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BackgroundEarly in the COVID-19 pandemic, peak viral loads coincided with symptom onset. We hypothesized that in a highly immune population, symptom onset might occur earlier in infection, coinciding with lower viral loads.MethodsWe assessed SARS-CoV-2 and influenza A viral loads relative to symptom duration in recently-tested adults. Symptomatic participants ≥16y presenting to testing sites in Georgia (4/2022-4/2023; Omicron variant predominant) provided symptom duration. Nasal swab samples were tested by the Xpert Xpress SARS-CoV-2/Flu/RSV assay and Ct values recorded. Nucleoprotein concentrations in SARS-CoV-2 PCR-positive samples were measured by Single Molecule Array. To estimate hypothetical antigen rapid diagnostic test (Ag RDT) sensitivity on each day after symptom onset, percentages of individuals with Ct value ≤30 or ≤25 were calculated.ResultsOf 621 SARS-CoV-2 PCR-positive individuals (64.1% women, median 40.9y), 556/621 (89.5%) had a history of vaccination, natural infection, or both. By both Ct value and antigen concentration measurements, median viral loads rose from the day of symptom onset and peaked on the fourth day. Ag RDT sensitivity estimates were 35.7-71.4% on the first day, 63.9-78.7% on the third day, and 78.6-90.6% on the fourth day of symptoms.In 74 influenza A PCR-positive individuals (55.4% women; median 35.0y), median influenza viral loads peaked on the second day of symptoms.ConclusionsIn a highly immune adult population, median SARS-CoV-2 viral loads peaked on the fourth day of symptoms. Influenza A viral loads peaked soon after symptom onset. These findings have implications for ongoing use of Ag RDTs for COVID-19 and influenza.Key PointsIn a highly immune adult population, median SARS-CoV-2 viral loads by cycle threshold and antigen measurements peaked on the fourth day of symptoms, with implications for testing practice. In contrast, viral loads for influenza A peaked soon after symptom onset.

Faced with the COVID-19 pandemic, the US system for developing and testing technologies was challenged in unparalleled ways. This article describes the multi-institutional, transdisciplinary team of the “RADxSM Tech Test Verification Core” and its role in expediting evaluations of COVID-19 testing devices. Expertise related to aspects of diagnostic testing was coordinated to evaluate testing devices with the goal of significantly expanding the ability to mass screen Americans to preserve lives and facilitate the safe return to work and school. Focal points included: laboratory and clinical device evaluation of the limit of viral detection, sensitivity, and specificity of devices in controlled and community settings; regulatory expertise to provide focused attention to barriers to device approval and distribution; usability testing from the perspective of patients and those using the tests to identify and overcome device limitations, and engineering assessment to evaluate robustness of design including human factors, manufacturability, and scalability.

Introduction Exercise and dietary behavioral counseling are effective clinical practices recommended by the U.S. Preventive Services Task Force to reduce cardiovascular disease risk among high-risk individuals. Methods Medical Expenditure Panel Survey data from 2002 to 2015 were analyzed in 2018. Prevalence ratios of exercise, dietary, and both types of counseling among individuals with overweight or obesity with additional cardiovascular disease risk factors were calculated and adjusted for demographic covariates (N=116,048). Adjusted prevalence ratios were calculated for sociodemographic and health factors associated with counseling receipt using 2014–2015 data. Results From 2002 to 2015, adjusted prevalence ratios ranged from 43% to 63%. Compared with 2002, receipt of both types of counseling was 6% higher in 2015 (49%, 95% CI=48%, 51%). In 2015, compared with privately insured people, those without insurance (prevalence ratio=0.91, 95% CI=0.84, 0.99) or on Medicare (prevalence ratio=0.77, 95% CI=0.73, 0.82) were less likely to receive counseling. Individuals with 3 (prevalence ratio=1.46, 95% CI=1.39, 1.54), 4 (prevalence ratio=1.74, 95% CI=1.63, 1.85), or 5 (prevalence ratio=1.89, 95% CI=1.67, 2.15) cardiovascular disease risk factors received counseling more frequently than those with 2 cardiovascular disease risk factors. Female participants (prevalence ratio=1.07, 95% CI=1.03, 1.11) and racial minorities (Hispanics: prevalence ratio=1.31, 95% CI=1.24, 1.38; Blacks: prevalence ratio=1.11, 95% CI=1.05, 1.18; Asians: prevalence ratio=1.12, 95% CI=1.01, 1.24) reported higher rates of counseling. Conclusions Despite modest improvements since 2002, up to 37% of individuals at high cardiovascular disease risk were not receiving exercise counseling, and 43% were not receiving dietary counseling in 2015. Continued implementation and scale up of effective programs to increase behavioral lifestyle counseling among high-risk populations are needed more than ever to mitigate the U.S. cardiometabolic disease burden.

Objectives: The purpose of this study was to evaluate differences in the metabolic pathways activated in late-pregnancy serum samples among African American women who went on to have term (≥37 weeks) labor induction requiring high total oxytocin doses to complete first-stage labor compared to those in similar women with low-oxytocin labor inductions. Study Design: Case–control study ( N = 27 women with labor induction with successful cervical ripening: 13 requiring the highest total doses of synthetic oxytocin to progress from 4- to 10-cm cervical dilation and 14 requiring the lowest total doses) with groups balanced on parity and gestational age. Serum samples obtained between 24 and 30 weeks’ gestation were analyzed using ultra-high-resolution metabolomics. Differentially expressed metabolites between high-oxytocin induction cases and low-oxytocin induction comparison subjects were evaluated using linear regression with xmsPANDA. Metabolic pathways analysis was conducted using Mummichog Version 2.0, with discriminating metabolites annotated using xMSannotator Version 1.3. Results: Labor processes were similar by group with the exception that cases received over 6 times more oxytocin between 4- and 10-cm cervical dilation than comparison women. Induction requiring high total doses of synthetic oxytocin was associated with late-pregnancy serum levels of metabolites from the linoleate and fatty acid activation pathways in term, African American women. Conclusion: Serum levels of several lipid metabolites predicted more complicated labor induction involving higher doses of synthetic oxytocin to complete first-stage labor. Further investigation in larger, more diverse cohorts of women is needed to identify potential targets to prevent failed labor induction.

BackgroundUpper respiratory samples for SARS-CoV-2 detection include the gold standard nasopharyngeal (NP) swab, and mid-turbinate (MT) nasal swabs, oropharyngeal (OP) swabs, and saliva. Following the emergence of the omicron (B.1.1.529) variant, limited preliminary data suggest that OP swabs or saliva samples may be more sensitive than nasal swabs, highlighting the need to understand differences in viral load across different sites.MethodsMT, OP, and saliva samples were collected from symptomatic individuals presenting for evaluation in Atlanta, GA, in January 2022. Longitudinal samples were collected from a family cohort following COVID-19 exposure to describe detection of viral targets over the course of infection.ResultsSARS-CoV-2 RNA and nucleocapsid antigen measurements demonstrated a nares-predominant phenotype in a familial cohort. A consistent dominant location for SARS-CoV-2 was not found among 54 individuals. Positive percent agreement for virus detection in MT, OP and saliva specimens were 66.7 [54.1–79.2], 82.2 [71.1–93.4], and 72.5 [60.3–84.8] by RT-PCR, respectively, and 46.2 [32.6–59.7], 51.2 [36.2–66.1], and 72.0 [59.6–84.4] by ultrasensitive antigen assay. The composite of positive MT or OP assay was not significantly different than either alone for both RT-PCR and antigen assay (PPA 86.7 [76.7–96.6] and 59.5 [44.7–74.4], respectively).ConclusionsOur data suggest that SARS-CoV-2 nucleocapsid and RNA exhibited similar kinetics and diagnostic yield in three upper respiratory sample types across the duration of symptomatic disease. Collection of OP or combined nasal and OP samples does not appear to increase sensitivity versus validated nasal sampling for rapid detection of viral antigen.

Background Coronavirus disease 2019 (COVID-19) testing policies for symptomatic children attending US schools or daycare vary, and whether isolated symptoms should prompt testing is unclear. We evaluated children presenting for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing to determine if the likelihood of having a positive SARS-CoV-2 test differed between participants with 1 symptom vs ≥2 symptoms, and to examine the predictive capability of isolated symptoms. Methods Participants aged Results Of 602 participants, 21.8% tested positive and 48.7% had a known or suspected close contact. Children reporting 1 symptom (n = 82; odds ratio [OR], 6.00 [95% confidence interval {CI}, 2.70–13.33]) and children reporting ≥2 symptoms (n = 365; OR, 5.25 [95% CI, 2.66–10.38]) were significantly more likely to have a positive COVID-19 test than asymptomatic children (n = 155), but they were not significantly different from each other (OR, 0.88 [95% CI, .52–1.49]). Sensitivity and PPV were highest for isolated fever (33% and 57%, respectively), cough (25% and 32%), and sore throat (21% and 45%); headache had low sensitivity (8%) but higher PPV (33%). Sensitivity and PPV of isolated congestion/rhinorrhea were 8% and 9%, respectively. Conclusions With high Delta variant prevalence, children with isolated symptoms were as likely as those with multiple symptoms to test positive for COVID-19. Isolated fever, cough, sore throat, or headache, but not congestion/rhinorrhea, offered the highest predictive value.

BackgroundCOVID-19 testing policies for symptomatic children attending U.S. schools or daycare vary, and whether isolated symptoms should prompt testing is unclear. We evaluated children presenting for SARS-CoV-2 testing to determine if the likelihood of having a positive SARS-CoV-2 test differed between participants with one versus ≥2 symptoms, and to examine the predictive capability of isolated symptoms.MethodsParticipants ≤ 18 years presenting for clinical SARS-CoV-2 molecular testing in six sites in urban/suburban/rural Georgia (July-October, 2021; delta variant predominant) were queried about individual symptoms. Participants were classified into three groups: asymptomatic, one symptom only, or ≥2 symptoms. SARS-CoV-2 test results and clinical characteristics of the three groups were compared. Sensitivity, specificity, and positive/negative predictive values (PPV/NPV) for isolated symptoms were calculated by fitting a saturated Poisson model.ResultsOf 602 participants, 21.8% tested positive and 48.7% had a known or suspected close contact. Children reporting one symptom (n=82; OR=6.00, 95% CI: 2.70-13.33) and children reporting ≥2 symptoms (n=365; OR=5.25: 2.66-10.38) were significantly more likely to have a positive COVID-19 test than asymptomatic children (n=155), but they were not significantly different from each other (OR=0.88: 0.52-1.49). Sensitivity/PPV were highest for isolated fever (33%/57%), cough (25%/32%), and sore throat (21%/45%); headache had low sensitivity (8%) but higher PPV (33%). Sensitivity/PPV of isolated congestion/rhinorrhea were 8%/9%.ConclusionsWith high delta variant prevalence, children with isolated symptoms were as likely as those with multiple symptoms to test positive for COVID-19. Isolated fever, cough, sore throat, or headache, but not congestion/rhinorrhea, offered highest predictive value.Key pointsIn an area with high community prevalence of the delta variant, children presenting with one symptom were as likely as those with two or more symptoms to test positive for SARS-CoV-2 infection. Isolated symptoms should be considered in testing decisions.

Pediatric liver transplantation rejection affects 20% of children. Currently, liver biopsy, expensive and invasive, is the best method of diagnosis. Discovery and validation of clinical biomarkers from blood or other biospecimens would improve clinical care. For this study, stored plasma samples were utilized from two cross-sectional cohorts of liver transplant patients at Children’s Healthcare of Atlanta. High resolution metabolic profiling was completed using established methods. Children with (n = 18) or without (n = 25) acute cellular rejection were included in the analysis (n = 43 total). The mean age of these racially diverse cohorts ranged from 12.6 years in the rejection group and 13.6 years in the no rejection group. Linear regression provided 510 significantly differentiating metabolites between groups, and OPLS-DA showed 145 metabolites with VIP > 2. A total of 95 overlapping significant metabolites between OPLS-DA and linear regression analyses were detected. Pathway analysis (p 500 significant metabolites. This result suggests that development of a non-invasive biomarker-based test is possible for rejection screening.

The impact of repeated sample collection on COVID-19 test performance is unknown. The FDA and CDC currently recommend the primary collection of diagnostic samples to minimize the perceived risk of false-negative findings. We therefore evaluated the association between repeated sample collection and test performance among 325 symptomatic patients undergoing COVID-19 testing in Atlanta, GA. High concordance was found between consecutively collected mid-turbinate samples with both molecular (n = 74, 100% concordance) and antigen-based (n = 147, 97% concordance, kappa = 0.95, CI = 0.88–1.00) diagnostic assays. Repeated sample collection does not decrease COVID-19 test performance, demonstrating that multiple samples can be collected for assay validation and clinical diagnosis.

While there has been significant progress in the development of rapid COVID-19 diagnostics, as the pandemic unfolds, new challenges have emerged, including whether these technologies can reliably detect the more infectious variants of concern and be viably deployed in non-clinical settings as “self-tests”. Multidisciplinary evaluation of the Abbott BinaxNOW COVID-19 Ag Card (BinaxNOW, a widely used rapid antigen test, included limit of detection, variant detection, test performance across different age-groups, and usability with self/caregiver-administration. While BinaxNOW detected the highly infectious variants, B.1.1.7 (Alpha) first identified in the UK, B.1.351 (Beta) first identified in South Africa, P.1 (Gamma) first identified in Brazil, B.1.617.2 (Delta) first identified in India and B.1.2, a non-VOC, test sensitivity decreased with decreasing viral loads. Moreover, BinaxNOW sensitivity trended lower when devices were performed by patients/caregivers themselves compared to trained clinical staff, despite universally high usability assessments following self/caregiver-administration among different age groups. Overall, these data indicate that while BinaxNOW accurately detects the new viral variants, as rapid COVID-19 tests enter the home, their already lower sensitivities compared to RT-PCR may decrease even more due to user error.

The National Institutes of Health (NIH) launched the Rapid Acceleration of Diagnostics (RADxSM) Tech initiative to support the development and commercialization of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) point-of-care test devices. The primary objective of the Clinical Studies Core (CSC) was to perform SARS-CoV-2 device studies involving diverse populations and settings. Within a few months, the infrastructure for clinical studies was developed, including a master protocol, digital study platform, data management system, single IRB, and multi-site partnerships. Data from some studies are being used to support Emergency Use Authorization of novel SARS-CoV-2 test devices. The CSC reduced the typical time and cost of developing medical devices and highlighted the impactful role of academic and NIH partnership in addressing public health needs at a rapid pace during a global pandemic. The structure, deployment, and lessons learned from this experience are widely applicable to future in vitro diagnostic device clinical studies.

Purpose: One third of the U.S. adult population is estimated to have prediabetes. Hispanics have a 50% higher type 2 diabetes (T2DM) death rate compared to non-Hispanic whites, yet low participation in lifestyle change programs, making this subgroup an important target for prevention efforts. The purpose of this study was to determine the effects of an intervention implementing the Center for Disease Control and Prevention (CDC) National Diabetes Prevention Program (NDPP) plus recreational soccer (RS) in Hispanic men. Methods: Overweight and obese Hispanic men, aged 30-57 years with prediabetes at screening were recruited from the community. Enrolled participants were divided into three cohorts. Trained soccer coaches led 30-minute facilitated discussion of the NDPP modules after each RS session, with two sessions per week for 3 months and once per week for the following 3 months. The 1-hour RS sessions followed the Football Fitness curriculum structure. Standardized study assessments included body mass index, waist circumference, multi-frequency bioelectrical impedance analysis (InBody 270), blood pressure, hemoglobin A1c, and validated field physical fitness tests (figure of 8 run, handgrip strength, vertical jump, modified sit-ups, dynamic push-ups, one leg stand and Yo-Yo intermittent sprint test). Mixed models assessed the outcomes as a function of time and cohort and incorporated an unstructured covariance structure to examine the difference between baseline and 6 months. All analyses were conducted as intent-to-treat and generated using SAS v 9.4. Results: Hispanic males (n=41; mean age 41.7 [0.1] years) were obese at baseline (mean BMI 32.7, standard error [0.7], mean weight 93.9 [2.2] kg). After 6 months of the NDPP+RS intervention, there were significant changes in systolic and diastolic blood pressure (-6.6 [2.4]; p=0.01 and -6.1 [1.7] mmHg; p2 (ml/kg/min) (0.4 [0.2]; p=0.04. Despite significant reductions in weight (-3.8 kg [0.7]; p Conclusion: Among middle-aged Latino men, broad-ranging significant improvements in body composition, physical fitness, HbA1c and blood pressure were observed after 6 months of participating in lifestyle education plus RS.

PURPOSE: One third of the U.S. adult population is estimated to have prediabetes. Hispanics have a 50% higher type 2 diabetes (T2DM) death rate compared to non-Hispanic whites, yet low participation in lifestyle change programs, making this subgroup an important target for prevention efforts. The purpose of this study was to determine the effects of an exercise intervention implementing the Center for Disease Control and Prevention (CDC) National Diabetes Prevention Program (NDPP) plus recreational soccer (RS) in Hispanic men. METHODS: Overweight and obese Hispanic men, aged 30–57 years with prediabetes at screening were recruited from the community. Trained soccer coaches led 30-min facilitated discussion of the NDPP modules after each RS session, with two wkly sessions delivered over 12 wks, then once a wk until 24 wks. The 1-h RS sessions followed the Football Fitness curriculum structure. Standardized study assessments included objectively measured physical activity via fitness tracker, physical fitness via validated field tests, GPS soccer specific metrics and behavior change questionnaires. Mixed models assessed the outcomes as a function of time and cohort and incorporated an unstructured covariance structure to examine the difference between baseline, 12 and 24 wks. All analyses were conducted as intent-to-treat and generated using SAS v 9.4. RESULTS: Hispanic males (n=41; mean age 41.9 [6.2 SD] years) were obese at baseline (mean BMI 32.7, standard error [0.7]). After 24 wks of the NDPP+RS intervention, there were significant beneficial changes in vertical jump (2.8 [1.3] cm; p=0.048), agility and lower extremity muscular power (figure 8-run) at 12 wks (−4.7% change; p=0.001) and 24 wks (−7.2% change; p

Hypertensive disorders of pregnancy (HDP) are the most common cardiometabolic complications of pregnancy, affecting nearly 10% of US pregnancies and contributing substantially to maternal and infant morbidity and mortality. In the US, women of African American race are at increased risk for HDP. Early biomarkers that reliably identify women at risk for HDP remain elusive, yet are essential for the early identification and targeting of interventions to improve maternal and infant outcomes. We employed high-resolution metabolomics (HRM) to identify metabolites and metabolic pathways that were altered in early (8-14 weeks) gestation serum samples of pregnant African American women who developed HDP after 20 weeks’ gestation (n=20)—either preeclampsia (PE; n=11) or gestational hypertension (gHTN; n=9)—compared to those who delivered full term without complications (n=80). We found four metabolic pathways that were significantly (p<0.05) altered in women who developed PE and five pathways that were significantly (p<0.05) altered in women who developed gHTN compared to women who delivered full term without complications. We also found that four specific metabolites (p<0.05) were distinctly upregulated (retinoate, kynurenine) or downregulated (SN-glycero-3-phosphocholine, 2′4′-dihydroxyacetophenone) in women who developed PE compared to gHTN. These findings support that there are systemic metabolic disruptions that are detectable in early pregnancy (8-14 weeks of gestation) among pregnant African American women who develop PE and gHTN. Furthermore, the early pregnancy metabolic disruptions associated with PE and gHTN are distinct, implying they are unique entities rather than conditions along a spectrum of the same disease process despite the common clinical feature of high blood pressure.

ObjectiveTo develop and evaluate a Nutrition Transition-FFQ (NT-FFQ) to measure nutrition transition among adolescents in South India.DesignWe developed an interviewer-administered NT-FFQ comprising a 125-item semi-quantitative FFQ and a twenty-seven-item eating behaviour survey. The reproducibility and validity of the NT-FFQ were assessed using Spearman correlations, intra-class correlation coefficients (ICC), and levels of agreement using Bland–Altman and cross-classification over 2 months (NT-FFQ1 and NT-FFQ2). Validity of foods was evaluated against three 24-h dietary recalls (24-HR). Face validity of eating behaviours was evaluated through semi-structured cognitive interviews. The reproducibility of eating behaviours was assessed using weighted kappa (κw) and cross-classification analyses.SettingVijayapura, India.SubjectsA representative sample of 198 adolescents aged 14–18 years.ResultsReproducibility of NT-FFQ: Spearman correlations ranged from 0·33 (pulses) to 0·80 (red meat) and ICC from 0·05 (fruits) to 1·00 (tea). On average, concordance (agreement) was 60 % and discordance was 7 % for food groups. For eating behaviours,κwranged from 0·24 (eating snacks while watching television) to 0·67 (eating lunch at home) with a mean of 0·40. Validity of NT-FFQ: Spearman correlations ranged from 0·11 (fried traditional foods) to 0·70 (tea) and ICC ranged from 0·02 (healthy global foods) to 1·00 (grains). The concordance and discordance were 48 % and 8 %, respectively. Bland–Altman plots showed acceptable agreement between NT-FFQ2 and 24-HR. The eating behaviours had acceptable face validity.ConclusionsThe NT-FFQ has good reproducibility and acceptable validity for food intake and eating behaviours. The NT-FFQ can quantify the nutrition transition among Indian adolescents.

The State of Cannabis Research Legislation in 2020 U.S. researchers lack appropriate access to commercially available cannabis products for clinical trials. Meanwhile, patients continue to use stat...

Malnutrition is common in patients with active tuberculosis (TB), yet little information is available on serial dietary intake or body composition in TB disease.To evaluate macronutrient intake and body composition in individuals with newly diagnosed TB over time.Adults with active pulmonary TB (n = 191; 23 with multidrug resistant TB (MDR-TB) and 36 culture-negative household contacts (controls) enrolled in a clinical trial of high-dose cholecalciferol (vitamin D3) were studied. Macronutrient intake was determined at baseline, 8 and 16 weeks. Serial body composition was assessed by body mass index (BMI; kg/m(2)) and bioelectrical impedance analysis (BIA) to estimate fat mass and fat-free mass. Descriptive statistics, repeated measures ANOVA for changes over time and linear regression were used.At baseline, mean daily energy, protein, fat and carbohydrate (CHO) intakes were significantly higher, and body weight, BMI, fat-free mass and fat mass were significantly lower, between TB subjects and controls. These remained significant after adjusting for age, gender, employment status and smoking. In all TB subjects, baseline mean daily intakes of energy, fat and protein were adequate when compared to the US Dietary Reference Intakes and protein significantly increased over time (p 0.0001). Body weight, BMI, and fat and fat-free mass increased over time. MDR-TB patients exhibited lower body weight and fat-free mass over time, despite similar daily intake of kcal, protein, and fat.Macronutrient intake was higher in TB patients than controls, but TB-induced wasting was evident. As macronutrient intake of TB subjects increased over time, there was a parallel increase in BMI, while body composition proportions were maintained. However, individuals with MDR-TB demonstrated concomitantly decreased body weight and fat-free mass over time versus drug-sensitive TB patients, despite increased macronutrient intake. Thus, MDR-TB appears to blunt anabolism to macronutrient intake, likely reflecting the catabolic effects of TB.

Background: Validated noninvasive biomarkers to assess treatment response in pediatric nonalcoholic fatty liver disease (NAFLD) are lacking. We aimed to validate alanine aminotransferase (ALT), a monitoring biomarker for change in liver histology. Methods: A retrospective analysis using data from the TONIC trial. NAFLD histologic assessments were defined by: Fibrosis score, NAFLD activity score (NAS), nonalcoholic steatohepatitis (NASH), and a combination of NASH resolution and fibrosis (NASH + fibrosis). Analysis was performed using classification and regression trees (CART) as well as logistic regression. Results: Mean ALT for the child over 96 weeks and percent change of ALT from baseline to 96 weeks were significant predictors of progression of NAFLD for each histologic assessment (p < 0.001 for fibrosis score, NASH, and NASH + fibrosis and p < 0.05 for NAS). Mean ALT adjusted for age, sex and ethnicity was a better predictor for change in NASH (81.8 (11.0) ROC (receiver operating characteristic curve) mean (SD (Standard derivation))) and NASH + fibrosis (77.8 (11.2)), compared to change in NAS (63 (17.7)) and fibrosis (58.6 (11.1)). Conclusion: Mean ALT over 96 weeks is a reasonable proxy of histologic improvement of NASH and NASH + fibrosis. These findings support ALT as a valid monitoring biomarker of histologic change over time in children with NASH and fibrosis.

Background Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in children, and currently, there are no FDA-approved therapies. Plasminogen activator inhibitor-1 (PAI-1) is elevated in children with NAFLD and associated with increased disease severity. Losartan potassium (losartan) is an angiotensin II receptor blocker (ARB) that reduces PAI-1 production and improves insulin sensitivity that has been proposed as a treatment for pediatric NAFLD but has not previously been tested. Methods This was an 8-week randomized, double-blind, placebo-controlled, phase 2a, crossover study (with a 6-week washout between conditions) for safety and preliminary efficacy of losartan 50 mg a day taken orally in 12 normotensive children with biopsy proven nonalcoholic steatohepatitis (NASH). Results Twelve children enrolled in the study, and nine completed all visits. No changes in blood pressure or serious adverse events occurred during the study. Trends in improvement in alanine aminotransferase (ALT), aspartate aminotransferase (AST), and homeostatic model assessment insulin resistance (HOMA-IR) were seen with losartan treatment compared to the placebo time-period. More participants decreased ALT on losartan as compared to placebo (89% [8 out 9] vs. 56% [5 out of 9], respectively). Conclusions This data provides preliminary evidence that losartan treatment is safe over 8 weeks in children with NAFLD and supports consideration of larger studies to test its efficacy. Trial registration URL and trial identification number: https://clinicaltrials.gov/show/NCT01913470, NCT01913470. Date registered: August 1, 2013.

Background While associated with obesity, the cause of the rapid rise in prevalence of nonalcoholic fatty liver disease (NAFLD) in children, which is highest among Hispanics, is not well understood. Animal experiments have demonstrated that arsenic exposure contributes to liver injury. Our objective was to examine the association between arsenic exposure and NAFLD in humans and to determine if race/ethnicity modifies the association. Methods Urinary inorganic arsenic concentrations among those ≥12 years in the National Health and Nutrition Examination Survey, 2005–2014 were used to assess the cross-sectional association with serum alanine aminotransferase (ALT) levels, a marker of liver dysfunction. We excluded high alcohol consumers (>4–5 drinks/day; n = 939), positive hepatitis B or C (n = 2330), those missing body mass index (n = 100) and pregnant women (n = 629) for a final sample of 8518. Arsenic was measured using liquid chromatography coupled with mass spectrometry and ALT was measured using standard methods. Sampling weights were used to obtain national estimates. Due to lack of normality, estimates were log transformed and are presented as geometric means. Logistic regression models controlling for age, sex, income, and weight category estimate adjusted odd ratios (aOR) of elevated ALT by quartile of arsenic and tested for effect modification by race/ethnicity and weight. Elevated ALT was defined as >25 IU/L and >22 IU/L for boys and girls ≤17 years, respectively and >30 IU/L and >19 IU/L for men and women, respectively. Results Among all, aOR of elevated ALT were higher among those in the highest vs. lowest arsenic quartile (referent), 1.4 (95% confidence interval [CI]: 1.1, 1.7) with a borderline significant interaction (p = 0.07) by race/ethnicity but not weight (p = 0.4). In analysis stratified by race/ethnicity, aOR of elevated ALT among those in the 4th quartile were higher among Mexican Americans, 2.0 (CI: 1.3, 3.1) and non-Hispanic whites only, aOR 1.4 (CI: 1.1, 1.8) despite the fact that obesity prevalence was highest among non-Hispanic blacks. Conclusions Our findings demonstrate a positive association between urinary arsenic exposure and risk of NAFLD among U.S. adolescents and adults that is highest among Mexican Americans and among those obese, regardless of race/ethnicity.

Background: Tuberculosis, including multidrug-resistant tuberculosis (MDR-TB), is a major global health problem. Individuals with tuberculosis disease commonly exhibit vitamin D deficiency, which may adversely affect immunity and the response to therapy. Objective: We determined whether adjunctive high-dose vitamin D3 supplementation improves outcomes in individuals with pulmonary tuberculosis disease. Design: The study was a double-blind, randomized, placebo-controlled, intent-to-treat trial in 199 individuals with pulmonary tuberculosis disease in Tbilisi, Georgia. Subjects were randomly assigned to receive oral vitamin D3 [50,000 IUs (1.25 mg) thrice weekly for 8 wk and 50,000 IU every other week for 8 wk] or a placebo concomitant with standard first-line antituberculosis drugs. The primary outcome was the time for the conversion of a Mycobacterium tuberculosis (Mtb) sputum culture to negative. Results: Baseline characteristics between groups were similar. Most subjects (74%) were vitamin D deficient (plasma 25-hydroxyvitamin D [25(OH)D] concentration

There is an increasing need to understand long-term metabolic changes and resultant comorbidities because life expectancy is increasing after pediatric kidney and liver transplants. We evaluated differences in classic and novel cardiometabolic biomarkers among obese and normal weight adolescent transplant recipients. We enrolled a total of 80 adolescent (mean±SD, 14.8 years ±3.0) transplant recipients (63 kidney, 17 liver) with mean duration from transplantation of 6.0 (±4.1) years. Among kidney transplant recipients, overweight and obese individuals had higher leptin (16.7 vs 7.5 μg/mL, P

Little is known regarding the subsequent course of non-alcoholic fatty liver disease (NAFLD) diagnosed in childhood. The objectives of this single-center study were to gather data on long-term health outcomes and to assess the feasibility of contacting former pediatric patients. In a large pediatric medical center, electronic records were searched to initially identify 162 former patients who had a liver biopsy between 2000 and 2010. Of these, 44 subjects met the criteria for age at follow-up (≥18 year) and biopsy-proven NAFLD, and were recruited via postal and electronic mail. Participants were invited to complete a brief telephone survey on current health status. Supplemental data was also obtained from pediatric medical charts of all subjects. At NAFLD diagnosis, 18% of subjects had diabetes, 91% were obese, 61% had NASH, and 56% had fibrosis on biopsy. At follow-up, 10 subjects (23%) responded to the survey. Based on the survey and chart review, after a mean follow-up of 4.5 years, 5 additional subjects developed diabetes for a period prevalence of 30%, and most subjects (78%) remained obese at last follow-up. Additional prospective studies are needed to fully describe the longitudinal risks associated with pediatric NAFLD, and will require multi-dimensional strategies to successfully recruit former patients.

Purpose of Review The purpose of this study is to review the role of plasminogen activator inhibitor-1 (PAI-1) in pediatric obesity and nonalcoholic fatty liver disease (NAFLD).

Background: Few studies have examined the quality and adequacy of dietary intake in patients attempting to limit sodium. Objective: The aim of this study was to provide a comprehensive analysis of the dietary intake of persons with heart failure (HF) in the Southern United States who have been advised to limit their sodium intake. Methods: Three-day food diaries were completed by 114 New York Heart Association class II and III persons with HF enrolled in a family partnership intervention study, which were reviewed by a dietitian and analyzed using validated nutritional software. The Harris-Benedict equation for sedentary adults was used to determine macronutrient intake adequacy. Demographic information and clinical data were obtained through patient report and medical record review. Results: Dietary sodium ingestion ranged from 522 to 9251 mg/d (mean [SD], 2671 [1432] mg/d), with 38 (33.3%) individuals consuming the recommended 2000 mg/d or less in this sample (age, 28Y78 years; 64.0% men; 57.0% African American). Mean (SD) caloric intake for the total sample was 1674 (636) kcal/d, with participants eating 99% of the recommended daily allowance (RDA) of protein, 63% of the RDA of carbohydrates, and 89% of the RDA of fat. Participants eating 2000 mg or less of sodium consumed significantly less calories (P G .001), protein (P G .001), carbohydrates (P = .008), and fat (P G .001), but not fiber (P =. 103), compared with those consuming more than 2000 mg of sodium after adjusting for body mass index. When analyzed by amount of sodium consumption, persons ingesting 2000 mg or less of sodium per day ate significantly less grains (P = .001) and meat and beans (P = .004) and had less intake of the micronutrients calcium (P G .001), zinc (P = .002), and thiamine (P = .05). Conclusion: Only one-third of participants with HF who have been instructed on a low-sodium diet reported consuming the RDA of 2000 mg or less, indicating the need for further dietary instruction with a particular focus on modifying the Southern US diet.

Background Cystic fibrosis (CF) is a chronic catabolic disease often requiring hospitalization for acute episodes of worsening pulmonary exacerbations. Limited data suggest that vitamin D may have beneficial clinical effects, but the impact of vitamin D on systemic metabolism in this setting is unknown. Objective We used high-resolution metabolomics (HRM) to assess the impact of baseline vitamin D status and high-dose vitamin D3 administration on systemic metabolism in adults with CF with an acute pulmonary exacerbation. Design Twenty-five hospitalized adults with CF were enrolled in a randomized trial of high-dose vitamin D3 (250,000 IU vitamin D3 bolus) versus placebo. Age-matched healthy subjects served as a reference group for baseline comparisons. Plasma was analyzed with liquid chromatography/ultra-high resolution mass spectrometry. Using recent HRM bioinformatics and metabolic pathway enrichment methods, we examined associations with baseline vitamin D status (sufficient vs. deficient per serum 25-hydroxyvitamin D concentrations) and the 7-day response to vitamin D3 supplementation. Results Several amino acids and lipid metabolites differed between CF and healthy control subjects, indicative of an overall catabolic state. In CF subjects, 343 metabolites differed (P Conclusions Numerous metabolic pathways detected by HRM varied in association with vitamin D status and high-dose vitamin D3 supplementation in adults with CF experiencing a pulmonary exacerbation. Overall, these pilot data suggest an anti-catabolic effect of high-dose vitamin D3 in this clinical setting.