Exploratory study evaluating the relationships between perinatal adversity, oxidative stress, and infant neurodevelopment across the first year of life.

Early childhood adversity increases risk for negative lifelong impacts on health and wellbeing. Identifying the risk factors and the associated biological adaptations early in life is critical to develop scalable early screening tools and interventions. Currently, there are limited, reliable early childhood adversity measures that can be deployed prospectively, at scale, to assess risk in pediatric settings. The goal of this two-site longitudinal study was to determine if the gold standard measure of oxidative stress, F2-Isoprostanes, is potentially a reliable measure of a physiological response to adversity of the infant and mother. The study evaluated the independent relationships between F2-Isoprostanes, perinatal adversity and infant neurocognitive development. The study included mother-infant dyads born >36 weeks' gestation. Maternal demographic information and mental health assessments were utilized to generate a perinatal cumulative risk score. Infants' development was assessed at 6 and 12 months and both mothers and infants were assayed for F2-isoprostane levels in blood and urine, respectively. Statistical analysis revealed that cumulative risk scores correlated with higher maternal (p = 0.01) and infant (p = 0.05) F2-isoprostane levels at 6 months. Infant F2-isoprostane measures at 2 months were negatively associated with Mullen Scales of Early Learning Composite scores at 12 months (p = 0.04). Lastly, higher cumulative risk scores predicted higher average maternal F2-isoprostane levels across the 1-year study time period (p = 0.04). The relationship between perinatal cumulative risk scores and higher maternal and infant F2-isoprostanes at 6 months may reflect an oxidative stress status that informs a sensitive period in which a biomarker can be utilized prospectively to reveal the physiological impact of early adversity.

Association of census-tract level gentrification and income inequality with 6-year incidence of metabolic syndrome in the Hispanic Community Health Study/Study of Latinos, an epidemiologic cohort study.

BACKGROUND: Metabolic syndrome varies by socio-demographic characteristics, with younger (18-29 years) and older (50-69 years) Hispanic/Latino having higher prevalence compared to other groups. While there is substantial research on neighborhood influences on cardiometabolic health, there are mixed findings regarding the effects of gentrification and few studies have included Hispanic/Latinos. The role of neighborhood income inequality on metabolic health remains poorly understood. OBJECTIVES: Examined associations of neighborhood gentrification and income inequality with metabolic syndrome (MetSyn) using data from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). DESIGN, SETTING AND PARTICIPANTS: The HCHS/SOL is a community-based cohort of adults of Hispanic/Latinos (aged 18-74). Analyses included 6710 adults who did not meet criteria for MetsS at baseline (2008-2011) and completed the visit 2 examination (2014-2017). Poisson regressions estimated odds ratios (IRR) and 95% confidence intervals (CI) for neighborhood gentrification and change in income inequality with MetSyn incidence. MAIN OUTCOME AND EXPOSURE MEASURES: Gentrification was measured with an index that included changes (2000 to 2006-2010) in education, poverty, and income. Change in neighborhood income inequality (2005-2009 to 2012-2016) was measured using the Gini coefficient of income distribution. MetSyn was defined using National Cholesterol Education Program Adult Treatment Panel III criteria. RESULTS: Among 6647 Hispanic/Latino adults, 23% (N = 1530) had incident MetSyn. In models adjusted for socio-demographic, health insurance status, and neighborhood characteristics, gentrification (IRR, 1.00, 95%CI, 0.96-1.03) and income inequality change (IRR, 1.00, 95%CI, 0.99-1.00) were not associated with MetSyn at visit 2. There was no association between cross-sectional income inequality (2005-2009) and MetSyn at visit 2 (IRR, 0.97, 95%CI, 0.82-1.15). CONCLUSION: Neighborhood gentrification and income inequality change were not associated with incidence of MetSyn over 6 years among Hispanic/Latino adults. This study demonstrated that income-based residential changes alone may not be sufficient to explain neighborhood influences on health outcomes among this population.

Differences in gut microbiota and fecal bile acids between Caucasian and Hispanic children and young adults with ulcerative colitis.

Ulcerative Colitis (UC) is an inflammatory bowel disease (IBD) that has been associated with gut dysbiosis. Changes in the gut microbiome lead to changes in bile acids (BA) metabolism, which changes the BA profiles in patients with UC. We conducted this study to investigate the differences in bile acids and gut microbiota between Hispanic and Caucasian children and young adults with UC. Twenty-seven Caucasian and 20 Hispanic children and young adults with UC were enrolled in the study. BAs were extracted from the subjects' stool samples and analyzed by liquid chromatography-mass spectrometry. Microbial DNA was also extracted from the stool samples to perform 16s rRNA amplicon sequencing. The median levels of cholic acid and taurolithocholic acid were found to be significantly higher in Hispanic children and young adults with UC compared to their Caucasian counterparts. The abundance of the gut microbiota that metabolizes BAs such as Proteobacteria, Pseudomonadaceae, Pseudomonas, Ruminococcus gnavus, and Escherichia coli were also all significantly higher in Hispanic children and young adults as well. The distinct BA profile that we found in Hispanic children and young adults with UC, in addition to the unique composition of their gut microbiome, provide them with a protective gut environment against inflammation, which is contrary to the common believe that Hispanics have worse IBD.

StocSum: stochastic summary statistics for whole genome sequencing studies.

Genomic summary statistics, usually defined as single-variant test results from genome-wide association studies, have been widely used to advance the genetics field in a wide range of applications. Applications that involve multiple genetic variants also require their correlations or linkage disequilibrium (LD) information, often obtained from an external reference panel. In practice, it is usually difficult to find suitable external reference panels that represent the LD structure for underrepresented and admixed populations, or rare genetic variants from whole genome sequencing (WGS) studies, limiting the scope of applications for genomic summary statistics. Here we introduce StocSum, a novel reference-panel-free statistical framework for generating, managing, and analyzing stochastic summary statistics using random vectors. We develop various downstream applications using StocSum including single-variant tests, conditional association tests, gene-environment interaction tests, variant set tests, as well as meta-analysis and LD score regression tools. We demonstrate the accuracy and computational efficiency of StocSum using two cohorts from the Trans-Omics for Precision Medicine Program. StocSum will facilitate sharing and utilization of genomic summary statistics from WGS studies, especially for underrepresented and admixed populations.

Nutritional Blood Concentration Biomarkers in the Hispanic Community Health Study/Study of Latinos: Measurement Characteristics and Power.

Measurement error is a major issue in self-reported diet that can distort diet-disease relationships. Use of blood concentration biomarkers has the potential to mitigate the subjective bias inherent in self-reporting. As part of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) baseline visit (2008-2011), self-reported information on diet was collected from all participants (n = 16,415). The HCHS/SOL also included annual telephone follow-up, as well as a second (2014-2017) and third (2020-2023) clinic visit. Blood concentration biomarkers for carotenoids, tocopherols, retinol, vitamin B12, and folate were measured in a subset of participants (n = 476) as part of the Study of Latinos: Nutrition and Physical Activity Assessment Study (SOLNAS) (2010-2012). We examined the relationships among biomarker levels, self-reported intake, Hispanic/Latino background (Central American, Cuban, Dominican, Mexican, Puerto Rican, or South American), and other participant characteristics in this diverse cohort. We built regression calibration-based prediction equations for 10 nutritional biomarkers and used a simulation to study the power of detecting a diet-disease association in a multivariable Cox model using a predicted concentration level. Good statistical power was observed for some nutrients with high prediction model R2 values, but further research is needed to understand how best to realize the potential of these dietary biomarkers. This study provides a comprehensive examination of several nutritional biomarkers within the HCHS/SOL, characterizing their associations with subject characteristics and the influence of the measurement characteristics on the power to detect associations with health outcomes.

Serum 1,25-dihydroxyvitamin D levels in the diagnosis and pathogenesis of nutritional rickets - a multivariable re-analysis of a case-control study.

BACKGROUND: A multivariable logistic regression model resulting from a case-control study of nutritional rickets in Nigerian children suggested that higher levels of serum 25(OH)D may be required to prevent nutritional rickets in populations with low-calcium intakes. OBJECTIVES: This current study evaluates if adding serum 1,25-dihydroxyvitamin D [1,25(OH)2D] to that model shows that increased levels of serum 1,25(OH)2D are independently associated with risk of children on low-calcium diets having nutritional rickets. METHODS: Multivariable logistic regression analysis was used to model the association between serum 1,25(OH)2D and risk of having nutritional rickets in cases (n = 108) and controls (n = 115) after adjusting for age, sex, weight-for age z-score, religion, phosphorus intake and age began walking and the interaction between serum 25(OH)D and dietary calcium intake (Full Model). RESULTS: Serum 1,25(OH)2D levels were significantly higher (320 pmol/L vs. 280 pmol/L) (P = 0.002), and 25(OH)D levels were lower (33 nmol/L vs. 52 nmol/L) (P < 0.0001) in children with rickets than in control children. Serum calcium levels were lower in children with rickets (1.9 mmol/L) than in control children (2.2 mmol/L) (P < 0.001). Dietary calcium intakes were similarly low in both groups (212 mg/d) (P = 0.973). In the multivariable logistic model, 1,25(OH)2D was independently associated with risk of having rickets [coefficient = 0.007 (95% confidence limits: 0.002-0.011)] after adjusting for all variables in the Full Model. CONCLUSIONS: Results confirmed theoretical models that in children with low dietary calcium intake, 1,25(OH)2D serum concentrations are higher in children with rickets than in children without rickets. The difference in 1,25(OH)2D levels is consistent with the hypothesis that children with rickets have lower serum calcium concentrations which prompt the elevation of PTH levels resulting in an elevation of 1,25(OH)2D levels. These results support the need for additional studies to identify dietary and environmental risks for nutritional rickets.

Association of neighborhood segregation with 6-year incidence of metabolic syndrome in the Hispanic community health study/study of Latinos.

PURPOSE: Examine the association between neighborhood segregation and 6-year incident metabolic syndrome (MetSyn) in the Hispanic Community Health Study/Study of Latinos. METHODS: Prospective cohort of adults residing in Miami, Chicago, the Bronx, and San Diego. The analytic sample included 6,710 participants who did not have MetSyn at baseline. The evenness and exposure dimensions of neighborhood segregation, based on the Gini and Isolation indices, respectively, were categorized into quintiles (Q). Racialized economic concentration was measured with the Index of Concentration at the Extremes (continuously and Q). RESULTS: Exposure, but not evenness, was associated with higher disease odds (Q1 (lower segregation) vs. Q4, OR = 1.53, 95% CI = 1.082.17; Q5, OR = 2.29, 95% CI = 1.493.52). Economic concentrationprivilege (continuous OR = 0.87, 95% CI = 0.770.98), racial concentrationracialized privilege (Q1 (greater concentration) vs. Q2 OR = 0.75, 95% CI = 0.541.04; Q3 OR = 0.68, 95% CI = 0.441.05; Q4 OR = 0.68, 95% CI = 0.451.01; Q5 OR = 0.64, 95% CI = 0.420.98)(continuous OR = 0.93, 95% CI = 0.821.04), and racialized economic concentrationprivilege (i.e., higher SES non-Hispanic White, continuous OR = 0.86, 95% CI = 0.760.98) were associated with lower disease odds. CONCLUSION: Hispanics/Latino adults residing in neighborhoods with high segregation had higher risk of incident MetSyn compared to those residing in neighborhoods with low segregation. Research is needed to identify the mechanisms that link segregation to poor metabolic health.

Accelerometer-Measured Latent Physical Activity Profiles and Neurocognition Among Middle-Aged and Older Hispanic/Latino Adults in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

OBJECTIVES: Derive latent profiles of accelerometry-measured moderate-vigorous physical activity (MVPA) for Hispanic/Latino adults, examine associations between latent MVPA profiles and neurocognition, and describe profiles via self-reported MVPA. METHODS: Complex survey design methods were applied to cross-sectional data from 7,672 adults ages 45-74 years in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL; 2008-2011). MVPA was measured via hip-worn accelerometers. Latent profile analysis was applied to derive latent MVPA profiles (minutes/day of week). Neurocognition was assessed with the Brief-Spanish English Verbal Learning Test (B-SEVLT) Sum, B-SEVLT Recall, Controlled Oral Word Association Test (word fluency), and Digit Symbol Substitution (DSS) test. All tests were z-scored, and a global neurocognition score was generated by averaging across scores. Survey linear regression models were used to examine associations between latent MVPA profiles and neurocognitive measures. Self-reported MVPA domains were estimated (occupational, transportation, and recreational) for each latent profile. RESULTS: Four latent MVPA profiles from the overall adult target population (18-74 years) were derived and putatively labeled: No MVPA, low, moderate, and high. Only the high MVPA profile (compared to moderate) was associated with lower global neurocognition. Sensitivity analyses using latent MVPA profiles with only participants aged 45-74 years showed similar profiles, but no associations between latent MVPA profiles and neurocognition. The occupational MVPA domain led in all latent MVPA profiles. DISCUSSION: We found no consistent evidence to link accelerometry-measured MVPA profiles to neurocognitive function. Research to better characterize the role of high occupational MVPA in relation to neurocognition among Hispanic/Latino adults are needed.

Citizenship Status and Mortality Among Young Latino Adults in the U.S., 1998‒2015.

INTRODUCTION: Although Latino immigrants, especially noncitizens, endure structural factors that may increase their risk of death at younger ages, little is known about their risk of death in young adulthood. This study evaluates mortality differences across citizenship status among young Latino adults (aged 18-44 years) in the U.S. METHODS: This study used the National Health Interview Survey (1998-2014) with mortality follow-up through 2015. Cox regression models adjusted for age and sex were used to determine baseline differences in mortality. Models adjusted for socioeconomic factors (i.e., English proficiency, education, poverty, and health insurance) were used to determine whether socioeconomic conditions attenuate mortality differences. RESULTS: Participants included noncitizens (n=48,388), naturalized citizens (n=16,241), and U.S.-born citizens (n=63,388). Noncitizens (hazard ratio [HR]=1.40, 95% CI=1.31, 1.51), but not naturalized citizens (HR=1.04, 95% CI=0.94, 1.16), were at greater risk of all-cause death than U.S.-born citizens. Both noncitizens (HR=2.46, 95% CI=2.07, 2.92) and naturalized citizens (HR=1.76, 95% CI=1.40, 2.21) were more likely to die of cancer. Noncitizens were also at a greater risk of death because of cardiometabolic diseases (HR=1.46, 95% CI=1.20, 1.78) and accidents (HR=1.33, 95% CI=1.14, 1.55). Socioeconomic factors attenuated differences in all-cause, cardiometabolic, and accidental deaths, but not differences in cancer mortality. CONCLUSIONS: Contrary to the long-held notion of the healthy migrant, young Latino immigrants, especially noncitizens, are at increased risk of death than their U.S.-born counterparts. Efforts to reduce these disparities should focus on improving their socioeconomic conditions and healthcare access early in adulthood.

Does a Bleeding Disorder Lessen the Efficacy of the 52-mg Levonorgestrel-Releasing Intrauterine System for Heavy Menstrual Bleeding in Adolescents? A Retrospective Multicenter Study.

PURPOSE: The aim of this study is to compare the patient-reported bleeding outcomes and complication rates with the use of the 52-mg levonorgestrel-releasing intrauterine system (52-LNG-IUS) for treatment of heavy menstrual bleeding (HMB) among adolescents with and without a diagnosed inherited bleeding disorder (BD) within the first 12 months after insertion. METHODS: Retrospective chart review was conducted of adolescents ages 14-21 years, with and without an inherited BD, who underwent 52-LNG-IUS insertion between September 2013 and February 2020 for the treatment of HMB. RESULTS: One hundred forty-four 52-LNG-IUS insertions among 139 subjects were evaluated. Fifty-nine (41%) of these were among adolescents with a diagnosed inherited BD, and 85 (59%) were among those without a BD. Among subjects with follow-up, documentation of patient-reported bleeding outcome, and a retained IUS (92/144), both groups subjectively reported improvement in bleeding outcome, with 91.7% (33/36) of those with a BD and 94.6% (53/56) of those without a BD reporting that bleeding outcome was better than prior to IUS insertion (p = .675). There was no statistically significant difference in the rate of spontaneous expulsion (p = .233), with the rate of expulsion in the first 12 months after placement among those with a BD of 13.7% (7/51) and 6.8% for those without a BD (5/72). DISCUSSION: Adolescents with HMB both with and without an inherited BD benefit from the 52-LNG-IUS for the treatment of HMB. Rates of spontaneous IUS expulsion are not statistically different regardless of the presence of a BD and are similar to rates found in other studies of intrauterine device use in adolescents.

Prevalence of pulmonary hypertension on echocardiogram in children with severe obstructive sleep apnea.

STUDY OBJECTIVES: Pulmonary hypertension (PH) is a rare yet serious complication of obstructive sleep apnea (OSA). Echocardiographic screening for PH is recommended in children with severe OSA, but the health care burden of universal screening is high. We sought to determine the prevalence of PH on echocardiogram among children with severe OSA and identify variables associated with a positive PH screen. METHODS: Retrospective study of 318 children with severe OSA (obstructive apnea-hypopnea index ≥ 10 events/h) and echocardiogram within 1 year of polysomnogram. PH-positive echocardiogram was defined by peak tricuspid regurgitation velocity ≥ 2.5 m/s and/or 2 or more right-heart abnormalities suggestive of elevated pulmonary artery pressure. Patient characteristics and polysomnogram data were compared to identify factors associated with PH. RESULTS: Twenty-six children (8.2%; 95% confidence interval [CI] 5.4-11.8%) had echocardiographic evidence of PH. There was no difference in age, sex, body mass index, obstructive apnea-hypopnea index, or oxygenation indices between patients with and without PH. Sleep-related hypoventilation (end-tidal CO2 > 50 mmHg for > 25% of total sleep time) was present in 25% of children with PH compared with 6.3% of children without PH (adjusted prevalence ratio = 2.73; 95% CI 1.18-6.35). Forty-six percent of children (12/26) with PH had Down syndrome vs 14% (41/292) without PH (adjusted prevalence ratio = 3.11; 95% CI 1.46-6.65). CONCLUSIONS: There was a relatively high prevalence of PH on echocardiogram in our cohort of children with severe OSA. The findings of increased PH prevalence among children with sleep-related hypoventilation or Down syndrome may help inform the development of targeted screening recommendations for specific pediatric OSA populations. CITATION: Maloney MA, Davidson Ward SL, Su JA, et al. Prevalence of pulmonary hypertension on echocardiogram in children with severe obstructive sleep apnea. J Clin Sleep Med. 2022;18(6):1629-1637.

Intra-trial Mean 25(OH)D and PTH Levels and Risk of Falling in Older Men and Women in the Boston STOP IT Trial.

CONTEXT: Supplementation with vitamin D has the potential to both reduce and increase risk of falling, and parathyroid hormone (PTH) may contribute to fall risk. OBJECTIVE: To assess the associations of intra-trial mean circulating levels of 25-hydroxyvitamin D [25(OH)D] and PTH on incident falls in healthy older adults. DESIGN: Observational within a clinical trial. SETTING: The Bone Metabolism Laboratory at the USDA Nutrition Center at Tufts University. PARTICIPANTS: 410 men and women age ≥65 years who participated in the 3-year Boston STOP IT trial to determine the effect of supplementation with 700 IU of vitamin D3 plus calcium on incident falls (secondary endpoint). Intra-trial exposures of 25(OH)D and PTH were calculated as the mean of biannual measures up to and including the first fall. MAIN OUTCOME MEASURES: Incidence of first fall. RESULTS: Intra-trial mean 25(OH)D was significantly associated with risk of falling in a U-shaped pattern; the range associated with minimal risk of falling was approximately 20 to 40 ng/mL. PTH was not significantly associated with risk of falling. CONCLUSIONS: The findings highlight the importance of maintaining the circulating 25(OH)D level between 20 and 40 ng/mL, the range that is also recommended for bone health. At PTH levels within the normal range, there was no detectible independent association of PTH with fall risk.

Interlaboratory comparison of 25-hydroxyvitamin D assays: Vitamin D Standardization Program (VDSP) Intercomparison Study 2 - Part 1 liquid chromatography - tandem mass spectrometry (LC-MS/MS) assays - impact of 3-epi-25-hydroxyvitamin D3 on assay performance.

An interlaboratory comparison study was conducted by the Vitamin D Standardization Program (VDSP) to assess the performance of liquid chromatography - tandem mass spectrometry (LC-MS/MS) assays used for the determination of serum total 25-hydroxyvitamin D (25(OH)D), which is the sum of 25-hydroxyvitamin D2 (25(OH)D2) and 25-hydroxyvitamin D3 (25(OH)D3). A set of 50 single-donor samples was assigned target values for concentrations of 25(OH)D2, 25(OH)D3, 3-epi-25-hydroxyvitamin D3 (3-epi-25(OH)D3), and 24R,25-dihydroxyvitamin D3 (24R,25(OH)2D3) using isotope dilution liquid chromatography - tandem mass spectrometry (ID LC-MS/MS). VDSP Intercomparison Study 2 Part 1 includes results from 14 laboratories using 14 custom LC-MS/MS assays. Assay performance was evaluated using mean % bias compared to the assigned target values and using linear regression analysis of the test assay mean results and the target values. Only 53% of the LC-MS/MS assays met the VDSP criterion of mean % bias ≤ |±5%|. For the LC-MS/MS assays not meeting the ≤ |±5%| criterion, four assays had mean % bias of between 12 and 21%. Based on multivariable regression analysis using the concentrations of the four individual vitamin D metabolites in the 50 single-donor samples, the performance of several LC-MS/MS assays was found to be influenced by the presence of 3-epi-25(OH)D3. The results of this interlaboratory study represent the most comprehensive comparison of LC-MS/MS assay performance for serum total 25(OH)D and document the significant impact of the lack of separation of 3-epi-25(OH)D3 and 25(OH)D3 on assay performance, particularly with regard to mean % bias.

Interlaboratory comparison of 25-hydroxyvitamin D assays: Vitamin D Standardization Program (VDSP) Intercomparison Study 2 - Part 2 ligand binding assays - impact of 25-hydroxyvitamin D2 and 24R,25-dihydroxyvitamin D3 on assay performance.

An interlaboratory comparison study was conducted by the Vitamin D Standardization Program (VDSP) to assess the performance of ligand binding assays (Part 2) for the determination of serum total 25-hydroxyvitamin D [25(OH)D]. Fifty single-donor samples were assigned target values for concentrations of 25-hydroxyvitamin D2 [25(OH)D2], 25-hydroxyvitamin D3 [25(OH)D3], 3-epi-25-hydroxyvitamin D3 [3-epi-25(OH)D3], and 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3] using isotope dilution liquid chromatography-tandem mass spectrometry (ID LC-MS/MS). VDSP Intercomparison Study 2 Part 2 includes results from 17 laboratories using 32 ligand binding assays. Assay performance was evaluated using mean % bias compared to the assigned target values and using linear regression analysis of the test assay mean results and the target values. Only 50% of the ligand binding assays achieved the VDSP criterion of mean % bias ≤ |± 5%|. For the 13 unique ligand binding assays evaluated in this study, only 4 assays were consistently within ± 5% mean bias and 4 assays were consistently outside ± 5% mean bias regardless of the laboratory performing the assay. Based on multivariable regression analysis using the concentrations of individual vitamin D metabolites in the 50 single-donor samples, most assays underestimate 25(OH)D2 and several assays (Abbott, bioMérieux, DiaSorin, IDS-EIA, and IDS-iSYS) may have cross-reactivity from 24R,25(OH)2D3. The results of this interlaboratory study represent the most comprehensive comparison of 25(OH)D ligand binding assays published to date and is the only study to assess the impact of 24R,25(OH)2D3 content using results from a reference measurement procedure.

Assessment of serum total 25-hydroxyvitamin D assays for Vitamin D External Quality Assessment Scheme (DEQAS) materials distributed at ambient and frozen conditions.

The Vitamin D External Quality Assessment Scheme (DEQAS) distributes human serum samples four times per year to over 1000 participants worldwide for the determination of total serum 25-hydroxyvitamin D [25(OH)D)]. These samples are stored at -40 °C prior to distribution and the participants are instructed to store the samples frozen at -20 °C or lower after receipt; however, the samples are shipped to participants at ambient conditions (i.e., no temperature control). To address the question of whether shipment at ambient conditions is sufficient for reliable performance of various 25(OH)D assays, the equivalence of DEQAS human serum samples shipped under frozen and ambient conditions was assessed. As part of a Vitamin D Standardization Program (VDSP) commutability study, two sets of the same nine DEQAS samples were shipped to participants at ambient temperature and frozen on dry ice. Twenty-eight laboratories participated in this study and provided 34 sets of results for the measurement of 25(OH)D using 20 ligand binding assays and 14 liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods. Equivalence of the assay response for the frozen versus ambient DEQAS samples for each assay was evaluated using multi-level modeling, paired t-tests including a false discovery rate (FDR) approach, and ordinary least squares linear regression analysis of frozen versus ambient results. Using the paired t-test and confirmed by FDR testing, differences in the results for the ambient and frozen samples were found to be statistically significant at p < 0.05 for four assays (DiaSorin, DIAsource, Siemens, and SNIBE prototype). For all 14 LC-MS/MS assays, the differences in the results for the ambient- and frozen-shipped samples were not found to be significant at p < 0.05 indicating that these analytes were stable during shipment at ambient conditions. Even though assay results have been shown to vary considerably among different 25(OH)D assays in other studies, the results of this study also indicate that sample handling/transport conditions may influence 25(OH)D assay response for several assays.

Vitamin D, Calcium, Magnesium, and Potassium Consumption and Markers of Glucose Metabolism in the Hispanic Community Health Study/Study of Latinos.

OBJECTIVE: This was a cross-sectional study associating vitamin D, calcium, magnesium, and potassium intakes with markers of glucose metabolism in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). METHODS: HCHS/SOL is a multicenter, prospective, population-based cohort study on Hispanics/Latinos aged 18-74 years in the US. For this analysis, we included 10,609 participants who were free of diabetes. Analysis of covariance was used to assess associations of a range of micronutrient intake on the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), Hemoglobin A1c (HbA1c), and 2-hour post-oral glucose tolerance test (2h-plasma glucose) separately for normoglycemic and with pre-diabetes, after controlling for important confounders. All analyses accounted for the complex sample design and sampling weights. RESULTS: HOMA-IR levels were significantly lower among adults with intakes in the highest quartile for vitamin D, magnesium, and potassium compared to the respective lowest quartiles, for those with normoglycemia and pre-diabetes, even after adjusting for confounders, such as diet quality (p < 0.05). For those with pre-diabetes, HOMA-IR levels were also significantly lower for those in the highest quartile of calcium intake. However, 2h-plasma glucose was significantly higher in those with intakes higher than quartile 1 for vitamin D and calcium among those with normoglycemia and significantly higher in quartile 3 of potassium intake for those with pre-diabetes, p < 0.05. No significant associations were found for HbA1c in either group. CONCLUSIONS: Higher consumption of vitamin D, magnesium, and potassium are associated with optimal levels of HOMA-IR among participants with normoglycemia and pre-diabetes.

Association of Accelerometer-Measured Physical Activity and Cardiovascular Health in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

INTRODUCTION: Evidence regarding the associations between accelerometer-measured moderate-vigorous physical activity (MVPA) and cardiovascular health (CVH) indicators among Hispanic/Latino adults are unavailable. METHODS: Examined cross-sectional data from 12,008 Hispanic/Latino adults aged 18-74 years participating in the Hispanic Community Health Study/Study of Latinos. Accelerometer-measured MVPA was assessed categorically and dichotomously per 2008 PA guidelines. Adverse and ideal CVH indicators were determined by standard cut-points for blood glucose, total cholesterol, blood pressure, body mass index (BMI), and smoking. A composite of low CV risk, defined as achieving all ideal CVH indicators, was included. Adjusted Poisson regression models and complex survey design methods were used for all analyses. RESULTS: Compared to high MVPA, lower MVPA categories were associated with higher prevalence of all adverse CVH indicators, except hypertension, and with lower prevalence of low CV risk and ideal blood glucose, blood pressure, and BMI. Similarly, non-adherence to PA guidelines was associated with a higher prevalence of diabetes (16%), hypercholesterolemia (9%), obesity (28%), and smoking (9%); and lower prevalence of low CV risk (24%), ideal blood glucose (6%), ideal blood pressure (6%), and ideal BMI (22%). CONCLUSION: Overall, high accelerometer-measured MVPA and meeting PA guidelines were associated with favorable CVH in Hispanic/Latino adults.

Increased Autoimmunity in Individuals With Down Syndrome and Moyamoya Disease.

Objective: To determine if elevated rates of autoimmune disease are present in children with both Down syndrome and moyamoya disease given the high rates of autoimmune disease reported in both conditions and unknown etiology of angiopathy in this population. Methods: A multi-center retrospective case-control study of children with Down syndrome and moyamoya syndrome, idiopathic moyamoya disease, and Down syndrome without cerebrovascular disease was performed. Outcome measures included presence of autoimmune disease, presence of autoantibodies and angiopathy severity data. Comparisons across groups was performed using the Kruskal-Wallis, χ2 and multivariate Poisson regression. Results: The prevalence of autoimmune disease were 57.7, 20.3, and 35.3% in persons with Down syndrome and moyamoya syndrome, idiopathic moyamoya disease, and Down syndrome only groups, respectively (p < 0.001). The prevalence of autoimmune disease among children with Down syndrome and moyamoya syndrome is 3.2 times (p < 0.001, 95% CI: 1.82-5.58) higher than the idiopathic moyamoya group and 1.5 times (p = 0.002, 95% CI: 1.17-1.99) higher than the Down syndrome only group when adjusting for age and sex. The most common autoimmune diseases were thyroid disorders, type I diabetes and Celiac disease. No individuals with idiopathic moyamoya disease had more than one type of autoimmune disorder while 15.4% of individuals with Down syndrome and moyamoya syndrome and 4.8% of individuals with Down syndrome only had >1 disorder (p = 0.05, 95%CI: 1.08-6.08). Interpretation: This study reports elevated rates of autoimmune disease in persons with Down syndrome and moyamoya syndrome providing a nidus for study of the role of autoimmunity in angiopathy in this population.

Cardiovascular disease and risk of incident diabetes mellitus: Findings from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

BACKGROUND: Studies have reported an association between prevalent cardiovascular disease (CVD) and risk of diabetes mellitus (DM). However, factors that may explain the association remain unclear. We examined the association of prevalent CVD with incident DM and assessed whether weight gain and medication use may explain the association. METHODS: Data from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) Visit 1 (2008-2011) and Visit 2 (2014-2017) were used to compare incidence of DM among individuals with and without self-reported CVD at Visit 1. A total of 1899 individuals with self-reported CVD were matched to controls free of self-reported CVD at Visit 1 using 1:1 propensity score matching. Covariates included in the propensity model were sociodemographic characteristics, lifestyle factors, comorbid conditions, and study site. The effect of self-reported CVD on incident DM was examined using a generalized estimating equation. The mediating effects of weight gain and use of cardiovascular medications were evaluated. RESULTS: Covariate distributions were similar among individuals with and without self-reported CVD. The incidence of DM among persons with self-reported CVD was 15.3% vs 12.7% among those without self-reported CVD. Compared to individuals without self-reported CVD, individuals with self-reported CVD had a 24% increased risk for incident DM (odds ratio = 1.24, 95% confidence interval = 1.01, 1.51). The association between self-reported CVD and DM was mediated by the use of beta-blockers (proportion explained = 25.4%), statins (proportion explained = 18%), and diuretics (proportion explained = 8%). We found that weight gain did not explain the observed association. CONCLUSIONS: Prevalent cardiovascular disease was associated with a significant increased risk of incident diabetes. The observed association was partially explained by some medications used to manage CVD.

Association of Subjective Social Status With Life's Simple 7s Cardiovascular Health Index Among Hispanic/Latino People: Results From the HCHS/SOL.

Background Evidence suggests that subjective (perceived) social status (SSS) may predict health outcomes more strongly than objective social status, but little is known about the relationship between SSS and cardiovascular health (CVH). This study focuses on this relationship among diverse Hispanic/Latino adults because while poor CVH profiles are prevalent in this population, immigration complicates attempts to measure their social status. Methods and Results We analyzed baseline HCHS/SOL (Hispanic Community Health Study/Study of Latinos) data on 15 374 Hispanic/Latino adults aged 18 to 74 years in 2008 to 2011. SSS was assessed using the McArthur Scale, a 10-rung "social ladder." CVH was based on levels of 7 metrics defined by the American Heart Association. Linear and logistic regressions were used to examine cross-sectional associations of SSS with CVH (overall and single metrics) after adjusting for objective social status, demographic, and health factors. Less than half of the population (46%) had Ideal scores in ≥4 metrics of CVH. In multivariable-adjusted models, an increase in SSS was associated with a higher overall CVH score (ß=0.04; 95% CI, 0.01-0.06) and greater likelihood of Ideal levels of body mass index, physical activity, and fasting blood glucose levels. Nativity and time in the United States modified the association between SSS and Ideal smoking. Conclusions Subjective measures of social status can enhance an understanding of CVH among Hispanic/Latino people. Future studies should explore the stability of SSS over time in comparison with objective social status and the mechanisms through which SSS may influence CVH.