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Type 1 diabetes (T1D) is an autoimmune disease in which pathogenic lymphocytes target autoantigens expressed in pancreatic islets, leading to the destruction of insulin-producing β-cells. Zinc transporter 8 (ZnT8) is a major autoantigen abundantly present on the β-cell surface. This unique molecular target offers the potential to shield β-cells against autoimmune attacks in T1D. Our previous work showed that a monoclonal antibody (mAb43) against cell-surface ZnT8 could home in on pancreatic islets and prevent autoantibodies from recognizing β-cells. This study demonstrates that mAb43 binds to exocytotic sites on the β-cell surface, masking the antigenic exposure of ZnT8 and insulin after glucose-stimulated insulin secretion. In vivo administration of mAb43 to NOD mice selectively increased the proportion of regulatory T cells in the islet, resulting in complete and sustained protection against T1D onset as well as reversal of new-onset diabetes. The mAb43-induced self-tolerance was reversible after treatment cessation, and no adverse effects were exhibited during long-term monitoring. Our findings suggest that mAb43 masking of the antigenic exposure of β-cells suppresses the immunological cascade from B-cell antigen presentation to T cell–mediated β-cell destruction, providing a novel islet-targeted and antigen-specific immunotherapy to prevent and reverse clinical T1D. Article Highlights: mAb43, a zinc transporter 8 (ZnT8)–specific monoclonal antibody, provides lasting protection against autoimmune diabetes in NOD mice. The in vivo islet specificity of mAb43 enables targeted therapy to enhance safety. High-affinity binding of mAb43 to the extracellular surface of ZnT8 shields β-cells from antigenic exposure. β-Cell masking results in a localized increase in regulatory T cells in the pancreatic islet. Prolonged mAb43 treatment clears destructive insulitis, preserves β-cell mass, and reverses seroconversion of insulin autoantibodies in NOD mice. The immunological processes bridging the masking of specific cell-surface autoantigens and the broad suppression of polyspecific T-cell autoimmunity are still unclear. [ABSTRACT FROM AUTHOR]

We developed a rapid in vitro digestion/Caco-2 cell culture model for assessing relative bioavailabilities of iron in foods and meals. The objective of the present study was to determine how closely our Caco-2 model reflects the human response. Meals described in published reports of studies on effects of varying levels of ascorbic acid (AA) and tannic acid (TA) on iron absorption by human subjects were carefully replicated. Iron absorption ratios (iron absorption from meals containing AA or TA divided by iron absorption from identical meals without these enhancers or inhibitors) were determined using the Caco-2 model. Ferritin formation by the Caco-2 cells was used as an indicator of iron absorption. Response patterns of effects of AA and TA on absorption ratios (AR) calculated from Caco-2 and human data were very similar: AA increased ARs in a dose-response manner and TAs decreased AR. The natural logs of the ARs determined in Caco-2 and human studies were correlated: R = 0.935 (P = 0.012) and 0.927 (P = 0.007) for AA and TA, respectively. When results from meals with AA and TA were pooled, a linear relation between the natural logs of ARs from Caco-2 and human studies was observed (R - 0.968, P < 0.001). We conclude that our Caco-2 model accurately predicts the human response to AA and TA in the meals we tested. If future work reproduces the precision and accuracy shown in this paper for predicting iron bioavailability to humans, then the implications for saving time and resources in iron bioavailability measurements are considerable. KEY WORDS: * iron bioavailability * Caco-2 * ascorbic acid * tannic acid

Abstract Background With a secular trend of increasing colorectal cancer (CRC) screening, concerns about disparities in CRC screening also have been rising. It is unclear if CRC screening varies geographically, if area-level poverty rate affects CRC screening, and if individual-level characteristics mediate the area-level effects on CRC screening. Methods Using 2006 Missouri Behavioral Risk Factor Surveillance System (BRFSS) data, a multilevel study was conducted to examine geographic variation and the effect of area-level poverty rate on CRC screening use among persons age 50 or older. Individuals were nested within ZIP codes (ZIP5 areas), which in turn, were nested within aggregations of ZIP codes (ZIP3 areas). Six groups of individual-level covariates were considered as potential mediators. Results An estimated 51.8% of Missourians aged 50 or older adhered to CRC screening recommendations. Nearly 15% of the total variation in CRC screening lay between ZIP5 areas. Persons residing in ZIP5 areas with ≥ 10% of poverty rate had lower odds of CRC screening use than those residing in ZIP5 areas with Conclusion Large geographic variation of CRC screening exists in Missouri. Area-level poverty rate, independent of individual-level characteristics, is a significant predictor of CRC screening, but it only explains a small portion of the geographic heterogeneity of CRC screening. Individual-level factors we examined do not mediate the effect of the area-level poverty rate on CRC screening. Future studies should identify other area- and individual-level characteristics associated with CRC screening in Missouri.

Chronic diseases are the major causes of premature death, disability and loss of quality of life in Missouri. The prevalence of many chronic diseases, conditions and risk behaviors is greater in Missouri than the U.S. The medical costs for treating chronic diseases are a burden on the state's economy and will increase as the population ages. Prevention and control of chronic diseases is essential to the physical and economic health of Missourians.

Reducing tobacco use among young people is an important public health goal. This article summarizes the results of the analysis of Missouri Youth Tobacco Survey (YTS) data collected between 2003 and 2009. The YTS collects information regarding tobacco use and related issues among Missouri public middle and high school students. Downward trends in initiation of tobacco use and current cigarette smoking occurred during this period. However, increased implementation of evidence-based interventions is needed to continue the progress seen during this period.

Objective: To evaluate the effectiveness of the peer counselling (PC) programme on breast-feeding initiation among participants in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) in Missouri, and to identify factors that facilitate breast-feeding initiation., Design: We used the data from the 2006 Missouri Pregnancy Nutrition Surveillance System, Missouri Live Birth Records and the Missouri WIC programme to compare breast-feeding initiation rates between PC and non-PC agencies. We used multilevel logistic regression, with individual participants being nested within agencies, to control for individual- and agency-level characteristics., Results: The breast-feeding initiation rate in PC agencies was significantly higher than in non-PC agencies among prenatal participants, but the difference was not significant among postpartum participants. After controlling for maternal sociodemographic characteristics, compared with prenatal cases in non-PC agencies, prenatal cases in PC agencies were more likely to initiate breast-feeding (OR = 1.21; 95 % CI 1.03, 1.43), whereas postpartum cases were less likely to initiate breast-feeding. Among prenatal participants in PC agencies, longer duration of prenatal WIC enrolment was associated with a higher rate of breast-feeding initiation. After adjusting for maternal sociodemographic characteristics and other agency-level characteristics, participants of PC agencies with an international board-certified lactation consultant were more likely to initiate breast-feeding than participants of PC agencies without such a consultant (OR = 1.21; 95 % CI 1.01, 1.45)., Conclusions: Prenatal participation in the WIC breast-feeding PC programme (especially participation early during pregnancy) was associated with an increased rate of breast-feeding initiation in Missouri.

Eliminating racial disparities in cancer is a key goal of national organizations and those in Missouri. The purpose of this study is to provide trends in cancer incidence (1996-2003) and mortality (1990-2005) over time with special emphasis on disparities between African-Americans and whites in Missouri. Overall changes in incidence rates suggest that by 2006 the racial disparity will be eliminated. However, African-Americans will continue to have higher mortality rates unless more aggressive interventions are implemented.

This study used the Smoking-Attributable Mortality, Morbidity and Economic Cost (SAMMEC) software developed by the Centers for Disease Control and Prevention to assess the health consequences and economic burden due to smoking in Missouri. During 2000-2004, cigarette smoking resulted in 9,600 deaths (17.5% of all deaths), 132,103 Years of Potential Life Lost, and $2.4 billion in productivity loss annually in Missouri. These data show that Missouri suffers enormous human and financial losses from smoking.

Introduction: Gestational diabetes mellitus (GDM) affects approximately 2% to 4% of all pregnant women in the United States each year. Women who have had GDM are at high risk for developing nongestational diabetes. The objective of this study was to assess the prevalence of modifiable risk factors for developing diabetes among women with previous GDM only., Methods: Cross-sectional data for nonpregnant women from the 2003 Behavioral Risk Factor Surveillance System were used to estimate and compare the prevalence of modifiable risk factors among three groups: nonpregnant women with previous GDM only, nonpregnant women with current diabetes, and nonpregnant women without diabetes., Results: In 2003, 7.6% of nonpregnant women aged 18 years and older in the United States had current self-reported physician-diagnosed diabetes, and 1.5% had previous GDM only. Compared with women without diabetes, women with previous GDM only had higher prevalence of no leisure-time physical activity (32.0% vs 25.7%), overweight (62.2% vs 49.0%), and obesity (29.4% vs 20.0%). After adjusting for sociodemographic variables, women with previous GDM only were more likely to have no leisure-time physical activity (prevalence odds ratio [POR], 1.4; 95% confidence interval [CI], 1.2-1.7) and more likely to be overweight (POR, 1.8; 95% CI, 1.6-2.2) or obese (POR, 1.7; 95% CI, 1.4-2.1), compared with women with no diabetes., Conclusion: Women with previous GDM are more likely to have modifiable risk factors for developing diabetes than women without diabetes. More attention to this issue is needed from health care providers and public health officials to encourage the promotion of healthy lifestyles during and after pregnancy.