CEBPA repression by MECOM blocks differentiation to drive aggressive leukemias.

Acute myeloid leukemias (AMLs) have an overall poor prognosis with many high-risk cases co-opting stem cell gene regulatory programs, yet the mechanisms through which this occurs remain poorly understood. Increased expression of the stem cell transcription factor, MECOM, underlies one key driver mechanism in largely incurable AMLs. How MECOM results in such aggressive AML phenotypes remains unknown.

Regulated GATA1 expression as a universal gene therapy for Diamond-Blackfan anemia.

Gene therapy using hematopoietic stem and progenitor cells is altering the therapeutic landscape for patients with hematologic, immunologic, and metabolic disorders but has not yet been successfully developed for individuals with the bone marrow failure syndrome Diamond-Blackfan anemia (DBA). More than 30 mutations cause DBA through impaired ribosome function and lead to inefficient translation of the erythroid master regulator GATA1, providing a potential avenue for therapeutic intervention applicable to all patients with DBA, irrespective of the underlying genotype. Here, we report the development of a clinical-grade lentiviral gene therapy that achieves erythroid lineage-restricted expression of GATA1.

Acculturation and Health Status in the Children's Healthy Living Program in the Pacific Region.

Acculturation/enculturation has been found to impact childhood health and obesity status. The objective of this study is to use cross-sectional data to examine the association between proxies of adult/caregiver acculturation/enculturation and child health status (Body Mass Index [BMI], waist circumference [WC], and acanthosis nigricans [AN]) in the U.S.

Incidence of Hypertriglyceridemia in Patients on Propofol, Clevidipine, or Both.

Background: Propofol and clevidipine (PC) are commonly used in the treatment of critically ill patients. While both medications are lipid emulsions, there is limited evidence concerning the incidence of hypertriglyceridemia (HTG) when these agents are used individually or concurrently.

Objective: The objective of this study is to determine the effects of propofol, clevidipine, or concurrent PC on triglycerides (TGs) and related outcomes in critically ill adults.

Diet Quality of Young Children in the US-Affiliated Pacific's Children's Healthy Living (CHL) Program.

Background: Childhood diet can impact health outcomes over the life course. Few studies have assessed dietary quality among infants and children in the US-Affiliated Pacific (USAP) region.

Objective: The aim of this study was to examine the differences in diet quality among Pacific children in the Children's Healthy Living (CHL) program by Pacific jurisdiction and by their World Bank Income Group (WBIG) level.

Children's Dietary Intake by Early Care and Education Setting in the US Affiliated Pacific.

Objective: Examine differences in dietary intake of children aged 2-5 years in early care and education (ECE) setting in the US Affiliated Pacific (USAP).

Design: Secondary analysis of cross-sectional data collected by the Children's Healthy Living program.

Participants: Children (n = 1,423) with complete dietary records and information on the ECE setting.

Food Security is Associated with Higher Diet Quality Among Children of the US-Affiliated Pacific Region.

Background: The prevalence of food insecurity and its relationship to diet quality are factors impacting the health of persons living across the United States-affiliated Pacific region (USAP).

Objectives: The aim of this study was to describe characterize the relationship between household food security status and diet quality of 2- to 8-y-old children across jurisdictions in the USAP.

Methods: Baseline data from 2- to 8-y-olds (n = 3099) enrolled in the Children's Healthy Living Program for Remote Underserved Minority Populations in the Pacific region, an obesity prevention study conducted in communities across Alaska, American Samoa, Commonwealth of the Northern Mariana Islands (CNMI), Guam, and Hawaii, and a concomitant prevalence study in communities across the Freely Associated States (FAS) (the Federated States of Micronesia: Kosrae, Pohnpei, Chuuk, Yap; Republic of Marshall Islands; Republic of Palau) were collected in 2012.

A genetic disorder reveals a hematopoietic stem cell regulatory network co-opted in leukemia.

The molecular regulation of human hematopoietic stem cell (HSC) maintenance is therapeutically important, but limitations in experimental systems and interspecies variation have constrained our knowledge of this process. Here, we have studied a rare genetic disorder due to MECOM haploinsufficiency, characterized by an early-onset absence of HSCs in vivo. By generating a faithful model of this disorder in primary human HSCs and coupling functional studies with integrative single-cell genomic analyses, we uncover a key transcriptional network involving hundreds of genes that is required for HSC maintenance.

Food Group, Macronutrient Intake, and Metabolic Status in the US-Affiliated Pacific's Children's Healthy Living (CHL) Program.

Background: The Children's Healthy Living study provided dietary intake information for understudied Native Hawaiian and Other Pacific Islander (NHOPI) young children.

Objectives: Our objective was to describe food group and macronutrient intakes of NHOPI children in the US-Affiliated Pacific region (USAP), overall and by jurisdiction, income level, and metabolic status.

Methods: We evaluated 2-8-y-olds (n = 3520) in a cross-sectional cluster sampled study using 2 d of dietary records completed by caregivers using provided tools, quantified by a specially developed food composition table and compared with US dietary recommendations.

Maintenance Outcomes of the Children's Healthy Living Program on Overweight, Obesity, and Acanthosis Nigricans Among Young Children in the US-Affiliated Pacific Region: A Randomized Clinical Trial.

Importance: Few obesity prevention trials among children have demonstrated sustainable outcomes in the long term.

Objectives: To sustain a community-wide decrease in the prevalence of overweight and obesity among young children in the US-affiliated Pacific region.

Design, Setting, And Participants: In the Children's Healthy Living community-randomized clinical trial, hierarchical modeling comparing the change in intervention and control communities accounted for community randomization (community clustering with jurisdictions), and adjusted for the age and sex distribution of the assessed children in a cross-sectional design.

CRISPR/Cas9 mutagenesis reveals a role for ABCB1 in gut immune responses to Vibrio diazotrophicus in sea urchin larvae.

The ABC transporter ABCB1 plays an important role in the disposition of xenobiotics. Embryos of most species express high levels of this transporter in early development as a protective mechanism, but its native substrates are not known. Here, we used larvae of the sea urchin Strongylocentrotus purpuratus to characterize the early life expression and role of Sp-ABCB1a, a homolog of ABCB1.

The Affordability of a Thrifty Food Plan-based Market Basket in the United States-affiliated Pacific Region.

In an effort to characterize food costs in the United States (US)-affiliated Pacific Region, a first-time food cost survey was conducted in March 2014. A market basket survey was developed using an adaptation of the US Department of Agriculture Thrifty Food Plan. Surveys were conducted in the states of Alaska and Hawai'i; Portland, Oregon; the US-affiliated Pacific Islands of American Samoa (American Samoa); Commonwealth of the Northern Mariana Islands; the island of Pohnpei within the Federated States of Micronesia; Guam; Republic of the Marshall Islands; and Republic of Palau.

Estimating intervention dose of the multilevel multisite children's healthy living program intervention.

Increased community collective efficacy (CE), defined as social cohesion among neighbors and their willingness to intervene for common good, is associated with improved community health outcomes. However, processes to increase CE and estimate its dose within an intervention are not well understood. The 2 year Children's Healthy Living (CHL) intervention aimed to improve child behaviors known to affect obesity.

The painted sea urchin, Lytechinus pictus, as a genetically-enabled developmental model.

Although sea urchins are one of the oldest and most widely used marine model systems, few species have been routinely kept in culture through multiple generations. The workhorse of the field is the purple urchin Strongylocentrotus purpuratus. However, one disadvantage of S.

Effect of the Children's Healthy Living Program on Young Child Overweight, Obesity, and Acanthosis Nigricans in the US-Affiliated Pacific Region: A Randomized Clinical Trial.

Importance: Pacific Islanders have among the highest rates of obesity and type 2 diabetes in the world. Targeting children is critical for primary prevention.

Objectives: To prevent young child overweight and obesity and to improve health in the US-Affiliated Pacific region via the Children's Healthy Living Program.

Quality assurance of data collection in the multi-site community randomized trial and prevalence survey of the children's healthy living program.

Background: Quality assurance plays an important role in research by assuring data integrity, and thus, valid study results. We aim to describe and share the results of the quality assurance process used to guide the data collection process in a multi-site childhood obesity prevalence study and intervention trial across the US Affiliated Pacific Region.

Methods: Quality assurance assessments following a standardized protocol were conducted by one assessor in every participating site.

Recruitment Strategies and Lessons Learned from the Children's Healthy Living Program Prevalence Survey.

The US Affiliated Pacific region's childhood obesity prevalence has reached epidemic proportions. To guide program and policy development, a multi-site study was initiated, in collaboration with partners from across the region, to gather comprehensive information on the regional childhood obesity prevalence. The environmental and cultural diversity of the region presented challenges to recruiting for and implementing a shared community-based, public health research program.

Assessing intervention fidelity in a multi-level, multi-component, multi-site program: the Children's Healthy Living (CHL) program.

Addressing complex chronic disease prevention, like childhood obesity, requires a multi-level, multi-component culturally relevant approach with broad reach. Models are lacking to guide fidelity monitoring across multiple levels, components, and sites engaged in such interventions. The aim of this study is to describe the fidelity-monitoring approach of The Children's Healthy Living (CHL) Program, a multi-level multi-component intervention in five Pacific jurisdictions.

Evaluation of the Hemodynamic Effects of Intravenous Amiodarone Formulations During the Maintenance Phase Infusion.

Background: Two of the excipients in intravenous formulations of amiodarone, polysorbate 80 and benzyl alcohol, have been shown to cause hypotension. A newer formulation of amiodarone, which contains cyclodextrin, is devoid of these excipients.

Objective: To evaluate the change in mean arterial pressure when utilizing 2 intravenous amiodarone formulations.