Multisystem inflammatory syndrome in children (MIS-C) is a severe, post-infectious sequela of SARS-CoV-2 infection(1,2), yet the pathophysiological mechanism connecting the infection to the broad inflammatory syndrome remains unknown. Here we leveraged a large set of samples from patients with MIS-C to identify a distinct set of host proteins targeted by patient autoantibodies including a particular autoreactive epitope within SNX8, a protein involved in regulating an antiviral pathway associated with MIS-C pathogenesis. In parallel, we also probed antibody responses from patients with MIS-C to the complete SARS-CoV-2 proteome and found enriched reactivity against a distinct domain of the SARS-CoV-2 nucleocapsid protein. The immunogenic regions of the viral nucleocapsid and host SNX8 proteins bear remarkable sequence similarity. Consequently, we found that many children with anti-SNX8 autoantibodies also have cross-reactive T cells engaging both the SNX8 and the SARS-CoV-2 nucleocapsid protein epitopes. Together, these findings suggest that patients with MIS-C develop a characteristic immune response to the SARS-CoV-2 nucleocapsid protein that is associated with cross-reactivity to the self-protein SNX8, demonstrating a mechanistic link between the infection and the inflammatory syndrome, with implications for better understanding a range of post-infectious autoinflammatory diseases.

Multisystem inflammatory syndrome in children (MIS-C) is a severe, post-infectious sequela of SARS-CoV-2 infection, yet the pathophysiological mechanism connecting the infection to the broad inflammatory syndrome remains unknown. Here we leveraged a large set of MIS-C patient samples (n=199) to identify a distinct set of host proteins that are differentially targeted by patient autoantibodies relative to matched controls. We identified an autoreactive epitope within SNX8, a protein expressed primarily in immune cells which regulates an antiviral pathway associated with MIS-C pathogenesis. In parallel, we also probed the SARS-CoV-2 proteome-wide MIS-C patient antibody response and found it to be differentially reactive to a distinct domain of the SARS-CoV-2 nucleocapsid (N) protein relative to controls. This viral N region and the mapped SNX8 epitope bear remarkable biochemical similarity. Furthermore, we find that many children with anti-SNX8 autoantibodies also have T-cells cross-reactive to both SNX8 and this distinct domain of the SARS-CoV-2 N protein. Together, these findings suggest that MIS-C patients develop a distinct immune response against the SARS-CoV-2 N protein that is associated with cross reactivity to the self-protein SNX8, demonstrating a link from the infection to the inflammatory syndrome. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.

BACKGROUND: Autoantibodies against type I IFNs occur in approximately 10% of adults with life-threatening coronavirus disease 2019 (COVID-19). The frequency of anti-IFN autoantibodies in children with severe sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is unknown. OBJECTIVE: We quantified anti-type I IFN autoantibodies in a multicenter cohort of children with severe COVID-19, multisystem inflammatory syndrome in children (MIS-C), and mild SARS-CoV-2 infections. METHODS: Circulating anti-IFN-α2 antibodies were measured by a radioligand binding assay. Whole-exome sequencing, RNA sequencing, and functional studies of peripheral blood mononuclear cells were used to study any patients with levels of anti-IFN-α2 autoantibodies exceeding the assay's positive control. RESULTS: Among 168 patients with severe COVID-19, 199 with MIS-C, and 45 with mild SARS-CoV-2 infections, only 1 had high levels of anti-IFN-α2 antibodies. Anti-IFN-α2 autoantibodies were not detected in patients treated with intravenous immunoglobulin before sample collection. Whole-exome sequencing identified a missense variant in the ankyrin domain of NFKB2, encoding the p100 subunit of nuclear factor kappa-light-chain enhancer of activated B cells, aka NF-κB, essential for noncanonical NF-κB signaling. The patient's peripheral blood mononuclear cells exhibited impaired cleavage of p100 characteristic of NFKB2 haploinsufficiency, an inborn error of immunity with a high prevalence of autoimmunity. CONCLUSIONS: High levels of anti-IFN-α2 autoantibodies in children and adolescents with MIS-C, severe COVID-19, and mild SARS-CoV-2 infections are rare but can occur in patients with inborn errors of immunity.

CDC COVID-19 surveillance systems monitor SARS-CoV-2 antibody prevalence to collect information about asymptomatic, undiagnosed, and unreported disease using national convenience samples of blood donor data from commercial laboratories (1,2). However, nonrandom sampling of data from these systems could affect prevalence estimates (1-3). The National Health and Nutrition Examination Survey (NHANES) collects SARS-CoV-2 serology data among a sample of the general U.S. civilian population (4). In addition, NHANES collects self-reported COVID-19 vaccination and disease history, and its statistical sampling design is not based on health care access or blood donation. Therefore, NHANES data can be used to better quantify asymptomatic SARS-CoV-2 infection prevalence and seropositivity attained through infection without vaccination. Preliminary NHANES 2021-2022 results indicated that 41.6% of adults aged ≥18 years had serology indicative of past infection and that 43.7% of these adults, including 57.1% of non-Hispanic Black or African American (Black) adults, reported never having had COVID-19, possibly representing asymptomatic infection. In addition, 25.5% of adults whose serology indicated past infection reported never having received COVID-19 vaccination. Prevalences of seropositivity in the absence of vaccination were higher among younger adults and Black adults, reflecting the lower observed vaccination rates among these groups (5). These findings raise health equity concerns given the disparities observed in SARS-CoV-2 infection and COVID-19 vaccination. Results from NHANES 2021-2022 can guide ongoing efforts to achieve vaccine equity in COVID-19 primary vaccination series and booster dose coverage.

BACKGROUND: Serum folate forms were measured in the US population during recent NHANES to assess folate status. OBJECTIVE: We describe post-folic acid-fortification concentrations of serum folate forms in the fasting US population >/=1 y from the NHANES 2011-2016. METHODS: We measured 5 biologically active folates and 1 oxidation product (MeFox) of 5-methyltetrahydrofolate (5-methyl-THF). We calculated geometric means of 5-methyl-THF, unmetabolized folic acid (UMFA), nonmethyl folate (sum of tetrahydrofolate, 5-formyltetrahydrofolate, and 5,10-methenyltetrahydrofolate), total folate (sum of above biomarkers), and MeFox by demographic, physiologic, and lifestyle variables; estimated the magnitude of variables on biomarker concentrations after covariate adjustment; and determined the prevalence of UMFA >2 nmol/L. RESULTS: After demographic adjustment, age, sex, and race-Hispanic origin were significantly associated with most folate forms. MeFox increased with age, while 5-methyl-THF, UMFA, and nonmethyl folate displayed U-shaped age patterns. Compared with non-Hispanic whites, non-Hispanic blacks had 23% lower predicted 5-methyl-THF but comparable UMFA; non-Hispanic Asians had comparable 5-methyl-THF but 28% lower UMFA; Hispanics, non-Hispanic Asians, and non-Hispanic blacks had approximately 20% lower MeFox. After additional physiologic and lifestyle adjustment, predicted UMFA and MeFox concentrations were 43% and 112% higher, respectively, in adults with chronic kidney disease and 17% and 15% lower, respectively, in adults consuming daily 1-<2 alcoholic beverages; 5-methyl-THF concentrations were 20% lower in adult smokers. The prevalence of UMFA >2 nmol/L was highest in persons aged >/=70 y (9.01%) and lowest in those aged 12-19 y (1.14%). During 2011-2014, the prevalence was 10.6% in users and 2.22% in nonusers of folic acid-containing supplements. CONCLUSIONS: In fasting persons >/=1 y, the demographic, physiologic, and lifestyle characteristics observed with serum total folate differed among folate forms, suggesting biological and/or genetic influences on folate metabolism. High UMFA was mostly observed in supplement users and older persons.

BACKGROUND: Enriched cereal-grain products have been fortified in the United States for >20 y to improve folate status in women of reproductive age and reduce the risk of folic acid-responsive neural tube birth defects (NTDs). OBJECTIVES: Our objectives were to assess postfortification changes in folate status in the overall US population and in women aged 12-49 y and to characterize recent folate status by demographic group and use of folic acid-containing supplements. METHODS: We examined cross-sectional serum and RBC folate data from the NHANES 1999-2016. RESULTS: Serum folate geometric means increased from 2007-2010 to 2011-2016 in persons aged >/=1 y (38.7 compared with 40.6 nmol/L) and in women (35.3 compared with 37.0 nmol/L), whereas RBC folate showed no significant change. Younger age groups, men, and Hispanic persons showed increased serum and RBC folate concentrations, whereas non-Hispanic black persons and supplement nonusers showed increased serum folate concentrations. The folate insufficiency prevalence (RBC folate <748 nmol/L; NTD risk) in women decreased from 2007-2010 (23.2%) to 2011-2016 (18.6%) overall and in some subgroups (e.g., women aged 20-39 y, Hispanic and non-Hispanic black women, and supplement nonusers). After covariate adjustment, RBC folate was significantly lower in all age groups (by approximately 10-20%) compared with persons aged >/=60 y and in Hispanic (by 8.2%), non-Hispanic Asian (by 12.1%), and non-Hispanic black (by 20.5%) compared with non-Hispanic white women (2011-2016). The 90th percentile for serum ( approximately 70 nmol/L) and RBC ( approximately 1800 nmol/L) folate in supplement nonusers aged >/=60 y was similar to the geometric mean in users (2011-2014). CONCLUSIONS: Blood folate concentrations in the US population overall and in women have not decreased recently, and folate insufficiency rates are approximately 20%. Continued monitoring of all age groups is advisable given the high folate status particularly in older supplement users.

BACKGROUND: Understanding measurement error in sodium and potassium intake is essential for assessing population intake and studying associations with health outcomes. OBJECTIVE: The aim of this study was to compare sodium and potassium intake derived from 24-h dietary recall (24HDR) with intake derived from 24-h urinary excretion (24HUE). DESIGN: Data were analyzed from 776 nonpregnant, noninstitutionalized US adults aged 20-69 y who completed 1-to-2 24HUE and 24HDR measures in the 2014 NHANES. A total of 1190 urine specimens and 1414 dietary recalls were analyzed. Mean bias was estimated as mean of the differences between individual mean 24HDR and 24HUE measurements. Correlations and attenuation factors were estimated using the Kipnis joint-mixed effects model accounting for within-person day-to-day variability in sodium excretion. The attenuation factor reflects the degree to which true associations between long-term intake (estimated using 24HUEs) and a hypothetical health outcome would be approximated using a single 24HDR: values near 1 indicate close approximation and near 0 indicate bias toward null. Estimates are reported for sodium, potassium, and the sodium: potassium (Na/K) ratio. Model parameters can be used to estimate correlations/attenuation factors when multiple 24HDRs are available. RESULTS: Overall, mean bias for sodium was -452 mg (95% CI: -646, -259), for potassium -315 mg (CI: -450, -179), and for the Na/K ratio -0.04 (CI: -0.15, 0.07, NS). Using 1 24HDR, the attenuation factor for sodium was 0.16 (CI: 0.09, 0.21), for potassium 0.25 (CI:0.16, 0.36), and for the Na/K ratio 0.20 (CI: 0.10, 0.25). The correlation for sodium was 0.27 (CI: 0.16, 0.37), for potassium 0.35 (CI: 0.26, 0.55), and for the Na/K ratio 0.27 (CI: 0.13, 0.32). CONCLUSIONS: Compared with 24HUE, using 24HDR underestimates mean sodium and potassium intake but is unbiased for the Na/K ratio. Additionally, using 24HDR as a measure of exposure in observational studies attenuates the true associations of sodium and potassium intake with health outcomes.

Background: Both excessive sodium intake and obesity are risk factors for hypertension and cardiovascular disease. The association between sodium intake and obesity is unclear, with few studies assessing sodium intake using 24-h urine collection. Objectives: Our objective was to assess the association between usual 24-h sodium excretion and measures of adiposity among US adults. Methods: Cross-sectional data were analyzed from a sample of 730 nonpregnant participants aged 20-69 y who provided up to 2 complete 24-h urine specimens in the NHANES 2014 and had data on overweight or obesity [body mass index (kg/m2) >/=25] and central adiposity [waist circumference (WC): >88 cm for women, >102 cm for men]. Measurement error models were used to estimate usual sodium excretion, and multiple linear and logistic regression models were used to assess its associations with measures of adiposity, adjusting for sociodemographic, health, and dietary variables [i.e., energy intake or sugar-sweetened beverage (SSB) intake]. All analyses accounted for the complex survey sample design. Results: Unadjusted mean +/- SE usual sodium excretion was 3727 +/- 43.5 mg/d and 3145 +/- 55.0 mg/d among participants with and without overweight/obesity and 3653 +/- 58.1 mg/d and 3443 +/- 35.3 mg/d among participants with or without central adiposity, respectively. A 1000-mg/d higher sodium excretion was significantly associated with 3.8-units higher BMI (95% CI: 2.8, 4.8) and a 9.2-cm greater WC (95% CI: 6.9, 11.5 cm) adjusted for covariates. Compared with participants in the lowest quartile of sodium excretion, the adjusted prevalence ratios in the highest quartile were 1.93 (95% CI: 1.69, 2.20) for overweight/obesity and 2.07 (95% CI: 1.74, 2.46) for central adiposity. The associations also were significant when adjusting for SSBs, instead of energy, in models. Conclusions: Higher usual sodium excretion is associated with overweight/obesity and central adiposity among US adults.

Background: 24-h urine collections are the suggested method to measure daily urinary potassium excretion (uK) but are costly and burdensome to implement. Objective: This study tested how well existing equations with the use of spot urine samples can estimate 24-h uK and if accuracy varies by timing of spot urine collection, age, race, or sex. Design: This cross-sectional study used data from 407 participants aged 18-39 y from the Washington, DC area in 2011 and 554 participants aged 45-79 y from Chicago in 2013. Spot urine samples were collected in individual containers for 24 h, and 1 for each timed period (morning, afternoon, evening, and overnight) was selected. For each selected timed spot urine, 24-h uK was predicted through the use of published equations. Difference (bias) between predicted and measured 24-h uK was calculated for each timed period and within age, race, and sex subgroups. Individual-level differences were assessed through the use of Bland-Altman plots and correlation tests. Results: For all equations, regardless of the timing of spot urine, mean bias was usually significantly different than 0. No one prediction equation was unbiased across all sex, race, and age subgroups. With the use of the Kawasaki and Tanaka equations, 24-h uK was overestimated at low levels and underestimated at high levels, whereas observed differential bias with the Mage equation was in the opposite direction. Depending on prediction equation and timing of urine sample, 61-75% of individual 24-h uKs were misclassified among 500-mg incremental categories from <1500 to ≥3000 mg. Correlations between predicted and measured 24-h uK were poor to moderate (0.19-0.71). Conclusion: Because predicted 24-h uK accuracy varies by timing of spot urine collection, published prediction equations, and within age-race-sex subgroups, study results making use of predicted 24-h uK in association with health outcomes should be interpreted with caution. It is possible that a more accurate prediction equation can be developed leading to different results.

Importance: In 2010, the Institute of Medicine (now the National Academy of Medicine) recommended collecting 24-hour urine to estimate US sodium intake because previous studies indicated 90% of sodium consumed was excreted in urine. Objective: To estimate mean population sodium intake and describe urinary potassium excretion among US adults. Design, Setting, and Participants: In a nationally representative cross-sectional survey of the US noninstitutionalized population, 827 of 1103 (75%) randomly selected, nonpregnant participants aged 20 to 69 years in the examination component of the National Health and Nutrition Examination Survey (NHANES) collected at least one 24-hour urine specimen in 2014. The overall survey response rate for the 24-hour urine collection was approximately 50% (75% [24-hour urine component response rate] x 66% [examination component response rate]). Exposures: 24-hour collection of urine. Main Outcomes and Measures: Mean 24-hour urinary sodium and potassium excretion. Weighted national estimates of demographic and health characteristics and mean electrolyte excretion accounting for the complex survey design, selection probabilities, and nonresponse. Results: The study sample (n = 827) represented a population of whom 48.8% were men; 63.7% were non-Hispanic white, 15.8% Hispanic, 11.9% non-Hispanic black, and 5.6% non-Hispanic Asian; 43.5% had hypertension (according to 2017 hypertension guidelines); and 10.0% reported a diagnosis of diabetes. Overall mean 24-hour urinary sodium excretion was 3608 mg (95% CI, 3414-3803). The overall median was 3320 mg (interquartile range, 2308-4524). In secondary analyses by sex, mean sodium excretion was 4205 mg (95% CI, 3959-4452) in men (n = 421) and 3039 mg (95% CI, 2844-3234) in women (n = 406). By age group, mean sodium excretion was 3699 mg (95% CI, 3449-3949) in adults aged 20 to 44 years (n = 432) and 3507 mg (95% CI, 3266-3748) in adults aged 45 to 69 years (n = 395). Overall mean 24-hour urinary potassium excretion was 2155 mg (95% CI, 2030-2280); by sex, 2399 mg (95% CI, 2253-2545) in men and 1922 mg (95% CI, 1757-2086) in women; and by age, 1986 mg (95% CI, 1878-2094) in adults aged 20 to 44 years and 2343 mg (95% CI, 2151-2534) in adults aged 45 to 69 years. Conclusions and Relevance: In cross-sectional data from a 2014 sample of US adults, estimated mean sodium intake was 3608 mg per day. The findings provide a benchmark for future studies.

Background -Higher levels of sodium and lower levels of potassium intake are associated with higher blood pressure. However, the shape and magnitude of these associations can vary by study participant characteristics or intake assessment method. Twenty-four hour urinary excretion of sodium and potassium are unaffected by recall errors and represent all sources of intake, and were collected for the first time in a nationally representative US survey. Our objective was to assess the associations of blood pressure and hypertension with 24-hour urinary excretion of sodium and potassium among US adults. Methods -Cross-sectional data from 766 participants aged 20-69 years with complete blood pressure and 24-hour urine collections in the 2014 National Health and Nutrition Examination Survey, a nationally-representative survey of the US noninstitutionalized population. Usual 24-hour urinary electrolyte excretion (sodium, potassium, and their ratio) was estimated from up to two collections on non-consecutive days, adjusting for day-to-day variability in excretion. Outcomes included systolic and diastolic blood pressure from the average of 3 measures and hypertension status, based on average blood pressure ≥140/90 and anti-hypertensive medication use. Results -After multivariable adjustment, each 1000 mg difference in usual 24-hour sodium excretion was directly associated with systolic (4.58 mmHg, 95% confidence interval 2.64,6.51) and diastolic (2.25 mmHg, 95% CI 0.83,3.67) blood pressures. Each 1000 mg difference in potassium excretion was inversely associated with systolic blood pressure (-3.72 mmHg, 95% CI -6.01,-1.42). Each 0.5 unit difference in sodium-to-potassium ratio was directly associated with systolic blood pressure (1.72 mmHg, 95% CI 0.76, 2.68). Hypertension was linearly associated with progressively higher sodium and lower potassium excretion; compared with the lowest quartiles of excretion, the adjusted odds of hypertension for the highest quartiles were 4.22 (95% CI 1.36, 13.15) for sodium, and 0.38 (95% CI 0.17, 0.87) for potassium, respectively, P<0.01 for trends. Conclusions -These cross-sectional results show a strong dose-response association between urinary sodium excretion and blood pressure, and an inverse association between urinary potassium excretion and blood pressure, in a nationally representative sample of US adults.

We examined the population distribution of urinary sodium concentrations and the validity of existing equations predicting 24-hour sodium excretion from a single spot urine sample among older adults with and without hypertension. In 2013, 24-hour urine collections were obtained from 554 participants in the Multi-Ethnic Study of Atherosclerosis and the Coronary Artery Risk Development in Young Adults study, who were aged 45-79 years and of whom 56% were female, 58% were African American, and 54% had hypertension, in Chicago, Illinois. One-third provided a second 24-hour collection. Four timed (overnight, morning, afternoon, and evening) spot urine specimens and the 24-hour collection were analyzed for sodium and creatinine concentrations. Mean 24-hour sodium excretion was 3,926 (standard deviation (SD), 1,623) mg for white men, 2,480 (SD, 1,079) mg for white women, 3,454 (SD, 1,651) mg for African-American men, and 3,397 (SD, 1,641) mg for African-American women, and did not differ significantly by hypertensive status. Mean bias (difference) in predicting 24-hour sodium excretion from the timed spot urine specimens ranged from -182 (95% confidence interval: -285, -79) to 1,090 (95% confidence interval: 966, 1,213) mg/day overall. Although the Tanaka equation using the evening specimen produced the least bias overall, no single equation worked well across subgroups of sex and race/ethnicity. A single spot urine sample is not a valid indicator of individual sodium intake. New equations are needed to accurately estimate 24-hour sodium excretion for older adults.

BACKGROUND: Twenty-four-hour urine sodium excretion is recommended for monitoring population sodium intake. Because of concerns about participation and completion, sodium excretion has not been collected previously in US nationally representative surveys. OBJECTIVE: We assessed the feasibility of implementing 24-h urine collections as part of a nationally representative survey. DESIGN: We selected a random half sample of nonpregnant US adults aged 20-69 y in 3 geographic locations of the 2013 NHANES. Participants received explicit instructions, started and ended the urine collection in a urine study mobile examination center, and answered questions about their collection. Among those with a complete 24-h urine collection, a random one-half were asked to collect a second 24-h urine sample. Sodium, potassium, chloride, and creatinine excretion were analyzed. RESULTS: The final NHANES examination response rate for adults aged 20-69 y in these 3 study locations was 71%. Of those examined (n = 476), 282 (59%) were randomly selected to participate in the 24-h urine collection. Of these, 212 persons [75% of those selected for 24-h urine collection; 53% (equal to 71% x 75% of those selected for the NHANES)] collected a complete initial 24-h specimen and 92 persons (85% of 108 selected) collected a second complete 24-h urine sample. More men than women completed an initial collection (P = 0.04); otherwise, completion did not vary by sociodemographic characteristics, body mass index, education, or employment status for either collection. Mean 24-h urine volume and sodium excretion were 1964 +/- 1228 mL and 3657 +/- 2003 mg, respectively, for the first 24-h urine sample, and 2048 +/- 1288 mL and 3773 +/- 1891 mg, respectively, for the second collection. CONCLUSION: Given the 53% final component response rate and 75% completion rate, 24-h urine collections were deemed feasible and implemented in the NHANES 2014 on a subsample of adults aged 20-69 y to assess population sodium intake. This study was registered at clinicaltrials.gov as NCT02723682.

In view of continuing unanswered questions regarding the geographical and demographic distribution of cardiovascular disease, and recent discoveries about the effects of dietary nitrate on cardiovascular physiology, the National Heart, Lung, and Blood Institute (NHLBI) convened a workshop to identify approaches to address how best to incorporate the study of nitrate exposures into ongoing studies of cardiovascular epidemiology. The NHLBI invited speakers who had made recent contributions to the study of the functions of nitrate on the cardiovascular system, on the occurrence of nitrate in foods and drinking water, or who had expert knowledge of cardiovascular surveys with wide geographical variability and therefore the greatest potential variability in dietary and drinking water nitrate. Because of the history of research on the possible carcinogenicity of nitrite, an expert in this field was also invited. The following document is a synthesis of the material presented and discussed and of literature cited at the workshop. The workshop from which this article is derived was funded and convened by the NHLBI.

In the United States, breastfeeding initiation rates have risen to 80%.1 We report secular trends of breastfeeding initiation and duration by birth weight using nationally representative data from the National Health and Nutrition Examination Survey (NHANES).

INTRODUCTION: Although decline in muscle mass and quality and resulting declines in muscle strength are associated with aging, more research is needed in general populations to assess the utility of handgrip strength as an indicator of muscle strength and cardiovascular disease risk. METHODS: Data from 4,221 participants aged ≥20 years in the 2011-2012 cycle of National Health and Nutrition Examination Survey were analyzed during 2014-2015. Standing isometric relative handgrip strength (calculated as maximal absolute handgrip strength from both hands divided by BMI) was used to predict cardiovascular biomarkers, including blood pressure (measured systolic and diastolic blood pressure); serum lipids (total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides); and plasma insulin and glucose. RESULTS: Results from regression analyses showed that higher relative grip strength was significantly associated with lower systolic blood pressure, triglycerides, and plasma insulin and glucose, and higher high-density lipoprotein cholesterol in male and female participants (p<0.05 for all). Secondary descriptive analyses found that absolute handgrip strength increased significantly with increasing weight status, but relative handgrip strength decreased significantly with increasing weight status. CONCLUSIONS: Results suggest that increased relative handgrip strength may be associated with a better profile of cardiovascular health biomarkers among U.S. adults. Relative grip strength, which both adjusts for the confounding of mass and assesses concomitant health risks of increased body size and low muscle strength, may be a useful public health measure of muscle strength.

The purposes of this study were to use the National Health and Nutrition Examination Study (NHANES 2011-12) data to determine nationally representative combined-hand grip strength ranges and percentile information by sex and age group, examine trends in strength across age by sex, and to determine the relative proportion of children and adults falling into established Health Benefit Zones (HBZ). Results indicate that mean strength was greater among males than females, increased linearly for children and in a quadratic fashion among adults for both sexes. Grip strength peaked in the 30 -39 year age group for both men (216.4lbs) and women (136.5lbs) with subsequent age groups showing gradual decline, ps < .0001. Relative and absolute increase in grip strength was greater for males than for females, but relative decrease from peak strength was less among women than men. Although absolute strength was greater among men than women, HBZ data indicated that a higher percentage of males than females overall and at each age group fell into the Needs Improvement zone, with differences particularly pronounced during adolescence and older adulthood. These data provide the first nationally representative population estimates of combined-hand grip strength and percentile information from childhood through senescence, and suggest consideration of HBZ information in conjunction with grip strength to improve surveillance data interpretation and intervention planning.

BACKGROUND: High US sodium intake and national reduction efforts necessitate developing a feasible and valid monitoring method across the distribution of low-to-high sodium intake. OBJECTIVE: We examined a statistical approach using timed urine voids to estimate the population distribution of usual 24-h sodium excretion. METHODS: A sample of 407 adults, aged 18-39 y (54% female, 48% black), collected each void in a separate container for 24 h; 133 repeated the procedure 4-11 d later. Four timed voids (morning, afternoon, evening, overnight) were selected from each 24-h collection. We developed gender-specific equations to calibrate total sodium excreted in each of the one-void (e.g., morning) and combined two-void (e.g., morning + afternoon) urines to 24-h sodium excretion. The calibrated sodium excretions were used to estimate the population distribution of usual 24-h sodium excretion. Participants were then randomly assigned to modeling (n = 160) or validation (n = 247) groups to examine the bias in estimated population percentiles. RESULTS: Median bias in predicting selected percentiles (5th, 25th, 50th, 75th, 95th) of usual 24-h sodium excretion with one-void urines ranged from -367 to 284 mg (-7.7 to 12.2% of the observed usual excretions) for men and -604 to 486 mg (-14.6 to 23.7%) for women, and with two-void urines from -338 to 263 mg (-6.9 to 10.4%) and -166 to 153 mg (-4.1 to 8.1%), respectively. Four of the 6 two-void urine combinations produced no significant bias in predicting selected percentiles. CONCLUSIONS: Our approach to estimate the population usual 24-h sodium excretion, which uses calibrated timed-void sodium to account for day-to-day variation and covariance between measurement errors, produced percentile estimates with relatively low biases across low-to-high sodium excretions. This may provide a low-burden, low-cost alternative to 24-h collections in monitoring population sodium intake among healthy young adults and merits further investigation in other population subgroups. This study was registered at clinicaltrials.gov as NCT01631240.

BACKGROUND: Limited data are available on the accuracy of 24-h dietary recalls used to monitor US sodium and potassium intakes. OBJECTIVE: We examined the difference in usual sodium and potassium intakes estimated from 24-h dietary recalls and urine collections. DESIGN: We used data from a cross-sectional study in 402 participants aged 18-39 y ( approximately 50% African American) in the Washington, DC, metropolitan area in 2011. We estimated means and percentiles of usual intakes of daily dietary sodium (dNa) and potassium (dK) and 24-h urine excretion of sodium (uNa) and potassium (uK). We examined Spearman's correlations and differences between estimates from dietary and urine measures. Multiple linear regressions were used to evaluate the factors associated with the difference between dietary and urine measures. RESULTS: Mean differences between diet and urine estimates were higher in men [dNa - uNa (95% CI) = 936.8 (787.1, 1086.5) mg/d and dK - uK = 571.3 (448.3, 694.3) mg/d] than in women [dNa - uNa (95% CI) = 108.3 (11.1, 205.4) mg/d and dK - uK = 163.4 (85.3, 241.5 mg/d)]. Percentile distributions of diet and urine estimates for sodium and potassium differed for men. Spearman's correlations between measures were 0.16 for men and 0.25 for women for sodium and 0.39 for men and 0.29 for women for potassium. Urinary creatinine, total caloric intake, and percentages of nutrient intake from mixed dishes were independently and consistently associated with the differences between diet and urine estimates of sodium and potassium intake. For men, body mass index was also associated. Race was associated with differences in estimates of potassium intake. CONCLUSIONS: Low correlations and differences between dietary and urinary sodium or potassium may be due to measurement error in one or both estimates. Future analyses using these methods to assess sodium and potassium intake in relation to health outcomes may consider stratifying by factors associated with the differences in estimates from these methods. This trial was registered at clinicaltrials.gov as NCT01631240.

BACKGROUND AND OBJECTIVES: Regular aerobic and muscle-strengthening physical activity in youth has been positively associated with health and may help prevent obesity. The purpose of this study is to provide reference values on 4 core, upper, and lower body measures of muscle strength among US children and adolescents and to investigate the association between these measures of strength and weight status. METHODS: We assessed muscular strength using 4 different tests (plank, modified pull-up, knee extension, and grip strength) in 1224 youth aged 6 to 15 years collected during the 2012 National Health and Nutrition Examination Survey National Youth Fitness Survey. Mean and median estimates are provided by gender, age, and weight status. Weight status was defined based on standard categories of obesity, overweight, normal weight, and underweight using the gender-specific BMI-for-age Centers for Disease Control and Prevention growth charts. RESULTS: There were significant positive trends with age for each of the strength tests (P < .001) except the modified pull-up among girls. The length of time the plank was held decreased as weight status increased for both girls and boys (P < .001). As weight status increased the number of modified pull-ups decreased (P < .001 boys and girls). Scores on the knee extension increased as weight status increased (P < .01). Grip strength increased as weight status increased (P < .01). CONCLUSIONS: Increasing weight status had a negative association with measures of strength that involved lifting the body, but was associated with improved performances on tests that did not involve lifting the body.

BACKGROUND: Collecting a 24-h urine sample is recommended for monitoring the mean population sodium intake, but implementation can be difficult. OBJECTIVE: The objective was to assess the validity of published equations by using spot urinary sodium concentrations to predict 24-h sodium excretion. DESIGN: This was a cross-sectional study, conducted from June to August 2011 in metropolitan Washington, DC, of 407 adults aged 18-39 y, 48% black, who collected each urine void in a separate container for 24 h. Four timed voids (morning, afternoon, evening, and overnight) were selected from each 24-h collection. Published equations were used to predict 24-h sodium excretion with spot urine by specimen timing and race-sex subgroups. We examined mean differences with measured 24-h sodium excretion (bias) and individual differences with the use of Bland-Altman plots. RESULTS: Across equations and specimens, mean bias in predicting 24-h sodium excretion for all participants ranged from -267 to 1300 mg (Kawasaki equation). Bias was least with International Cooperative Study on Salt, Other Factors, and Blood Pressure (INTERSALT) equations with morning (-165 mg; 95% CI: -295, 36 mg), afternoon (-90 mg; -208, 28 mg), and evening (-120 mg; -230, -11 mg) specimens. With overnight specimens, mean bias was least when the Tanaka (-23 mg; 95% CI: -141, 95 mg) or Mage (-145 mg; -314, 25 mg) equations were used but was statistically significant when using the Tanaka equations among females (216 to 243 mg) and the Mage equations among races other than black (-554 to -372 mg). Significant over- and underprediction occurred across individual sodium excretion concentrations. CONCLUSIONS: Using a single spot urine, INTERSALT equations may provide the least biased information about population mean sodium intakes among young US adults. None of the equations evaluated provided unbiased estimates of individual 24-h sodium excretion. This trial was registered at clinicaltrials.gov as NCT01631240.

BACKGROUND: Median urine iodine concentration (UIC; microg/L) in spot urine samples is recommended for monitoring population iodine status. Other common measures are iodine:creatinine ratio (I/Cr; microg/g) and estimated 24-hr urine iodine excretion (UIE; I/Cr*predicted 24-hr Cr; microg/d). Despite different units, these measures are often used interchangeably, and it is unclear how they compare with the reference standard 24-hr UIE. METHODS: Volunteers aged 18-39y collected all their urine samples for 24-hours (n=400); voids from morning, afternoon, evening, overnight, and a composite 24-h sample were analyzed for iodine. We calculated median observed 24-hr UIE and 24-hr UIC, and spot UIC, I/Cr, and 2 measures of estimated UIE calculated using predicted 24-hr Cr from published estimates by Kesteloot & Joosens (varies by age and sex) and published equations by Mage (varies by age, sex, race, and anthropometric measures). We examined mean differences and relative difference across iodine excretion levels using Bland-Altman plots. RESULTS: Median 24-hr UIE was 173.6 microg/d and 24-hr UIC was 144.8 microg/L. From timed spot urine samples, estimates were UIC: 147.3-156.2 microg/L, I/Cr: 103.6-114.3 microg/g, estimated 24-hr UIE (Kesteloot & Joosens): 145.7-163.3 microg/d, and estimated 24-hr UIE (Mage): 176.5-187.7 microg/d. Iodine measures did not vary consistently by timing of spot urine collection. Compared with observed 24-hr UIE, on average, estimated (Mage) 24-hr UIE was not significantly different, while estimated 24-hr UIE (Kesteloot& Joosens) was significantly different for some race/sex groups. Compared with 24-hr UIC, on average, spot UIC did not differ. CONCLUSIONS: Estimates of UIC, I/Cr, and estimated 24h-hr UIE (I/Cr*predicted 24-hr Cr) from spot urine samples should not be used interchangeably. Estimated 24-hr UIE, where predicted 24-hr Cr varies by age, sex, race, and anthropometric measures and was calculated with prediction equations using data from the sample, was more comparable to observed 24-hr UIE than when predicted 24-hr Cr was from published estimates from a different population. However, currently no cutoffs exist to interpret population estimated 24-hr UIE values.

Because of the logistic complexity, excessive respondent burden, and high cost of conducting 24-h urine collections in a national survey, alternative strategies to monitor sodium intake at the population level need to be evaluated. We conducted a calibration study to assess the ability to characterize sodium intake from timed-spot urine samples calibrated to a 24-h urine collection. In this report, we described the overall design and basic results of the study. Adults aged 18-39 y were recruited to collect urine for a 24-h period, placing each void in a separate container. Four timed-spot specimens (morning, afternoon, evening, and overnight) and the 24-h collection were analyzed for sodium, potassium, chloride, creatinine, and iodine. Of 481 eligible persons, 407 (54% female, 48% black) completed a 24-h urine collection. A subsample (n = 133) collected a second 24-h urine 4-11 d later. Mean sodium excretion was 3.54 +/- 1.51 g/d for males and 3.09 +/- 1.26 g/d for females. Sensitivity analysis excluding those who did not meet the expected creatinine excretion criterion showed the same results. Day-to-day variability for sodium, potassium, chloride, and iodine was observed among those collecting two 24-h urine samples (CV = 16-29% for 24-h urine samples and 21-41% for timed-spot specimens). Among all race-gender groups, overnight specimens had larger volumes (P < 0.01) and lower sodium (P < 0.01 -P = 0.26), potassium (P < 0.01), and chloride (P < 0.01) concentrations compared with other timed-spot urine samples, although the differences were not always significant. Urine creatinine and iodine concentrations did not differ by the timing of collection. The observed day-to-day and diurnal variations in sodium excretion illustrate the importance of accounting for these factors when developing calibration equations from this study.

The National Health and Nutrition Examination Survey 2005-2006 included questions on awareness of the Dietary Guidelines for Americans (DGA), the Food Guide Pyramid, and the 5 A Day for Better Health Program. Prevalence of awareness of federal dietary guidance was estimated and differences were tested across demographic traits, health characteristics, and diet-related attitudes and behavior. The continuous National Health and Nutrition Examination Survey uses a nationally representative cross-sectional sample design. The analytic sample consisted of 5,499 persons aged 16 years and older with complete data. Among persons aged 16 years and older, 83.8% had heard of at least one of the initiatives: 49.2% had heard of the DGA, 80.6% had heard of the Food Guide Pyramid, and 51.2% had heard of the 5 A Day program. There was a linear trend of decreasing awareness of at least one of the guidance efforts with increasing age. Differences by sex, race/ethnicity, education, and income were also observed. Differences by body mass index were not statistically significant; however, significant differences were seen with fatalistic beliefs about body weight. Differences by smoking, self-assessed diet quality, and eating out frequency were not statistically significant after adjustment for sex, age, race/ethnicity, education, and income. These results may be useful in promotion of the upcoming edition of the DGA and to suggest population groups that may benefit from strengthened and more innovative education efforts at the public health program level and at the clinic level.

Data from the 1999-2004 National Health and Nutrition Examination Survey were used to describe the distribution of cardiorespiratory fitness and its association with obesity and leisure-time physical activity (LTPA) for adults 20-49 years of age without physical limitations or indications of cardiovascular disease. A sample of 7,437 adults aged 20-49 years were examined at a mobile examination center. Of 4,860 eligible for a submaximal treadmill test, 3,250 completed the test and were included in the analysis. The mean maximal oxygen uptake ( max) was estimated as 44.5, 42.8, and 42.2 mL/kg/minute for men 20-29, 30-39, and 40-49 years of age, respectively. For women, it was 36.5, 35.4, and 34.4 mL/kg/minute for the corresponding age groups. Non-Hispanic black women had lower fitness levels than did non-Hispanic white and Mexican-American women. Regardless of gender or race/ethnicity, people who were obese had a significantly lower estimated maximal oxygen uptake than did nonobese adults. Furthermore, a positive association between fitness level and LTPA participation was observed for both men and women. These results can be used to track future population assessments and to evaluate interventions. The differences in fitness status among population subgroups and by obesity status or LTPA can also be used to develop health policies and targeted educational campaigns.