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Background: Youth with type 1 diabetes (T1D) are encouraged to participate in physical activity (PA). Studies have identified fear of hypoglycemia (FOH) as a barrier to participating in PA. Objectives: To examine (a) PA patterns in youth with T1D by age group and (b) the relationship between both parental and youth FOH and youth PA. Methods: A cross‐sectional analysis from the SEARCH cohort study visit of youth ages 10 to 17 years with T1D (n = 1129) was conducted. Linear regression models estimated the association between self‐reported number of days of vigorous PA (VPA) and moderate PA (MPA) and both youth‐ and parent‐reported FOH. Multivariable models were adjusted for age, sex, race, duration of T1D, HbA1c, use of continuous glucose monitoring (CGM), recent severe hypoglycemia, primary insulin regimen, and BMI. Results: Participants were 52% female, had mean (sd) age 14.4 (4.2) years, diabetes duration 7.5 years (1.8), HbA1c 9.2% (1.7). Older youth were less likely to engage in VPA (P <.01), or sports teams (P <.01), but more likely to engage in MPA (P <.01). Higher youth FOH (behavior subscale) was associated with increased levels of VPA (β (se) 0.30 (0.11), P =.01) but not significantly associated with MPA (P =.06). There was no statistically significant association between parental FOH and youth PA. Conclusions: In SEARCH participants with T1D, VPA, and team sports participation declined with age, while MPA increased. We observed that higher scores on the youth FOH behavioral subscale were associated with increased VPA levels, suggesting that FOH may be less of a barrier to PA than previously thought. [ABSTRACT FROM AUTHOR]

Objective To evaluate whether hormonal contraceptives, used before or in early pregnancy, confer increased risk of preterm birth or reduced fetal growth. Design Population-based cohort study conducted by the Norwegian Institute of Public Health (Mother and Child Cohort Study, 1998-2008) with linkage to the Norwegian Prescription Registry and to the Medical Birth Registry of Norway. Setting Norway. Population Of the 48 615 pregnancies meeting study inclusion criteria, 44 734 pregnancies were included in the complete case analysis. Methods We characterised hormonal contraception by type (combination oral, progestin-only oral, vaginal ring, transdermal, and injectable) and specific progestin component. We used generalised estimating equations to estimate the odds of adverse outcome according to formulation used. Several sensitivity analyses were conducted. Main outcome measures Preterm birth, small for gestational age. Results We observed a positive association between use of a combination oral contraceptive and preterm birth for all exposure periods (e.g. adjusted odds ratio 1.21, 95% confidence interval 1.04-1.41 for last use 12 to >4 months before conception); combination contraceptives containing the progestin norethisterone were consistently related to risk. Other types of hormonal contraception were generally not associated with preterm birth; none were related to small for gestational age. Observed associations were robust to sensitivity analyses. Conclusion Hormonally active agents may exert dose-, agent-, and timing-specific effects on growth and development. We found that the particular progestin component is important when assessing the potential for adverse effects among former users of hormonal contraceptives. [ABSTRACT FROM AUTHOR]

The susceptibility of Haemophilus influenzae to penicillin V and G, ampicillin and cefuroxime was investigated by MIC, disc and tablet diffusion methods, using chocolate agar as test medium, to determine the prevalence of ampicillin-resistant isolates and the optimal method for their detection. Eighty-six isolates were clinical isolates collected prospectively from July to September 1998 and 22 isolates were clinical isolates with decreased susceptibility to ampicillin previously referred to the reference laboratory. Eighty-seven isolates were ampicillin-susceptible and 16 were ampicillin-resistant. Thirteen produced beta-lactamases. Among the consecutive isolates 12.8% were resistant. With each of the Rosco Neo-sensitabs containing penicillin G, 2.5 microg ampicillin and 33 microg ampicillin, 3 very major errors occurred (resistant isolates misinterpreted as susceptible) and 5-13 major errors (susceptible isolates misinterpreted as resistant). The AB biodisk containing ampicillin (10 microg) was superior to the penicillin V and G discs, i.e. only 1 very major error occurred and major and minor errors were infrequent. The cefuroxime disc identified 4/8 beta-lactamase-negative ampicillin-resistant isolates. Thus, for susceptibility testing with chocolate agar as test medium, the use of an inoculum of 10(5) colony-forming units, 10 microg ampicillin discs and interpretative zone diameters of > or = 28 mm indicating susceptibility and < or = 25 mm indicating resistance was found to produce reliable identification of ampicillin-resistant isolates of H. influenzae. [ABSTRACT FROM AUTHOR]

Background and Aims: Eosinophilic esophagitis (EoE) has been continually increasing in prevalence but current estimates are lacking. We aimed to determine updated estimates of the prevalence and medical costs associated with EoE in the United States., Methods: We used two large administrative databases, MarketScan and Medicare, and International Classification of Disease codes to calculate annual prevalence of EoE, as well as age- and sex- stratified estimates, standardized to the U.S., Population: Health care utilization, including medications and endoscopic procedures was quantified, and annual EoE-associated costs were estimated., Results: We identified 20,435 EoE cases in MarketScan in 2022 and 1,913 EoE cases in Medicare in 2017. This translated to prevalences of 163.08 cases/100,000 and 64.83 cases/ 100,000 in MarketScan and Medicare, respectively. There was a 5-fold increase in prevalence in both databases since 2009. In MarketScan, prevalence was higher among males (204.45/100,000 vs 122.06/100,000 among females); for both sexes, peak prevalence was from 40-44years. Standardized to the U.S. population, the prevalence of EoE was 142.5/100,000, extrapolating to 472,380 cases. Total EoE-associated healthcare costs were estimated to be $1.32 billion in 2024 dollars after accounting for inflation., Conclusions: The prevalence of EoE continues to increase, with a rate of 1 in 617 in 2022 in those <65 years of age, and 1 in 1562 in 2017 those ≥65 years. Standardized to the U.S. population, the overall prevalence was approximately 1 in 700. EoE-associated annual costs were estimated to be $1.3 billion in 2024 dollars, representing a substantial financial burden., (Copyright © 2024. Published by Elsevier Inc.)

Background: Early-life factors such as preterm birth or very low birthweight (VLBW) are associated with increased cardiovascular disease risk. However, it remains unknown whether this is due to an increased risk of obesity (unhealthy central adiposity) because studies have predominantly defined obesity based on BMI, an imprecise adiposity measure. Objective: Investigate if adolescents born preterm with VLBW have a higher risk of unhealthy central adiposity compared to term-born peers. Study Design: Cross-sectional analysis of data from a prospective cohort study of 177 individuals born preterm with VLBW (<1500 g) and 51 term-born peers (birthweight ≥2500 g). Individuals with congenital anomalies, genetic syndromes, or major health conditions were excluded. Height, weight, waist circumference, skin fold thickness, and dual energy X-ray absorptiometry body composition were measured at age 14 years. We calculated BMI percentiles and defined overweight/obesity as BMI ≥85th percentile for age and sex. We estimated the preterm-term differences in overweight/obesity prevalence and adiposity distribution with multivariable generalized linear models. Results: There was no difference in small for gestational age status or overweight/obesity prevalence. Compared to term, youth born preterm with VLBW had lower BMI z-score [ β -0.38, 95% confidence limits (CL) -0.75 to -0.02] but no differences in adiposity apart from subscapular-to-triceps ratio (STR; β 0.18, 95% CL 0.08 to 0.28). Conclusions: Adolescents born preterm with VLBW had smaller body size than their term-born peers and had no differences in central adiposity except greater STR.

The Consortium of Eosinophilic Gastrointestinal disease Researchers (CEGIR) and The International Gastrointestinal Eosinophil Researchers (TIGERs) organized a daylong symposium at the 2024 annual meeting of the American Academy of Allergy, Asthma & Immunology. The symposium featured new discoveries in basic and translational research as well as debates on the mechanisms and management of eosinophilic gastrointestinal diseases. Updates on recent clinical trials and consensus guidelines were also presented. We summarize the updates on eosinophilic gastrointestinal diseases presented at the symposium., Competing Interests: Disclosure statement Supported by U54AI117804 (Consortium of Eosinophilic Gastrointestinal Disease Researchers), which is part of the Rare Disease Clinical Research Network (RDCRN), an initiative of the Office of Rare Disease Research (ORDR), National Center for Advancing Translational Sciences (NCATS), and is funded through collaboration between National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH)/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NCATS, and in part by the Division of Intramural Research, NIAID/NIH. CEGIR is also supported by patient advocacy groups including American Partnership for Eosinophilic Disorders (APFED), Campaign Urging Research for Eosinophilic Diseases (CURED), and Eosinophilic Family Coalition (EFC). As a member of the RDCRN, CEGIR is also supported by its Data Management and Coordinating Center (DMCC) (U2CTR002818). Funding support for the DMCC is provided by the NCATS and the National Institute of Neurological Disorders and Stroke (NINDS). B.L.W. was funded by NIH/NIAID (K23AI158813). E.M.A. was funded by the NIH (KL2TR002552, K12TR004410). S.S.A. was funded by NIH/NIDDK (R56AI092135). S.J.A. was funded by NIH/National Heart, Lung, and Blood Institute (NHLBI) (R01HL153170). D.A.H. was directly supported by the Hartwell Foundation, the Food Allergy Fund, and a faculty development award from the American Academy of Allergy, Asthma & Immunology. Allergy research in the Hill laboratory was supported by NIH/NHLBI (R01HL162715) and the Children’s Hospital of Philadelphia Research Institute. J.W.C. was supported by the NIH (K23DK129784). F.L.K. was funded by APFED HOPE Pilot Grant 2023 and NIH/NIAID K23AI171085. M.A.R. was funded by the NIH (K08AI148456). L.A.S. was supported by NIH/NIAID (R01AI168134). The contents are those of the authors and do not necessarily represent the official views or an endorsement by the NIH or other funders. None of the funding sources had a role in the design or conduct of the study. Disclosure of potential conflict of interest: B. L. Wright reports in-kind support from Regeneron in the form of study drug (dupilumab and placebo) for a clinical trial of milk oral immunotherapy. J. P. Abonia reports receipt of payment or honoraria for lectures from Takeda Global Research and Development; participation on a data safety monitoring board for OctaPharma USA; and receipt of grants or contracts from Cures Within Reach and Celgene. E. M. Abud is coinventor of patent WO/2018/160496 (microglia differentiation and use); serves as advisory board member and consulting agreements with StemPharm and Neucyte; and reports advisory board participation for Amgen and AstraZeneca. S. S. Aceves is coinventor of oral viscous budesonide, patented by the University of California, San Diego, and licensed by Takeda (oral budesonide suspension); has acted as speaker for Regeneron/Sanofi; and has received research funding from Bristol Myers Squibb. S. J. Ackerman is chief science officer and executive board member of EnteroTrack; has received patents on the Esophageal String Test (EST); has consulted for Areteia Pharmaceuticals; and has participated on the medical advisory panel of the American Partnership for Eosinophilic Disorders (APFED). M. Braskett reports acting as scientific advisor to Bryn Pharma; and receipt of royalties from UpToDate. J. W. Chang reports consulting for Regeneron/Sanofi, Takeda, and Bristol Myers Squibb. M. Chehade reports consulting for Regeneron/Sanofi, Adare/Ellodi, AstraZeneca, Bristol Myers Squibb, Allakos, Shire/Takeda, Phathom, and Recludix Pharma; and receipt of research funding from Regeneron, Allakos, AstraZeneca, Adare/Ellodi, Bristol Myers Squibb, Danone, and Shire/Takeda. G. M. Constantine reports speaker honoraria from PeerView CME. C. M. Davis reports research funding from NIH/NIAID, DBV, Regeneron, AstraZeneca, Takeda, and Allergenis; and educational funding from Genentech. E. S. Dellon reports research funding from Adare/Ellodi, Allakos, Arena/Pfizer, AstraZeneca, Eupraxia, Ferring, GSK, Meritage, Miraca, Nutricia, Celgene/Receptos/BMS, Regeneron, Revolo, and Shire/Takeda; consulting for Abbott, AbbVie, Adare/Ellodi, Aimmune, Akesobio, Alfasigma, ALK, Allakos, Amgen, Apollo, Aqilion, Arena/Pfizer, Aslan, AstraZeneca, Avir, Biorasi, Bryn, Calypso, Celgene/Receptos/BMS, Celldex, Eli Lilly, EsoCap, Eupraxia, Dr Falk Pharma, Ferring, GSK, Gossamer Bio, Holoclara, Invea, Knightpoint, Landos, LucidDx, Morphic, Nexstone Immunology/Uniquity, Nutricia, Parexel/Calyx, Phathom, Regeneron, Revolo, Robarts/Alimentiv, Salix, Sanofi, Shire/Takeda, Target RWE, and Upstream Bio; and receipt of educational grants from Allakos, Aqilion, Holoclara, and Invea. R. Durban reports consulting for Sanofi, AstraZeneca, Reckitt/Mead Johnson Nutrition, Abbott Nutrition, and Nutricia North America. D. A. Hill has received a patent related to the utilization of food-specific T-cell responses for the diagnosis and management of EoE. E. T. Jensen reports consulting fees from Regeneron, Jazz Pharmaceuticals, and TARGET-RWE. A. Kewalramani reports sitting on the Sanofi Mid-Atlantic Regional Respiratory Field medical advisory board. P. Khoury and A. D. Klion report royalties from UpToDate. F. L. Kuang reports research funding from AstraZeneca. E. C. McGowan reports funding from NIH/NIAID and American College of Gastroenterology; and consulting for Regeneron/Sanofi and Takeda. J. M. Spergel reports grant support from the NIH, Regeneron/Sanofi, and Novartis; and has consulted for Regeneron/Sanofi, Allakos, Readysetfood, Novartis, and Bristol Myers Squibb. A. M. Uchida reports consulting for Regeneron/Sanofi, Takeda, and AstraZeneca. J. B. Wechslerc reports consulting for Allakos, Ellodi, Regeneron/Sanofi/Genzyme, Bristol Myers Squibb, Invea Therapeutics, CellDex, and AstraZeneca; and clinical trial/research funding from Allakos and Regeneron/Sanofi. R. D. Pesek reports consulting for Regeneron. The rest of the authors declare that they have no relevant conflicts of interest., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Background: A major challenge in epidemiology is knowing when an exposure effect is large enough to be clinically important, in particular how to interpret a difference in mean outcome in unexposed/exposed groups. Where it can be calculated, the proportion/percentage beyond a suitable cut-point is useful in defining individuals at high risk to give a more meaningful outcome. In this simulation study we compute differences in outcome means and proportions that arise from hypothetical small effects in vulnerable sub-populations., Methods: Data from over 28,000 mother/child pairs belonging to the Environmental influences on Child Health Outcomes Program were used to examine the impact of hypothetical environmental exposures on mean birthweight, and low birthweight (LBW) (birthweight < 2500g). We computed mean birthweight in unexposed/exposed groups by sociodemographic categories (maternal education, health insurance, race, ethnicity) using a range of hypothetical exposure effect sizes. We compared the difference in mean birthweight and the percentage LBW, calculated using a distributional approach., Results: When the hypothetical mean exposure effect was fixed (at 50, 125, 167 or 250g), the absolute difference in % LBW (risk difference) was not constant but varied by socioeconomic categories. The risk differences were greater in sub-populations with the highest baseline percentages LBW: ranging from 3.1-5.3 percentage points for exposure effect of 125g. Similar patterns were seen for other mean exposure sizes simulated., Conclusions: Vulnerable sub-populations with greater baseline percentages at high risk fare worse when exposed to a small insult compared to the general population. This illustrates another facet of health disparity in vulnerable individuals., (© 2024. The Author(s).)

Background: The aim of this study was to evaluate associations between pre-pregnancy maternal obesity and adolescent blood pressures (BPs) among children born extremely preterm., Methods: This longitudinal observational cohort study included participants in the multicenter Extremely Low Gestational Age Newborn (ELGAN) study, born before 28 weeks of gestation, recruited at birth between 2002 and 2004, and followed prospectively through late adolescence. Between 2015 and 2022, three oscillometric BPs were obtained from participants (mean age 17.8 years). We used linear regression modeling to evaluate the association between maternal self-reported pre-pregnancy body mass index (BMI) and offspring adolescent systolic BP (SBP). In secondary analyses, we evaluated the association between maternal pre-pregnancy and offspring preadolescent (10-year-old) BMI and between offspring preadolescent BMI and adolescent SBP., Results: The 100 (24%) participants born to a mother with a history of pre-pregnancy obesity (BMI ≥ 30) had a greater mean SBP of 120.5 (± 14.3) mmHg compared to the 324 (76%) of adolescents born to mothers without pre-pregnancy obesity (SBP 115.6 (± 12.0) mmHg). Pre-pregnancy obesity was associated with higher offspring BMI (aβ 10.8, 95% CI 2.3, 19.2), and higher offspring BMI was associated with higher adolescent SBP (aβ 0.12, 95% CI 0.09,0.16)., Conclusions: For ELGANs, higher maternal pre-pregnancy BMI was associated with higher adolescent SBP. Findings from secondary analyses suggest potential mediation through preadolescent BMI. Future research directions include multi-level interventions to reduce maternal pre-pregnancy obesity, followed by offspring obesity prevention interventions as a way of reducing intergenerational cardiovascular disease in high-risk infants born extremely preterm., (© 2024. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Objective: To evaluate associations between change in weight z score after neonatal intensive care unit (NICU) discharge and neurodevelopmental outcomes and obesity at 12-48 months of age among individuals born very preterm., Study Design: This secondary analysis used data from infants born very preterm participating in the Environmental influences on Child Health Outcomes cohort (n = 1400). Growth during infancy was calculated as change in weight z score between NICU discharge and follow-up at a mean of 27 months of age. Very low weight gain was defined as a change in weight z score <-1.67; very high weight gain was a change in weight z score >1.67. Neurodevelopmental outcomes included the Bayley Scales of Infant and Toddler Development, Child Behavior Checklist 1.5-5 years, and Modified Checklist for Autism in Toddlers. Multivariable linear regression was used to estimate associations between increase in weight z score and neurodevelopmental outcomes., Results: Very low weight gain between NICU discharge and follow-up (experienced by 6.4% of participants) was associated with lower scores on cognitive (adjusted mean difference: -4.26; 95% CI: -8.55, -0.04) and language (adjusted mean difference: -4.80; 95% CI: -9.70, -0.11) assessments. Very high weight gain (experienced by 13.6% of participants) was associated with an increased obesity risk (adjusted relative risk: 6.20; 95% CI: 3.99, 9.66) but not with neurodevelopmental outcomes., Conclusions: Very high weight gain in the first 12-48 months after NICU discharge was associated with a higher risk of obesity at follow-up; very low weight gain was associated with lower scores on cognitive and language assessments., Competing Interests: Declaration of Competing Interest Research reported in this publication was supported by the Environmental influences on Child Health Outcomes (ECHO) Program, Office of the Director, National Institutes of Health, under Award Numbers U2COD023375 (B. Smith, PI), U24OD023382 (Data Analysis Center), U24OD023319 (R. Gershon, PI) with co-funding from the Office of Behavioral and Social Science Research, UH3OD023348 (T M. O'Shea, PI; R.C. Fry, PI), 2UG1HD027904 (J. Maron, PI), UH3OD023320 (JL Aschner, PI), UH3OD023347 (BM Lester, PI), UG3OD035513 (A. Stroustrup, PI). The authors declare no conflicts of interest. The sponsor, National Institutes of Health (NIH), participated in the overall design and implementation of the ECHO Program, which was funded as a cooperative agreement between NIH and grant awardees. The sponsor approved the Steering Committee-developed ECHO protocol and its amendments including COVID-19 measures. The sponsor had no access to the central database, which was housed at the ECHO Data Analysis Center. Data management and site monitoring were performed by the ECHO Data Analysis Center and Coordinating Center. All analyses for scientific publication were performed by the study statistician, independently of the sponsor. The lead author wrote all drafts of the manuscript and made revisions based on co-authors and the ECHO Publication Committee (a subcommittee of the ECHO Operations Committee) feedback without input from the sponsor. The study sponsor did not review nor approve the manuscript for submission to the journal., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Asthma and obesity are frequent outcomes among individuals born extremely preterm and are associated with decreased lifespan. Neonatal inflammation is associated with chronic neurodevelopmental disorders; however, it is less studied in association with other later childhood chronic disorders in this population., Methods: Fourteen hospitals in 5 U.S. states enrolled 1506 infants born before 28 weeks of gestation in the Extremely Low Gestational Age Newborn cohort in 2004-2014. Neonatal blood spots were collected on postnatal days 1, 7, 14, 21, and 28, and used to measure 14 inflammation-related proteins. Associations were evaluated between high (top quartile) levels of proteins and two chronic health disorders at ages 10 and 15 years: physician-diagnosed asthma and obesity (body mass index ≥95th percentile)., Results: Few associations were found between high levels of 14 inflammation-related proteins, either on a single day or on multiple days, and either asthma or obesity. Similarly, few associations were found in analyses stratified by sex or presence/absence of prenatal inflammation., Conclusions: In extremely preterm newborns, systemic elevations of inflammation-related proteins during the neonatal period were not associated with childhood asthma and obesity outcomes at 10 or 15 years of age., Impact: In the large multi-center Extremely Low Gestational Age Newborn (ELGAN) cohort, sustained elevation of neonatal levels of inflammation-related proteins was not consistently associated with asthma or obesity outcomes at 10 or 15 years of age. This finding contrasts with reported associations of perinatal inflammation with obesity at 2 years and neurodevelopmental disorders at 2-15 years in the ELGANs, suggesting that unlike neurodevelopment, peripubertal obesity and asthma may be driven by later childhood exposures. Future research on perinatal mechanisms of childhood asthma and obesity should account for both fetal and later exposures and pathways in addition to inflammation at birth., (© 2024. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Despite increasing prevalence of hypertension in youth and high adult cardiovascular mortality rates, the long-term consequences of youth-onset hypertension remain unknown. This is due to limitations of prior research such as small sample sizes, reliance on manual record review, and limited analytic methods that did not address major biases. The Study of the Epidemiology of Pediatric Hypertension (SUPERHERO) is a multisite retrospective Registry of youth evaluated by subspecialists for hypertension disorders. Sites obtain harmonized electronic health record data using standardized biomedical informatics scripts validated with randomized manual record review. Inclusion criteria are index visit for International Classification of Diseases Diagnostic Codes, 10th Revision (ICD-10 code)-defined hypertension disorder ≥January 1, 2015 and age <19 years. We exclude patients with ICD-10 code-defined pregnancy, kidney failure on dialysis, or kidney transplantation. Data include demographics, anthropomorphics, U.S. Census Bureau tract, histories, blood pressure, ICD-10 codes, medications, laboratory and imaging results, and ambulatory blood pressure. SUPERHERO leverages expertise in epidemiology, statistics, clinical care, and biomedical informatics to create the largest and most diverse registry of youth with newly diagnosed hypertension disorders. SUPERHERO's goals are to (i) reduce CVD burden across the life course and (ii) establish gold-standard biomedical informatics methods for youth with hypertension disorders., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

Background: Early-life programming due to prematurity and very low birth weight (VLBW, <1500 g) is believed to contribute to development of hypertension, but the mechanisms remain unclear. Experimental data suggest that altered pressure natriuresis (increased renal perfusion pressure promoting sodium excretion) may be a contributing mechanism. We hypothesize that young adults born preterm will have a blunted pressure natriuresis response to mental stress compared with those born term., Methods: In this prospective cohort study of 190 individuals aged 18-23 years, 156 born preterm with VLBW and 34 controls born term with birth weight at least 2500 g, we measured urine sodium/creatinine before and after a mental stress test and continuous blood pressure before and during the stress test. Participants were stratified into groups by the trajectory at which mean arterial pressure (MAP) increased following the test. The group with the lowest MAP trajectory was the reference group. We used generalized linear models to assess poststress urine sodium/creatinine relative to the change in MAP trajectory and assessed the difference between groups by preterm birth status., Results: Participants' mean age was 19.8 years and 57% were women. Change in urine sodium/creatinine per unit increase in MAP when comparing middle trajectory group against the reference group was greater in those born preterm [β 5.4%, 95% confidence interval (95% CI) -11.4 to 5.3] than those born term (β 38.5%, 95% CI -0.04 to 92.0), interaction term P = 0.002., Conclusion: We observed that, as blood pressure increased following mental stress, young adults born preterm exhibited decreased sodium excretion relative to term-born individuals., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To evaluate the association between prenatal maternal health and socioeconomic status (SES) and health-related quality of life (QoL) among 10-year-old children born extremely preterm., Design/ Methods: Retrospective analysis of the Extremely Low Gestational Age Newborns (ELGAN) Study cohort of infants born < 28 weeks gestational age. QoL was assessed at 10 years of age using the Pediatric Quality of Life Inventory. Multivariate regression models were used for analyses., Results: Of 1198 participants who survived until 10 years of age, 889 (72.2%) were evaluated. Lower maternal age, lack of college education; receipt of public insurance and Supplemental Nutrition Assistance Program (SNAP) were associated with lower QoL scores. Specific maternal health factors were also associated with lower child QoL scores., Conclusions: Specific, potentially modifiable, maternal health and social factors are associated with lower scores on a measure of parent-reported child QoL across multiple domains for children born extremely preterm., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Aims: To examine, among youth and young adults (YYA) with type 1 diabetes (T1D), the association of household food insecurity (HFI) with: 1) HbA 1c and 2) episodes of diabetic ketoacidosis (DKA) and severe hypoglycemia., Methods: HFI was assessed using the U.S. Household Food Security Survey Module in SEARCH for Diabetes in Youth participants with T1D between 2016 and 2019. Linear and logistic regression models adjusted for age, diabetes duration, sex, race, ethnicity, clinic site, parent/participant education, household income, health insurance, and diabetes technology use., Results: Of 1830 participants (mean age 20.8 ± 5.0 years, 70.0 % non-Hispanic White), HbA 1c was collected for 1060 individuals (mean HbA1c 9.2 % ± 2.0 %). The prevalence of HFI was 16.4 %. In the past 12 months, 18.2 % and 9.9 % reported an episode of DKA or severe hypoglycemia, respectively. Compared to participants who were food secure, HFI was associated with a 0.33 % (95 % CI 0.003, 0.657) higher HbA 1c level. Those with HFI had 1.58 (95 % CI 1.13, 2.21) times the adjusted odds of an episode of DKA and 1.53 (95 % CI 0.99, 2.37) times the adjusted odds of an episode of severe hypoglycemia as those without HFI., Conclusions: HFI is associated with higher HbA 1c levels and increased odds of DKA in YYA with T1D., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Despite the rising prevalence and incidence of eosinophilic esophagitis (EoE), the etiology and pathophysiology remain unknown. Studies to date suggest that complex interactions between genetic and environmental risk factors result in the development and presentation of disease. Examining environmental factors both in the early life and later life exposures offers potential clues for the development of EoE, although challenges exist in making causal inferences due to diagnostic delay and access, ascertainment biases, and misclassification of cases. The authors review studies supporting early life factors as etiologic factors in the development of EoE., Competing Interests: Disclosure Study concept and design: J.W. Chang and E.T. Jensen. Drafting of the article: J.W. Chang and E.T. Jensen. Critical revision of the article: J.W. Chang and E.T. Jensen. This work was supported by funding in part by NIH, United States awards K23DK129784 (J.W. Chang), R01AI139126 (E.T. Jensen), and R01ES031940 (E.T. Jensen)., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Study of the near-UV photodissociation dynamics for monolayer (ML) quantities of CH 3 I on thin films of a series of fluorobenzenes and benzene (1-25 ML) grown on a Cu(100) substrate finds that in addition to gas-phase-like neutral photodissociation, CH 3 I dissociation can be enhanced via electronic energy transfer to the CH 3 I following photoabsorption in several of the thin films studied. Distinct CH 3 photofragment kinetic energy distributions are found for CH 3 I photodissociation on C 6 H 5 F, 1,4-C 6 H 4 F 2 and C 6 H 6 thin films, and distinguished from neutral photodissociation pathways using polarized incident light. The effective photodissociation cross section for CH 3 I on these thin films is increased as compared to that for the higher F-count fluorobenzene thin films due to the additional photodissociation pathway available. Quenching by the metal substrate of the photoexcitation via this new pathway suggests a significantly longer timescale for excitation than that of neutral CH 3 I photodissociation. The observations support a mechanism in which neutral photoexcitation in the thin film ( i.e. an exciton) is transported to the interface with CH 3 I, and transfers the electronic excitation to the CH 3 I which then dissociates. The unimodal CH 3 photofragment distribution and observed kinetic energies on the fluorobenzene thin films suggest that the dissociation occurs via the 3 Q 1 excited state of CH 3 I.

Background: The demographic characteristics of patients with eosinophilic gastrointestinal diseases (EGIDs) are poorly understood. Population-based assessments of EGID demographics may indicate health disparities in diagnosis., Objectives: We aimed to characterize the demographic distribution of EGIDs and evaluate the potential for bias in reporting patient characteristics., Methods: We conducted a systematic review, extracting data on age, sex, gender, race, ethnicity, body mass index, insurance, and urban/rural residence on EGID patients and the source population. Differences in proportions were assessed by chi-square tests. Demographic reporting was compared to recent guidelines., Results: Among 50 studies that met inclusion/exclusion criteria, 12 reported ≥1 demographic feature in both EGID and source populations. Except for age and sex or gender, demographics were rarely described (race = 4, ethnicity = 1, insurance = 1) or were not described (body mass index, urban/rural residence). A higher proportion of male subjects was observed for EoE or esophageal eosinophilia relative to the source population, but no difference in gender or sex distribution was observed for other EGIDs. "Sex" and "gender" were used interchangeably, and frequently only the male proportion was reported. Reporting of race and ethnicity was inconsistent with guidelines., Conclusion: Current data support a male predominance for EoE only. Evidence was insufficient to support enrichment of EGIDs in any particular racial, ethnic, or other demographic group. Population-based studies presenting demographics on both cases and source populations are needed. Implementation of guidelines for more inclusive reporting of demographic characteristics is crucial to prevent disparities in timely diagnosis and management of patients with EGIDs., Competing Interests: Supported by U54AI117804 (Consortium of Eosinophilic Gastrointestinal Disease Researchers), which is part of the Rare Disease Clinical Research Network, an initiative of the Office of Rare Disease Research, National Center for Advancing Translational Sciences (NCATS), and is funded through collaboration between the National Institute of Allergy and Infectious Diseases (NIAID), the National Institute of Diabetes and Digestive and Kidney Diseases, NCATS, and patient advocacy groups including the American Partnership for Eosinophilic Disorders, Campaign Urging Research for Eosinophilic Disease (CURED), and Eosinophilic Family Coalition (EFC). This work was also funded in part by the Division of Intramural Research, NIAID, National Institutes of Health. Disclosure of potential conflict of interest: M. Chehade served as consultant for Regeneron, Allakos, Adare/Ellodi, Shire/Takeda, AstraZeneca, Sanofi, Bristol Myers Squibb, Phathom, Recludix Pharma, and Nexstone Immunology; and received research funding from Regeneron, Allakos, Shire/Takeda, AstraZeneca, Adare/Ellodi, Danone, and Bristol Myers Squibb. A. B. Muir has served on medical advisory board for Bristol Myers Squibb and Nexstone Immunology; and has received research funding from Morphic. M. H. Collins has received research funding from AstraZeneca, Ception, GSK, Meritage Pharma Inc, Receptos/Celgene/BMS, Regeneron Pharmaceuticals and Shire, a Takeda company; and is consultant for Allakos, Arena Pharmaceuticals, AstraZeneca, Calypso Biotech, EsoCap Biotech, GlaxoSmithKline, Receptos/Celgene/BMS, Regeneron Pharmaceuticals, Robarts Clinical Trials Inc/Alimentiv Inc and Shire, a Takeda company. C. M. Davis has received research funding from the National Institutes of Health/National Institute of Allergy and Infectious Disease (Consortium of Food Allergy Research/Consortium of Eosinophilic Gastrointestinal Researchers), DBV Technologies, DBV, Aimmune Therapeutics, Regeneron Pharmaceuticals, and Allergenis. G. T. Furuta is chief medical officer at EnteroTrack; consultant for Shire/Takeda; and has received grant funding from Arena and Holoclara. S. Gupta is consultant/data safety and monitoring board member or author for Adare, BMS, QOL, Takeda, MedScape, PVI, ViaSkin, and UpToDate; and has received research support from Allakos, Ellodi, and AstraZeneca. P. Khoury has received research funding from American Partnership for Eosinophilic Disorders. K. A. Peterson is consultant or served as advisor for AGA, Alladapt, AstraZeneca, Allakos, Bristol Meyers Squibb, Ellodi, Lucid, Nexstone, Peerview, Regeneron, Takeda, and WebMD; has received research support from AstraZeneca, Allakos, Adare, Regeneron-Sanofi, and Revolo; served as speaker for AGA, Regeneron, Peerview, Takeda, Allakos, and WebMD; received grant support (unrestricted) from Allakos and Chobani; and holds equity in Nexeos Bio. E. T. Jensen has received consultant fees from Regeneron, Jazz Pharmaceuticals, and TARGET-RWE. The rest of the authors declare that they have no relevant conflicts of interest., (© 2024 The Author(s).)

Background: Vitamin D deficiency is associated with atopic and immune-mediated diseases but has not been extensively assessed in eosinophilic esophagitis (EoE). We aimed to assess if vitamin D levels in newly diagnosed EoE patients were lower than in non-EoE controls and examine levels in relation to EoE clinical features., Methods: This secondary analysis of a prospective cohort study used data and biosamples from adults who underwent outpatient esophagogastroduodenoscopy. Before each procedure, blood was obtained and stored at -80 o C. Serum 25-hydroxy-vitamin D 3 (25(OH)D 3 ) was measured by ELISA. Levels for cases and controls were compared at baseline. Within cases, 25(OH)D 3 levels were compared for clinical, endoscopic, and histologic measures., Results: We analyzed 40 EoE and 40 non-EoE controls. Mean serum 25(OH)D 3 level was slightly lower in EoE patients than controls (30.9 ± 15.3 ng/mL vs. 35.9 ± 15.4; p = 0.15). After controlling for age, sex, and race, adjusted levels were 10.8 ng/mL lower in EoE patients (95% CI: -19.0, -2.5), but 25(OH)D 3 deficiency (< 20ng/mL) was similar in cases and controls (20% vs. 15%; p = 0.56). Levels of 25(OH)D 3 were not associated with differences in clinical or endoscopic features of EoE, and EREFS and eosinophil counts did not significantly correlate with 25(OH)D 3 levels (R of -0.28 [p = 0.08] and - 0.01 [p = 0.93], respectively). 25(OH)D 3 levels were lower in EoE cases with lamina propria fibrosis (23.2 ± 9.6 vs. 45.0 ± 17.7; p = 0.03)., Conclusions: After adjusting for age, sex, and race, 25(OH)D 3 levels were lower in EoE cases than controls, but deficiency was not common. 25(OH)D 3 levels were generally similar across most EoE disease features., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Reducing healthcare disparities among children is extremely important given the potential impact of these disparities on long-term health-related quality of life (HRQL). Race and parental socioeconomic status (SES) are associated with child HRQL, but these associations have not been studied in infants born extremely preterm (EP), a population at increased risk for physical, cognitive, and psychosocial impairments. Achieving health equity for infants born EP across their life course requires identifying the impact of racism and SES on HRQL., Objective: We aimed to evaluate the association between self-reported maternal race, SES factors, and HRQL among 10-year-old children born EP., Design/methods: Participants were identified from an ongoing multicenter prospective longitudinal study of Extremely Low Gestational Age Newborns (ELGAN Study), born between 2002 and 2004, and evaluated at 10 years of age using the Pediatric quality of life (QoL) Inventory completed by their parent or guardian, assessing physical, emotional, social, school, and total (composite) QoL domains. Multivariable regression models were used to evaluate the relationship between QoL scores and self-identified maternal race, adjusting for SES factors (education level, marital status, and public insurance)., Results: Of 1,198 study participants who were alive at 10 years of age, 863 (72.0%) were evaluated at 10 years of age. Differences in mean 10-year QoL scores across racial groups were observed and were significant on univariate analysis. However, these associations attenuated when adjusted for the marital status, public insurance status, and education status of mothers. A comparison of children with English as the primary language spoken at home vs. any other language revealed a significant difference only in school QoL, in which non-English language was associated with more favorable school QoL scores., Conclusions: Among 10-year-old children born EP, differences in parent-reported QoL were associated with maternal SES factors but not with race. Our results suggest that interventions designed to improve the SES of mothers may enhance the QoL of children born EP. Furthermore, these results underscore that race is a social construct, rather than a biological variable, as we work toward greater equity in care provision., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Call, Oran, O'Shea, Jensen, Frazier, Vaidya, Shenberger, Gogcu, Msall, Kim, Jalnapurkar, Fry and Singh.)

Introduction: Emerging evidence suggests a high burden of psychosocial comorbidities in patients with eosinophilic esophagitis (EoE), although factors associated with this burden have not been explored. We aimed to increase understanding of the psychosocial burden of EoE and assess factors that are associated with disease burden., Methods: We conducted a cross-sectional study of patients with EoE (n = 87) recruited from a single-center, multidisciplinary pediatric eosinophilic gastrointestinal disorders clinic (2019-2021). Participants (aged 8-18 years) completed validated assessments during routine clinic visit to assess EoE symptoms (Pediatric Eosinophilic Esophagitis Symptom Score version 2.0), quality of life (Pediatric Quality of LIfe- Eosinophilic Esophagitis), anxiety state and trait (State-Trait Anxiety Score for Children), somatization (Child Somatic Symptoms Inventory 24), sleep disordered breathing (Pediatric Sleep Questionnaire) and, in a subset (n = 35), resilience (Connor Davidson Resilience Scale). Clinical and demographic data were collected., Results: Participants were at a mean (SD) age of 12.8 (3.1) years, and 26% (n = 23) were female. Shorter disease duration (6-12 months) was associated with higher symptom burden ( P = 0.03), somatization ( P < 0.01), and anxiety (State-Trait Anxiety Score for Children Trait P < 0.01) scores. Participants with neurodevelopmental comorbidities had higher anxiety trait, somatization, sleep disordered breathing, and lower quality of life ( P < 0.01 for all). Symptom burden was significantly associated with increased somatic symptoms (adjusted β [aβ] = 0.34; 95% confidence interval 0.23-0.45) and decreased quality of life (aβ = -0.42; 95% confidence interval -0.59 to -0.25) but not state anxiety, trait anxiety, or disordered sleep breathing., Discussion: Pediatric patients with a recent diagnosis of EoE can experience higher EoE symptoms, somatization, and anxiety when compared with those with a longer-standing diagnosis. Patients earlier in their diagnosis and with neurodevelopmental disorders may experience increased somatization and anxiety that may warrant additional support services., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Short-chain fatty acids (SCFAs) have been extensively studied for potential beneficial roles in glucose homeostasis and risk of diabetes; however, most of this research has focused on butyrate, acetate, and propionate. The effect on metabolism of branched SCFAs (BSCFAs; isobutyrate, isovalerate, and methylbutyrate) is largely unknown. In a cohort of 219 non-Hispanic White participants and 126 African American participants, we examined the association of BSCFA with dysglycemia (prediabetes and diabetes) and oral glucose tolerance test-based measures of glucose and insulin homeostasis, as well as with demographic, anthropometric, lifestyle, and lipid traits, and other SCFAs. We observed a bimodal distribution of BSCFAs, with 25 individuals having high levels (H-BSCFA group) and 320 individuals having lower levels (L-BSCFA group). The prevalence of dysglycemia was lower in the H-BSCFA group compared with the L-BSCFA group (16% vs. 49%; P = 0.0014). This association remained significant after adjustment for age, sex, race, BMI, and levels of other SCFAs. Consistent with the lower rate of dysglycemia, fasting and postprandial glucose levels were lower and the disposition index was higher in the H-BSCFA group. Additional findings in H-BSCFA versus L-BSCFA included lower fasting and postprandial C-peptide levels and lower insulin clearance without differences in insulin levels, insulin sensitivity, insulin secretion, or other variables examined, including diet and physical activity. As one of the first human studies associating higher BSCFA levels with lower odds of dysglycemia and improved glucose homeostasis, this study sets the stage for further investigation of BSCFA as a novel target for prevention or treatment of diabetes., (© 2024 by the American Diabetes Association.)

Background: Typically, child exposure to food insecurity is assessed by caregiver reports of household food security. Child report has the potential for greater accuracy because it pertains only to the child whose experiences may differ from caregiver reports., Objective: We assessed if adolescent-reported food insecurity was associated with levels of hemoglobin A 1c (HbA 1c ), acute diabetes-related complications, depressive symptoms, and disordered eating behaviors in adolescents with type 1 diabetes, independently from household food security., Methods: In a cross-sectional analysis of the multicenter SEARCH for Diabetes in Youth Cohort Study (phase 4, 2016-2019) including 601 adolescents aged 10-17 y with type 1 diabetes and their caregivers, household food security, and adolescent-reported food security were assessed using the 18-item Household Food Security Survey Module and the 6-item Child Food Security Assessment questionnaire. Age-stratified (10-13 and 14-17) regression models were performed to estimate independent associations, adjusting for sociodemographics, clinical factors, and household food security., Results: Food insecurity was reported by 13.1% (n = 79) of adolescents and 15.6% (n = 94) of caregivers. Among adolescent-caregiver dyads, 82.5% (n = 496) of reports were concordant and 17.5% (n = 105) discordant, Cohen's κ= 0.3. Adolescent-reported food insecurity was not independently associated with HbA 1c , diabetic ketoacidosis, and severe hypoglycemia, including in age-stratified analyses. Adolescent-reported food insecurity was independently associated with elevated odds of depressive symptoms [odds ratio (OR): 3.6; 95% confidence interval (CI): 1.3, 10.3] and disordered eating behaviors (OR: 2.5, 95% CI: 1.4, 4.6) compared with adolescents reporting food security; these associations remained in both age groups for disordered eating behaviors and in the older group for depressive symptoms., Conclusions: Adolescents with type 1 diabetes may experience food insecurity differently than caregivers. Adolescent-reported food insecurity was independently associated with depressive symptoms and disordered eating behaviors and thus may be an important attribute to assess in addition to household food security in adolescents with type 1 diabetes., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Although eosinophilic gastrointestinal diseases, including eosinophilic esophagitis, have been described over the past 2 to 3 decades, barriers to diagnosis and treatment are common and compounded by issues related to social determinants of health, race, ethnicity, and access to care. These barriers contribute to delays in diagnosis, resulting in persistent inflammation in the gastrointestinal tract, which can have significant consequences, including fibrostenotic complications in adults, failure to thrive in children, and decreased quality of life in all affected patients. In this commentary, we summarize gaps in knowledge regarding the epidemiology of eosinophilic gastrointestinal diseases, highlight barriers to diagnosis, discuss potential approaches based on best practices in other atopic and chronic gastrointestinal diseases, and provide recommendations for reducing barriers to timely diagnosis of eosinophilic gastrointestinal diseases in underserved populations., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Objective: To examine the association between diabetes stigma, socioeconomic status, psychosocial variables, and substance use in adolescents and young adults (AYAs) with type 1 or type 2 diabetes., Research Design and Methods: This is a cross-sectional analysis of AYAs from the SEARCH for Diabetes in Youth study who completed a survey on diabetes-related stigma, generating a total diabetes stigma score. Using multivariable modeling, stratified by diabetes type, we examined the relationship of diabetes stigma with variables of interest., Results: Of the 1,608 AYAs who completed the diabetes-related stigma survey, 78% had type 1 diabetes, and the mean age was 21.7 years. Higher diabetes stigma scores were associated with food insecurity (P = 0.001), disordered eating (P < 0.0001), depressive symptoms (P < 0.0001), and decreased health-related (P < 0.0001) and diabetes-specific quality of life (P < 0.0001)., Conclusions: Diabetes stigma is associated with food insecurity, disordered eating, and lower psychosocial well-being., (© 2024 by the American Diabetes Association.)

The prevalence of youth-onset type 2 diabetes (T2D) and childhood obesity has been rising steadily 1 , producing a growing public health concern 1 that disproportionately affects minority groups 2 . The genetic basis of youth-onset T2D and its relationship to other forms of diabetes are unclear 3 . Here we report a detailed genetic characterization of youth-onset T2D by analysing exome sequences and common variant associations for 3,005 individuals with youth-onset T2D and 9,777 adult control participants matched for ancestry, including both males and females. We identify monogenic diabetes variants in 2.4% of individuals and three exome-wide significant (P < 2.6 × 10 -6 ) gene-level associations (HNF1A, MC4R, ATXN2L). Furthermore, we report rare variant association enrichments within 25 gene sets related to obesity, monogenic diabetes and β-cell function. Many youth-onset T2D associations are shared with adult-onset T2D, but genetic risk factors of all frequencies-and rare variants in particular-are enriched within youth-onset T2D cases (5.0-fold increase in the rare variant and 3.4-fold increase in common variant genetic liability relative to adult-onset cases). The clinical presentation of participants with youth-onset T2D is influenced in part by the frequency of genetic risk factors within each individual. These findings portray youth-onset T2D as a heterogeneous disease situated on a spectrum between monogenic diabetes and adult-onset T2D., (© 2024. The Author(s).)

Context: Uric acid's role in cardiovascular health in youth with type 1 diabetes is unknown., Objective: Investigate whether higher uric acid is associated with increased blood pressure (BP) and arterial stiffness over time in adolescents and young adults with type 1 diabetes and if overweight/obesity modifies this relationship., Methods: Longitudinal analysis of data from adolescents and young adults with type 1 diabetes from 2 visits (mean follow up 4.6 years) in the SEARCH for Diabetes in Youth multicenter prospective cohort study from 2007 to 2018. Our exposure was uric acid at the first visit and our outcome measures were the change in BP, pulse wave velocity (PWV), and augmentation index between visits. We used multivariable linear mixed-effects models and assessed for effect modification by overweight/obesity., Results: Of 1744 participants, mean age was 17.6 years, 49.4% were female, 75.9% non-Hispanic White, and 45.4% had a follow-up visit. Mean uric acid was 3.7 mg/dL (SD 1.0). Uric acid was not associated with increased BP, PWV-trunk, or augmentation index over time. Uric acid was marginally associated with PWV-upper extremity (β = .02 m/s/year, 95% CI 0.002 to 0.04). The magnitude of this association did not differ by overweight/obesity status., Conclusion: Among adolescents and young adults with type 1 diabetes, uric acid was not consistently associated with increased BP or arterial stiffness over time. These results support findings from clinical trials in older adults with diabetes showing that lowering uric acid levels does not improve cardiovascular outcomes., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To determine whether greater duration of simultaneous exposure to antimicrobials with high nephrotoxicity risk combined with lower-risk antimicrobials (simultaneous exposure) in the neonatal intensive care unit (NICU) is associated with worse later kidney health in adolescents born preterm with very low birth weight (VLBW)., Study Design: Prospective cohort study of participants born preterm with VLBW (<1500 g) as singletons between January 1, 1992, and June 30, 1996. We defined simultaneous exposure as a high-risk antimicrobial, such as vancomycin, administered with a lower-risk antimicrobial on the same date in the NICU. Outcomes were serum creatinine, estimated glomerular filtration rate (eGFR), and first-morning urine albumin-creatinine ratio (ACR) at age 14 years. We fit multivariable linear regression models with days of simultaneous exposure and days of nonsimultaneous exposure as main effects, adjusting for gestational age, birth weight, and birth weight z-score., Results: Of the 147 out of 177 participants who had exposure data, 97% received simultaneous antimicrobials for mean duration 7.2 days (SD 5.6). No participant had eGFR <90 ml/min/1.73 m 2 . The mean ACR was 15.2 mg/g (SD 38.7) and 7% had albuminuria (ACR >30 mg/g). Each day of simultaneous exposure was associated only with a 1.04-mg/g higher ACR (95% CI 1.01 to 1.06)., Conclusions: Despite frequent simultaneous exposure to high-risk combined with lower-risk nephrotoxic antimicrobials in the NICU, there were no clinically relevant associations with worse kidney health identified in adolescence. Although future studies are needed, these findings may provide reassurance in a population thought to be at increased risk of chronic kidney disease., Competing Interests: Declaration of Competing Interest This research was supported by the National Institutes of Health (Eunice Kennedy Shriver National Institute of Child Health and Human Development P01-HD047584 and P01-HD084227, National Heart, Lung, and Blood Institute R01-HL146818, National Center for Research Resources M01-RR07122, and National Center for Advancing Translational Sciences UL1-TR001420); the American Heart Association (14GRNT20480131 and 18TPA34170522); and Forsyth Medical Center and Wake Forest University School of Medicine Department of Pediatrics research funds. Dr. South additionally reports funding from the National Institutes of HealthNational Heart, Lung, and Blood Institute K23-HL148394, L40-HL148910, and R56-HL164434. The authors report no conflicts of interest relevant to this study., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The Consortium of Eosinophilic Gastrointestinal Diseases and The International Gastrointestinal Eosinophil Researchers organized a day-long symposium at the 2022 Annual Meeting of the American Academy of Allergy, Asthma & Immunology. The symposium featured a review of recent discoveries in the basic biology and pathogenesis of eosinophilic gastrointestinal diseases (EGIDs) in addition to advances in our understanding of the clinical features of EGIDs. Diagnostic and management approaches were reviewed and debated, and clinical trials of emerging therapies were highlighted. Herein, we briefly summarize the breakthrough discoveries in EGIDs., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Importance: Eosinophilic esophagitis (EoE), a chronic disease with significant patient and health care burden, has increased rapidly in incidence across many countries. Elucidating risk factors for disease development is a priority for health care practitioners and patients., Objective: To evaluate the association of maternal and infant use of antibiotics and acid suppressants with the development of EoE., Design, Setting, and Participants: This was a population-based, case-control study of pediatric EoE (1996-2019) in Denmark using pathology, prescription, birth, inpatient, and outpatient health registry data and with complete ascertainment of all EoE cases among Danish residents born between 1997 and 2018. Study data were analyzed from September 2020 to August 2023., Exposures: Maternal and infant use of antibiotics and acid suppressants, examining medication class, timing, and frequency of use., Main Outcome and Measure: Development of EoE., Results: Included in the study was a total of 392 cases and 3637 sex- and year of birth-matched controls with a median (IQR) age of 11.0 (6.0-15.0) years, 2772 male individuals (68.8%), and 1257 female individuals (31.2%). Compared with children with no antibiotic prescriptions filled during infancy, those with any use of an antibiotic had an associated 40% increase in risk of EoE (adjusted odds ratio [aOR], 1.4; 95% CI, 1.1-1.7). Those with 3 or more prescriptions had an associated 80% increase in risk of EoE (aOR, 1.8; 95% CI, 1.3-2.5). Frequency of maternal antibiotic use was associated with an increased risk (1 prescription: aOR, 1.4; 95% CI, 1.0-1.8; 3≤ prescriptions: aOR, 2.1; 95% CI, 1.4-3.2). Risk was highest for use in the third trimester and in the first 6 months from birth. Any acid suppressant use in infancy was associated with increased risk of EoE (aOR, 15.9; 95% CI, 9.1-27.7). Restriction of cases to those diagnosed at 5 years or older yielded similar results (aOR, 11.6; 95% CI, 5.5-24.8). For maternal use, 3 or more prescriptions were associated with an increased risk of EoE for her offspring (aOR, 5.1; 95% CI, 1.8-14.8)., Conclusions and Relevance: Maternal and infant antibiotic use were associated with increased risk of developing EoE, in a dose-response manner, and the magnitude of association was highest for exposure near the time of delivery. Increased risk was also observed with maternal and infant acid suppressant use. Exposure during early life, a period of known developmental susceptibility, may confer the greatest risk and opportunity for risk mitigation.

We aimed to determine whether residential proximity to permitted swine facilities was associated with an increased risk of eosinophilic esophagitis (EoE) by conducting a case-control study using 2 complementary data sources: 1 from a tertiary care center (n = 401 cases and 1805 controls) and 1 from a large pathology group (n = 904 cases and 4074 controls). Addresses of the subjects and swine facilities were geocoded, and adjusted odds of EoE relative to proximity to and density of swine facilities were calculated. We observed a positive association between proximity to a permitted swine facility (<1 mile) and odds of EoE (adjusted odds ratio R, 2.56; 95% CI, 1.33-4.95) in the tertiary center data; density of farms (>10 farms/census tract) was also positively associated (adjusted odds ratio, 2.76; 95% CI, 1.30-5.84). However, this association was not observed in the pathology database. Though proximity to and density of swine operations were associated with EoE, associations were sensitive to the database used., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Introduction: We previously identified 18 CpG methylation biomarkers associated with treatment response to topical corticosteroids (tCS) in eosinophilic esophagitis (EoE). In this study, in an independent cohort, we assessed the validity of these CpG sites as treatment response biomarkers., Methods: DNA was extracted from prospectively biobanked esophageal biopsies from patients with newly diagnosed EoE enrolled in a randomized trial of 2 tCS formulations. Histologic response was defined as <15 eosinophils per high-power field. Pretreatment DNA methylation was assayed on the Illumina Human MethylationEPIC BeadChip. Logistic regression and area under the receiver operating characteristic curve analyses, adjusting for chip, position on the chip, age, sex, and baseline eosinophil count, were computed to test for an association between DNA methylation and treatment response at the 18 previously identified CpG sites., Results: We analyzed 88 patients (58 histologic responders, 30 nonresponders), with a mean age of 38 ± 16 years, 64% male, 97% White race. Of the 18 CpG sites, 13 met quality control criteria, and 3 were associated with responder status ( P < 0.012), including sites within UNC5B (cg26152017), ITGA6 (cg01044293), and LRRC8A (cg13962589). All 3 showed evidence of reduced methylation in treatment responders, consistent with the original discovery associations. The predictive probability for nonresponse with all 3 CpG sites was strong (area under the receiver operating characteristic curve = 0.79)., Discussion: We validated epigenetic biomarkers (CpG methylation sites) for the prediction of tCS response in patients with EoE in an independent population. While not all previously identified markers replicated, 3 demonstrated a relatively high predictive probability for response to treatment and hold promise for guiding tCS treatment in EoE., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Introduction: Early-life exposures have been associated with an increased risk of eosinophilic esophagitis (EoE); however, most studies to date have been conducted at referral centers and are subject to recall bias. By contrast, we conducted a nationwide, population-based and registry-based case-control study of prenatal, intrapartum, and neonatal exposures, using data collected prospectively through population-based Danish health and administrative registries., Methods: We ascertained all EoE cases in Denmark (birth years 1997-2018). Cases were sex and age matched to controls (1:10) using risk-set sampling. We obtained data on prenatal, intrapartum, and neonatal factors, i.e., pregnancy complications, mode of delivery, gestational age at delivery, birthweight (expressed as a z-score), and neonatal intensive care unit (NICU) admission. We used conditional logistic regression to compute the crude and adjusted odds ratios (aOR) of EoE in relation to each prenatal, intrapartum, and neonatal factor, thus providing an estimate of incidence density ratios with 95% confidence intervals (CI)., Results: In the 393 cases and 3,659 population controls included (median age at index date, 11 years [interquartile range, 6-15]; 69% male), we observed an association between gestational age and EoE, peaking at 33 vs 40 weeks (aOR 3.6 [95% CI 1.8-7.4]), and between NICU admission and EoE (aOR 2.8 [95% CI 1.2-6.6], for a NICU hospitalization of 2-3 weeks vs no admission). In interaction analyses, we observed a stronger association between NICU admission and EoE in infants born at term than in preterm infants (aOR 2.0 [95% CI 1.4-2.9] for term infants and aOR 1.0 [95% CI 0.5-2.0] for preterm infants). We also observed an association between pregnancy complications and EoE (aOR 1.4 [95% CI 1.0-1.9]). Infants who were very growth restricted at birth had an increased rate of EoE (aOR 1.4 [95% CI: 1.0-1.9] for a z-score of -1.5 vs a z-score of 0). Mode of delivery was not associated with EoE., Discussion: Prenatal, intrapartum, and neonatal factors, particularly preterm birth and NICU admission, were associated with development of EoE. Further research is needed to elucidate the mechanisms underlying the observed associations., (Copyright © 2023 by The American College of Gastroenterology.)

In response to the social inequities that exist in health care, the NIH-funded Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR) recently formed a diversity committee to examine systemic racism and implicit bias in the care and research of eosinophilic gastrointestinal diseases (EGIDs). Herein, we describe our process, highlighting milestones and issues addressed since the committee's inception, which we hope will inspire other researchers to enhance diversity, equity, inclusion, and accessibility (DEIA) in their fields. Our journey began by establishing mission and vision statements to define the purpose of the committee. Regular discussion of diversity-related topics was incorporated into existing meetings and web-based materials were shared. This was followed by educational initiatives, including establishing a library of relevant publications and a speaker series to address DEIA topics. We then established a research agenda focused on the following actionable items: (1) to define what is known about the demographics of EGIDs by systematic review of population-based studies; (2) to develop a practical tool for reporting participant demographics to reduce bias in EGID literature; (3) to examine health disparities in the care of individuals with eosinophilic esophagitis who present to the emergency department with an esophageal food impaction; (4) to examine how access to a gastroenterologist affects the conclusions of published research examining the prevalence of pediatric eosinophilic esophagitis; and (5) to develop a model for examining the dimensions of diversity, and provide a framework for CEGIR's ongoing projects and data capture. In addition to promoting consciousness of DEIA, this initiative has fostered inclusivity among CEGIR members and will continue to inspire positive changes in EGID care and research., Competing Interests: MC received consultant fees from Regeneron, Adare/Ellodi, AstraZeneca, Sanofi, Bristol Myers Squibb, Recludix Pharma, Allakos, Shire/Takeda, Phathom, and received research funding from Regeneron, Allakos, Shire/Takeda, AstraZeneca, Adare/Ellodi, Danone. GFuruta serves as CMO for EnteroTrack and received research funding from Arena/Pfizer, Holoclara, and NIH. JPA received payment or honoraria for lectures from Takeda Global Research and Development, participated on a Data Safety Monitoring Board for OctaPharma USA, Inc., and received grants or contracts from Cures Within Reach and Celgene. SA received consultant fees for Regeneron, AstraZeneca, Bristol Meyers Squibb, research funding from Implicit Biosciences, is co-inventor of oral viscous budesonide UCSD patent Takeda license, and received educational speaker fees from Sanofi/Genzyme, Regeneron. MHC received research funding from AstraZeneca, Ception, GlaxoSithKline, Meritage Pharma Inc., Receptos/Celgene/BMS, Regeneron Pharmaceuticals and Shire, a Takeda company, and is a consultant for Allakos, Arena Pharmaceuticals, AstraZeneca, Calypso Biotech, EsoCap Biotech, GlaxoSmithKline, Receptos/Celgene/BMS, Regeneron Pharmaceuticals, Robarts Clinical Trials Inc./Alimentiv, Inc. and Shire, a Takeda company. ESD received research funding from Adare/Ellodi, Allakos, Arena, AstraZeneca, GSK, Meritage, Miraca, Nutricia, Celgene/Receptos/BMS, Regeneron, Revolo, Shire/Takeda, consultant fees from Abbott, Abbvie, Adare/ Ellodi, Aimmune, Akesobio, Alfasigma, ALK, Allakos, Amgen, Aqilion, Arena/Pfizer, Aslan, AstraZeneca, Avir, Biorasi, Calypso, Celgene/Receptos/BMS, Celldex, Eli Lilly, EsoCap, Eupraxia, Ferring, GSK, Gossamer Bio, Holoclara, Invea, Landos, LucidDx, Morphic, Nexstone Immunology, Nutricia, Parexel/Calyx, Phathom, Regeneron, Revolo, Robarts/Alimentiv, Salix, Sanofi, Shire/Takeda, Target RWE, Upstream Bio, and educational grants from Allakos, Holoclara, Invea. GFalk received consultant fees for Adare/Ellodi, Allakos, Bristol Myers Squibb/Celgene, Lucid, Nexstone, Phathom, Regeneron/Sanofi, Shire/Takeda, Upstream Bio, and research support from Adare/Ellodi, Allakos, Arena/Pfizer, Bristol Myers Squibb/Celgene, Lucid, Nexteos, Regeneron/Sanofi, Shire/Takeda. SG is a Consultant/DSMB member/author for Adare, BMS, QOL, Takeda, MedScape, PVI, ViaSkin, and UpToDate, and received research support from Allakos, Ellodi, AstraZeneca. ETJ received consulting fees for Regeneron Pharmaceuticals and Jazz Pharmaceuticals. PK received funding from APFED. DM has received past honoraria from GSK for awareness activities unrelated to this publication and/or disease state. MR is a consultant for Pulm One, Spoon Guru, ClostraBio, Serpin Pharm, Allakos, Celldex, Nextstone One, Bristol Myers Squibb, Astra Zeneca, Ellodi Pharma, GlaxoSmith Kline, Regeneron/Sanofi, Revolo Biotherapeutics, and Guidepoint and has an equity interest in the first seven listed, and royalties from reslizumab (Teva Pharmaceuticals), PEESSv2 (Mapi Research Trust) and UpToDate. MR is an inventor of patents owned by Cincinnati Children’s Hospital. JS received grant support from Regeneron/Sanofi, Novartis, NIH, FARE, consulting fees from Regeneron, Sanofi, Alladapt, Readysetfood, ARS Pharmacy, and royalties from Uptodate. ABM received research funding from Morphic and served on medical advisory board for Bristol Myers Squib and Nextone Immunology. VM received consultant fees from Allakos, Regeneron, Sanofi, and Shire/Takeda, and served on an adjudication board for Alladapt. CD received research funding from DBV Technologies, Food Allergy Research and Education, Allergenis, Regeneron Pharmaceuticals, Pfizer, and consultant or advisory board fees for Aimmune Therapeutics. JBW has received consultant fees from Allakos, Ellodi, Regeneron, Sanofi/Genzyme, AstraZeneca, and Invea Therapeutics, and clinical trial/research funding from Allakos, Invea Therapeutics, and Sanofi-Regeneron. BLW, DDB, AK, GE, GH, KK, EK, SKyle, PM, PM-K, CS, MJS, G-YY, KS, NM, SKesh, PB, MS, AZ, AP, AH, and GF have no conflicts of interest to declare., (© The Author(s), 2023.)

Objective: Investigate if antenatal corticosteroids (ANCS) are associated with worse kidney function in adolescence and if greater adiposity magnifies this association., Study Design: Prospective cohort of 162 14-year-olds born preterm with very low birth weight (<1500 g). Outcomes were estimated glomerular filtration rate (eGFR) and first-morning urine albumin-to-creatinine ratio (UACR). We used adjusted generalized linear models, stratified by waist-to-height ratio (WHR) ≥ 0.5., Results: Fifty-five percent had ANCS exposure and 31.3% had WHR ≥ 0.5. In adjusted analyses of the entire cohort, ANCS was not significantly associated with eGFR or UACR. However, the ANCS-eGFR association was greater in those with WHR ≥ 0.5 (β -16.8 ml/min/1.73 m 2 , 95% CL -31.5 to -2.1) vs. WHR < 0.5: (β 13.9 ml/min/1.73 m 2 , 95% CL -0.4 to 28.1), interaction term p = 0.02., Conclusion: ANCS exposure was not associated with worse kidney function in adolescence, though ANCS may be associated with lower eGFR if children develop obesity by adolescence., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Objectives: Early life exposures increase risk of eosinophilic esophagitis (EoE), but it is unknown whether they contribute to increased risk for non-EoE eosinophilic gastrointestinal diseases (EGIDs). We aimed to assess the association between prenatal, antenatal, and early life factors and non-EoE EGIDs., Methods: We conducted a case-control study based in EGID Partners, an online patient-centered research network. Adults (≥18 years) with non-EoE EGIDs, caregivers of children <18 years of age with an EGID, and non-EGID adult controls were eligible. Subjects completed our Early Life Exposure Questionnaire, detailing maternal and early childhood exposures. We assessed for associations between non-EoE EGIDs and early life exposures, focusing on exposures previously evaluated in association with EoE., Results: We analyzed 61 non-EoE EGID cases and 20 controls. Of the EGID cases, 14 had eosinophilic gastritis, 19 had eosinophilic enteritis, 6 had eosinophilic colitis, and 22 had multiple areas affected; additionally, 30 had esophageal involvement. Relative to controls, EGID cases were more likely to have had antenatal/perinatal pregnancy-related complications (43% vs 13%; p = 0.02), NICU admission (20% vs 0%; p = 0.03), and antibiotics in infancy (43% vs 10%; p = 0.01). With adjustment for age at diagnosis, we observed increased odds of an EGID for pregnancy complications (aOR 3.83; 95% CI: 0.99-14.9) and antibiotic use in infancy (aOR 7.65; 95% CI: 1.28-45.7)., Conclusions: Early life factors, including pregnancy complications, NICU admission, and antibiotics in infancy, were associated with development of non-EoE EGIDs. The impact of early life exposures on non-EoE EGID pathogenic mechanisms should be investigated., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Chemical and molecular-based computers may be promising alternatives to modern silicon-based computers. In particular, hybrid systems, where tasks are split between a chemical medium and traditional silicon components, may provide access and demonstration of chemical advantages such as scalability, low power dissipation, and genuine randomness. This work describes the development of a hybrid classical-molecular computer (HCMC) featuring an electrochemical reaction on top of an array of discrete electrodes with a fluorescent readout. The chemical medium, optical readout, and electrode interface combined with a classical computer generate a feedback loop to solve several canonical optimization problems in computer science such as number partitioning and prime factorization. Importantly, the HCMC makes constructive use of experimental noise in the optical readout, a milestone for molecular systems, to solve these optimization problems, as opposed to in silico random number generation. Specifically, we show calculations stranded in local minima can consistently converge on a global minimum in the presence of experimental noise. Scalability of the hybrid computer is demonstrated by expanding the number of variables from 4 to 7, increasing the number of possible solutions by 1 order of magnitude. This work provides a stepping stone to fully molecular approaches to solving complex computational problems using chemistry., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Objective: The objective of this study was to evaluate hemagglutinin stem-specific antibody response to the influenza vaccine during pregnancy and its transfer to the infant., Methods: The authors assessed antibody titers among maternal participants and their paired neonate's cord blood (CB) using enzyme-linked immunoassay. Fifteen pregnant participants pre-2019 and post-2019 seasonal influenza vaccine were compared with 18 prenatally vaccinated participants with paired neonatal CB samples. Total IgG and IgG subclass titers specific for whole vaccine antigens versus recombinant hemagglutinin stem-specific antigen were compared using Wilcoxon exact test., Results: Hemagglutinin stem-specific IgG was boosted more robustly than whole vaccine titers when comparing postvaccine versus prevaccine log 2 IgG ratios (P = 0.04). Hemagglutinin stem-specific IgG titers were boosted postvaccination (prevaccine: 14.5 [95% confidence interval, 13.8-15.2] vs. postvaccine: 16 [95% confidence interval, 15.2-16.8], P = 0.004). While IgG to whole vaccine was similar in neonatal CB and maternal plasma (P = 0.09), hemagglutinin stem-specific IgG concentrated in CB (P = 0.002), which was dominated by IgG1 subclass (analysis of variance P < 0.05)., Conclusion: These data demonstrate the ability of pregnant women to generate a more robust antibody response to the stem region compared with the head region of hemagglutinin with transplacental transfer of IgG., (© 2023 The Authors. International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

Objective: To determine the prevalence, progression, and modifiable risk factors associated with the development of diabetic retinopathy (DR) in a population-based cohort of youth-onset diabetes., Research Design and Methods: We conducted a multicenter, population-based prospective cohort study (2002-2019) of youth and young adults with youth-onset type 1 diabetes (n = 2,519) and type 2 diabetes (n = 447). Modifiable factors included baseline and change from baseline to follow-up in BMI z score, waist/height ratio, systolic and diastolic blood pressure z score, and A1C. DR included evidence of mild or moderate nonproliferative DR or proliferative retinopathy. Prevalence estimates were standardized to estimate the burden of DR, and inverse probability weighting for censoring was applied for estimating risk factors for DR at two points of follow-up., Results: DR in youth-onset type 1 and type 2 diabetes is highly prevalent, with 52% of those with type 1 diabetes and 56% of those with type 2 diabetes demonstrating retinal changes at follow-up (mean [SD] 12.5 [2.2] years from diagnosis). Higher baseline A1C, increase in A1C across follow-up, and increase in diastolic and systolic blood pressure were associated with the observation of DR at follow-up for both diabetes types. Increase in A1C across follow-up was associated with retinopathy progression. BMI z score and waist/height ratio were inconsistently associated, with both positive and inverse associations noted., Conclusions: Extrapolated to all youth-onset diabetes in the U.S., we estimate 110,051 cases of DR developing within ∼12 years postdiagnosis. Tight glucose and blood pressure management may offer the opportunity to mitigate development and progression of DR in youth-onset diabetes., (© 2023 by the American Diabetes Association.)

Importance: Treatment challenges exist for younger adults with type 1 (T1D) and type 2 diabetes (T2D). Health care coverage, access to, and use of diabetes care are not well delineated in these high-risk populations., Objective: To compare patterns of health care coverage, access to, and use of diabetes care and determine their associations with glycemia among younger adults with T1D and with T2D., Design, Setting, and Participants: This cohort study analyzed data from a survey that was jointly developed by 2 large, national cohort studies: the SEARCH for Diabetes in Youth (SEARCH) study, an observational study of individuals with youth-onset T1D or T2D, and the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study, a randomized clinical trial (2004-2011) followed by an observational study (2012-2020). The interviewer-directed survey was administered during in-person study visits in both studies between 2017 and 2019. Data analyses were performed between May 2021 and October 2022., Main Outcomes and Measures: Survey questions addressed health care coverage, usual sources of diabetes care, and frequency of care use. Glycated hemoglobin (HbA1c) levels were assayed in a central laboratory. Patterns of health care factors and HbA1c levels were compared by diabetes type., Results: The analysis included 1371 participants (mean [range] age, 25 [18-36] years; 824 females [60.1%]), of whom 661 had T1D and 250 had T2D from the SEARCH study and 460 had T2D from the TODAY study. Participants had a mean (SD) diabetes duration of 11.8 (2.8) years. More participants with T1D than T2D in both the SEARCH and TODAY studies reported health care coverage (94.7%, 81.6%, and 86.7%), access to diabetes care (94.7%, 78.1%, and 73.4%), and use of diabetes care (88.1%, 80.5%, and 73.6%). Not having health care coverage was associated with significantly higher mean (SE) HbA1c levels in participants with T1D in the SEARCH study (no coverage, 10.8% [0.5%]; public, 9.4% [0.2%]; private, 8.7% [0.1%]; P < .001) and participants with T2D from the TODAY study (no coverage, 9.9% [0.3%]; public, 8.7% [0.2%]; private, 8.7% [0.2%]; P = .004). Medicaid expansion vs without expansion was associated with more health care coverage (participants with T1D: 95.8% vs 90.2%; participants with T2D in SEARCH: 86.1% vs 73.9%; participants with T2D in TODAY: 93.6% vs 74.2%) and lower HbA1c levels (participants with T1D: 9.2% vs 9.7%; participants with T2D in SEARCH: 8.4% vs 9.3%; participants with T2D in TODAY: 8.7% vs 9.3%). The T1D group incurred higher median (IQR) monthly out-of-pocket expenses than the T2D group ($74.50 [$10.00-$309.00] vs $10.00 [$0-$74.50])., Conclusions and Relevance: Results of this study suggested that lack of health care coverage and of an established source of diabetes care were associated with significantly higher HbA1c levels for participants with T1D, but inconsistent results were found for participants with T2D. Increased access to diabetes care (eg, through Medicaid expansion) may be associated with improved health outcomes, but additional strategies are needed, particularly for individuals with T2D.

Objective: To examine the association between diabetes stigma and HbA1c, treatment plan and acute and chronic complications in adolescents and young adults (AYAs) with type 1 or type 2 diabetes., Research Design and Methods: The SEARCH for Diabetes in Youth study is a multicenter cohort study that collected questionnaire, laboratory, and physical examination data about AYAs with diabetes diagnosed in childhood. A five-question survey assessed frequency of perceived diabetes-related stigma, generating a total diabetes stigma score. We used multivariable linear modeling, stratified by diabetes type, to examine the association of diabetes stigma with clinical factors, adjusting for sociodemographic characteristics, clinic site, diabetes duration, health insurance, treatment plan, and HbA1c., Results: Of 1,608 respondents, 78% had type 1 diabetes, 56% were female, and 48% were non-Hispanic White. The mean (SD) age at study visit was 21.7 (5.1) years (range, 10-24.9). The mean (SD) HbA1c was 9.2% (2.3%; 77 mmol/mol [2.0 mmol/mol]). Higher diabetes stigma scores were associated with female sex and higher HbA1c (P < 0.01) for all participants. No significant association between diabetes stigma score and technology use was observed. In participants with type 2 diabetes, higher diabetes stigma scores were associated with insulin use (P = 0.04). Independent of HbA1c, higher diabetes stigma scores were associated with some acute complications for AYAs with type 1 diabetes and some chronic complications for AYAs with type 1 or type 2 diabetes., Conclusions: Diabetes stigma in AYAs is associated with worse diabetes outcomes and is important to address when providing comprehensive diabetes care., (© 2023 by the American Diabetes Association.)

Background: The incidence of diabetes is increasing in children and young people. We aimed to describe the incidence of type 1 and type 2 diabetes in children and young people aged younger than 20 years over a 17-year period., Methods: The SEARCH for Diabetes in Youth study identified children and young people aged 0-19 years with a physician diagnosis of type 1 or type 2 diabetes at five centres in the USA between 2002 and 2018. Eligible participants included non-military and non-institutionalised individuals who resided in one of the study areas at the time of diagnosis. The number of children and young people at risk of diabetes was obtained from the census or health plan member counts. Generalised autoregressive moving average models were used to examine trends, and data are presented as incidence of type 1 diabetes per 100 000 children and young people younger than 20 years and incidence of type 2 diabetes per 100 000 children and young people aged between 10 years and younger than 20 years across categories of age, sex, race or ethnicity, geographical region, and month or season of diagnosis., Findings: We identified 18 169 children and young people aged 0-19 years with type 1 diabetes in 85 million person-years and 5293 children and young people aged 10-19 years with type 2 diabetes in 44 million person-years. In 2017-18, the annual incidence of type 1 diabetes was 22·2 per 100 000 and that of type 2 diabetes was 17·9 per 100 000. The model for trend captured both a linear effect and a moving-average effect, with a significant increasing (annual) linear effect for both type 1 diabetes (2·02% [95% CI 1·54-2·49]) and type 2 diabetes (5·31% [4·46-6·17]). Children and young people from racial and ethnic minority groups such as non-Hispanic Black and Hispanic children and young people had greater increases in incidence for both types of diabetes. Peak age at diagnosis was 10 years (95% CI 8-11) for type 1 diabetes and 16 years (16-17) for type 2 diabetes. Season was significant for type 1 diabetes (p=0·0062) and type 2 diabetes (p=0·0006), with a January peak in diagnoses of type 1 diabetes and an August peak in diagnoses of type 2 diabetes., Interpretation: The increasing incidence of type 1 and type 2 diabetes in children and young people in the USA will result in an expanding population of young adults at risk of developing early complications of diabetes whose health-care needs will exceed those of their peers. Findings regarding age and season of diagnosis will inform focused prevention efforts., Funding: US Centers for Disease Control and Prevention and US National Institutes of Health., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Preconception counseling is recommended for all women with diabetes starting at puberty to convey the importance of optimal diabetes management for maternal and fetal outcomes. This study included 622 female participants from the SEARCH for Diabetes in Youth study with a mean age of 22.2 years (range 14-35 years). Only 53.7% reported ever receiving preconception counseling, which was significantly lower among women seeing pediatric providers than those seeing adult or all-age providers. Older age and history of prior pregnancy were associated with increased odds of reporting having received preconception counseling. Identification of barriers to delivering preconception counseling to young females with diabetes and strategies to overcome them are needed to reduce the risk for pregnancy complications and adverse offspring health outcomes., Competing Interests: No potential conflicts of interest relevant to this article were reported., (© 2023 by the American Diabetes Association.)

The chemistry of zirconium-based metal-organic polyhedra (ZrMOPs) is often limited by their poor solubilities. Despite their attractive features-including high yielding and facile syntheses, predictable topologies, high stability, and tunability-problematic solubilities have caused ZrMOPs to be under-studied and under-applied. Although these cages have been synthesized with a wide variety of carboxylate-based bridging ligands, we explored a new method for ZrMOP functionalization via node-modification, which we hypothesized could influence solubility. Herein, we report ZrMOPs with benzyl-, vinylbenzyl-, and trifluoromethylbenzyl-pendant groups decorating cyclopentadienyl moieties. The series was characterized by 1 H/ 19 F NMR, high-resolution mass spectrometry, infrared spectroscopy, and single-crystal X-ray diffraction. The effects of node functionalities on ZrMOP solubility were quantified using inductively coupled plasma mass spectrometry. Substitution caused a decrease in water solubility, but for certain organic solvents, e.g. DMF, solubility could be enhanced by ∼20×, from 16 μM for the unfunctionalized cage to 310 μM for the vinylbenzyl- and trifluoromethylbenzyl-cages.

Objective: We evaluated the association of household food insecurity (FI) with cognition in youth and young adults with type 1 diabetes (T1D) or type 2 diabetes (T2D)., Design: In this cross-sectional study, age-adjusted scores for composite Fluid Cognition, and sub-domain scores for Receptive Language and Inhibitory Control and Attention, were modeled stratified by diabetes-type using linear regression, with FI in the past year as the predictor, controlling for covariates. Tests for processing speed, inhibitory control/attention, working memory, episodic memory, and cognitive flexibility were administered to measure composite Fluid Cognition score. The NIHT-CB Picture Vocabulary Test was used to assess Crystallized Cognition score and rapid identification of congruent versus noncongruent items were used to assess Inhibitory Control and Attention score., Setting: The SEARCH for Diabetes in Youth study, representative of 5 U.S. states., Participants: Included 1574 youth and young adults with T1D or T2D, mean age of 21 years, mean diabetes duration of 11 years, 51% non-Hispanic white, and 47% had higher HbA1c levels (>9% HbA1c)., Results: Approximately 18% of the 1,240 participants with T1D and 31% of the 334 with T2D experienced FI. The food-insecure group with T1D had a lower composite Fluid Cognition score (β= -2.5, 95% confidence interval (CI)= -4.8, -0.1) and a lower Crystallized Cognition score (β= -3.4, CI= -5.6, -1.3) than food-secure peers. Findings were attenuated to non-significance after adjustment for demographics. Among T2D participants, no associations were observed. In participants with T1D effect modification by glycemic levels were found in the association between FI and composite Fluid Cognition score but adjustment for socioeconomic characteristics attenuated the interaction (p=0.0531)., Conclusions: Food-insecure youth and young adults with T1D or T2D did not have different cognition compared to those who were food-secure after adjustment for confounders. Longitudinal research is needed to further understand relations amongst these factors., Competing Interests: Conflicts of interest The authors declare that there is no conflict of interest regarding the publication of this article.

Aims/hypotheses: People with type 1 (T1D) or type 2 diabetes (T2D) who also have diabetes complications can have pronounced cognitive deficits. It remains unknown, however, whether and how multiple diabetes complications co-occur with cognitive dysfunction, particularly in youth-onset diabetes., Methods: Using data from the SEARCH for Diabetes in Youth study cohort, a prospective longitudinal cohort, we examined clustering of complications and their underlying clinical factors with performance on cognitive tests in young adults with youth-onset T1D or T2D. Cognition was assessed via the NIH Toolbox Cognition Battery. The main cognitive variables were age-corrected scores for composite fluid cognition and associated cognitive subdomains. Diabetes complications included retinopathy, microalbuminuria, and peripheral neuropathy (PN). Lipids, systolic blood pressure (SBP), hemoglobin A1c, and other clinical factors were included in the analyses. Clustering was applied separately to each group (T1D=646; T2D=165). A three-cluster(C) solution was identified for each diabetes type. Mean values and frequencies of all factors were compared between resulting clusters., Results: The average age-corrected score for composite fluid cognition differed significantly across clusters for each group (p<0.001). People with T1D and the lowest average fluid cognition scores had the highest frequency of self-reporting at least one episode of hypoglycemia in the year preceding cognitive testing and the highest prevalence of PN. Persons with T2D and the lowest average fluid cognition scores had the highest SBP, the highest central systolic and diastolic blood pressures, and highest prevalence of PN., Conclusions/interpretations: These findings highlight shared (PN) and unique factors (hypoglycemia in T1D; SBP in T2D) that could be targeted to potentially mitigate cognitive issues in young people with youth-onset diabetes., Competing Interests: CONFLICT OF INTEREST The authors declare no conflicts of interest.

Objective: To evaluate associations between changes in weight, length, and weight/length ratio during infancy and outcomes later in life among individuals born extremely preterm., Study Design: Among participants in the Extremely Low Gestational Age Newborn (ELGAN) study, we measured weight and length at discharge from the neonatal intensive care unit (NICU) and at age 2 years and evaluated neurocognitive, psychiatric, and health outcomes at age 10 years and 15 years. Using multivariable logistic regression, we estimated associations between gains in weight, length, and weight/length ratio z-scores between discharge and 2 years and outcomes at 10 and 15 years. High gain was defined as the top quintile of change; low gain, as the bottom quintile of change., Results: High gains in weight and weight/length were associated with greater odds of obesity at 10 years, but not at 15 years. These associations were found only for females. High gain in length z-score was associated with lower odds of obesity at 15 years. The only association found between high gains in growth measures and more favorable neurocognitive or psychiatric outcomes was between high gain in weight/length and lower odds of cognitive impairment at age 10 years., Conclusions: During the 2 years after NICU discharge, females born extremely preterm with high gains in weight/length or weight have greater odds of obesity at 10 years, but not at 15 years. Infants with high growth gains in the 2 years after NICU discharge have neurocognitive and psychiatric outcomes in middle childhood and adolescence similar to those of infants with lower gains in weight and weight/length., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose of Review: As the rising prevalence and incidence of eosinophilic esophagitis (EoE) has quickly outpaced the rate of esophageal biopsies, particularly in Westernized countries, several studies have suggested a link between intrinsic genetic and extrinsic environmental risk factors and the development, presentation, and diagnosis of EoE. This review aims to critically assess existing studies describing the role of the environment on the development, symptomatic presentation, and diagnosis of this recently recognized chronic immune-mediated disease., Recent Findings: We present and critically evaluate the working hypotheses and supportive studies thus far on environmental factors on EoE, describe sources of potential bias in diagnosis due to socioeconomic factors and thus undermining studies of EoE etiology, and highlight opportunities for future research. As genetics alone do not explain the rapid rise of EoE, we must look to environmental, or extrinsic, factors both in the early-life period which shape the development of the gut microbiome, as well as later life contributing to diagnosis of this new disease. Future etiologic studies linking risk factors to EoE development in individual patients are needed., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)