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Serendipity berry plant (Dioscoreophyllum cumminsii (Stapf) Diels) is the source of a naturally sweet protein referred to as monellin. The safety of serendipity berry sweet protein (SBSP) containing single polypeptide monellin (MON) expressed in Komagataella phaffii (formerly Pichia pastoris) and produced via precision fermentation was examined comprehensively through assessments of in vitro and in silico protein digestion, in silico allergenicity, in vitro genotoxicity (reverse mutation and mammalian micronucleus assays), and 14-day and 90-day oral (dietary) toxicity studies in rats. There was no indication of allergenicity for SBSP in the in silico analyses. Results from both in vitro and in silico protein digestibility assessments indicated that SBSP is digested upon ingestion and would therefore be unlikely to pose a toxigenic or allergenic risk to consumers. SBSP was non-genotoxic in in vitro assays and showed no adverse effects in the 14-day or 90-day toxicity studies up to the highest dose tested. The 90-day toxicity study supports a NOAEL for SBSP of 1954 mg/kg bw/day, which corresponds to a NOAEL for MON of 408 mg/kg bw/day., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The author(s) declared potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Tina Wang and Jason Ryder are employees of Oobli, Inc. Elaine Freeman, Rachel Ward, and Mary Murphy are employees of Exponent, Inc. Oobli, Inc. is a client of Exponent, Inc., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Sodium intake in the USA exceeds recommendations. The replacement of added sodium chloride (NaCl) with potassium chloride (KCl) provides a potential strategy to reduce sodium intake., Objective: The purpose of this study was to quantitatively estimate changes in intakes of sodium and potassium by the US population assuming use of potassium-based NaCl replacers in top dietary sodium sources., Methods: Data collected in the What We Eat in America (WWEIA) component of the 2015-2016 and 2009-2010 NHANES were used to identify top-ranking sources of dietary sodium among the population aged 2 y and older based on contributions from food categories aligning with the FDA draft guidance for voluntary sodium reduction. Predicted nutrient intakes were estimated in models assuming total and feasible and practical (F&P) replacement of added NaCl with KCl in foods and ingredients within the top food sources of sodium. An expert elicitation was conducted to collect information on the F&P KCl replacement of added NaCl., Results: Using 2015-2016 consumption data, the total replacement of added NaCl with KCl in the 18 top-ranking sources of dietary sodium results in a predicted sodium intake of 2004 mg/d from the replacement of 1406 mg/d sodium with 1870 mg/d potassium as KCl. Modeled F&P replacement predicted sodium intakes of 3117 mg/d (range of 2953 to 3255 mg/d) from the replacement of 294 mg/d sodium (155 to 457 mg/d) with 390 mg/d potassium (206 to 608 mg/d). Similar results are seen with 2009-2010 data., Conclusions: The F&P replacement of NaCl with KCl in top-ranking sources of dietary sodium modeled in this study can result in decreased sodium to a level consistent with the short-term intake goal targeted by the FDA of 3000 mg/d, with the mean potassium intake remaining in the range recommended for the apparently healthy population., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Purpose: To understand the consequences of the 3q29 deletion on medical, neurodevelopmental, psychiatric, brain structural, and neurological sequalae by systematic evaluation of affected individuals. To develop evidence-based recommendations using these data for effective clinical care., Methods: Thirty-two individuals with the 3q29 deletion were evaluated using a defined phenotyping protocol and standardized data collection instruments., Results: Medical manifestations were varied and reported across nearly every organ system. The most severe manifestations were congenital heart defects (25%) and the most common were gastrointestinal symptoms (81%). Physical examination revealed a high proportion of musculoskeletal findings (81%). Neurodevelopmental phenotypes represent a significant burden and include intellectual disability (34%), autism spectrum disorder (38%), executive function deficits (46%), and graphomotor weakness (78%). Psychiatric illness manifests across the lifespan with psychosis prodrome (15%), psychosis (20%), anxiety disorders (40%), and attention deficit-hyperactivity disorder (ADHD) (63%). Neuroimaging revealed structural anomalies of the posterior fossa, but on neurological exam study subjects displayed only mild or moderate motor vulnerabilities., Conclusion: By direct evaluation of 3q29 deletion study subjects, we document common features of the syndrome, including a high burden of neurodevelopmental and neuropsychiatric phenotypes. Evidence-based recommendations for evaluation, referral, and management are provided to help guide clinicians in the care of 3q29 deletion patients.

Background: Rapid changes to how maternity health care is delivered has occurred in many countries across the globe in response to the COVID-19 pandemic. Maternity care provisions have been challenged attempting to balance the needs and safety of pregnant women and their care providers. Women experiencing a pregnancy after loss (PAL) during these times face particularly difficult circumstances., Aim: In this paper we highlight the situation in three high income countries (Australia, Ireland and USA) and point to the need to remember the unique and challenging circumstances of these PAL families. We suggest new practices may be deviating from established evidence-based guidelines and outline the potential ramifications of these changes., Findings: Recommendations for health care providers are suggested to bridge the gap between the necessary safety requirements due to the pandemic, the role of the health care provider, and the needs of families experiencing a pregnancy after loss., Discussion: Changes to practices i.e. limiting the number of antenatal appointments and access to a support person may have detrimental effects on both mother, baby, and their family. However, new guidelines in maternity care practices developed to account for the pandemic have not necessarily considered women experiencing pregnancy after loss., Conclusion: Bereaved mothers and their families experiencing a pregnancy after loss should continue to be supported during the COVID-19 pandemic to limit unintended consequences., (Copyright © 2020 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.)

Background: Many American adults have one or more chronic diseases related to a poor diet, resulting in significant direct and indirect economic impacts. The 2015-2020 Dietary Guidelines for Americans (DGA) recognized that dietary patterns may be more relevant for predicting health outcomes compared with individual diet elements and recommended three healthy patterns based on evidence of favorable associations with many chronic disease risk factors and outcomes. Health economic assessments provide a model to estimate the potential influence on costs associated with changes in chronic disease risk resulting from improved diet quality in the US adult population., Objective: To estimate the impact on health care costs associated with increased conformance with the three healthy patterns recommended in the 2015-2020 DGA, including the Healthy US-Style, the Healthy Mediterranean-Style, and the Healthy Vegetarian eating patterns., Methods: Recent moderate- to high-quality meta-analyses of health outcomes associated with increased conformance with the Healthy US-Style eating pattern as measured by the Healthy Eating Index (HEI) or the Healthy Mediterranean-Style eating pattern measured by a Mediterranean diet score (MED) were identified. Given the lack of quantification of the association between an increased conformance with a vegetarian pattern and health outcomes, the analysis was limited to studies that evaluated Healthy US-style and Healthy Mediterranean-style eating patterns. The 2013-2014 What We Eat in America data provided estimates of conformance with these two eating patterns using the HEI-2015 and the 9-point MED among the US adult population. Risk estimates quantifying the association between eating patterns and health outcomes were combined with the eating pattern score increase under two conformance scenarios: increasing the average HEI-2015 and MED by 20% and increasing the average HEI-2015 and MED to achieve 80% of complete conformance. The resulting change in risk was combined with published data on annual health care and indirect costs, inflated to 2017 US dollars to estimate cost. To address double counting, costs were adjusted to minimize potential overlap of comorbidities., Results: Overall modeled cost savings were $16.7 billion (range=$6.7 billion to $25.4 billion) to $31.5 billion (range=$23.9 billion to $38.9 billion) based on a 20% increase in the MED and HEI-2015, respectively, resulting from reductions in cardiovascular disease, cancer, and type 2 diabetes for both patterns and including Alzheimer's disease and hip fractures for the MED. In the case that diet quality of US adults were to improve to achieve 80% of the maximum MED and HEI-2015, cost savings were estimated at $88.2 billion (range=$35.7 billion to $133 billion) and $55.1 billion (range=$41.8 billion to $68.2 billion), respectively., Conclusions: This is the first study quantifying savings from all health outcomes identified to be associated with the HEI and the MED to assess conformance with two eating patterns recommended as part of the 2015-2020 DGA. Findings from this study suggest that increasing conformance with healthy eating patterns among US adults could reduce costs, with billions of dollars in potential savings., (Copyright © 2019 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

Various surgical techniques exist for rotator cuff repair that provide a suitable environment for tendon-bone healing. Arthroscopic recreation of transosseous repairs, which had previously been performed by open or miniopen techniques, can now be performed; however, arthroscopic, transosseous passage of suture material can be challenging technically. There are potential biologic and cost-saving advantages of arthroscopic transosseous rotator cuff repair that make an efficient and reproducible technique desirable for arthroscopists. The technique for arthroscopic transosseous rotator cuff repair using a knotless anchor-based system is demonstrated in the current Technical Note. Potential advantages of this construct include excellent biomechanics, enhanced footprint vascularization, and utility in poor bone quality while using minimal anchor numbers. Further studies will be needed to elucidate healing rates and clinical outcomes.

Background: Periconception folic acid supplementation is widespread, but how it interacts with cobalamin status is rarely considered., Objective: The aim of this study was to investigate whether first-trimester folate-cobalamin interactions affect pregnancy cobalamin status, hematologic variables, and pregnancy outcomes., Design: In the longitudinal Reus-Tarragona Birth Cohort study from <12 gestational weeks throughout pregnancy, fasting plasma and red blood cell (RBC) folate, plasma cobalamin, holotranscobalamin (holoTC), methylmalonic acid (MMA), total homocysteine (tHcy), hemoglobin, mean cell volume (MCV), postglucose-load serum glucose, gestational hypertension, gestational age at birth, and birth weight were recorded in 563 participants., Results: The highest plasma folate concentrations occurred in the first trimester when folic acid supplement use was extensive. Supplementation beyond the first trimester interacted with time of pregnancy on plasma folate, RBC folate, and tHcy throughout pregnancy (P-interaction <0.001). Plasma folate and RBC folate were higher and tHcy was lower in continued supplement users than in nonusers. Elevated plasma folate (≥30 nmol/L) occurred in 78.9% of women who exceeded the recommended 400 µg folic acid/d. First-trimester folate-cobalamin status interactions were associated with MMA (P-interaction <0.001) throughout pregnancy. When plasma cobalamin was suboptimal (≤221 pmol/L; n = 36), participants with elevated plasma folate (n = 11) had higher MMA concentrations than did those with nonelevated plasma folate (n = 23). First-trimester folate-MMA status interactions were associated with MCV throughout pregnancy (P-interaction <0.01) and with cord plasma holoTC (P-interaction <0.05). The mean difference (95% CI) in MCV (fL) between women with elevated and nonelevated plasma folate status was -2.12 (-3.71, -0.52) for top-quartile plasma MMA (≥0.139 µmol/L) and 0.60 (-0.39, 1.60) for plasma MMA <0.139 µmol/L. Cord plasma holoTC was higher in women with elevated compared with nonelevated plasma folate status only for MMA <0.139 µmol/L. Folate-cobalamin interactions were not associated with the other investigated outcomes., Conclusion: First-trimester folate-cobalamin status interactions were associated with plasma MMA and MCV throughout pregnancy. This trial was registered at www.clinicaltrials.gov as NCT01778205.

Background: Although combinations of biologically relevant polymorphic variants affect folate status, most studies have focused on the effects of individual polymorphisms; however, these effects may be altered by interactions between polymorphisms., Objective: We investigated the individual and combined effects of polymorphisms that affect folate transport or metabolism on folate status., Methods: The associations between the methylenetetrahydrofolate reductase (MTHFR) 677C > T, methionine transferase reductase (MTRR) 66A > G, MTRR 524C > T, 5,10-methylenetetrahydrofolate dehydrogenase-5,10-methylenetetrahydrofolate cyclohydrolase-10-formyltetrahydrofolate synthetase (MTHFD1) 1958G > A, MTHFD1 -105C > T, dihydrofolate reductase (DHFR) 19-bp insertion/deletion, and solute carrier family 19A, member 1 (SLC19A1) 80G > A polymorphisms and fasting plasma folate (PF), red cell folate (RCF), and plasma total homocysteine (tHcy) were tested by ANCOVA and Cox regression analysis in 781 Spanish adults., Results: Folate deficiency (PF <7 nmol/L) was observed in 18.8% of the participants. Geometric mean PF (nmol/L) was lower in MTHFR 677TT (10.0; 95% CI: 9.2, 11.9) compared with 677CC (12.4; 95% CI: 11.6, 13.2; P < 0.001). RCF (nmol/L) was lower in MTHFR 677TT (652; 95% CI: 611, 695) compared with 677CC (889; 95% CI: 851, 929; P < 0.001) and in SLC19A1 80AA (776; 95% CI: 733, 822) compared with 80GG (861; 95% CI: 815, 910; P < 0.01). RCF and tHcy (μmol/L) did not differ in MTHFR + MTRR 677TT/524TT compared with 677CC/524CC: 780 (95% CI: 647, 941) compared with 853 (95% CI: 795, 915; P = 0.99) and 10.2 (95% CI: 8.4, 12.3) compared with 8.9 (95% CI: 8.5, 9.4; P = 0.99), respectively. The RR of lowest-tertile RCF (≤680 nmol/L) was 2.1 (95% CI: 1.0, 4.5) for MTHFR + MTRR 677TT/66GG compared with 677CC/66AA, 2.2 (95% CI: 1.2, 4.1) for MTHFR + MTHFD1 677TT/1958AA compared with 677CC/1958GG, 2.9 (95% CI: 1.4, 6.0) for MTHFR + MTHFD1 677TT/-105TT compared with 677CC/-105CC, and 3.5 (95% CI: 1.5, 8.1) for MTHFR + SLC19A1 677TT/80AA compared with 677CC/80GG. Confining the analysis to the MTHFR 677TT genotype, the risk of lowest-tertile RCF was reduced for MTHFR + MTRR 677TT/66GG compared with 677TT/66AA (RR: 0.5; 95% CI: 0.3, 0.9)., Conclusions: Folate status was lower in the MTHFR 677TT and SLC19A1 80AA genotypes compared with corresponding reference genotypes. Low folate status risk associated with the MTHFR 677TT genotype varied depending on its combination with other polymorphisms., (© 2016 American Society for Nutrition.)

Nearly all Americans (97%) report eating candy at least once per year; yet, on a given day, only approximately one-fourth of the US population aged ≥2 y consumes candy. Among all Americans, candy contributes a relatively small proportion of calories, added sugars, and saturated fat to the total diet, and recent research suggests that current levels of candy consumption are not associated with risk of weight gain and cardiovascular disease in children and adults. Providing guidance for the consumption of candy in moderation requires an understanding of various behavioral health-related factors that influence candy consumption. A roundtable of behavioral nutrition experts, researchers, and nutrition educators met to discuss recent data on intakes of candy, health outcomes associated with usual candy intake, and the impact of behavioral strategies, including restriction, education, and environmental awareness, on modifying eating behaviors to achieve moderate intakes of candy. Restricting access to palatable foods, whether self-imposed or by parental control, may have potentially negative consequences. Techniques and insight into how to adopt "moderation" in candy consumption, from effective parental practices to environmental strategies that facilitate behavior change without a high degree of effort, were identified as important next steps toward sustainable dietary guidance related to the role of candy and other treats in a healthy lifestyle., (© 2015 American Society for Nutrition.)

Dynamic standing balance is essential to perform functional activities and is included in the treatment of many lower extremity injuries. Physiotherapists utilize many methods to restore standing balance including stability exercises, functional retraining, and manual therapy. The purpose of this study was to investigate the effects of a rearfoot distraction manipulation on dynamic standing balance. Twenty healthy participants (age: 24.4 ± 2.8 years; height: 162.9 ± 37.7 cm; mass: 68.0 ± 4.8 kg; right leg dominant = 20) completed this study. Following familiarization, dynamic standing balance was assessed during: (1) an experimental condition immediately following a rearfoot distraction manipulation, and (2) a control condition. Dominant leg balance was quantified using the Y-balance test which measures lower extremity reach distances. Reach distances were normalized to leg length and measured in the anterior, posteromedial and posterolateral directions. Overall balance was calculated through the summing of all normalized directions. Paired t-tests and Wilcoxon rank tests were used to compare balance scores for parametric and non-parametric data as appropriate. Significance was set at 0.05 a priori. Effect size (ES) was calculated to determine the clinical impact of the manipulation. Increased reach distances (indicating improved balance) were noted following manipulation for overall balance (p = 0.03, ES = 0.26) and in the posteromedial direction (p = 0.01, ES = 0.42). Reach distances did not differ for the anterior (p = 0.11, ES = 0.16) or posterolateral (p = 0.11, ES = 0.25) components. Dynamic standing balance improved after a rearfoot distraction manipulation in healthy participants. It is hypothesized that manual therapy applied to the foot and ankle may be beneficial to augment other therapeutic modalities when working with patients to improve dynamic standing balance., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

The Nutrition Facts panel on food labels in the United States currently displays Daily Values (DVs) that are based on outdated RDAs. The FDA has indicated that it plans to update the DVs based on the newer Dietary Reference Intakes (DRIs), but there is controversy regarding the best method for calculating new DVs from the DRIs. To better understand the implications of DV revisions, assuming that manufacturers choose to maintain current label claims for micronutrients from voluntarily fortified foods, we modeled intake of 8 micronutrients using NHANES 2007-2008 data and 2 potential methods for calculating DVs: the population-weighted Estimated Average Requirement (EAR) and the population-coverage RDA. In each scenario, levels of fortified nutrients were adjusted to maintain the current %DV. Usual nutrient intakes and percentages with usual intakes less than the EAR were estimated for the U.S. population and subpopulations aged ≥ 4 y (n = 7976). For most nutrients, estimates of the percentage of the U.S. population with intakes below the EAR were similar regardless of whether the DV corresponded to the population-weighted EAR or the population-coverage RDA. Potential decreases were observed in adequacy of nutrients of concern for women of childbearing age, namely iron and folate (up to 9% and 3%, respectively), adequacy of calcium among children (up to 6%), and adequacy of vitamin A intakes in the total population (5%) assuming use of the population-weighted EAR compared with the population-coverage RDA for setting the DV. Results of this modeling exercise will help to inform decisions in revising the DVs.

Background: Folate, choline, and betaine participate in homocysteine metabolism. It is not known whether they interact during pregnancy., Objective: The objective was to investigate how folate status affects choline, betaine, and dimethylglycine during pregnancy., Design: Fasting plasma folate, cobalamin, free choline, betaine, dimethylglycine, and total homocysteine (tHcy) were measured longitudinally at <12, 15, 24-27, and 34 gestational weeks (GW); at labor (nonfasting); and in the cord in participants (n = 522) from the Reus-Tarragona Birth Cohort (NUTrició i Creixement Intrauterí Retardat phase). Timing, dose, and duration of folic acid supplement use were recorded. Folate status was classified as below (low) or above (high) median plasma folate at baseline (27.6 nmol/L) and at 24-27 GW (11.4 nmol/L). Associations between folate or betaine with tHcy were investigated by using multiple linear regression analysis., Results: Plasma betaine decreased by 34.8% (1.0%) throughout pregnancy, and dimethylglycine increased by 39.7% (2.7%) between 24-27 GW and labor (all P < 0.001). Compared with high folate status, low status was associated with a higher dimethylglycine/betaine ratio from 15 GW and with lower plasma betaine and higher dimethylglycine from 24 to 27 GW, for the rest of pregnancy. Regression analysis showed that by 24-27 GW, both plasma folate and betaine were inversely associated with tHcy when folate status was low and that the association between betaine and tHcy depended on folate status at 24-27 and 34 GW (interaction terms: P < 0.001 and P < 0.01). Betaine was inversely associated with tHcy at labor regardless of folate status., Conclusion: Low folate status enhances the reduction in betaine and the increase in dimethylglycine during pregnancy and strengthens the association between betaine and tHcy. This trial was registered at clinicaltrials.gov as NCT01778205.

Objective: To understand the association between parenting and children's dietary fat consumption, this study tested a comprehensive model of parenting that included parent household rules, parent modeling of rules, parent mediated behaviors, and parent support., Design: Cross-sectional., Setting: Baseline data from the MOVE/me Muevo project, a recreation site-based obesity prevention and control intervention trial., Participants: Five hundred forty-one parents of children between the ages of 5 and 8 years and living in San Diego County., Main Outcome Measure: Children's fat consumption based on parent report using a short food frequency questionnaire., Analysis: A hierarchical linear regression was conducted. In exploratory analyses, a stepwise backward elimination approach was used., Results: Children's fat consumption was positively associated with parent household rules (P < .01) and negatively associated with parent modeling of rules (P < .01)., Conclusions and Implications: Controlling parenting behaviors, such as rule setting, are associated with more frequent fat consumption, whereas role modeling healthful behaviors is associated with less frequent fat consumption. Changing parenting behaviors with regard to how they feed their children is a logical avenue for improving eating behaviors., (Copyright © 2012 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.)

Background: Individuals consuming diets dense in fruits and vegetables consume an array of phytonutrients as well as recognized nutritional components, including vitamins, minerals, and fiber. There is a growing body of evidence that phytonutrients may play positive roles in health., Objective: The purpose of this research was to estimate usual intakes of nine individual phytonutrients by Americans consuming recommended levels of fruits and vegetables compared to intakes by adults not meeting these recommendations, and to identify contributions of food sources to total phytonutrient intakes. The phytonutrients examined in this study are found predominantly in fruits and vegetables., Design: Food consumption data from the National Health and Nutrition Examination Surveys 2003-2006 and phytonutrient concentration data from US Department of Agriculture databases and the published literature were used to estimate energy-adjusted usual intakes. Student's t tests were used to compare mean energy-adjusted phytonutrient intakes between subpopulations who consumed recommended amounts of fruits and vegetables vs those who did not. Percentage contributions of each phytonutrient by food source were estimated for all adults., Results: Energy-adjusted intakes of all phytonutrients other than ellagic acid were considerably higher among both men and women meeting dietary recommendations for fruit and vegetable intakes compared to those not meeting the recommendations; energy-adjusted intakes of ellagic acid were higher only among women meeting vs not meeting the recommendations. For five of the nine phytonutrients (α-carotene, β-cryptoxanthin, lycopene, hesperetin, and ellagic acid), a single food accounted for 64% or more of the total intake of the phytonutrient., Conclusions: Energy-adjusted intakes of carotenoids and flavonoids are higher among men and women whose diets conform to dietary guidance for fruits and vegetables. A limited number of foods provide the majority of these phytonutrients. Findings from this research provide important reference information on the phytonutrient contributions of a diet rich in fruits and vegetables.

Background: Total pancreatectomy (TP) is performed for various indications. Historically, morbidity and mortality have been high. Recent series reporting improved peri-operative mortality have renewed interest in TP. We performed a national review of TP including indication, patient/hospital characteristics, complications and peri-operative mortality., Methods: The Nationwide Inpatient Sample (NIS) was queried to identify TPs performed during 1998 to 2006. Univariate analyses were used to compare patient/hospital characteristics. Multivariable logistic regression was performed to identify predictors of in-hospital mortality. Post-operative complications/disposition were assessed., Results: From 1998 to 2006, 4013 weighted patient-discharges occurred for TP. Fifty-three per cent were male; mean age 58 years., Indication: neoplastic disease 67.8%. Post-operative complications occurred in 28%. Univariate analyses: TPs increased significantly (1998, n = 384 vs. 2006 n = 494, P < 0.01). 77.1% of TPs occurred in teaching hospitals (P < 0.0001), 86.4% in hospitals performing or = 70 Adjusted odds ratio (AOR) 3.4, 95% confidence interval (CI) 1.33-8.67], select patient comorbidities and year (referent = 2004-2006; 1998-2000 AOR 2.70; 95% CI 1.41-5.14) independently predicted in-patient mortality whereas hospital surgical volume did not., Discussion: TP is increasingly performed nationwide with a concomitant decrease in peri-operative mortality. Patient characteristics, rather than hospital volume, predicted increased mortality.

Folate receptor (FR)-blocking autoantibodies (FR-autoantibodies) have been reported in women with neural tube defect-affected pregnancies and subfertility and in children with progressive neurodevelopment disorders. We investigated their prevalence and association with folate status and milk intake in adults unexposed to folic acid fortification. A cross-sectional study of a randomly selected representative sample of a Spanish population (aged 18-75 y) stratified by age and gender was performed. Plasma and red cell folate, plasma cobalamin, fasting plasma total homocysteine (tHcy) concentration, methylenetetrahydrofolate reductase C677T polymorphism, and FR-autoantibody titer were determined in blood samples from 787 fasting participants. Lifestyle data were collected and milk intake estimated from a 3-d dietary record. FR-autoantibody prevalence was 7.2% [0.30 +/- 0.27 nmol (mean +/- SD) FR blocked/L], equally affecting men and women of all ages. Plasma and red cell folate and tHcy did not differ between carriers and noncarriers of FR-autoantibodies. Milk intake was higher in carriers (225 +/- 199 g/d) than in noncarriers (199 +/- 147 g/d) (P < 0.01). The risk of having FR-autoantibodies increased progressively with increasing quintile of milk intake and was significant in the highest quintile (> or =307 g/d) compared with the lowest (< or =67 g/d) [odds ratio (OR), 2.41 [95% CI: 1.02, 5.69]; P < 0.05; linear trend, P = 0.02]. We concluded that FR-autoantibodies occur in men and women of all ages and do not affect indicators of folate status such as plasma and red cell folate and tHcy. Higher milk intake is associated with increased risk of having FR-autoantibodies.

To explore the variability in biosensor studies, 150 participants from 20 countries were given the same protein samples and asked to determine kinetic rate constants for the interaction. We chose a protein system that was amenable to analysis using different biosensor platforms as well as by users of different expertise levels. The two proteins (a 50-kDa Fab and a 60-kDa glutathione S-transferase [GST] antigen) form a relatively high-affinity complex, so participants needed to optimize several experimental parameters, including ligand immobilization and regeneration conditions as well as analyte concentrations and injection/dissociation times. Although most participants collected binding responses that could be fit to yield kinetic parameters, the quality of a few data sets could have been improved by optimizing the assay design. Once these outliers were removed, the average reported affinity across the remaining panel of participants was 620 pM with a standard deviation of 980 pM. These results demonstrate that when this biosensor assay was designed and executed appropriately, the reported rate constants were consistent, and independent of which protein was immobilized and which biosensor was used.

Objective: Little research has been conducted on health effects associated with consumption of flavored milk. The purposes of this study were to compare nutrient intakes and body measures among children and adolescents drinking flavored milk (with or without plain milk), exclusively plain milk, and no milk., Design: Data used in the study included intakes reported in 24-hour dietary recalls and height and weight measurements collected during a physical examination in the 1999--2002 National Health and Nutrition Examination Surveys. The milk drinking status of each person was identified, and nutrient intakes and body mass index (BMI) measures were determined by milk drinking status., Subjects: The study population included 7,557 children and adolescents aged 2 to 18 years., Statistical Analysis: Comparisons among mean milk intakes, energy and nutrient intakes, and BMI measures by milk drinking status were completed using linear regression analysis., Results: Children and adolescents who included flavored milk in their diets reported higher total milk intakes than consumers of exclusively plain milk (P<0.05). Intakes of vitamin A, calcium, phosphorus, magnesium, potassium, and saturated fat (adjusted for energy intake and age) were generally comparable among milk drinking groups, whereas intakes by milk nondrinkers were significantly lower (P<0.05). Among females aged 12 to 18 years, calcium intakes by flavored and exclusively plain milk drinkers were 992+/-41.5 and 1,038+/-22.5 mg/day, respectively, whereas intake by nondrinkers was 576+/-11.7 mg/day. Intake of added sugars did not differ between flavored milk drinkers and milk nondrinkers. BMI measures of milk drinkers were comparable to or lower than measures of nondrinkers (P<0.05)., Conclusions: Findings from this study suggest that consumption of either flavored or plain milk is associated with a positive influence on nutrient intakes by children and adolescents and is not associated with adverse effects on BMI measures.

Objective: Dietary fiber represents a broad class of undigested carbohydrate components. The components vary in chemical and physical nature and in their physiological outcomes. Resistant starch is starch that escapes digestion in the small intestine and that may be fermented in the large intestine. The purpose of this study was to estimate consumption of resistant starch by the US population and to identify key sources of dietary resistant starch., Design: A database of resistant starch concentrations in foods was developed from the publicly available literature. These concentrations were linked to foods reported in 24-hour dietary recalls from participants in the 1999-2002 National Health and Nutrition Examination Surveys and estimates of resistant starch intakes were generated., Subjects: The study population included 18,305 nonbreastfeeding individuals in the United States., Statistical Analysis: The dietary intake of resistant starch was determined for 10 US subpopulations defined by age, sex, and race/ethnicity. Three estimates of resistant starch intake were made for each person based on the minimum, mean, and maximum concentrations of resistant starch in the foods consumed., Results: Americans aged 1 year and older were estimated to consume approximately 4.9 g resistant starch per day based on mean resistant starch concentrations (range 2.8 to 7.9 g resistant starch per day). Breads, cooked cereals/pastas, and vegetables (other than legumes) contributed 21%, 19%, and 19% of total resistant starch intake, respectively, and were top sources of resistant starch., Conclusions: Findings from this study suggest that the estimated intake of resistant starch by Americans is approximately 3 to 8 g per person per day. These estimates of resistant starch intake provide a valuable reference for researchers and food and nutrition professionals and will allow for more accurate estimates of total intakes of carbohydrate compounds that escape digestion in the small intestine.

Compromised cobalamin status during pregnancy may put both mother and child at risk of deficiency during lactation and subsequent development. We investigated whether changes in cobalamin status during pregnancy are associated with impaired status in the mother and the cord. Plasma cobalamin, methylmalonic acid (MMA), and holotranscobalamin (holoTC) concentrations were determined in 92 women at preconception, 8, 20, and 32 wk of pregnancy, at labor, and in the cord. All variables [geometric mean percentiles 10, 90 (P(10), P(90))] were significantly reduced from preconception [cobalamin: 293 (155, 535) pmol/L; holoTC: 63 (38,98) pmol/L; MMA: 0.12 (0.09, 0.17) micromol/L] by 20 wk of pregnancy [cobalamin: 230 (123, 432) pmol/L; holoTC: 48 (34,78) pmol/L; MMA: 0.11 (0.08, 0.15) micromol/L P < 0.001]. Plasma cobalamin and holoTC remained lower throughout the remainder of pregnancy [32 wk: 198 (107, 339); labor: 224 (117, 444); P < 0.001] and [32 wk: 45 (26,82); labor: 40 (23,79); P < 0.05], respectively. By 32 wk, MMA was greater than preconception [0.14 (0.09, 0.20) micromol/L; P < 0.01]. Plasma holoTC at 32 wk and at labor was negatively correlated with cord MMA (r = -0.51, P < 0.001 and r = -0.40, P < 0.01, respectively). Women with lower holoTC at preconception had greater increases in MMA at 32 wk and at labor. Maternal MMA at 32 wk and at labor was significantly and independently associated with cord MMA only in women with lower holoTC at preconception (regression models: R(2) = 0.707, 0.682, respectively; P < 0.01). The moderate increases observed in the cobalamin biomarker, MMA, during pregnancy may indicate a functional depletion in intracellular cobalamin status.

A total of 22 individuals participated in this benchmark study to characterize the thermodynamics of small-molecule inhibitor-enzyme interactions using Biacore instruments. Participants were provided with reagents (the enzyme carbonic anhydrase II, which was immobilized onto the sensor surface, and four sulfonamide-based inhibitors) and were instructed to collect response data from 6 to 36 degrees C. van't Hoff enthalpies and entropies were calculated from the temperature dependence of the binding constants. The equilibrium dissociation and thermodynamic constants determined from the Biacore analysis matched the values determined using isothermal titration calorimetry. These results demonstrate that immobilization of the enzyme onto the sensor surface did not alter the thermodynamics of these interactions. This benchmark study also provides insights into the opportunities and challenges in carrying out thermodynamic studies using optical biosensors.

Background: Native-American populations are disproportionately burdened by chronic liver disease, and the prevalence of hepatitis C (HCV) in native Americans is unknown., Purpose: To determine the prevalence of hepatitis C in a local native-American population via a prospective screening study., Procedures: Two-hundred-forty-three native Americans (161 females/82 males) using an urban clinic and representing > 30 tribes from across the United States were screened. Mean age was 41 +/- 1 years. Hepatitis-C screening was by anti-HCV with confirmation by HCV RNA. A questionnaire assessed potential risk factors for HCV., Findings: Anti-HCV antibodies were found in 11.5% (95% CI: 7.5-15.5%). HCV RNA was present by polymerase chain reaction (PCR) in 8.6% (95% CI: 5.1-12.1%) and was more common in males [13.4% (95% CI: 6.0-20.8%)] than females [6.2% (95% CI: 2.5-9.9%)]. The most common potential risk factors for chronic HCV infection were intravenous (IV) drug or cocaine use (p < 0.0001), tattoos > 5 years old (p < 0.0001) and having a sexual partner with HCV (p = 0.0063)., Conclusion: HCV prevalence is higher in an urban native-American clinic population than reported in the general U.S. population. Use of IV drugs is the most prevalent risk factor, but tattoos and sexual transmission may also be important.

Concerns about vitamin D status in the United States have resurfaced due to increasing reports of insufficiency and deficiency. Few foods contain vitamin D naturally, and currently few foods are fortified in the United States. Intakes of vitamin D in the United States from food and food plus supplements by age, sex, and race/ethnicity group were estimated. Individuals > or = 1 y old who participated in the 1999-2000 National Health and Nutrition Examination Survey (NHANES 1999-2000) were included in the analysis. Vitamin D intake by non-Hispanic (NH) white, NH black, Mexican American, and all individuals in the United States was estimated and compared with recommended levels. Vitamin D intakes were highest among children and teenagers, and lowest in the oldest age categories. Among children age 1-8 y, adequate intake (AI) levels for vitamin D from food were met or exceeded by 69% of Mexican American, 59% of NH white, and 48% of NH black subpopulations. Among adults > or = 51 y old, only 4% met or exceeded the AI from food alone. Few women 19-50 y old or men and women > or = 51 y old were estimated to consume recommended vitamin D levels from food. Mean dietary intakes of vitamin D from food plus supplements were consistently highest among NH white populations, although only small proportions of all those > or = 51 y old had intakes above the recommended levels. The large discrepancy between vitamin D intake by older individuals from food plus supplements and recommended levels, especially for NH black and Mexican American adults, warrants intervention.

Vaso-occlusion is a hallmark of sickle cell disease. Agonist-induced activation of sickle red blood cells (SS RBCs) promotes their adhesion to vascular proteins, potentially contributing to vasoocclusion. Previously, we described a cyclic adenosine monophosphate (cAMP)-dependent increase in SS RBC adhesion to laminin. Here, we investigated whether Rap1, a small guanosine triphosphatase (GTPase) known to promote integrin-mediated adhesion in other cells, was involved in this signaling pathway. We found that agonists known to induce cAMP signaling promoted the GTP-bound, active state of Rap1 in SS RBCs. The cAMP-dependent exchange factor Epac (exchange protein directly activated by cAMP) is a likely upstream activator of Rap1, since Epac is present in these cells and the Epac-specific cAMP analog 8CPT-2-Me (8-(4-cholorophenylthio)-2'-O-methyl-cAMP) activated Rap1 and promoted SS RBC adhesion to laminin. This 8CPT-2-Me-stimulated adhesion was integrin independent, since it was insensitive to RGD peptide or antibodies against the only known integrin on SS RBCs, alpha4beta1. However, this adhesion was completely inhibited by either a soluble version of basal cell adhesion molecule/Lutheran (BCAM/LU) or a BCAM/LU adhesion-blocking anti-body. Surprisingly, 8CPT-2-Me-activated Rap1 did not promote SS RBC adhesion to a known alpha4beta1 ligand, vascular cell adhesion molecule 1 (VCAM-1). These results demonstrate that Epac-induced Rap1 activation in SS RBCs promotes BCAM/LU-mediated adhesion to laminin. Thus, Epac-mediated Rap1 activation may represent an important signaling pathway for promoting SS RBC adhesion.

C-reactive protein (CRP) has been proposed as an independent risk factor for cardiovascular disease. In this study we sought to investigate the association between several nutritional and lifestyle factors and serum CRP concentration in a population-based study. We studied 359 individuals (172 women, 187 men; age range 18-75 years) randomly selected from the town hall's registers and assessed their daily dietary intake using a 3-day estimated-food record. The median serum CRP concentration was 1.40 mg/L (range <0.10-47.48 mg/L; geometric mean 1.20 mg/L). We noted significant and independent direct associations between CRP and age, body-mass index, female sex, and serum triglyceride concentration. Bivariate analysis showed a significant inverse association between CRP and many nutrients (e.g., carbohydrates, proteins, lipids, thiamine, pyridoxine, tocopherol, and folate), but multiple-regression analysis indicated that only the effect of dietary folate intake was not dependent on other factors. Differences in folate intake did not produce changes in plasma homocysteine concentration, and we detected no negative correlation between dietary folate intake and log homocysteine (r = .02, P = .711). Strong positive correlations between the intake of folate and numerous other nutrients were found. This population-based study shows that a higher folate intake, in addition to other known constitutive and lifestyle factors, is significantly associated with a lower serum CRP concentration.

Mean intake of vitamin D in the United States was estimated from food and food plus supplements and compared with recommended intake levels. US men, nonpregnant and nonlactating women, and nonbreastfeeding children aged 1 year and older who participated in the Third National Health and Nutrition Examination Survey (NHANES III, 1988-1994) or the Continuing Survey of Food Intakes by Individuals 1994-1996, 1998 (CSFII 1994-1996, 1998) were included in the estimates. Intake of vitamin D from food sources and dietary supplements was not meeting recommended levels. The lowest intakes of vitamin D from food were reported by female teenagers and female adults. The highest intakes of vitamin D from food sources were reported by male teenagers. Dairy products were the primary sources of both vitamin D and calcium. Additional food fortification as well as dietary and supplement guidance are needed for the general population.

Background: Fasting plasma total homocysteine (tHcy) decreases during pregnancy. Previous reports suggested that this is due to folic acid supplementation, hemodilution, or a decrease in albumin. However, these hypotheses have not been tested in a longitudinal study., Objective: We investigated the relation between pregnancy-related physiologic changes and tHcy in a group of healthy women who were either unsupplemented or supplemented with folic acid., Design: In a longitudinal study from preconception throughout pregnancy, we studied 54 unsupplemented women and 39 women who were supplemented with folic acid during the second or third trimester of pregnancy. tHcy, hematocrit, and serum albumin were determined preconceptionally and at 8, 20, and 32 wk of pregnancy., Results: For the entire group, geometric mean tHcy concentrations at preconception (8.2 micro mol/L) were significantly greater (P < 0.001) than those at 8 wk of pregnancy (6.4 micro mol/L). When the unsupplemented and supplemented groups were regarded separately, geometric mean tHcy concentrations at preconception were significantly greater than those at 20 (5.22 and 4.18 micro mol/L, respectively) and 32 (5.16 and 4.42 micro mol/L, respectively) wk of pregnancy (P < 0.001 for both). Mean reductions from preconception concentrations at 8, 20, and 32 wk of pregnancy were significantly greater (P < 0.001) for tHcy (-11.5%, -25.5%, and -24.5%, respectively) than for hematocrit (-1.9%, -4.2%, and -4.3%, respectively) or serum albumin (-1.1%, -9.8%, and -13.4%, respectively). There was no correlation between changes in either hematocrit or serum albumin and changes in tHcy., Conclusions: This study refutes the previous explanations for the reduction in plasma tHcy known to occur in pregnancy, namely, folic acid supplementation, hemodilution, and a decrease in serum albumin. We suggest that the changes may be endocrine-based.

Objective: To examine the tracking (ie, the stability over time) of dietary intake in Mexican-American and white children aged 4 to 12 years., Subjects: Children 4 years of age (n=351) were assessed at baseline and 65% (n=228) completed the 8-year study., Design: Cardiovascular disease-related dietary intake was defined as energy, percent of energy from fat, and sodium (mg/1,000 kcal). From age 4 to 7 years, a modified 24-hour recall with observation of lunch and dinner and interview of the primary food preparer for unobserved foods was used to describe dietary intake. For children aged 11 to 12 years, a standardized 24-hour recall was used., Statistical Analyses: A mixed effects model that adjusted for sex, ethnicity, and measurement wave allowed for separation of shorter-term variations in diet from more stable ("between subject") variations. Extent of between-subject variance is an indication of tracking., Results: From age 4 to age 7, there were statistically significant between-subject variance components for energy (P<.00001), percent of energy from fat (P<.00001), and sodium per 1,000 kcals (P<.001); for ages 11 and 12, energy intake was significant (P<.00001). There were no significant associations for dietary intake from age 4 to 12 years., Conclusions/applications: It seems that dietary intakes are stable over short periods and at earlier ages compared with longer intervals and later ages. Nutrition interventions are needed in childhood and throughout adolescence.

Intermediate-phase clinical results of 51 low-pressure (LP) and 234 standard-pressure (SP) fixation porcine Carpentier-Edwards (CE) valves implanted between 1977 and 1991 were compared for valve-related events. Group similarities included New York Heart Association functional class, ejection fraction, and sex. Patients with SP valves were younger (mean age, 58 versus 68 years; p = 0.0001). There were 20 in-hospital deaths (8.6%) in the SP valve group and 5 (9.8%) in the LP valve group (p = 0.79). Follow-up was 99%, with a mean of 104 months in the SP valve group versus 55 months in the SP valve group (p = 0.0001). The actuarial survival rate was 48.2% and 22.3% at 10 and 15 years, respectively, in the SP valve group and 34.1% at 10 years in the LP valve group (p = 0.42). Freedom from events at 5, 10, and 15 years in the SP valve group and at 5 years in the LP valve group was as follows: for late valve-related events, 86.3%, 51.4% and 20.2%, respectively, in the SP valve group versus 85% in the LP valve group (p = 0.44); for valve-related death, 96.4%, 93.6%, and 87.3% in the SP valve group versus 100% in the LP valve group (p = 0.20); for structural valve failure, 96%, 68%, and 35% in the SP valve group versus 100% in the LP valve group (p = 0.09); and for reoperation, 95%, 61%, and 30% in the SP valve group versus 92% in the LP valve group (p = 0.82). In conclusion, this study revealed no significant statistical difference between LP and SP valves. In the LP valve group, structural valve failure/valve-related death was not observed, perhaps indicating a more favorable result. Absolute verification of this trend awaits long-term follow-up.