Compound haploinsufficiencies of Ebf1 and Runx1 genes impede B cell lineage progression.

Early B cell factor (EBF)1 is essential for B lineage specification. Previously, we demonstrated the synergistic activation of Cd79a (mb-1) genes by EBF1 and its functional partner, RUNX1. Here, we identified consequences of Ebf1 haploinsufficiency together with haploinsufficiency of Runx1 genes in mice. Although numbers of "committed" pro-B cells were maintained in Ebf1(+/-)Runx1(+/-) (ER(het)) mice, activation of B cell-specific gene transcription was depressed in these cells. Expression of genes encoding Aiolos, kappa0 sterile transcripts, CD2 and CD25 were reduced and delayed in ER(het) pro-B cells, whereas surface expression of BP-1 was increased on late pro-B cells in ER(het) mice. Late pre-B and immature and mature B cells were decreased in the bone marrow of Ebf1(+/-) (E(het)) mice and were nearly absent in ER(het) mice. Although we did not observe significant effects of haploinsuficiencies on IgH or Igkappa rearrangements, a relative lack of Iglambda rearrangements was detected in E(het) and ER(het) pre-B cells. Together, these observations suggest that B cell lineage progression is impaired at multiple stages in the bone marrow of E(het) and ER(het) mice. Furthermore, enforced expression of EBF1 and RUNX1 in terminally differentiated plasmacytoma cells activated multiple early B cell-specific genes synergistically. Collectively, these studies illuminate the effects of reduced Ebf1 dosage and the compounding effects of reduced Runx1 dosage. Our data confirm and extend the importance of EBF1 in regulating target genes and Ig gene rearrangements necessary for B cell lineage specification, developmental progression, and homeostasis.

Opposing effects of SWI/SNF and Mi-2/NuRD chromatin remodeling complexes on epigenetic reprogramming by EBF and Pax5.

Transcriptionally silent genes are maintained in inaccessible chromatin. Accessibility of these genes requires their modification by chromatin remodeling complexes (CRCs), which are recruited to promoters by sequence-specific DNA-binding proteins. Early B-cell factor (EBF), which is crucial for B-cell lineage specification, reprograms mb-1 (Ig-alpha) promoters by increasing chromatin accessibility and initiating the loss of DNA methylation. In turn, this facilitates promoter activation by Pax5. Here, we investigated the roles of ATP-dependent CRCs in these mechanisms. Fusion of EBF and Pax5 with the ligand-binding domain of ERalpha allowed for 4-hydroxytamoxifen-dependent, synergistic activation of mb-1 transcription in plasmacytoma cells. Knock-down of the SWI/SNF ATPases Brg1 and Brm inhibited transcriptional activation by EBF:ER and Pax5:ER. In contrast, knock-down of the Mi-2/NuRD complex subunit Mi-2beta greatly enhanced chromatin accessibility and mb-1 transcription in response to the activators. The reduction of Mi-2beta also propagated DNA demethylation in response to EBF:ER and Pax5:ER, resulting in fully unmethylated mb-1 promoters. In EBF- or EBF/Pax5-deficient fetal liver cells, both EBF and Pax5 were required for efficient demethylation of mb-1 promoters. Together, our data suggest that Mi-2/NuRD is important for the maintenance of hypermethylated chromatin in B cells. We conclude that SWI/SNF and Mi-2/NuRD function in opposition to enable or limit the reprogramming of genes by EBF and Pax5 during B-cell development.

Low Serum Vitamin D Concentrations Are Associated with Insulin Resistance in Mexican Children and Adolescents.

Previous studies in the Mexican adult population have suggested a relationship between low levels of serum concentrations of serum vitamin D with impaired glucose tolerance, metabolic syndrome, and diabetes, regardless of the presence of obesity. The aim of this study is to investigate the relationship between serum vitamin D levels and the factors linked to insulin resistance. A total of 533 children and adolescents from the "Reference Values of Body Composition in the Pediatric Population of Mexico City" study are assessed. Body composition, dietary, and lifestyle data are obtained. Serum vitamin D, insulin, and glucose are also measured. Associations are tested using multiple linear and logistic regression models. Approximately 90% of children and adolescents in this study have sub-optimal vitamin D levels (<30 ng/mL). An inverse relationship between insulin resistance and serum vitamin D is observed (OR (odds ratios) = 2.9; 95% CI (95% confidence intervals): 1.1, 7.2; p-trend 0.03). Low serum vitamin D levels are associated with insulin resistance in the pediatric population. The present study provides additional evidence for the role of vitamin D in insulin resistance. Our findings suggest the supplementation of vitamin D may be helpful in preventing insulin resistance and subsequent diabetes.

Effectiveness of the Nutritional App "MyNutriCart" on Food Choices Related to Purchase and Dietary Behavior: A Pilot Randomized Controlled Trial.

OBJECTIVE: To pilot test the effectiveness of "MyNutriCart", a smartphone application (app) that generates healthy grocery lists, on diet and weight. METHODS: A pilot randomized trial was conducted to test the efficacy of using the "MyNutriCart" app compared to one face-to-face counseling session (Traditional group) in Hispanic overweight and obese adults. Household food purchasing behavior, three 24-h food recalls, Tucker's semi-quantitative food frequency questionnaire (FFQ), and weight were assessed at baseline and after 8 weeks. Statistical analyses included t tests, a Poisson regression model, and analysis of covariance (ANCOVA) using STATA. RESULTS: 24 participants in the Traditional group and 27 in the App group completed the study. Most participants were women (>88%), with a mean age of 35.3 years, more than a high school education (>80%), a family composition of at least three members, and a mean baseline body mass index (BMI) of 34.5 kg/m². There were significant improvements in household purchasing of vegetables and whole grains, in individual intakes of refined grains, healthy proteins, whole-fat dairies, legumes, 100% fruit juices, and sweets and snacks; and in the individual frequency of intake of fruits and cold cuts/cured meats within the intervention group (p < 0.05). However, no significant differences were found between groups. No changes were detected in weight. CONCLUSIONS: "MyNutriCart" app use led to significant improvements in food-related behaviors compared to baseline, with no significant differences when compared to the Traditional group. Cost and resource savings of using the app compared to face-to-face counseling may make it a good option for interventionists.

The Role of Social-Emotional and Social Network Factors in the Relationship Between Academic Achievement and Risky Behaviors.

BACKGROUND: We examined whether standardized test scores and grades are related to risky behaviors among low-income minority adolescents and whether social networks and social-emotional factors explained those relationships. METHODS: We analyzed data from 929 high school students exposed by natural experiment to high- or low-performing academic environments in Los Angeles. We collected information on grade point average (GPA), substance use, sexual behaviors, participation in fights, and carrying a weapon from face-to-face interviews and obtained California math and English standardized test results. Logistic regression and mediation analyses were used to examine the relationship between achievement and risky behaviors. RESULTS: Better GPA and California standardized test scores were strongly associated with lower rates of substance use, high-risk sexual behaviors, and fighting. The unadjusted relative odds of monthly binge drinking was 0.72 (95% confidence interval, 0.56-0.93) for 1 SD increase in standardized test scores and 0.46 (95% confidence interval, 0.29-0.74) for GPA of B- or higher compared with C+ or lower. Most associations disappeared after controlling for social-emotional and social network factors. Averaged across the risky behaviors, mediation analysis revealed social-emotional factors accounted for 33% of the relationship between test scores and risky behaviors and 43% of the relationship between GPA with risky behaviors. Social network characteristics accounted for 31% and 38% of the relationship between behaviors with test scores and GPA, respectively. Demographic factors, parenting, and school characteristics were less important explanatory factors. CONCLUSIONS: Social-emotional factors and social network characteristics were the strongest explanatory factors of the achievement-risky behavior relationship and might be important to understanding the relationship between academic achievement and risky behaviors.

Development and Evaluation of a Nutritional Smartphone Application for Making Smart and Healthy Choices in Grocery Shopping.

OBJECTIVES: This study developed a smartphone nutritional application (app) for making smart and healthy choices when purchasing food in grocery stores and tested its feasibility, usability, satisfaction and acceptability. METHODS: "MyNutriCart" was developed following the ADDIE (analysis, design, development, implementation, and evaluation) model. The goals of the app were to improve food selection when purchasing foods in the grocery stores based on a pre-defined budget, to improve dietary patterns based on the Dietary Guidelines for Americans, and to improve weight status. It was evaluated within a pilot randomized trial using a convenient sample of 26 overweight or obese adults aged 21-45 years for 8 weeks. RESULTS: The developed app provided a grocery list of healthy foods to meet the individual requirements of all family members within a budget following the recommendations of the Dietary Guidelines for Americans. The average use of the app was 75% on each purchase and only 37% of the recommended products were purchased. The main reasons for not purchasing the recommended items were that participants did not like these (28.5%) and that the item was unavailable in the supermarket (24.3%). Over 50% of participants considered the app as feasible, usable, satisfactory, and acceptable (p < 0.05). CONCLUSIONS: "MyNutriCart" is the first available app for making smart and healthy choices when purchasing food in grocery stores. This app could be used as a tool to translate recommendations into a practical grocery list that meet the needs of a family within a budget.

High dose intravenous vitamin c treatment in a patient with lung cancer: A case report.

Lung cancer is one of the most common cancers in both men and women. According to Dr. Abram Hoffer, patients with a better nutritional plan and daily Vitamin C supplementation improved their life quality. In this case report we present the case of a 56-year-old Hispanic male patient diagnosed with lung cancer on 2012. After undergoing surgery and chemotherapy, he started a high dose intravenous Vitamin C protocol on December 2013. The treatment continued until June 2015, when the patient decided to stop the treatment. A maximum of 75 gr of Vitamin C in 1,000 cc lactated Ringer's was given three times a week in a period over a year and a half. Patient's CEA levels continued to be within normal levels while high doses of Vitamin C infusions were given. Many case reports suggest that patients with lung cancer that received high doses of intravenous Vitamin C can live up to 10 years. A level of Vitamin C in plasma above 400 mg/dL is toxic to tumor cells, this can be achieved with periodic Vitamin C infusions. Our case support that the usage of high doses of IV Vitamin C can be effective in the treatment of patients with cancer without secondary effects.