Disparities in Patient Family Social Determinants of Health in a Large Urban Pediatric Health System.

INTRODUCTION: This analysis sought to identify disparities in social determinants of health (SDOH) outcomes at a Texas pediatric hospital. METHODS: This retrospective study used electronic health records of pediatric patients families surveyed August -December 2022. Outcomes for health literacy, social support, food, transportation, energy, digital, and housing insecurity, and tobacco exposure were analyzed across demographic categories. RESULTS: Among 15,294 respondents to the survey (mean child age, 8.73 years; 43.68% Hispanic, 29.73% non-Hispanic White, 18.27% non-Hispanic Black, 6.79% other race/ethnicity; 53.95% male), 50.25% of respondents reported at least one SDOH, whereas 23.39% reported two or more SDOH. The most prevalent SDOH was lack of social support (3,456, 23.91%). Hispanic, non-Hispanic Black, and other race/ethnicity respondents, non-English speakers, and public insurance users had higher odds of reporting almost all SDOH in logistic regression models adjusted for age, race/ethnicity, language, gender, and insurance type. DISCUSSION: Race/ethnicity, language, and insurance type disparities were identified for all SDOH.

Prevalence of the metabolic syndrome by household food insecurity status in the United States adolescent population, 2001-2020: a cross-sectional study.

BACKGROUND: Household food insecurity (FI) is a modifiable social determinant of health linked to chronic health outcomes. Little is known, however, about the prevalence of metabolic syndrome (MetS) in pediatric population-based studies by household FI status. OBJECTIVES: The objective of the study was to estimate the prevalence of the MetS by household FI status over the past 2 decades. METHODS: This cross-sectional study used data from the 2001-2020 National Health and Nutrition Examination Survey (NHANES). Participants were nonpregnant adolescents ages 12- 18 y in United States. The prevalence of MetS [elevated waist circumference and >2 of the following risk factors: elevated blood pressure, and fasting glucose, triglyceride, and/or low high-density lipoprotein (HDL) cholesterol concentrations] by FI status was evaluated using chi-square and logistic regression analyses. RESULTS: The estimated prevalence of MetS was 2.66% [95% confidence interval (CI): 2.28%, 3.09%] in the final analytical sample (unweighted N = 12,932). A total of 3.39% (95% CI: 2.53%, 4.53%) of adolescents from FI households had MetS compared to 2.48% (95% CI: 2.11%, 2.9%) among adolescents with no household FI. Hispanic adolescents had the highest prevalence of MetS (3.73%, 95% CI: 3.05, 4.56) compared with adolescents who identified as non-Hispanic White (2.78%, 95% CI: 2.25, 3.43), non-Hispanic Black (1.58%, 95% CI: 1.19, 2.10). Adolescents with household FI (23.20%) were more likely to have MetS [odds ratio (OR): 1.38; 95% CI: 1.02, 1.88; I=0.039) compared with adolescents with no household FI, but in fully adjusted models this was not significant (OR: 1.13; 95% CI: 0.75, 1.72). CONCLUSIONS: Using the most current NHANES data, the estimated prevalence of MetS in adolescents in United States was slightly higher among those from FI households. However, after adjusting for potential confounders, the relationship between household FI and MetS was nonsignificant, highlighting the complexity of factors contributing to MetS in this population. Hispanic adolescents share a disproportionate burden of MetS compared with their non-Hispanic counterparts.

Family-based pediatric weight management interventions in US primary care settings targeting children ages 6-12 years old: A systematic review guided by the RE-AIM framework.

Obesity is a pandemic that disproportionately affects children from vulnerable populations in the USA. Current treatment approaches in primary care settings in the USA have been reported to be insufficient at managing pediatric obesity, primarily due to implementation challenges for healthcare systems and barriers for families. While the literature has examined the efficacy of pediatric obesity interventions focused on internal validity, it lacks sufficient reporting and analysis of external validity necessary for successful translation to primary care settings. We conducted a systematic review of the primary-care-setting literature from January 2007 to March 2020 on family-based pediatric weight management interventions in both English and/or Spanish for children ages 6-12 years in the USA using the Reach, Efficacy/Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework. A literature search, using PRISMA guidelines, was conducted in January 2022 using the following electronic databases: Medline Ovid, Embase, and Cochrane Library. 22 270 records were screened, and 376 articles were reviewed in full. 184 studies were included. The most commonly reported dimensions of the RE-AIM framework were Reach (65%), Efficacy/Effectiveness (64%), and Adoption (64%), while Implementation (47%) and Maintenance (42%) were less often reported. The prevalence of reporting RE-AIM construct indicators ranged greatly, from 1% to 100%. This systematic review underscores the need for more focus on external validity to guide the development, implementation, and dissemination of future pediatric obesity interventions based in primary care settings. It also suggests conducting additional research on sustainable financing for pediatric obesity interventions.

Pediatric weight management research focused on primary care centers for children ages 6­12 in the USA has typically focused on assessing the effectiveness of the intervention rather than how to translate and disseminate such interventions into different settings for diverse populations, or external validity. Using the Reach, Efficacy/Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework, we conducted a systematic review to report how existing research reports external validity.

Pediatric Telehealth Expansion in Response to COVID-19.

Introduction: Telehealth utilization has been steadily increasing for the past two decades and has been recognized for its ability to access rural and underserved populations. The advent of COVID-19 in March 2020 limited the feasibility of in-person healthcare visits which in turn increased telehealth demand and use. However, the long-term impacts of COVID-19 on the telehealth sector of the healthcare industry, and particularly on pediatric healthcare volume demand and subsequent expansion, are yet to be determined. Objective and Methods: To understand the impact of COVID-19 on telehealth utilization, volume demand, and expansion in one large pediatric healthcare system serving greater Dallas-Fort Worth, Texas, data on telehealth clinic visits by month, pre-COVID and post/current-COVID were compared. A quasi-experimental pretest-posttest design analysis compared telehealth visit counts from 54 ambulatory pediatric health specialties. Pre-post new patient counts were also analyzed via chi square. Results: Total telehealth visit counts significantly increased between March-October 2019 (2,033 visits) compared to March-October 2020 (54,276 visits). Mean monthly telehealth visits increased by 6,530 visits, or 2,569.75% over the same time period (p < 0.0001). In October 2020, total telehealth visits were still 1,194.78% above 2019 levels (345 visits in 2019 vs. 4467 visits in 2020). Discussion: Results here show a substantial volume increase in telehealth-delivered pediatric healthcare and resource utilization as a response to COVID-19. This provides a template for permanent adoption of pediatric telehealth delivery post pandemic. Further investigation is needed to determine impacts upon resource allocation, processes, and general models and standard of care to assist facilities and programs to better address the needs of the pediatric populations they serve in the post-COVID era.

Potential Utility of School-Based Telehealth in the Era of COVID-19.

BACKGROUND: The COVID-19 pandemic presents unique opportunities for preexisting school telemedicine programs to reach pediatric populations that might otherwise experience a lapse in health care services. METHODS: A retrospective analysis of one of the largest school-based telemedicine programs in the country, based in the Dallas-Fort Worth (DFW), Texas was conducted that included 7021 pediatric patients who engaged in telehealth visits from 2014 to 2019. RESULTS: Asthma or other respiratory disease was the primary diagnosis (28.4%), followed by injury or trauma (18.4%), digestive disorders (6.9%), and ear/eye/skin disease (6.9%). More participants were from the North (34.4%) and West (33.2%) ISD compared to the South (20.6%) and East (11.7%) schools. Likewise, the majority of COVID-19 cases were in the North (61.8%) and West (31.6%) DFW regions, leading to 989 (59.9%) and 551 (33.4%) deaths, respectively. CONCLUSIONS: School-based telehealth programs have the potential to reach large pediatric populations most in need of health care due to COVID-19-related lapses in services, and to address COVID-19-related health issues as schools reopen. In the future, utilization could be expanded to contact tracing, testing, and screening for COVID-19.

Colonic Epithelial-Derived Selenoprotein P Is the Source for Antioxidant-Mediated Protection in Colitis-Associated Cancer.

BACKGROUND & AIMS: Patients with inflammatory bowel disease (IBD) demonstrate nutritional selenium deficiencies and are at greater risk of developing colon cancer. Previously, we determined that global reduction of the secreted antioxidant selenium-containing protein, selenoprotein P (SELENOP), substantially increased tumor development in an experimental colitis-associated cancer (CAC) model. We next sought to delineate tissue-specific contributions of SELENOP to intestinal inflammatory carcinogenesis and define clinical context. METHODS: Selenop floxed mice crossed with Cre driver lines to delete Selenop from the liver, myeloid lineages, or intestinal epithelium were placed on an azoxymethane/dextran sodium sulfate experimental CAC protocol. SELENOP loss was assessed in human ulcerative colitis (UC) organoids, and expression was queried in human and adult UC samples. RESULTS: Although large sources of SELENOP, both liver- and myeloid-specific Selenop deletion failed to modify azoxymethane/dextran sodium sulfate-mediated tumorigenesis. Instead, epithelial-specific deletion increased CAC tumorigenesis, likely due to elevated oxidative stress with a resulting increase in genomic instability and augmented tumor initiation. SELENOP was down-regulated in UC colon biopsies and levels were inversely correlated with endoscopic disease severity and tissue S100A8 (calprotectin) gene expression. CONCLUSIONS: Although global selenium status is typically assessed by measuring liver-derived plasma SELENOP levels, our results indicate that the peripheral SELENOP pool is dispensable for CAC. Colonic epithelial SELENOP is the main contributor to local antioxidant capabilities. Thus, colonic SELENOP is the most informative means to assess selenium levels and activity in IBD patients and may serve as a novel biomarker for UC disease severity and identify patients most predisposed to CAC development.

Plasma selenoprotein P concentration and lung cancer risk: results from a case-control study nested within the Shanghai Men's Health Study.

Selenoprotein P (SELENOP) is a major selenoenzyme in plasma and linked to antioxidant properties and possibly to lung cancer; however, supporting evidence is limited. We investigated the association between pre-diagnostic plasma SELENOP concentration and lung cancer risk in a case-control study of 403 cases and 403 individually matched controls nested within the Shanghai Men's Health Study. SELENOP concentration in pre-diagnostic plasma samples was measured by a sandwich enzyme-linked immunosorbent assay. Cases were diagnosed with lung cancer between 2003 and 2010. Multivariate conditional logistic regression was used to estimate odds ratios (OR) and the corresponding 95% confidence intervals (CI) for studying the association between plasma SELENOP concentration and lung cancer risk. Cases had slightly lower plasma SELENOP concentration than controls (4.3 ± 1.2 versus 4.4 ± 1.1 mg/l, P difference = 0.09). However, the multivariate analysis showed no association between plasma SELENOP concentration and lung cancer risk among all participants (OR = 1.08, 95% CI = 0.54-2.14 for quartile 4 versus quartile 1), or by smoking status or tumor aggressiveness. In contrast, although the number of cases was limited, plasma SELENOP concentration was positively associated with lung adenocarcinoma risk (OR = 5.38, 95% CI = 1.89-15.35 for tertile 3 versus tertile 1), but not with squamous cell lung carcinoma (OR = 1.69, 95% CI = 0.43-6.70). Our study of adult men living in selenium non-deficient areas in China provides little support for the inverse association between pre-diagnostic plasma SELENOP concentration and lung cancer risk. Our finding of a positive association with risk of lung adenocarcinoma needs to be interpreted with caution.

Selenomethionine and methyl selenocysteine: multiple-dose pharmacokinetics in selenium-replete men.

According to the Nutritional Prevention of Cancer (NPC) trial, a selenized yeast supplement containing selenium, 200 mcg/day, decreased the incidence of total cancer, cancers of the prostate, colon and lung, and cancer mortality. The active agent in the selenized yeast supplement was assumed to be selenomethionine (SEMET), although the supplement had not been well speciated. The SELECT study, largely motivated by the NPC trial, enrolling nearly 40 times as many subjects, showed unequivocally that selenium 200 mcg/day, with selenium in the form of SEMET, does not protect selenium-replete men against prostate or other major cancer. The agent tested by SELECT, pure SEMET, could have been different from the selenized yeast tested in NPC. One of the selenium forms suspected of having chemopreventive effects, and which may have been present in the NPC agent, is methyl selenocysteine (MSC). This study, with 29 selenium-replete patients enrolled in a randomized, double-blind trial, compared the multiple-dose toxicity, pharmacokinetics and pharmacodynamics of MSC and SEMET. Patients were on trial for 84 days. No toxicity was observed. Although SEMET supplementation increased blood selenium concentration more than MSC did, neither form had a more than minimal impact on the two major selenoproteins: selenoprotein P(SEPP1) and glutathione peroxidase(GPX).

Human selenoprotein P and S variant mRNAs with different numbers of SECIS elements and inferences from mutant mice of the roles of multiple SECIS elements.

Dynamic redefinition of the 10 UGAs in human and mouse selenoprotein P (Sepp1) mRNAs to specify selenocysteine instead of termination involves two 3' UTR structural elements (SECIS) and is regulated by selenium availability. In addition to the previously known human Sepp1 mRNA poly(A) addition site just 3' of SECIS 2, two further sites were identified with one resulting in 10-25% of the mRNA lacking SECIS 2. To address function, mutant mice were generated with either SECIS 1 or SECIS 2 deleted or with the first UGA substituted with a serine codon. They were fed on either high or selenium-deficient diets. The mutants had very different effects on the proportions of shorter and longer product Sepp1 protein isoforms isolated from plasma, and on viability. Spatially and functionally distinctive effects of the two SECIS elements on UGA decoding were inferred. We also bioinformatically identify two selenoprotein S mRNAs with different 5' sequences predicted to yield products with different N-termini. These results provide insights into SECIS function and mRNA processing in selenoprotein isoform diversity.

Selenium deficiency occurs in some patients with moderate-to-severe cirrhosis and can be corrected by administration of selenate but not selenomethionine: a randomized controlled trial.

BACKGROUND: Selenomethionine, which is the principal dietary form of selenium, is metabolized by the liver to selenide, which is the form of the element required for the synthesis of selenoproteins. The liver synthesizes selenium-rich selenoprotein P (SEPP1) and secretes it into the plasma to supply extrahepatic tissues with selenium. OBJECTIVES: We conducted a randomized controlled trial to determine whether cirrhosis is associated with functional selenium deficiency (the lack of selenium for the process of selenoprotein synthesis even though selenium intake is not limited) and, if it is, whether the deficiency is associated with impairment of selenomethionine metabolism. DESIGN: Patients with Child-Pugh (C-P) classes A, B, and C (mild, moderate, and severe, respectively) cirrhosis were supplemented with a placebo or supranutritional amounts of selenium as selenate (200 or 400 µg/d) or as selenomethionine (200 µg/d) for 4 wk. Plasma SEPP1 concentration and glutathione peroxidase (GPX) activity, the latter due largely to the selenoprotein GPX3 secreted by the kidneys, were measured before and after supplementation. RESULTS: GPX activity was increased more by both doses of selenate than by the placebo in C-P class B patients. The activity was not increased more by selenomethionine supplementation than by the placebo in C-P class B patients. Plasma selenium was increased more by 400 µg Se as selenate than by the placebo in C-P class C patients. Within the groups who responded to selenate, there was a considerable variation in responses. CONCLUSION: These results indicate that severe cirrhosis causes mild functional selenium deficiency in some patients that is associated with impaired metabolism of selenomethionine. This trial was registered at clinicaltrials.gov as NCT00271245.

Selenoprotein P influences colitis-induced tumorigenesis by mediating stemness and oxidative damage.

Patients with inflammatory bowel disease are at increased risk for colon cancer due to augmented oxidative stress. These patients also have compromised antioxidant defenses as the result of nutritional deficiencies. The micronutrient selenium is essential for selenoprotein production and is transported from the liver to target tissues via selenoprotein P (SEPP1). Target tissues also produce SEPP1, which is thought to possess an endogenous antioxidant function. Here, we have shown that mice with Sepp1 haploinsufficiency or mutations that disrupt either the selenium transport or the enzymatic domain of SEPP1 exhibit increased colitis-associated carcinogenesis as the result of increased genomic instability and promotion of a protumorigenic microenvironment. Reduced SEPP1 function markedly increased M2-polarized macrophages, indicating a role for SEPP1 in macrophage polarization and immune function. Furthermore, compared with partial loss, complete loss of SEPP1 substantially reduced tumor burden, in part due to increased apoptosis. Using intestinal organoid cultures, we found that, compared with those from WT animals, Sepp1-null cultures display increased stem cell characteristics that are coupled with increased ROS production, DNA damage, proliferation, decreased cell survival, and modulation of WNT signaling in response to H2O2-mediated oxidative stress. Together, these data demonstrate that SEPP1 influences inflammatory tumorigenesis by affecting genomic stability, the inflammatory microenvironment, and epithelial stem cell functions.

Regulation of Selenium Metabolism and Transport.

Selenium is regulated in the body to maintain vital selenoproteins and to avoid toxicity. When selenium is limiting, cells utilize it to synthesize the selenoproteins most important to them, creating a selenoprotein hierarchy in the cell. The liver is the central organ for selenium regulation and produces excretory selenium forms to regulate whole-body selenium. It responds to selenium deficiency by curtailing excretion and secreting selenoprotein P (Sepp1) into the plasma at the expense of its intracellular selenoproteins. Plasma Sepp1 is distributed to tissues in relation to their expression of the Sepp1 receptor apolipoprotein E receptor-2, creating a tissue selenium hierarchy. N-terminal Sepp1 forms are taken up in the renal proximal tubule by another receptor, megalin. Thus, the regulated whole-body pool of selenium is shifted to needy cells and then to vital selenoproteins in them to supply selenium where it is needed, creating a whole-body selenoprotein hierarchy.

Phylogenetics of Bonamia parasites based on small subunit and internal transcribed spacer region ribosomal DNA sequence data.

The genus Bonamia (Haplosporidia) includes economically significant oyster parasites. Described species were thought to have fairly circumscribed host and geographic ranges: B. ostreae infecting Ostrea edulis in Europe and North America, B. exitiosa infecting O. chilensis in New Zealand, and B. roughleyi infecting Saccostrea glomerata in Australia. The discovery of B. exitiosa-like parasites in new locations and the observation of a novel species, B. perspora, in non-commercial O. stentina altered this perception and prompted our wider evaluation of the global diversity of Bonamia parasites. Samples of 13 oyster species from 21 locations were screened for Bonamia spp. by PCR, and small subunit and internal transcribed spacer regions of Bonamia sp. ribosomal DNA were sequenced from PCR-positive individuals. Infections were confirmed histologically. Phylogenetic analyses using parsimony and Bayesian methods revealed one species, B. exitiosa, to be widely distributed, infecting 7 oyster species from Australia, New Zealand, Argentina, eastern and western USA, and Tunisia. More limited host and geographic distributions of B. ostreae and B. perspora were confirmed, but nothing genetically identifiable as B. roughleyi was found in Australia or elsewhere. Newly discovered diversity included a Bonamia sp. in Dendostrea sandvicensis from Hawaii, USA, that is basal to the other Bonamia species and a Bonamia sp. in O. edulis from Tomales Bay, California, USA, that is closely related to both B. exitiosa and the previously observed Bonamia sp. from O. chilensis in Chile.

Selenoprotein P is the major selenium transport protein in mouse milk.

Selenium is transferred from the mouse dam to its neonate via milk. Milk contains selenium in selenoprotein form as selenoprotein P (Sepp1) and glutathione peroxidase-3 (Gpx3) as well as in non-specific protein form as selenomethionine. Selenium is also present in milk in uncharacterized small-molecule form. We eliminated selenomethionine from the mice in these experiments by feeding a diet that contained sodium selenite as the source of selenium. Selenium-replete dams with deletion of Sepp1 or Gpx3 were studied to assess the effects of these genes on selenium transfer to the neonate. Sepp1 knockout caused a drop in milk selenium to 27% of the value in wild-type milk and a drop in selenium acquisition by the neonates to 35%. In addition to decreasing milk selenium by eliminating Sepp1, deletion of Sepp1 causes a decline in whole-body selenium, which likely also contributes to the decreased transfer of selenium to the neonate. Deletion of Gpx3 did not decrease milk selenium content or neonate selenium acquisition by measurable amounts. Thus, when the dam is fed selenium-adequate diet (0.25 mg selenium/kg diet), milk Sepp1 transfers a large amount of selenium to neonates but the transfer of selenium by Gpx3 is below detection by our methods.

Selenoprotein P and apolipoprotein E receptor-2 interact at the blood-brain barrier and also within the brain to maintain an essential selenium pool that protects against neurodegeneration.

Selenoprotein P (Sepp1) and its receptor, apolipoprotein E receptor 2 (apoER2), account for brain retaining selenium better than other tissues. The primary sources of Sepp1 in plasma and brain are hepatocytes and astrocytes, respectively. ApoER2 is expressed in varying amounts by tissues; within the brain it is expressed primarily by neurons. Knockout of Sepp1 or apoER2 lowers brain selenium from ∼120 to ∼50 ng/g and leads to severe neurodegeneration and death in mild selenium deficiency. Interactions of Sepp1 and apoER2 that protect against this injury have not been characterized. We studied Sepp1, apoER2, and brain selenium in knockout mice. Immunocytochemistry showed that apoER2 mediates Sepp1 uptake at the blood-brain barrier. When Sepp1(-/-) or apoER2(-/-) mice developed severe neurodegeneration caused by mild selenium deficiency, brain selenium was ∼35 ng/g. In extreme selenium deficiency, however, brain selenium of ∼12 ng/g was tolerated when both Sepp1 and apoER2 were intact in the brain. These findings indicate that tandem Sepp1-apoER2 interactions supply selenium for maintenance of brain neurons. One interaction is at the blood-brain barrier, and the other is within the brain. We postulate that Sepp1 inside the blood-brain barrier is taken up by neurons via apoER2, concentrating brain selenium in them.

Isoform-specific binding of selenoprotein P to the ß-propeller domain of apolipoprotein E receptor 2 mediates selenium supply.

Sepp1 supplies selenium to tissues via receptor-mediated endocytosis. Mice, rats, and humans have 10 selenocysteines in Sepp1, which are incorporated via recoding of the stop codon, UGA. Four isoforms of rat Sepp1 have been identified, including full-length Sepp1 and three others, which terminate at the second, third, and seventh UGA codons. Previous studies have shown that the longer Sepp1 isoforms bind to the low density lipoprotein receptor apoER2, but the mechanism remains unclear. To identify the essential residues for apoER2 binding, an in vitro Sepp1 binding assay was developed using different Sec to Cys substituted variants of Sepp1 produced in HEK293T cells. ApoER2 was found to bind the two longest isoforms. These results suggest that Sepp1 isoforms with six or more selenocysteines are taken up by apoER2. Furthermore, the C-terminal domain of Sepp1 alone can bind to apoER2. These results indicate that apoER2 binds to the Sepp1 C-terminal domain and does not require the heparin-binding site, which is located in the N-terminal domain. Site-directed mutagenesis identified three residues of Sepp1 that are necessary for apoER2 binding. Sequential deletion of extracellular domains of apoER2 surprisingly identified the YWTD ß-propeller domain as the Sepp1 binding site. Finally, we show that apoER2 missing the ligand-binding repeat region, which can result from cleavage at a furin cleavage site present in some apoER2 isoforms, can act as a receptor for Sepp1. Thus, longer isoforms of Sepp1 with high selenium content interact with a binding site distinct from the ligand-binding domain of apoER2 for selenium delivery.