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There are well-documented inequities in the quality of care and health outcomes of minoritized youth. Patient safety and quality improvement (QI) work with an equity focus has been identified as an important strategy to remedy these existing inequities. In this article, we will present evidence of inequities in pediatric hospital-based care, describe root causes with a focus on structural racism, highlight existing frameworks for applying equity principles to patient safety and QI, and provide best practices and recommendations on evaluating patient safety and QI data towards advancing equity in pediatric hospital-based care., Competing Interests: Declaration of Competing Interest None for all authors., (Copyright © 2024 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate whether community factors that differentially affect the health of pregnant people contribute to geographic differences in infant mortality across the US., Study Design: This retrospective cohort study sought to characterize the association of a novel composite measure of county-level maternal structural vulnerabilities, the Maternal Vulnerability Index (MVI), with risk of infant death. We evaluated 11 456 232 singleton infants born at 22 0 of 7 through 44 6 of 7 weeks' gestation from 2012 to 2014. Using county-level MVI, which ranges from 0 to 100, multivariable mixed effects logistic regression models quantified associations per 20-point increment in MVI, with odds of death clustered at the county level and adjusted for state, maternal, and infant covariates. Secondary analyses stratified by the social, physical, and health exposures that comprise the overall MVI score. Outcome was also stratified by cause of death., Results: Rates of death were higher among infants from counties with the greatest maternal vulnerability (0.62% in highest quintile vs 0.32% in lowest quintile, [P < .001]). Odds of death increased 6% per 20-point increment in MVI (aOR: 1.06, 95% CI 1.04, 1.07). The effect estimate was highest with theme of Mental Health and Substance Abse (aOR 1.08; 95% CI 1.06, 1.09). Increasing vulnerability was associated with 6 of 7 causes of death., Conclusions: Community-level social, physical, and healthcare determinants indicative of maternal vulnerability may explain some of the geographic variation in infant death, regardless of cause of death. Interventions targeted to county-specific maternal vulnerabilities may reduce infant mortality., Competing Interests: Declaration of Competing Interest This study was supported by an NIH grant, 5T32HL098054-13 (Dr. Murosko). The NIH had no role in the design and conduct of the study. The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Research Design: Community-engaged qualitative study using inductive thematic analysis of semistructured interviews., Objective: To understand Latine immigrants' recent prenatal care experiences and develop community-informed strategies to mitigate policy-related chilling effects on prenatal care utilization., Background: Decreased health care utilization among immigrants due to punitive immigration policies (ie, the "chilling effect") has been well-documented among Latine birthing people both pre and postnatally., Patients and Methods: Currently or recently pregnant immigrant Latine people in greater Philadelphia were recruited from an obstetric clinic, 2 pediatric primary care clinics, and 2 community-based organization client pools. Thematic saturation was achieved with 24 people. Participants' pregnancy narratives and their perspectives on how health care providers and systems could make prenatal care feel safer and more comfortable for immigrants., Results: Participants' recommendations for mitigating the chilling effect during the prenatal period included training prenatal health care providers to sensitively initiate discussions about immigrants' rights and reaffirm confidentiality around immigration status. Participants suggested that health care systems should expand sources of information for pregnant immigrants, either by partnering with community organizations to disseminate information or by increasing access to trusted individuals knowledgeable about immigrants' rights to health care. Participants also suggested training non-medical office staff in the use of interpreters., Conclusion: Immigrant Latine pregnant and birthing people in greater Philadelphia described ongoing fear and confusion regarding the utilization of prenatal care, as well as experiences of discrimination. Participants' suggestions for mitigating immigration-related chilling effects can be translated into potential policy and programmatic interventions which could be implemented locally and evaluated for broader applicability., Competing Interests: D.M.W. is supported by the National Institutes of Health K23HD102526. The remaining authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Pancreatic β-cell dysfunction is a key feature of type 2 diabetes, and novel regulators of insulin secretion are desirable. Here we report that the succinate receptor (SUCNR1) is expressed in β-cells and is up-regulated in hyperglycemic states in mice and humans. We found that succinate acts as a hormone-like metabolite and stimulates insulin secretion via a SUCNR1-Gq-PKC-dependent mechanism in human β-cells. Mice with β-cell-specific Sucnr1 deficiency exhibit impaired glucose tolerance and insulin secretion on a high-fat diet, indicating that SUCNR1 is essential for preserving insulin secretion in diet-induced insulin resistance. Patients with impaired glucose tolerance show an enhanced nutritional-related succinate response, which correlates with the potentiation of insulin secretion during intravenous glucose administration. These data demonstrate that the succinate/SUCNR1 axis is activated by high glucose and identify a GPCR-mediated amplifying pathway for insulin secretion relevant to the hyperinsulinemia of prediabetic states.

Objective: Coronavirus disease 2019 (COVID-19) continues to have a profound impact on infant health care and health outcomes. In this study, we aimed to characterize the social impact of the first COVID-19 lockdown on families in a neonatal follow-up program (NFP). Given the ongoing increased use of telehealth across the medicine, we also evaluated for patient-level differences in virtual visit rates to identify patients at risk of follow-up challenges., Study Design: To assess the impact of virtual health care utilization, we conducted a retrospective cohort study to describe challenges associated with telemedicine use in this vulnerable patient population during our telemedicine epoch (March 13, 2020-July 31, 2020). We also looked for patient-level factors associated with attending NFP visits as scheduled. Finally, we summarized caregiver responses to a COVID-19 Obstacles Assessment Survey and assessed for racial disparities in these responses., Results: When comparing patients who completed their virtual visit to those who did not, we found no differences by infants' sex, birth weight, gestational age at birth, or caregiver self-reported race and ethnicity. However, infants whose visits did not occur were more often discharged with equipment or covered by public insurance. Nine percent of families reported food insecurity., Conclusion: During the initial COVID-19 lockdown, families with infants discharged from a neonatal intensive care unit (NICU) faced significant obstacles caring for their infants and attending scheduled follow-up visits. Infants in families with lower socioeconomic status or with increased medical complexity faced increased challenges in attending virtual follow-up visits during this epoch. Given the ongoing reliance on telemedicine in health care and the need to better prepare for future epidemics/pandemics, this study offers critical information that can assist neonatal teams in bolstering transitions to home and creating stronger safety nets for their patients after discharge., Key Points: · Telemedicine works well for high-risk neonatal populations.. · Infant medical complexity may be a risk factor for challenges attending neonatal follow-up visits.. · NICUs should work to prevent food insecurity postdischarge.., Competing Interests: None declared., (Thieme. All rights reserved.)

Importance: Immigrant birthing people have lower rates of preterm birth compared with their US-born counterparts. This advantage and associated racial and ethnic disparities across the gestational age spectrum have not been examined nationally., Objective: To examine associations of maternal nativity, ethnicity, and race with preterm birth., Design, Setting, and Participants: This cohort study used birth certificates from the National Vital Statistics System to analyze in-hospital liveborn singleton births in the US between January 1, 2009, and December 31, 2018. Data were analyzed from January to June 2023., Exposure: Mutually exclusive nativity, ethnicity, and race subgroups were constructed using nativity (defined as US-born or non-US-born), ethnicity (defined as Hispanic or non-Hispanic), and race (defined as American Indian or Alaska Native, Asian, Black, Native Hawaiian or Other Pacific Islander, White, or other [individuals who selected other race or more than 1 race])., Main Outcomes and Measures: The primary outcome of interest was preterm birth. Modified Poisson and multinomial logistic regression models quantified relative risk (RR) of preterm birth overall (<37 weeks' gestation) and by gestational category (late preterm: 34-36 weeks' gestation; moderately preterm: 29-33 weeks' gestation; and extremely preterm: <29 weeks' gestation) for each maternal nativity, ethnicity, and race subgroup compared with the largest group, US-born non-Hispanic White (hereafter, White) birthing people. The RR of preterm birth overall and by category was also measured within each racial and ethnic group by nativity. Models were adjusted for maternal demographic and medical covariates, birth year, and birth state., Results: A total of 34 468 901 singleton live births of birthing people were analyzed, with a mean (SD) age at delivery of 28 (6) years. All nativity, ethnicity, and race subgroups had an increased adjusted risk of preterm birth compared with US-born White birthing people except for non-US-born White (adjusted RR, 0.85; 95% CI, 0.84-0.86) and Hispanic (adjusted RR, 0.98; 95% CI, 0.97-0.98) birthing people. All racially and ethnically minoritized groups had increased adjusted risks of extremely preterm birth compared with US-born White birthing people. Non-US-born individuals had a decreased risk of preterm birth within each subgroup except non-Hispanic Native Hawaiian or Other Pacific Islander individuals, in which immigrants had significantly increased risk of overall (adjusted RR, 1.07; 95% CI, 1.01-1.14), moderately (adjusted RR, 1.10; 95% CI, 0.92-1.30), and late (adjusted RR, 1.11; 95% CI, 1.02-1.22) preterm birth than their US-born counterparts., Conclusions and Relevance: Results of this cohort study suggest heterogeneity of preterm birth across maternal nativity, ethnicity, and race and gestational age categories. Understanding these patterns could aid the design of targeted preterm birth interventions and policies, especially for birthing people typically underrepresented in research.

In 2022, 3.7 million children were born in the United States, of whom ∼600 000 received care from a neonatologist. The dramatic growth of the neonatal-perinatal medicine (NPM) workforce from 375 in 1975 to 5250 in 2022 has paralleled exploding clinical demand. As newborn medicine continues to push the limits of gestational viability and medical complexity, the NPM workforce must advance in numbers, clinical capability, scientific discovery, and leadership. This article, as part of an American Board of Pediatrics Foundation-sponsored supplement that is designed to project the future of the pediatric subspecialty workforce, features a discussion of the NPM workforce's history and current status, factors that have shaped its current profile, and some plausible scenarios of the workforce's needs and configuration in the future. In the article, we use an analytical model that forecasts the growth trajectory of the neonatologist workforce from 2020 through 2040. The model uses recent data on the number of neonatologists and clinical work equivalents per 100 000 children and projects future workforce supply under several theoretical scenarios created by modifying key baseline parameters. The predictions of this model confirm the need for a greater sustainable clinical capacity of the NPM workforce. Several future trends indicate that there may be geographic shortages of neonatologists, similar to expected shortages in other pediatric subspecialties. We do not address what an appropriate target for workforce size should be with the model or this article because the current and projected geographic variability in the NPM workforce and risk-appropriate care suggest that a uniform answer is unlikely., (Copyright © 2024 by the American Academy of Pediatrics.)

Objective: To determine changes in incretins, systemic inflammation, intestinal permeability and microbiome modifications 12 months after metabolic RYGB (mRYGB) in patients with type 2 diabetes (T2D) and their relationship with metabolic improvement., Materials and Methods: Prospective single-center non-randomized controlled study, including patients with class II-III obesity and T2D undergoing mRYGB. At baseline and one year after surgery we performed body composition measurements, biochemical analysis, a meal tolerance test (MTT) and lipid test (LT) with determination of the area under the curve (AUC) for insulin, C-peptide, GLP-1, GLP-2, and fasting determinations of succinate, zonulin, IL-6 and study of gut microbiota., Results: Thirteen patients aged 52.6 ± 6.5 years, BMI 39.3 ± 1.4 kg/m 2 , HbA 1c 7.62 ± 1.5% were evaluated. After mRYGB, zonulin decreased and an increase in AUC after MTT was observed for GLP-1 (pre 9371 ± 5973 vs post 15788 ± 8021 pM, P <0.05), GLP-2 (pre 732 ± 182 vs post 1190 ± 447 ng/ml, P <0.001) and C- peptide, as well as after LT. Species belonging to Streptococaceae, Akkermansiacea, Rickenellaceae, Sutterellaceae, Enterobacteriaceae, Oscillospiraceae, Veillonellaceae, Enterobacterales&#95;uc, and Fusobacteriaceae families increased after intervention and correlated positively with AUC of GLP-1 and GLP-2, and negatively with glucose, HbA 1c , triglycerides and adiposity markers. Clostridium perfringens and Roseburia sp. 40&#95;7 behaved similarly. In contrast, some species belonging to Lachnospiraceae, Erysipelotricaceae, and Rumnicocaceae families decreased and showed opposite correlations. Higher initial C-peptide was the only predictor for T2D remission, which was achieved in 69% of patients., Conclusions: Patients with obesity and T2D submitted to mRYGB show an enhanced incretin response, a reduced gut permeability and a metabolic improvement, associated with a specific microbiota signature., 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., (Copyright © 2023 Hernández-Montoliu, Rodríguez-Peña, Puig, Astiarraga, Guerrero-Pérez, Virgili, López-Urdiales, Osorio, Monseny, Lazzara, Sobrino, Pérez-Maraver, Pérez-Prieto, Pellitero, Fernández-Veledo, Vendrell and Vilarrasa.)

Objective: Succinate and succinate receptor 1 (SUCNR1) are linked to fibrotic remodeling in models of non-alcoholic fatty liver disease (NAFLD), but whether they have roles beyond the activation of hepatic stellate cells remains unexplored. We investigated the succinate/SUCNR1 axis in the context of NAFLD specifically in hepatocytes., Methods: We studied the phenotype of wild-type and Sucnr1 -/- mice fed a choline-deficient high-fat diet to induce non-alcoholic steatohepatitis (NASH), and explored the function of SUCNR1 in murine primary hepatocytes and human HepG2 cells treated with palmitic acid. Lastly, plasma succinate and hepatic SUCNR1 expression were analyzed in four independent cohorts of patients in different NAFLD stages., Results: Sucnr1 was upregulated in murine liver and primary hepatocytes in response to diet-induced NASH. Sucnr1 deficiency provoked both beneficial (reduced fibrosis and endoplasmic reticulum stress) and detrimental (exacerbated steatosis and inflammation and reduced glycogen content) effects in the liver, and disrupted glucose homeostasis. Studies in vitro revealed that hepatocyte injury increased Sucnr1 expression, which when activated improved lipid and glycogen homeostasis in damaged hepatocytes. In humans, SUCNR1 expression was a good determinant of NAFLD progression to advanced stages. In a population at risk of NAFLD, circulating succinate was elevated in patients with a fatty liver index (FLI) ≥60. Indeed, succinate had good predictive value for steatosis diagnosed by FLI, and improved the prediction of moderate/severe steatosis through biopsy when added to an FLI algorithm., Conclusions: We identify hepatocytes as target cells of extracellular succinate during NAFLD progression and uncover a hitherto unknown function for SUCNR1 as a regulator of hepatocyte glucose and lipid metabolism. Our clinical data highlight the potential of succinate and hepatic SUCNR1 expression as markers to diagnose fatty liver and NASH, respectively., Competing Interests: Declaration of competing interest None., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Importance: Appreciation for the effects of neighborhood conditions and community factors on perinatal health is increasing. However, community-level indices specific to maternal health and associations with preterm birth (PTB) have not been assessed., Objective: To examine the association of the Maternal Vulnerability Index (MVI), a novel county-level index designed to quantify maternal vulnerability to adverse health outcomes, with PTB., Design, Setting, and Participants: This retrospective cohort study used US Vital Statistics data from January 1 to December 31, 2018. Participants included 3 659 099 singleton births at 22 plus 0/7 to 44 plus 6/7 weeks of gestation born in the US. Analyses were conducted from December 1, 2021, through March 31, 2023., Exposure: The MVI, a composite measure of 43 area-level indicators, categorized into 6 themes reflecting physical, social, and health care landscapes. Overall MVI and theme were stratified by quintile (very low to very high) by maternal county of residence., Main Outcomes and Measures: The primary outcome was PTB (gestational age <37 weeks). Secondary outcomes were PTB categories: extreme (gestational age ≤28 weeks), very (gestational age 29-31 weeks), moderate (gestational age 32-33 weeks), and late (gestational age 34-36 weeks). Multivariable logistic regression quantified associations of MVI, overall and by theme, with PTB, overall and by PTB category., Results: Among 3 659 099 births, 298 847 (8.2%) were preterm (male, 51.1%; female, 48.9%). Maternal race and ethnicity included 0.8% American Indian or Alaska Native, 6.8% Asian or Pacific Islander, 23.6% Hispanic, 14.5% non-Hispanic Black, 52.1% non-Hispanic White, and 2.2% with more than 1 race. Compared with full-term births, MVI was higher for PTBs across all themes. Very high MVI was associated with increased PTB in unadjusted (odds ratio [OR], 1.50 [95% CI, 1.45-1.56]) and adjusted (OR, 1.07 [95% CI, 1.01-1.13]) analyses. In adjusted analyses of PTB categories, MVI had the largest association with extreme PTB (adjusted OR, 1.18 [95% CI, 1.07-1.29]). Higher MVI in the themes of physical health, mental health and substance abuse, and general health care remained associated with PTB overall in adjusted models. While the physical health and socioeconomic determinant themes were associated with extreme PTB, physical health, mental health and substance abuse, and general health care themes were associated with late PTB., Conclusions and Relevance: The findings of this cohort study suggest that MVI was associated with PTB even after adjustment for individual-level confounders. The MVI is a useful measure for county-level PTB risk that may have policy implications for counties working to lower preterm rates and improve perinatal outcomes.

Adipose tissue modulates energy homeostasis by secreting leptin, but little is known about the factors governing leptin production. We show that succinate, long perceived as a mediator of immune response and lipolysis, controls leptin expression via its receptor SUCNR1. Adipocyte-specific deletion of Sucnr1 influences metabolic health according to nutritional status. Adipocyte Sucnr1 deficiency impairs leptin response to feeding, whereas oral succinate mimics nutrient-related leptin dynamics via SUCNR1. SUCNR1 activation controls leptin expression via the circadian clock in an AMPK/JNK-C/EBPα-dependent manner. Although the anti-lipolytic role of SUCNR1 prevails in obesity, its function as a regulator of leptin signaling contributes to the metabolically favorable phenotype in adipocyte-specific Sucnr1 knockout mice under standard dietary conditions. Obesity-associated hyperleptinemia in humans is linked to SUCNR1 overexpression in adipocytes, which emerges as the major predictor of adipose tissue leptin expression. Our study establishes the succinate/SUCNR1 axis as a metabolite-sensing pathway mediating nutrient-related leptin dynamics to control whole-body homeostasis., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Physicians who identify as Black, Latinx, American Indian, Pacific Islander, and certain Asian subgroups represent racial and ethnic populations that are underrepresented in medicine (URM). While the proportion of URM pediatric trainees has remained unchanged, that of Neonatal-Perinatal Medicine (NPM) fellows has decreased. Informed by the medical literature and our lived experiences, we compiled and developed a list of recommendations to support NPM fellowship programs in the recruitment, retention, and promotion of URM trainees. We describe ten recommendations that address 1) creating a culture of inclusivity and psychological safety, 2) the critical appraisal of recruitment practices and climate, and 3) an inclusive and holistic fellowship application process. The first two themes lay the foundation, while the final theme spotlights our recommendations for URM recruitment. Each recommendation is a step towards improvement in recruitment and inclusion at a program., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

In the last years, extracellular vesicles (EVs), secreted by various cells and body fluids have shown extreme potential in biomedical applications. Increasing number of studies suggest that a protein corona could adhere to the surface of EVs which can have a fundamental effect on their function, targeting and therapeutical efficacy. However, removing and identifying these corona members is currently a challenging task to achieve. In this study we have employed red blood cell-derived extracellular vesicles (REVs) as a model system and three membrane active antimicrobial peptides (AMPs), LL-37, FK-16 and CM15, to test whether they can be used to remove protein corona members from the surface of vesicles. These AMPs were reported to preferentially exert their membrane-related activity via one of the common helical surface-covering models and do not significantly affect the interior of lipid bilayer bodies. The interaction between the peptides and the REVs was followed by biophysical techniques, such as flow-linear dichroism spectroscopy which provided the effective applicable peptide concentration for protein removal. REV samples were then subjected to subsequent size exclusion chromatography and to proteomics analysis. Based on the comparison of control REVs with the peptide treated samples, seventeen proteins were identified as external protein corona members. From the three investigated AMPs, FK-16 can be considered as the best candidate to further optimize EV-related applicability of AMPs. Our results on the REV model system envisage that membrane active peptides may become a useful set of tools in engineering and modifying surfaces of EVs and other lipid-based natural particles., Competing Interests: The authors report no conflict of interest., (© 2023 The Authors. Journal of Extracellular Biology published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles.)

Background: Racial/ethnic inequities in mother's milk provision for hospitalized preterm infants persist. The extent to which primary language contributes to these racial/ethnic inequities is unknown. Objective: Examine associations of maternal race/ethnicity and primary language with (1) any/exclusive mother's milk at hospital discharge and (2) the time to cessation of mother's milk provision during the hospitalization. Methods: We examined 652 mother/very-low-birthweight (VLBW) infant dyads at 9 level 3 neonatal intensive care units in Massachusetts from January 2017 to December 2018. We abstracted maternal race/ethnicity and language from medical records, and examined English and non-English-speaking non-Hispanic White (NHW), non-Hispanic Black (NHB), and Hispanic mothers of any race. We examined associations of race/ethnicity and language with (1) any/exclusive mother's milk at discharge (yes/no) using mixed-effects logistic regression and (2) cessation of mother's milk during the hospitalization using cox proportional hazard models, adjusting for gestational age, birthweight, and accounting for clustering by plurality and hospital. Results: Fifty-three percent were English-speaking NHW, 22% English-speaking NHB, 4% non-English-speaking NHB, 14% English-speaking Hispanic, and 7% non-English-speaking Hispanic. Compared with English-speaking NHW, NHB mothers (English adjusted odds ratio [aOR] 0.28 [0.17, 0.44]; and non-English-speaking aOR 0.55 [0.19, 0.98]), and non-English-speaking Hispanic mothers (aOR 0.29 [0.21, 0.87]) had lower odds of any mother's milk at discharge. In time-to-event analyses, non-English-speaking Hispanic (adjusted hazard ratio [aHR] 4.37 [2.20, 6.02]) and English-speaking NHB mothers (aHR 3.91 [1.41, 7.61] had the earliest cessation of mother's milk provision. Conclusion: In Massachusetts, maternal primary language was associated with inequities in mother's milk provision for VLBW infants with a differential effect for NHB and Hispanic mothers.

Significant racial and ethnic disparities exist in birth outcomes and complications related to prematurity. However, little is known about racial and ethnic variations in health outcomes after premature infants are discharged from the neonatal intensive care unit (NICU). We propose a novel, equity-focused conceptual model to guide future evaluations of post-discharge outcomes that centers on a multi-dimensional, comprehensive view of health, which we call thriving. We then apply this model to existing literature on post-discharge inequities, revealing a need for rigorous analysis of drivers and strength-based, longitudinal outcomes., Competing Interests: Disclosure statement The authors report no proprietary or commercial interest in any product mentioned or concept discussed in this article., (Copyright © 2022 Elsevier Inc. All rights reserved.)

I arrived to my shift early, nervous about caring for critically ill patients as a first-year fellow. I sat in the workroom alone, paralyzed, not sure how to preround despite being months into fellowship. The senior fellow appeared minutes before sign-out; fresh, knowledgeable, and calm, despite her busy night and lack of sleep. She asked me how I was doing. With tears in my eyes, my emotions poured out. I explained that I felt lost, unsure of myself, my place, and my knowledge. For the first time, I confessed out loud, "I don't think I'm supposed to be here. I have no idea what I'm doing." I could trust her in a way I couldn't trust others. She was like me: othered by her identity, minoritized by society. Though different from my own, her identity allowed her to understand my own experiences. We were different from one another and we were also the same. Unlike the senior faculty, it was safe to talk to her. And, unlike my other cofellows, there was a kinship between us in our otherness. She looked at me, closed the door, and shared words of strength that I needed to hear. I belonged. I was more than enough. She shared that the pressure I was experiencing was common among systematically minoritized individuals; she too had felt it before. Sitting with her, I was finally seen, supported, and comforted. As a peer mentor from a minoritized background, she provided a sense of security and belonging that had not been provided in my training and was distinct from the support of senior faculty., (Copyright © 2022 by the American Academy of Pediatrics.)

Background: Succinate is produced by both human cells and by gut bacteria and couples metabolism to inflammation as an extracellular signaling transducer. Circulating succinate is elevated in patients with obesity and type 2 diabetes and is linked to numerous complications, yet no studies have specifically addressed the contribution of gut microbiota to systemic succinate or explored the consequences of reducing intestinal succinate levels in this setting., Results: Using germ-free and microbiota-depleted mouse models, we show that the gut microbiota is a significant source of circulating succinate, which is elevated in obesity. We also show in vivo that therapeutic treatments with selected bacteria diminish the levels of circulating succinate in obese mice. Specifically, we demonstrate that Odoribacter laneus is a promising probiotic based on its ability to deplete succinate and improve glucose tolerance and the inflammatory profile in two independent models of obesity (db/db mice and diet-induced obese mice). Mechanistically, this is partly mediated by the succinate receptor 1. Supporting these preclinical findings, we demonstrate an inverse correlation between plasma and fecal levels of succinate in a cohort of patients with severe obesity. We also show that plasma succinate, which is associated with several components of metabolic syndrome including waist circumference, triglycerides, and uric acid, among others, is a primary determinant of insulin sensitivity evaluated by the euglycemic-hyperinsulinemic clamp., Conclusions: Overall, our work uncovers O. laneus as a promising next-generation probiotic to deplete succinate and improve glucose tolerance and obesity-related inflammation. Video Abstract., (© 2022. The Author(s).)

Neonatal patients and families from historically marginalized and discriminated communities have long been documented to have differential access to health care, disparate health care, and as a result, inequitable health outcomes. Fundamental to these processes is an understanding of what race and ethnicity represent for patients and how different levels of racism act as social determinants of health. The NICU presents a unique opportunity to intervene with regard to the detrimental ways in which structural, institutional, interpersonal, and internalized racism affect the health of newborn infants. The aim of this article is to provide neonatal clinicians with a foundational understanding of race, racism, and antiracism within medicine, as well as concrete ways in which health care professionals in the field of neonatology can contribute to antiracism and health equity in their professional careers., (Copyright © 2022 by the American Academy of Pediatrics.)

Objective: The advance of the pandemic in the large cities of the world with great virulence and the apparent heterogeneous distribution by factors of vulnerability, led us to propose this work. The objective of this study was to relate COVID-19 infection rates to the social vulnerability of the city of Madrid by district, in two different episodes, spring 2020 and summer 2020., Methods: Analytical cross-sectional study. Taking sociodemographic data of the entire population of the city of Madrid between the months of April and October 2020, together with the cumulative incidence rates of COVID-19, a linear regression analysis, correlation and factor analysis was carried out, relating the cumulative incidence rate of COVID-19 and the vulnerability indicator of the districts of the city of Madrid., Results: The results showed important differences between the two episodes of the pandemic: on one hand, the first had more relationship with health factors, while in the second, a relationship appeared with the groups of greater social vulnerability, territorially located in the South-East of the City and related in this case to social factors rather than health. Thus we see that the TIA x 100,000 in the first episode in Chamberí and Usera -two extreme districts in vulnerability- were 896 and 843 cases respectively, while in the second they were 3,708 and 6,258 cases., Conclusions: The territorial differences in the city become evident with the arrival of a generalised, universal event such as COVID-19, where vulnerability increases for everyone, with greater repercussions in those territories where it already had an impact., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Evidence of health disparities affecting newborns abounds. Although quality improvement (QI) methodology is often suggested as a tool to advance health equity, the impact of QI initiatives on disparities is variable. QI work may mitigate, worsen, or perpetuate existing disparities. QI projects designed without an intentional focus on equity promotion may foster intervention-generated inequalities that further disadvantage vulnerable groups. This article reviews disparities in perinatal and neonatal care, the impact of QI on health disparities, and the concept of "Equity-Focused Quality Improvement" (EF-QI). EF-QI differs from QI with an equity lens in that it is action-oriented and centered around equity. EF-QI initiatives purposely integrate equity throughout the fabric of the project and are inclusive, collaborative efforts that foreground and address the needs of disadvantaged populations. EF-QI principles are applicable at every stage of project conception, execution, analysis, and dissemination, and may provide opportunities for reducing disparities in neonatal care., (© 2021 Published by Elsevier Ltd.)

Objective: Territoriality is configured as an important axis of inequality. The objective of this study was to determine the level of association between territory and vulnerability, specifying proposals for territorial intervention using key socio-health indicators., Methods: Analytical cross-sectional study, which combined the analysis of the Health Survey Madrid City 2017 (n=9,513) and the vulnerability-ranking indicator of the same year (n=2,780,197), popu-lation of the city of Madrid in 2017, from the Data Bank of the Madrid City Council), prepared with the hierarchical analysis technique. Sociodemographic and health variables were included, such as self-perception of health status, quality of life in relation to health, tobacco consumption, alcohol, obesity, sedentary lifestyle and mental health (GHQ-12). The relationships were assessed with DE, 95% CI, Spearman correlation, B and β coefficients of multiple linear regression and the pair-point technique., Results: The links between health and vulnerability were: in health-self-perceived and HRQL, as global health variables, p<0.01 for women with territory and vulnerability; sedentary lifestyle for both sexes, was interpreted with 60-80% by territory and vulnerability; obesity was slightly linked to the te-ritory in women and explained 77%; mental health was not territorially related for the group, but it was significantly related to women, due to 64% of the variance; in tobacco there was a significant territorial link in men and vulnerability in 57%; finally, alcohol had a significant difference in men at the territorial level and explained in 72% in both sexes, inverted., Conclusions: The results support the behavior of global and specific health indicators with vulnerability, with a disaggregation by sex, which will allow planning adapted to the territory., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Aphasia is an acquired language disorder due to a cerebral lesion; it is characterized by errors in production, denomination, or comprehension of language. Although most aphasias are mixed, from a practical point of view they are classified into different types according to their main clinical features: Broca's aphasia, Wernicke's aphasia, conduction aphasia, transcortical aphasia, and alexia with or without agraphia. We present the clinical findings for the main subtypes of aphasia, illustrating them with imaging cases, and we provide an up-to-date review of the language network with images from functional magnetic resonance imaging and tractography., (Copyright © 2018 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.)

Diffusion tensor imaging (DTI) and tractography provide the neurosurgeon with a valid 3D view of the white matter tracts of the brain for the presurgical planning of the treatment of lesions close to eloquent areas, this being one of the principal clinical applications of this technique. In this article, we describe through practical cases the anatomic relationships of white matter tracts that are essential for language and reading, based on DTI studies and the excellent anatomic correlation with the intraoperative subcortical map.

The homeoprotein Six1 is overexpressed in many human cancers and is associated with increased tumor progression and metastasis. Recent studies have shown that Six1 is associated with poorer overall survival in advanced-stage colorectal cancer (CRC). In the current study, we explored the functional changes and molecular events associated with Six1 overexpression in a mouse model of CRC. An orthotopic model and a splenic injection metastasis model were used to investigate the role of Six1 in CRC tumor growth and metastasis using mouse colon adenocarcinoma MC38 cells overexpressing Six1. We found that overexpression of Six1 dramatically promotes CRC tumor growth and metastasis in vivo. Six1 overexpression in MC38 increased protein levels of aldehyde dehydrogenase-1 and expanded CD44+/CD166+ populations, indicating Six1 increased features of cancer stem cells. In addition, Six1 overexpression stimulated angiogenesis by upregulating the expression of vascular endothelial growth factor (VEGF). Six1-overexpressing tumor cells recruited tumor-associated macrophages (TAM) by increasing the expression of macrophage-specific colony stimulating factor, chemokine (C-C motif) ligand 2/5 and VEGF, further facilitating CRC tumor growth and metastasis. Furthermore, we determined that Six1 activated mitogen-activated protein kinase (MAPK) signaling in CRC cells. In summary, our studies strongly suggest that Six1 overexpression promotes CRC growth and metastasis and remodels tumor stroma by stimulating angiogenesis and recruiting TAM. MAPK activation may be a pivotal event in Six1-associated tumor progression, which may provide opportunities for pharmacologic intervention., (© The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Liver metastasis is the major cause of death from colorectal cancer (CRC). Understanding its mechanisms is necessary for timely diagnosis and development of effective therapies. Interleukin-33 (IL-33) is an IL-1 cytokine family member that uniquely functions as a cytokine and nuclear factor. It is released by necrotic epithelial cells and activated innate immune cells, functioning as an alarmin or an early danger signal. Its role in invoking type 2 immune response has been established; however, it has contrasting roles in tumor development and metastasis. We identified IL-33 as a potently upregulated cytokine in a highly metastatic murine CRC cell line and examined its role in tumor growth and metastasis to the liver. IL-33 was transgenically expressed in murine and human adenocarcinoma and carcinoma cell lines and their growth and spontaneous metastasis to the liver were assessed in orthotopic models of CRC in wild-type C57Bl/6 and Il33 knockout mice. The results showed that increased expression of IL-33 in CRC cells enhanced their tumor take, growth, and liver metastasis. Tumor- rather than host-derived IL-33 induced the enhanced recruitment of CD11b + GR1 + and CD11b + F4/80 + myeloid cells to remodel the tumor microenvironment by increased expression of mobilizing cytokines, and tumor angiogenesis by activating endothelial cells. IL-33 expression was elevated in patient tumor tissues, induced early in adenoma development, and activated by pro-inflammatory cytokines derived from the tumor microenvironment. The data suggest that tumor-derived IL-33 modulates the tumor microenvironment to potently promote colon carcinogenesis and liver metastasis, underscoring its potential as a therapeutic target. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Microbial infections are a major cause of infant mortality as a result of limitations in immune defences. Interleukin-27 (IL-27) is a heterodimeric cytokine produced primarily by leucocytes and is immunosuppressive toward lymphocytes and leucocytes. Our laboratory demonstrated that human neonatal macrophages express IL-27 more abundantly than adult macrophages. Similarly in mice, IL-27 expression is elevated early in life and maintained through infancy. To determine IL-27-regulated mechanisms that may limit immunity, we evaluated the expression of a number of genes in response to this cytokine in primary human neonatal macrophages. Indoleamine 2,3-dioxygenase (IDO) gene expression was increased dose-responsively by IL-27. We have previously demonstrated inhibition of T-cell proliferation and cytokine production by neonatal macrophage-generated IL-27, and IDO is often implicated in this negative regulation. An increase in IDO protein was demonstrated by immunofluorescence microscopy and was consistent with increased enzyme activity following treatment with IL-27. Inclusion of a soluble receptor to neutralize endogenous IL-27, decreased IDO expression and activity compared with untreated macrophages. In response to IL-27, neonatal macrophages phosphorylate signal transdcuer and activator of transcription 1 (STAT-1) and STAT-3. Both transcription factors are recruited to the IDO regulatory region. STAT-3 dominates during steady-state regulation by lower levels of endogenous IL-27 production. A shift to enhanced STAT-1 recruitment occurs during increased levels of exogenously supplied IL-27. These data suggest an interesting interplay of STAT-1 and STAT-3 to regulate IDO activity and immunosuppression in response to different levels of IL-27 in the microenvironment of the immune response that may further our understanding of this interesting cytokine., (© 2016 John Wiley & Sons Ltd.)

Study Objectives: To examine the association between race/ethnicity and sleep curtailment from infancy to mid-childhood, and to determine the extent to which socioeconomic and contextual factors both explain racial/ethnic differences and are independently associated with sleep curtailment., Methods: We studied 1,288 children longitudinally in Project Viva, a pre-birth cohort study, from 6 months to 7 years of age. The main exposure was the child's race/ethnicity. The main outcome was a sleep curtailment score from 6 months to 7 years. The score ranged from 0-13, where 0 indicated maximal sleep curtailment and 13 indicated never having curtailed sleep., Results: The mean (standard deviation) sleep curtailment score was 10.2 (2.7) points. In adjusted models (β [95% CI]), black (-1.92, [-2.39, -1.45] points), Hispanic (-1.58, [-2.43, -0.72] points), and Asian (-1.71, [-2.55, -0.86] points) children had lower sleep scores than white children. Adjustment for sociodemographic covariates attenuated racial/ethnic differences in sleep scores for black (by 24%) and Hispanic children (by 32%) but strengthened the differences for Asian children by 14%. Further adjustment for environmental and behavioral variables did not substantially change these differences. Independently, low maternal education, living in households with incomes < $70,000, viewing more TV, and having a TV in the child's bedroom were associated with lower sleep scores., Conclusions: Chronic sleep curtailment from infancy to mid-childhood was more prevalent among black, Hispanic, and Asian children. These differences were partially but not entirely explained by socio-contextual variables. Independently, children from lower socioeconomic status and those with greater exposures to TV also had greater sleep curtailment., (© 2016 Associated Professional Sleep Societies, LLC.)

Objective: To examine associations of chronic insufficient sleep with mid-childhood cardiometabolic health., Methods: At 6 months and yearly from 1 to 7 years, mothers participating in the Project Viva cohort reported children's 24-h sleep duration. The main exposure was a sleep curtailment score, ranging from 0 (maximal curtailment) to 13 (never having curtailed sleep). The main outcome was a mid-childhood metabolic risk score, derived as the mean of five sex- and cohort-specific z scores for waist circumference, systolic blood pressure, HDL cholesterol (scaled inversely), and log-transformed triglycerides and HOMA-IR; higher scores indicate higher risk., Results: The mean (SD) sleep score was 10.0 (2.8); 5.1% scored 0-4, 13.9% scored 5-7, 14.1% scored 8-9, 28.7% scored 10-11, and 38.3% scored 12-13. Mean (SD, range) metabolic risk score was -0.03 (0.6, -1.8 to 2.6). In multivariable models, the metabolic risk score difference for children with most versus least curtailed sleep was 0.29 units (95% confidence interval [CI]: 0.02, 0.57). Further adjustment for mid-childhood BMI z score attenuated this difference to 0.08 units (95% CI: -0.14, 0.30)., Conclusions: Chronic insufficient sleep from infancy to school-age was associated with higher mid-childhood metabolic risk. This association was explained by sleep duration's influence on mid-childhood adiposity., (© 2014 The Obesity Society.)

Ideal "smart" nanoparticles for drug delivery should enhance therapeutic efficacy without introducing side effects. To achieve that, we developed a drug delivery system (HCN) based on a polymer-drug conjugate of poly[2-(pyridin-2-yldisulfanyl)]-graft-poly(ethylene glycol) and camptothecin with an intracellularly cleavable linker and human epidermal growth factor receptor 2 (HER2) targeting ligands. An in vitro drug release study found that HCN was stable in the physiological environment and supersensitive to the stimulus of elevated intracellular redox potential, releasing all payloads in less than 30 min. Furthermore, confocal microscopy revealed that HCN could specifically enter HER2-positive cancer cells. As a consequence, HCN could effectively kill HER2-positive cancer cells while not affecting HER2-negative cells.

Six1, a member of the Six family of homeodomain transcription factors, is overexpressed in various human cancers, and SIX1 overexpression is associated with tumor progression and metastasis. Six1 messenger RNA levels increase during in vitro progression of human papillomavirus type 16 (HPV16)-immortalized human keratinocytes (HKc/HPV16) toward a differentiation-resistant (HKc/DR) phenotype. In this study, we show that HKc/DR-overexpressing Six1 exhibited a more mesenchymal phenotype, as characterized by a fibroblastic appearance and increased invasion. We utilized Whole Human Genome Microarrays to explore the gene expression changes associated with Six1 overexpression in HKc/DR. We found that overexpression of Six1 downregulated epithelial-related genes and upregulated mesenchymal-related genes, which suggests that Six1 overexpression induces epithelial-mesenchymal transition (EMT). Pathway analysis of the microarray data showed alterations in the transforming growth factor-beta (TGF-β) pathway, including enhanced expression of the TGF-β receptor type II (TβRII), and activation of the mitogen-activated protein kinase (MAPK) pathway in HKc/DR-overexpressing Six1, suggesting that Smad-independent pathways of TGF-β signaling may be involved in Six1-mediated EMT. p38 MAPK activation was required for sustained Six1-induced EMT and TβRII overexpression. Finally, we determined that Six1 overexpression in HKc/DR resulted in malignant conversion and increased the cancer stem cell (CSC)-like population. Thus, Six1 overexpression promotes EMT, CSCs properties and malignant conversion in HKc/DR through MAPK activation, which supports the possible use of p38-TβRII inhibitors for the treatment of cancers overexpressing Six1., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objectives: To examine the extent to which chronic sleep curtailment from infancy to mid-childhood is associated with total and central adiposity., Methods: We studied 1046 children participating in a prospective cohort study. At age 6 months and yearly from age 1 to 7 years, mothers reported their children's sleep duration in a usual 24-hour period. The main exposure was a sleep curtailment score from age 6 months to 7 years. The range of the total score was 0 to 13, where 0 indicated the maximal sleep curtailment and 13 indicated never having curtailed sleep. Outcomes in mid-childhood were BMI z score, dual X-ray absorptiometry total and trunk fat mass index (kg/m(2)), and waist and hip circumferences (cm)., Results: The mean (SD) sleep score was 10.2 (2.7); 4.4% scored a 0 to 4, indicating multiple exposures to sleep curtailment between age 6 months to 7 years, 12.3% scored 5 to 7, 14.1% scored 8 to 9, 28.8% scored 10 to 11, and 40.3% scored 12 to 13. In multivariable models, children who had a sleep score of 0 to 4 had a BMI z score that was 0.48 U (95% confidence interval, 0.13 to 0.83) higher than those who had a sleep score of 12 to 13. We observed similar associations of higher total and trunk fat mass index and waist and hip circumferences, and higher odds of obesity (odds ratio, 2.62; 95% confidence interval, 0.99 to 6.97) among children who had a score of 0 to 4 vs 12 to 13., Conclusions: Chronic sleep curtailment from infancy to school age was associated with higher overall and central adiposity in mid-childhood., (Copyright © 2014 by the American Academy of Pediatrics.)

HIV-associated neurocognitive disorder (HAND), characterized by a wide spectrum of behavioral, cognitive, and motor dysfunctions, continues to affect approximately 50 % of HIV(+) patients despite the success of combination antiretroviral drug therapy (cART) in the periphery. Of note, potential toxicity of antiretroviral drugs in the central nervous system (CNS) remains remarkably underexplored and may contribute to the persistence of HAND in the cART era. Previous studies have shown antiretrovirals (ARVs) to be neurotoxic in the peripheral nervous system in vivo and in peripheral neurons in vitro. Alterations in lipid and protein metabolism, mitochondrial damage, and oxidative stress all play a role in peripheral ARV neurotoxicity. We hypothesized that ARVs also induce cellular stresses in the CNS, ultimately leading to neuronal damage and contributing to the changing clinical and pathological picture seen in HIV-positive patients in the cART era. In this report, we show that ARVs are neurotoxic in the CNS in both pigtail macaques and rats in vivo. Furthermore, in vitro, ARVs lead to accumulation of reactive oxygen species (ROS), and ultimately induction of neuronal damage and death. Whereas ARVs alone caused some activation of the endogenous antioxidant response in vitro, augmentation of this response by a fumaric acid ester, monomethyl fumarate (MMF), blocked ARV-induced ROS generation, and neuronal damage/death. These findings implicate oxidative stress as a contributor to the underlying mechanisms of ARV-induced neurotoxicity and will provide an access point for adjunctive therapies to complement ARV therapy and reduce neurotoxicity in this patient population.

Colorectal cancer (CRC) is the third most frequent cancer and the third leading cause of cancer deaths in the United States (American Cancer Society, Cancer facts and figures 2012, 20121). The major cause of death is metastasis and frequently, the target organ is the liver. Successful metastasis depends on acquired properties in cancer cells that promote invasion and migration, and on multiple interactions between tumors and host-derived cells in the microenvironment. These processes, however, occur asymptomatically, thus, metastasis remains poorly understood and often diagnosed only at the final stage. To facilitate the elucidation of the mechanisms underlying these processes and to identify the molecular regulators, particularly at the early stages, we developed a mouse model of hepatic metastasis of CRC by cecal implantation of a mouse adenocarcinoma cell line in an immune competent host that reliably recapitulates all steps of tumor growth and metastasis within a defined period. By in vivo selection, we isolated cells of varying metastatic potential. The most highly metastatic CT26-FL3 cells produced liver metastasis as early as 10 days after implantation in 90 % of host mice. These cells expressed elevated levels of genes whose products promote invasion, migration, and mobilization of bone marrow derived cells (BMDCs). Mice bearing tumors from CT26-FL3 had elevated serum levels of OPN, MMP9, S100A8, S100A9, SAA3, and VEGFA that promote invasion and BMDC mobilization, and showed enhanced BMDC recruitment to the liver where they established a pre-metastatic niche. This model provides an important platform to characterize metastatic cells and elucidate tumor-host interactions and mechanisms that drive liver metastasis of CRC.

Microbial infections are a major cause of infant mortality worldwide because of impaired immune defences in this population. The nature of this work was to further understand the mechanistic limitations of the neonatal and infant immune response. Interleukin-27 (IL-27) is a heterodimeric cytokine of the IL-12 family that is produced primarily by antigen-presenting cells and is immunosuppressive toward a variety of immune cell types. We show that IL-27 gene expression is elevated in cord blood-derived macrophages relative to macrophages originating from healthy adults. We also evaluated the duration over which elevated IL-27 gene expression may impact immune responses in mice. Age-dependent analysis of IL-27 gene expression indicated that levels of IL-27 remained significantly elevated throughout infancy and then declined in adult mice. Flow cytometric analysis of intracellular cytokine-stained splenocytes further confirmed these results. Interleukin-27 may be induced during pregnancy to contribute to the immunosuppressive environment at the fetal-maternal interface because we demonstrate dose-responsive gene expression to progesterone in macrophages. Neutralization of IL-27 in neonatal macrophages improved the ability of these cells to limit bacterial replication. Moreover, neutralization of IL-27 during incubation with the Mycobacterium bovis bacillus Calmette-Guérin vaccine augmented the level of interferon-γ elicited from allogeneic CD4+ T lymphocytes. This suggests that blocking IL-27 during vaccination and infection may improve immune responses in newborn and infant populations. Furthermore, mice will be a suitable model system to further address these possibilities., (© 2013 John Wiley & Sons Ltd.)

The objectives were to evaluate prevalence of endometrial disease in patients treated with tamoxifen (TAM) and analyze the epidemiological, sonographic, hysteroscopic and histopathological findings. From January 1999 to December 2008, 152 breast cancer patients treated with TAM (20 mg/day), symptomatic (with bleeding) or asymptomatic, pre-and postmenopausal, were included consecutively in a prospective and observational follow-up study. Diagnostic methods were (TV) transvaginal ultrasound, hysteroscopy and curettage biopsy. TV ultrasound was performed every 12 months for 12 to 60 months. The patients' age were 62.76 years ± 10.24 the TAM-time: 36.24 ± 19. Adenocarcinoma was observed in 3/87 patients (3.45%) with risk factors and in 1/65 (1.54%) without them (RA 1.91, IC 95% 1.88-1.94). We found benign disease in 148 patients (97.37%) and adenocarcinomas in 4 (2.63%), one within a polyp. The 4 adenocarcinomas were detected in postmenopausal women (2 asymptomatic) with endometrial thicknesses equal or greater than 16 mm. The cancer risk was significantly increased in symptomatic (2.36 versus 0.42 in asymptomatic). Three adenocarcinomas were observed between 24 and 48 months of treatment. In conclusion, we suggest an adequate transvaginal ultrasound monitoring of asymptomatic patients treated with TAM, with removal of polyps, because atypia can be present hidden within, considering risk factors and exposure time. We suggest as an acceptable cut-off = 10 mm in asymptomatic postmenopausal patients.

Childhood obesity is prevalent, is of consequence, and disproportionately affects racial/ethnic minority populations. By the preschool years, racial/ethnic disparities in obesity prevalence and substantial differences in many risk factors for obesity are already present, suggesting that disparities in obesity prevalence have their origins in the earliest stages of life. The reasons for racial/ethnic variation in obesity are complex and may include differences in cultural beliefs and practices, level of acculturation, ethnicity-based differences in body image, and perceptions of media, sleep, and physical activity. In addition, racial/ethnic differences in obesity may evolve as a consequence of the socio- and environmental context in which families live. The primary care setting offers unique opportunities to intervene and alter the subsequent course of health and disease for children at risk for obesity. Regular visits during childhood allow both detection of elevated weight status and offer opportunities for prevention and treatment. Greater awareness of the behavioral, social–cultural, and environmental determinants of obesity among ethnic minority populations could assist clinicians in the treatment of obesity among diverse pediatric populations. Specific strategies include beginning prevention efforts early in life before obesity is present and recognizing and querying about ethnic- and culturally specific beliefs and practices, the role of the extended family in the household, and parents' beliefs of the causative factors related to their child's obesity. Efforts to provide culturally and linguistically appropriate care, family-based treatment programs, and support services that aim to uncouple socioeconomic factors from adverse health outcomes could improve obesity care for racial/ethnic minority children.

Eliminating racial/ethnic disparities in health and health care is a national priority, and obesity is a prime target. During the last 30 y in the United States, the prevalence of obesity among children has dramatically increased, sparing no age group. Obesity in childhood is associated with adverse cardio-metabolic outcomes such as hypertension, hyperlipidemia, and type II diabetes and with other long-term adverse outcomes, including both physical and psychosocial consequences. By the preschool years, racial/ethnic disparities in obesity prevalence are already present, suggesting that disparities in childhood obesity prevalence have their origins in the earliest stages of life. Several risk factors during pregnancy are associated with increased risk of offspring obesity, including excessive maternal gestational weight gain, gestational diabetes, smoking during pregnancy, antenatal depression, and biological stress. During infancy and early childhood, rapid infant weight gain, infant feeding practices, sleep duration, child's diet, physical activity, and sedentary practices are associated with the development of obesity. Studies have found substantial racial/ethnic differences in many of these early life risk factors for childhood obesity. It is possible that racial/ethnic differences in early life risk factors for obesity might contribute to the high prevalence of obesity among minority preschool-age children and beyond. Understanding these differences may help inform the design of clinical and public health interventions and policies to reduce the prevalence of childhood obesity and eliminate disparities among racial/ethnic minority children.

Tumors consist of a heterogeneous population of neoplastic cells infiltrated by an equally heterogeneous collection of nonneoplastic cells that comprise the tumor microenvironment. Tumor growth, invasion, and metastasis depend on multiple interactions between these cells. To assess their potential as therapeutic targets or vehicles for tumor specific delivery of therapeutic agents, we examined the contribution of bone marrow derived cells (BMDCs) to the intestinal tumor microenvironment. Hematopoietic stem cells expressing the enhanced green fluorescent protein (eGFP) were transplanted into lethally irradiated ApcMin/+ mice, and their engraftment was analyzed by confocal microscopy. The results showed abundant infiltration of eGFP cells into the small intestine, colon, and spleen compared to heart, muscle, liver, lung, and kidney. Within the intestine, there was a pronounced gradient of engraftment along the anterior to posterior axis, with enhanced infiltration into adenomas. Immunofluorescence analysis showed that osteopontin was expressed in tumor stromal cells but not in nontumor stromal populations, suggesting that gene expression in these cells is distinct. Tumor vasculature in ApcMin/+ mice was chaotic compared to normal intestinal regions. Our data suggest that BMDCs can be harnessed for tumor-targeted therapies to enhance antitumor efficacy.