Phenotypic age mediates effects of Life's Essential 8 on reduced mortality risk in US adults.

Objective: This study aimed to find out whether phenotypic age could mediate the protective effects of a healthy lifestyle on mortality. Methods: We included adult participants with available data for individual phenotypic age (PhenoAge) and Life's Essential 8 (LE8) scores from the National Health and Nutrition Examination Survey 2005-2010 (three cycles) and linked mortality records until 31 December 2019. Adjusted hazard ratios (HR) were estimated to evaluate the associations of PhenoAge and LE8 scores with all-cause and cardiovascular mortality risk. Mediation analyses were performed to estimate the proportional contribution of PhenoAge to the effect of LE8 on mortality risks. Results: A 1-year increment in PhenoAge was associated with a higher risk of all-cause (HR = 1.04 [95% confidence interval, 1.04-1.05]) and cardiovascular (HR = 1.04 [95% confidence interval, 1.04-1.05]) mortality, independent of chronological age, demographic characteristics, and disease history. High level of LE8 (score: 80-100) was associated with a 3.30-year younger PhenoAge. PhenoAge was estimated to mediate 36 and 22% of the effect of LE8 on all-cause and cardiovascular mortality, respectively (all P < 0.001). As for single-metric scores of LE8, PhenoAge mediated 30%, 11%, 9%, and 7% of the effects of the healthy diet, smoking status, blood pressure, and physical activity on all-cause mortality risk, respectively (all P < 0.05). Conclusion: Adherence to LE8 recommendations slows phenotypic aging. PhenoAge could mediate the effect of LE8 on mortality risk.

Habitual Iron Supplementation Associated with Elevated Risk of Chronic Kidney Disease in Individuals with Antihypertensive Medication.

The aim of this study was to examine the effects of habitual iron supplementation on the risk of CKD in individuals with different hypertensive statuses and antihypertension treatment statuses. We included a total of 427,939 participants in the UK Biobank study, who were free of CKD and with complete data on blood pressure at baseline. Cox proportional hazards regression models were used to examine the adjusted hazard ratios of habitual iron supplementation for CKD risk. After multivariable adjustment, habitual iron supplementation was found to be associated with a significantly higher risk of incident CKD in hypertensive participants (HR 1.12, 95% CI 1.02 to 1.22), particularly in those using antihypertensive medication (HR 1.21, 95% CI 1.08 to 1.35). In contrast, there was no significant association either in normotensive participants (HR 1.06, 95% CI 0.94 to 1.20) or in hypertensive participants without antihypertensive medication (HR 1.02, 95% CI 0.90 to 1.17). Consistently, significant multiplicative and additive interactions were observed between habitual iron supplementation and antihypertensive medication on the risk of incident CKD (p all interaction < 0.05). In conclusion, habitual iron supplementation was related to a higher risk of incident CKD among hypertensive patients, the association might be driven by the use of antihypertensive medication.

Novel Metabolites Associated With Blood Pressure After Dietary Interventions.

BACKGROUND: The blood pressure (BP) etiologic study is complex due to multifactorial influences, including genetic, environmental, lifestyle, and their intricate interplays. We used a metabolomics approach to capture internal pathways and external exposures and to study BP regulation mechanisms after well-controlled dietary interventions. METHODS: In the ProBP trail (Protein and Blood Pressure), a double-blinded crossover randomized controlled trial, participants underwent dietary interventions of carbohydrate, soy protein, and milk protein, receiving 40 g daily for 8 weeks, with 3-week washout periods. We measured plasma samples collected at baseline and at the end of each dietary intervention. Multivariate linear models were used to evaluate the association between metabolites and systolic/diastolic BP. Nominally significant metabolites were examined for enriching biological pathways. Significant ProBP findings were evaluated for replication among 1311 participants of the BHS (Bogalusa Heart Study), a population-based study conducted in the same area as ProBP. RESULTS: After Bonferroni correction for 77 independent metabolite clusters (α=6.49×10-4), 18 metabolites were significantly associated with BP at baseline or the end of a dietary intervention, of which 11 were replicated in BHS. Seven emerged as novel discoveries, which are as follows: 1-linoleoyl-GPE (18:2), 1-oleoyl-GPE (18:1), 1-stearoyl-2-linoleoyl-GPC (18:0/18:2), 1-palmitoyl-2-oleoyl-GPE (16:0/18:1), maltose, N-stearoyl-sphinganine (d18:0/18:0), and N6-carbamoylthreonyladenosine. Pathway enrichment analyses suggested dietary protein intervention might reduce BP through pathways related to G protein-coupled receptors, incretin function, selenium micronutrient network, and mitochondrial biogenesis. CONCLUSIONS: Seven novel metabolites were identified to be associated with BP at the end of different dietary interventions. The beneficial effects of protein interventions might be mediated through specific metabolic pathways.

Cumulative effect of metabolic risk factors on left ventricular geometry in those with versus without early-onset type 2 diabetes or prediabetes: The Coronary Artery Risk Development in Young Adults (CARDIA) study.

AIM: To investigate metabolic risk factors (RFs) that accumulated over 20 years related to left ventricular mass index (LVMI), relative wall thickness (RWT) and LV remodelling patterns in participants with versus without early-onset type 2 diabetes (T2D) or prediabetes (pre-D). METHODS: A total of 287 early-onset T2D/pre-D individuals versus 565 sociodemographic-matched euglycaemic individuals were selected from the Coronary Artery Risk Development in Young Adults (CARDIA) study, years 0-25. We used the area under the growth curve (AUC) derived from quadratic random-effects models of four or more repeated measures of RFs (fasting glucose [FG], insulin, triglycerides [TG], low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-c), total cholesterol (total-c), blood pressure and body mass index) to estimate the cumulative burden, and their associations with LV outcomes. RESULTS: One standard deviation greater AUC of log (TG) (per 0.48) and HDL-c (per 13.5 mg/dL) were associated with RWT (ß 0.21 and -0.2) in the early-onset T2D/pre-D group, but not in the euglycaemia group (ß 0.01 and 0.05, P interactions .02 and .03). In both the early-onset T2D/pre-D and euglycaemia groups, greater AUCs of log (FG) (per 0.17) and log (insulin) (per 0.43) were associated with higher RWT (ß ranges 0.12-0.24). Greater AUCs of systolic blood pressure (per 10 mmHg) and diastolic blood pressure (per 7.3 mmHg) were associated with higher RWT and LVMI, irrespective of glycaemic status (ß ranges 0.17-0.28). Cumulative TG (odds ratio 3.4, 95% confidence interval: 1.8-6.3), HDL-c (0.23, 0.09-0.59), total-c (1.9, 1.1-3.1) and FG (2.2, 1.25-3.9) were statistically associated with concentric hypertrophy in the T2D/pre-D group only. CONCLUSIONS: Sustained hyperglycaemia and hyperinsulinaemia are associated with RWT, and those individuals with early T2D/pre-D are potentially at greater risk because of their higher levels of glucose and insulin. Dyslipidaemia was associated with LV structural abnormalities in those individuals with early-onset T2D/pre-D.

Construction of Layer-Blocked Covalent Organic Framework Heterogenous Films via Surface-Initiated Polycondensations with Strongly Enhanced Photocatalytic Properties.

Imine-linked covalent organic frameworks (COFs) usually show high crystallinity and porosity, while vinyl-linked COFs have excellent semiconducting properties and stability. Therefore, achieving the advantages of imine- and vinyl-linkages in a single COF material is highly interesting but remains challenging. Herein, we demonstrate the fabrication of a layer-blocked COF (LB-COF) heterogeneous film that is composed of imine- and vinyl-linkages through two successive surface-initiated polycondensations. In brief, the bottom layer of imine-linked COF film was constructed on an amino-functionalized substrate via Schiff-base polycondensation, in which the unreacted aldehyde edges could be utilized for initiating aldol polycondensation to prepare the second layer of vinyl-linked COF film. The resultant LB-COF film displays excellent ordering due to the crystalline templating effect from the bottom imine-linked COF layer; meanwhile, the upper vinyl-linked COF layer could strongly enhance its stability and photocatalytic properties. The LB COF also presents superior performance in photocatalytic uranium extraction (320 mg g-1), which is higher than the imine-linked (35 mg g-1) and the vinyl-linked (295 mg g-1) counterpart. This study provides a novel surface-initiated strategy to synthesize layer-blocked COF heterogeneous films that combine the advantages of each building block.

Construction of Thiadiazole-Bridged sp2-Carbon-Conjugated Covalent Organic Frameworks with Diminished Excitation Binding Energy Toward Superior Photocatalysis.

Sp2-carbon-conjugated covalent organic frameworks (sp2c-COFs) have emerged as promising platforms for phototo-chemical energy conversion due to their tailorable optoelectronic properties, in-plane π-conjugations, and robust structures. However, the development of sp2c-COFs in photocatalysis is still highly hindered by their limited linkage chemistry. Herein, we report a novel thiadiazole-bridged sp2c-COF (sp2c-COF-ST) synthesized by thiadiazole-mediated aldol-type polycondensation. The resultant sp2c-COF-ST demonstrates high chemical stability under strong acids and bases (12 M HCl or 12 M NaOH). The electro-deficient thiadiazole together with fully conjugated and planar skeleton endows sp2c-COF-ST with superior photoelectrochemical performance and charge-carrier separation and migration ability. As a result, when employed as a photocathode, sp2c-COF-ST exhibits a significant photocurrent up to ∼14.5 µA cm-2 at 0.3 V vs reversible hydrogen electrode (RHE) under visible-light irradiation (>420 nm), which is much higher than those analogous COFs with partial imine linkages (mix-COF-SNT ∼ 9.5 µA cm-2) and full imine linkages (imi-COF-SNNT ∼ 4.9 µA cm-2), emphasizing the importance of the structure-property relationships. Further temperature-dependent photoluminescence spectra and density functional theory calculations demonstrate that the sp2c-COF-ST has smaller exciton binding energy as well as effective mass in comparison to mix-COF-SNT and imi-COF-SNNT, which suggests that the sp2c-conjugated skeleton enhances the exciton dissociation and carrier migration under light irradiation. This work highlights the design and preparation of thiadiazole-bridged sp2c-COFs with promising photocatalytic performance.

Maternal smoking during pregnancy links to childhood blood pressure through birth weight and body mass index: NHANES 1999-2018.

Maternal smoking during pregnancy (MSDP) is associated with lower birth weight, childhood obesity, and elevated blood pressure (BP) in offspring. We aimed to examine whether birth weight and body mass index (BMI) mediate the effect of MSDP on BP in children. The study included 14,713 children aged 8 to 15 years from the National Health and Nutrition Examination Surveys from 1999 to 2018. General third-variable models were used to examine the mediating effects of birth weight and BMI on the association of MSDP with BP. A total of 1928 (13.1%) children were exposed to MSDP. MSDP was associated with reduced birth weight (p < 0.001), increased BMI (p < 0.001), and elevated systolic BP (p = 0.005). MSDP was not associated with systolic BP after adjustment for birth weight and BMI z-score (p = 0.875), with 95.0% of the effect of MSDP on BP mediated by birth weight (39.1%) and BMI (55.9%). In conclusion, lower birth weight and increased obesity measures mediate the adverse effects of MSDP on BP in children. These findings provide novel mechanistic insight into the adverse effect of MSDP on BP in children and have implications for preventing hypertension in later life.

Novel Metabolites Are Associated With Thrombosis After Cardiac Surgery in Children With Congenital Heart Disease.

BACKGROUND: Thrombosis is a major complication after cardiac surgery in children with congenital heart disease. The mechanisms underlying thrombosis development remain poorly understood. We aimed to identify novel circulating metabolites before cardiac surgery that are associated with thrombosis after surgery in children with congenital heart disease. METHODS: In this prospective cohort study, all blood samples were drawn right before surgical incision and after the induction of anesthesia, and plasma was separated immediately under 4 °C. Untargeted metabolomic data were measured by Metabolon in plasma from children (age range, 0 days-18 years) with congenital heart disease undergoing cardiac surgery. The primary outcome was thrombosis within 30 days of surgery or before discharge. Associations of individual metabolites with thrombosis were assessed with logistic regression with false discovery rate correction for multiple comparison and adjustment for clinical characteristics; elastic net regression was used to select a prediction model. RESULTS: Out of 1115 metabolites measured in samples from 203 children, 776 met the quality control criteria. In total, 25 children (12.3%) developed thrombosis. Among the 776 metabolites, 175 were significantly associated with thrombosis (false discovery rate Q<0.05). The top 3 metabolites showing the strongest associations with thrombosis were eicosapentaenoate, stearidonate, and andro steroid monosulfate C19H28O6S (false discovery rate, 0.01 for all). Pathway analysis showed that the pathways of nicotinate and nicotinamide metabolism and glycerophospholipid metabolism were enriched (false discovery rate, 0.003 for both) and had significant impact on the development of thrombosis. In elastic net regression analysis, the area under the receiver operating-characteristic curve of a prediction model for thrombosis was 0.969 in the training sample (70% of the total sample) and 0.833 in the testing sample (the remaining 30%). CONCLUSIONS: We have identified promising novel metabolites and metabolic pathways associated with thrombosis. Future studies are warranted to confirm these findings and examine the mechanistic pathways to thrombosis.

Survival-to-Hospital Discharge in Neonates With Congenital Heart Disease Supported With Prolonged Extracorporeal Membrane Oxygenation.

Factors that determine early outcomes in neonates with congenital heart disease (CHD) supported with prolonged venoarterial extracorporeal membrane oxygenation (ECMO) are not known and contemporary multicenter data are limited. This Extracorporeal Life Support Organization registry-based retrospective cohort study included all neonates (age ≤28 days) with CHD supported with venoarterial ECMO >7 days at 111 centers in the United States from January 2011 to December 2020. The primary outcome was survival-to-hospital discharge, and the secondary outcome was ECMO survival (successful decannulation before hospital discharge or death). Of the 2,155 total ECMO runs, 948 neonates received prolonged ECMO (gestational age [mean ± SD] 37.9 ± 1.8 weeks; birth weight 3.1 ± 0.6 kg; ECMO duration 13.6 ± 11.2 days). The ECMO survival rate was 51.6% (489 of 948), and the survival-to-hospital discharge rate was 23.9% (226 of 948). Body weight at ECMO (odds ratio [OR] 0.59, 95% confidence interval [CI] 0.44 to 0.78/kg), gestational age (OR 0.89, 95% CI 0.79 to 1.00 per week), risk-adjusted congenital heart surgery-1 score (OR 1.22, 95% CI 1.04 to 1.45), and pump flow at 24 hours (OR 1.11, 95% CI 1.04 to 1.18 per 10 ml/kg/min) were significantly associated with survival-to-hospital discharge. Pre-ECMO mechanical ventilation duration, time to extubation after ECMO decannulation, and length of stay were inversely associated with hospital survival. Patient-specific (higher body weight and gestational age) and CHD-related (lower risk-adjusted congenital heart surgery-1 score) attributes are associated with better outcomes in neonates who receive prolonged venoarterial ECMO. Further elucidation of the factors associated with reduced survival to discharge in ECMO survivors is needed.

Synthesis of sp2 Carbon-Conjugated Covalent Organic Framework Thin-Films via Copper-Surface-Mediated Knoevenagel Polycondensation.

sp2 carbon-conjugated covalent organic framework (sp2 c-COF) featured with high π-conjugation, high chemical stabilities, and designable chemical structures, are thus promising for applications including adsorption and separation, optoelectronic devices, and catalysis. For the most of these applications, large-area and continuous films are required. However, due to the needs of harsh conditions in the formation of CC bonds, classical interfacial methodologies are challenged in the synthesis of sp2 c-COFs films. Herein, a novel and robust interfacial method namely copper-surface-mediated Knoevenagel polycondensation (Cu-SMKP), is shown for scalable synthesis of sp2 c-COF films on various Cu substrates. Using this approach, large-area and continuous sp2 c-COF films could be prepared on various complicated Cu surfaces with thickness from tens to hundreds of nanometers. The resultant sp2 c-COF films on Cu substrate could be used directly as functional electrode for extraction of uranium from spiked seawater, which gives an exceptionally uptake capacity of 2475 mg g-1 . These results delineate significant synthetic advances in sp2 c-COF films and implemented them as functional electrodes for uranyl capture.

Relationship Between Left Ventricular Hypertrophy and Diabetes Is Likely Bidirectional: A Temporality Analysis.

Background The temporal relationship between type 2 diabetes (T2DM) and left ventricular hypertrophy (LVH) is not well established. This study aims to examine the temporal sequence between T2DM and LVH/cardiac geometry patterns in middle-aged adults. Methods and Results The longitudinal cohort consisted of 1000 adults (682 White individuals and 318 Black individuals; 41.1% men; mean age, 36.2 years at baseline) who had data on fasting glucose/T2DM, left ventricular mass index (LVMI), and relative wall thickness collected twice at baseline and follow-up over 9.4 years on average. The cross-lagged path analysis model in 905 adults who did not take antidiabetic medications and the longitudinal prediction model in 1000 adults were used to examine the temporal relationships of glucose/T2DM with LVMI, LVH, relative wall thickness, and remodeling patterns. After adjustment for age, race, sex, smoking, alcohol drinking, body mass index, heart rate, hypertension, and follow-up years, the path coefficient from baseline LVMI to follow-up glucose was 0.088 (P=0.005); the path from baseline glucose to follow-up LVMI was -0.009 (P=0.758). The 2 paths between glucose and relative wall thickness were not significant. The path analysis parameters did not differ significantly between race, sex, and follow-up duration subgroups. Incidence of T2DM was higher in the baseline LVH group than in the normal LVMI group (24.8% versus 8.8%; P=0.017 for difference). Incidence of LVH and concentric LVH was higher in the baseline T2DM group than in the group without T2DM (50.0% versus 18.2% for LVH [P=0.005 for difference]; 41.7% versus 12.6% for concentric LVH [P=0.004 for difference]), with adjustment for covariates. Conclusions This study suggests that the temporal relationship between T2DM and LVH is likely bidirectional. The path from LVMI/LVH to glucose/T2DM is stronger than the path from glucose/T2DM to LVMI/LVH.

Monolayer-Assisted Surface-Initiated Schiff-Base-Mediated Aldol Polycondensation for the Synthesis of Crystalline sp2 Carbon-Conjugated Covalent Organic Framework Thin Films.

sp2 carbon-conjugated covalent organic frameworks (sp2c-COFs) with superb in-plane π-conjugations, high chemical stability, and robust framework structure are expected to be ideal films/membranes for a wide range of applications including energy-related devices and optoelectronics. However, so far, sp2c-COFs have been mainly limited to microcrystalline powders, and this consequently hampered their performances in devices. Herein, we report a simple and robust methodology to fabricate large-area, free-standing, and crystalline sp2c-COF films (TFPT-TMT and TB-TMT) on various solid substrates (e.g., fluorine-doped tin oxide, aluminum sheet, polyacrylonitrile membrane) by self-assembly monolayer-assisted surface-initiated Schiff-base-mediated aldol polycondensation (namely, SI-SBMAP). The resultant sp2c-COF films show lateral sizes up to 120 cm2 and tunable thickness from tens of nanometers to a few micrometers. Owing to the robust framework and highly ordered quasi-1D channels, the sp2c-COF membrane-based osmotic power generator presents an output power density of 14.1 W m-2 under harsh conditions, outperforming most reported COF membranes as well as commercialized benchmark devices (5 W m-2). This work demonstrates a simple and robust interfacial methodology for the fabrication of sp2c-COF films/membranes for green energy applications and potential optoelectronics.

Epigenome-wide meta-analysis of BMI in nine cohorts: Examining the utility of epigenetically predicted BMI.

This study sought to examine the association between DNA methylation and body mass index (BMI) and the potential of BMI-associated cytosine-phosphate-guanine (CpG) sites to provide information about metabolic health. We pooled summary statistics from six trans-ethnic epigenome-wide association studies (EWASs) of BMI representing nine cohorts (n = 17,034), replicated these findings in the Women's Health Initiative (WHI, n = 4,822), and developed an epigenetic prediction score of BMI. In the pooled EWASs, 1,265 CpG sites were associated with BMI (p < 1E-7) and 1,238 replicated in the WHI (FDR < 0.05). We performed several stratified analyses to examine whether these associations differed between individuals of European and African descent, as defined by self-reported race/ethnicity. We found that five CpG sites had a significant interaction with BMI by race/ethnicity. To examine the utility of the significant CpG sites in predicting BMI, we used elastic net regression to predict log-normalized BMI in the WHI (80% training/20% testing). This model found that 397 sites could explain 32% of the variance in BMI in the WHI test set. Individuals whose methylome-predicted BMI overestimated their BMI (high epigenetic BMI) had significantly higher glucose and triglycerides and lower HDL cholesterol and LDL cholesterol compared to accurately predicted BMI. Individuals whose methylome-predicted BMI underestimated their BMI (low epigenetic BMI) had significantly higher HDL cholesterol and lower glucose and triglycerides. This study confirmed 553 and identified 685 CpG sites associated with BMI. Participants with high epigenetic BMI had poorer metabolic health, suggesting that the overestimation may be driven in part by cardiometabolic derangements characteristic of metabolic syndrome.

Bidirectional temporal relationships between uric acid and insulin and their joint impact on incident diabetes.

BACKGROUND AND AIMS: This study aims to examine the temporal relationship between uric acid (UA) and insulin and their joint impact on T2DM in middle-aged adults. METHODS AND RESULTS: The cohort consisted of 1351 non-diabetic adults who had serum UA and insulin measured twice at baseline and follow-up over 7.7 years on average, and incidence of T2DM in the outcome survey12.2 years later. After adjusting for covariates, the path coefficient from baseline UA to follow-up insulin was 0.082 (p < 0.001); the path from baseline insulin to follow-up UA was 0.060 (p = 0.030). In the mediation model with baseline UA as the predictor, total effect of baseline UA on incident T2DM was 0.089 (p = 0.016). The mediation effect through follow-up insulin on the UA-T2DM association was 28.1%. The direct effect of baseline UA on T2DM (0.064) became nonsignificant (p = 0.078). In the mediation model with baseline insulin as the predictor, total effect of baseline insulin on T2DM was 0.218 (p < 0.001). The mediation effect through follow-up UA on the insulin-T2DM association was 5.5%. The direct effect of baseline insulin on T2DM (0.206) remained significant (p < 0.001). The baseline hyperinsulinemia-follow-up hyperuricemia group showed the highest incidence rate of T2DM (27.9%). CONCLUSIONS: The bidirectional temporal relationship suggests that UA and insulin influence each other in non-diabetic individuals, and the directionality plays pathogenic roles in the development of T2DM.

Long-Term Adiposity and Midlife Carotid Intima-Media Thickness Are Linked Partly Through Intermediate Risk Factors.

OBJECTIVE: This study aims to determine quantitatively the mediation effects of multiple cardiovascular risk factors on the associations of childhood body mass index (BMI) and its cumulative burden with adult carotid intima-media thickness (cIMT). METHODS: The longitudinal cohort consisted of 1391 adults who had been examined for BMI 4-15 times over 35.0 years on average since childhood and had data on adult cIMT, systolic blood pressure, low-density lipoprotein cholesterol, atherogenic index of plasma, and serum glucose. The area under the curve was used as a measure of cumulative burden of BMI. RESULTS: After adjusting for covariates, the total effects (standardized regression coefficient) of childhood BMI (0.138), adult BMI (0.111), and area under the curve of BMI (0.150) on cIMT were all significant (P<0.001) without mediators included in the model. The mediation effects of adult systolic blood pressure, glucose, atherogenic index of plasma and low-density lipoprotein cholesterol were 8.0%, 4.3%, 3.6%, and 0.0%, respectively, in the model with childhood BMI as the predictor, 23.4%, 15.3%, 12.6%, and 7.2%, respectively, with adult BMI as the predictor, and 14.7%, 8.7%, 6.0%, and 2.0%, respectively, with area under the curve of BMI as the predictor. The direct effects on cIMT were 0.117 (P<0.001) for childhood BMI, 0.046 (P=0.224) for adult BMI, and 0.103 (P<0.001) for area under the curve of BMI after removing the mediation effects. CONCLUSIONS: The long-term deleterious impact of adiposity on subclinical changes in vascular structure begins early in life and is accumulated over lifetime. Excess adiposity and higher cIMT are linked partly through other cardiovascular risk factors in later life, especially elevated blood pressure and glucose.

18F-FDG PET/CT and MR imaging features of liver metastases in gastrointestinal stromal tumors: a cross-sectional analysis.

Background: Early detection of gastrointestinal stromal tumor (GIST) liver metastases is crucial for the management and prognosis. In our experience, GIST liver metastases can display hypermetabolism on 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and marked enhancement on magnetic resonance imaging (MRI), which are uncommon in other tumors before treatment. Most literature focus on the imaging evaluation, prognosis after treatment and less is known about imaging features on both imaging methods before treatment. This study analyzes the imaging features of newly diagnosed GIST liver metastases on 18F-FDG PET/CT and MRI, with goal of improving diagnostic accuracy. Methods: This retrospective study included 55 patients with pathological or radiographical confirmed GIST liver metastases who underwent PET/CT (n=29), MRI (n=22), or both methods (n=4). PET/CT and MRI interpretation including lesion's morphologic features, number, density or signal intensity, hemorrhage, cystic changes or necrosis, maximum standardized uptake value (SUVmax) of liver metastases and liver background on PET imaging, degree and pattern of enhancement on MRI were obtained by two experienced nuclear medicine physicians and two radiologists respectively. Data are presented as numbers, percentages, means ± standard deviations or median (interquartile range). The correlation between diameter and SUVmax of metastases, and primary tumor SUVmax and synchronous liver metastases SUVmax were analyzed by Spearman's rank test. Results: On PET/CT visual analysis, 38.9%, 23.9%, and 37.2% of lesions showed significant hypermetabolism, slightly higher metabolism, and equal or lower metabolism than liver, respectively. There was a weak correlation between the diameter and SUVmax of liver metastases (rs =0.370, P<0.001), and a moderate correlation between SUVmax of synchronous liver metastases and the primary tumors (rs =0.492, P<0.001). On contrast-enhanced MRI, 90.8% of lesions showed heterogeneous enhancement in the arterial phase with the variable presentation, and 74.3% had different enhancement patterns between margins and intratumoral parenchyma. Conclusions: Liver lesions in GIST displaying significant, slight hypermetabolism on 18F-FDG PET/CT, marked or heterogeneous gradual enhancement within the intratumoral parenchyma with ring-like enhancement on MRI may denote the diagnosis of liver metastasis. However, GIST liver metastases may also display equal or lower metabolism than liver parenchyma on PET, making small lesions more difficult to diagnose.

Trends in the prevalence of metabolically healthy and unhealthy obesity in the US adult population: analysis of eight NHANES cross-sectional survey cycles, 1999-2014.

OBJECTIVE: To exam the time trend of the prevalence of metabolically healthy obesity (MHO) in the US adult population. DESIGN: Eight cross-sectional survey cycles. SETTING: National Health and Nutrition Examination Survey (NHANES), 1999-2014. PARTICIPANTS: 16 459 NHANES participants aged 20 years and older. PRIMARY OUTCOME MEASURE: MHO was defined as central obesity (waist circumference ≥102 cm for men and ≥88 cm for women) without any of the following conditions: elevated levels of blood pressure (≥130/85 mm Hg), glucose (≥100 mg/dL) and triglycerides (≥150 mm/dL); reduced levels of high-density lipoprotein cholesterol (<40 mg/dL for men and <50 mg/dL for women) or any medication use for high cholesterol, hypertension or diabetes. RESULTS: The prevalence of central obesity significantly increased from 45.2% in 1999-2000 to 56.7% in 2013-2014 (p=0.003). Over the same period, MHO prevalence among those with central obesity only slightly and non-significantly increased from 11.0% to 15.7% (p=0.38). However, MHO prevalence among women increased significantly (p=0.04) from 7.1% to 13.7%. Female gender, a younger age, being Hispanic and non-Hispanic black and high education (some college or above) were significantly (p<0.05) associated with higher prevalence of MHO. CONCLUSIONS: While the prevalence of central obesity in the US population has increased since 1999, the prevalence of MHO among those who are centrally obese remained fairly stable.

Associations Between Life-Course Lipid Trajectories and Subclinical Atherosclerosis in Midlife.

Importance: Childhood lipid levels have been associated with adult subclinical atherosclerosis; however, life-course lipid trajectories and their associations with cardiovascular disease risk are poorly characterized. Objectives: To examine the associations of lipid levels at different ages and discrete lipid trajectory patterns from childhood to adulthood with subclinical atherosclerosis in midlife. Design, Setting, and Participants: This cohort study used data from the Bogalusa Heart Study, a prospective, population-based cohort study conducted in a semirural, biracial community in Bogalusa, Louisiana, with follow-up from 1973 to 2016 (median follow-up, 36.8 years). Participants had 4 to 16 repeated measurements of lipids, including total cholesterol (TC), non-high-density lipoprotein cholesterol (non-HDL-C), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG), from childhood to midlife and adult measurement of carotid intima-media thickness (IMT). Statistical analyses were conducted from July 1 to December 31, 2021. Exposures: Age-specific lipid levels were estimated, and lipid trajectory patterns were identified using latent mixture modeling. Main Outcomes and Measures: Subclinical atherosclerosis measured by carotid IMT. Results: The study evaluated 1201 adults (mean [SD] age, 45.7 [6.8] years; 691 [57.5%] women and 510 [42.5%] men; 392 Black [32.6%] and 809 White [67.4%] individuals). Levels of all lipids at each age from 5 to 45 years were significantly associated with adult IMT. The magnitude of associations generally increased with age, and non-HDL-C (age 5 y: ß, 0.040; 95% CI, 0.025-0.055; age 45 y, ß, 0.049; 95% CI, 0.026-0.072) and LDL-C (age 5 y: ß, 0.039; 95% CI, 0.024-0.054; age 45 y, ß, 0.043; 95% CI, 0.023-0.063) showed the strongest associations. After adjusting for race, sex, and other cardiovascular risk factors, mean IMT values were significantly higher in the low-slow increase, low-rapid increase, and high-stable trajectory groups for TC (eg, high-stable group: mean difference, 0.152 mm; 95% CI, 0.059-0.244 mm), the low-slow increase, low-rapid increase, moderate-stable, and high-stable trajectory groups for non-HDL-C (eg, low-slow increase group: mean difference, 0.048 mm; 95% CI, 0.012-0.085 mm) and LDL-C (eg, low-rapid increase group: mean difference, 0.104 mm; 95% CI, 0.056-0.151 mm) and the low-rapid increase and moderate-stable trajectory groups for TG (eg, moderate-stable group: mean difference, 0.071 mm; 95% CI, 0.019-0.122 mm) vs the corresponding low-stable trajectory groups. These associations were slightly attenuated after further adjustment for lipid levels at baseline or follow-up. There were no significant differences in mean IMT among HDL-C trajectory groups. Conclusions and Relevance: In this cohort study, discrete life-course lipid trajectories were associated with the development of atherosclerosis in midlife. The findings emphasize the importance of maintaining optimal lipid levels across the lifespan.

The impact of COVID-19 on disease epidemiology, family dynamics, and social justice in Minnesota: All that you cannot see.

Objective: The COVID-19 pandemic presented a challenge to established seed grant funding mechanisms aimed at fostering collaboration in child health research between investigators at the University of Minnesota (UMN) and Children's Hospitals and Clinics of Minnesota (Children's MN). We created a "rapid response," small grant program to catalyze collaborations in child health COVID-19 research. In this paper, we describe the projects funded by this mechanism and metrics of their success. Methods: Using seed funds from the UMN Clinical and Translational Science Institute, the UMN Medical School Department of Pediatrics, and the Children's Minnesota Research Institute, a rapid response request for applications (RFAs) was issued based on the stipulations that the proposal had to: 1) consist of a clear, synergistic partnership between co-PIs from the academic and community settings; and 2) that the proposal addressed an area of knowledge deficit relevant to child health engendered by the COVID-19 pandemic. Results: Grant applications submitted in response to this RFA segregated into three categories: family fragility and disruption exacerbated by COVID-19; knowledge gaps about COVID-19 disease in children; and optimizing pediatric care in the setting of COVID-19 pandemic restrictions. A series of virtual workshops presented research results to the pediatric community. Several manuscripts and extramural funding awards underscored the success of the program. Conclusions: A "rapid response" seed funding mechanism enabled nascent academic-community research partnerships during the COVID-19 pandemic. In the context of the rapidly evolving landscape of COVID-19, flexible seed grant programs can be useful in addressing unmet needs in pediatric health.