence that a unique innate immune response in the CNS plays a critical role in host defense and clearance of toxic cell debris. Although complement has been implicated in neuronal impairment, axonal loss, and demyelination, some preliminary evidence suggests that the initial insult consequently activates surrounding cells to signal neuroprotective activities. Using two different models of experimental autoimmune encephalomyelitis, we herein demonstrate selective C1q complement activation on neuron cell bodies and axons. Interestingly, in brains with chronic but not acute experimental autoimmune encephalomyelitis, C3b opsonization of neuronal cell bodies and axons was consistently associated with robust neuronal expression of one of the most effective complement regulators, decay-accelerating factor (CD55). In contrast, levels of other complement inhibitors, complement receptor 1 (CD35), membrane cofactor protein (CD46), and CD59 were largely unaffected on neurons and reactive glial cells in both conditions. In vitro, we found that proinflammatory stimuli (cytokines and sublytic doses of complement) failed to up-regulate CD55 expression on cultured IMR32 neuronal cells. Interestingly, overexpression of GPI-anchored CD55 on IMR32 was capable of modulating raft-associated protein kinase activities without affecting MAPK activities and neuronal apoptosis. Critically, ectopic expression of decay-accelerating factor conferred strong protection of neurons against complement attack (opsonization and lysis). We conclude that increased CD55 expression by neurons may represent a key protective signaling mechanism mobilized by brain cells to withstand complement activation and to survive within an inflammatory site.