Improved vitamin D supplementation in hospitalized breastfed infants through electronic order modification and targeted provider education.

Objective: To examine effectiveness of an intervention promoting vitamin D supplementation in hospitalized breastfed infants.

Methods: Our urban tertiary care hospital instituted a 2-part intervention: brief education for providers on vitamin D guidelines and insertion of an opt-in order for vitamin D supplements into electronic admission order sets. Data downloads on admissions of patients aged <1 year were obtained.

Body mass index and waist circumference rather than body adiposity index are better surrogates for body adiposity in a Chinese population.

Background: Several studies have found that body adiposity index (BAI) is a better index of body adiposity than body mass index (BMI) in African and Mexican American adults. This study aims to evaluate the ability of BAI to predict body adiposity in Chinese children and adults.

Materials And Methods: In total, 2425 children and 5726 adults were recruited from rural China.

Corticospinal Motor Neurons Are Susceptible to Increased ER Stress and Display Profound Degeneration in the Absence of UCHL1 Function.

Corticospinal motor neurons (CSMN) receive, integrate, and relay cerebral cortex's input toward spinal targets to initiate and modulate voluntary movement. CSMN degeneration is central for numerous motor neuron disorders and neurodegenerative diseases. Previously, 5 patients with mutations in the ubiquitin carboxy-terminal hydrolase-L1 (UCHL1) gene were reported to have neurodegeneration and motor neuron dysfunction with upper motor neuron involvement.

Splice variants in the proteome: a promising and challenging field to targeted drug discovery.

The advent and improvement of high-throughput sequencing over the past decade leveraged the study of whole genomes and transcriptomes of different organisms at lower costs. In transcriptomics, RNA-Seq expands our capacity to understand gene expression in different tissues and pathologies, and how alternative splicing might affect the final protein sequence. Here, we discuss the association of using transcriptome and proteome high-throughput data to foster drug discovery.

Fibronectin affects transient MMP2 gene expression through DNA demethylation changes in non-invasive breast cancer cell lines.

Metastasis accounts for more than 90% of cancer deaths. Cells from primary solid tumors may invade adjacent tissues and migrate to distant sites where they establish new colonies. The tumor microenvironment is now recognized as an important participant in the signaling that induces cancer cell migration.

Molecular mechanisms and animal models of spinal muscular atrophy.

Spinal muscular atrophy (SMA), the leading genetic cause of infant mortality, is characterized by the degeneration of spinal motor neurons and muscle atrophy. Although the genetic cause of SMA has been mapped to the Survival Motor Neuron1 (SMN1) gene, mechanisms underlying selective motor neuron degeneration in SMA remain largely unknown. Here we review the latest developments and our current understanding of the molecular mechanisms underlying SMA pathogenesis, focusing on the animal model systems that have been developed, as well as new diagnostic and treatment strategies that have been identified using these model systems.

Nodal signaling promotes a tumorigenic phenotype in human breast cancer.

The Ras-ERK pathway is deregulated in approximately a third of human cancers, particularly those of epithelial origin. In aggressive, triple-negative, basal-like breast cancers, most tumors display increased MEK and ERK phosphorylation and exhibit a gene expression profile characteristic of Kras or EGFR mutant tumors; however, Ras family genetic mutations are uncommon in triple-negative breast cancer and EGFR mutations account for only a subset of these tumors. Therefore, the upstream events that activate MAPK signaling and promote tumor aggression in triple-negative breast cancers remain poorly defined.

Glycolysis inhibition and its effect in doxorubicin resistance in neuroblastoma.

Background/purpose: A common trait among cancers is the increased level of glycolysis despite adequate oxygen levels to support aerobic respiration. This has been shown repeatedly in different human malignancies. Glycolysis inhibitors, especially 3-bromopyruvate, have been shown to be effective chemotherapeutic agents.

Early Life Origins of Metabolic Syndrome: The Role of Environmental Toxicants.

Metabolic syndrome (MetS) affects more than 47 million people in the U.S. Even more alarming, MetS, once regarded as an "adult problem", has become increasingly common in children.

Do static and dynamic insulin resistance indices perform similarly in predicting pre-diabetes and type 2 diabetes?

Aims: We designed a study to compare the predictive power of static and dynamic insulin resistance indices for categorized pre-diabetes (PDM)/type 2 diabetes (DM).

Methods: Participants included 1134 adults aged 18-60 years old with normal glucose at baseline who completed both baseline and 6-years later follow-up surveys. Insulin resistance indices from baseline data were used to predict risk of PDM or DM at follow-up.

Melanoma tumor cell heterogeneity: a molecular approach to study subpopulations expressing the embryonic morphogen nodal.

As the frequency of melanoma increases, current treatment strategies are struggling to significantly impact patient survival. One of the critical issues in designing efficient therapies is understanding the composition of heterogeneous melanoma tumors in order to target cancer stem cells (CSCs) and drug-resistant subpopulations. In this review, we summarize recent findings pertinent to the reemergence of the embryonic Nodal signaling pathway in melanoma and its significance as a prognostic biomarker and therapeutic target.

Placental transfer and concentrations of cadmium, mercury, lead, and selenium in mothers, newborns, and young children.

There is an emerging hypothesis that exposure to cadmium (Cd), mercury (Hg), lead (Pb), and selenium (Se) in utero and early childhood could have long-term health consequences. However, there are sparse data on early life exposures to these elements in US populations, particularly in urban minority samples. This study measured levels of Cd, Hg, Pb, and Se in 50 paired maternal, umbilical cord, and postnatal blood samples from the Boston Birth Cohort (BBC).

MIR146A inhibits JMJD3 expression and osteogenic differentiation in human mesenchymal stem cells.

Chromatin remodeling is important for cell differentiation. Histone methyltransferase EZH2 and histone demethylase JMJD3 (KDM6B) modulate levels of histone H3 lysine 27 trimethylation (H3K27me3). Interplay between the two modulators influence lineage specification in stem cells.

Biphasic role of chondroitin sulfate in cardiac differentiation of embryonic stem cells through inhibition of Wnt/β-catenin signaling.

The glycosaminoglycan chondroitin sulfate is a critical component of proteoglycans on the cell surface and in the extracellular matrix. As such, chondroitin sulfate side chains and the sulfation balance of chondroitin play important roles in the control of signaling pathways, and have a functional importance in human disease. In contrast, very little is known about the roles of chondroitin sulfate molecules and sulfation patterns during mammalian development and cell lineage specification.

Association between sleep quality and C-reactive protein: results from national health and nutrition examination survey, 2005-2008.

Objective: Our objective was to explore the association between poor sleep quality and hs_CRP in an adult U.S. population.

Metabolic alterations in children with obstructive sleep apnea.

Importance: The incidence of obesity is rising in the United States and has been linked to Obstructive Sleep Apnea (OSA) even in young children. Understanding the role that obesity and OSA play in alterations in metabolic variables that can lead to serious health issues is essential to the care and counseling of affected children.

Objectives: To evaluate the association of alterations in metabolic variables, including insulin resistance, to OSA in young, obese children.

Nutrient content of school meals before and after implementation of nutrition recommendations in five school districts across two U.S. counties.

Objective: To compare changes in nutrient levels of school meals before and after implementation of nutrition interventions at five school districts in two, large U.S. counties.

SnapShot-Seq: a method for extracting genome-wide, in vivo mRNA dynamics from a single total RNA sample.

mRNA synthesis, processing, and destruction involve a complex series of molecular steps that are incompletely understood. Because the RNA intermediates in each of these steps have finite lifetimes, extensive mechanistic and dynamical information is encoded in total cellular RNA. Here we report the development of SnapShot-Seq, a set of computational methods that allow the determination of in vivo rates of pre-mRNA synthesis, splicing, intron degradation, and mRNA decay from a single RNA-Seq snapshot of total cellular RNA.

Identification of functional cooperative mutations of SETD2 in human acute leukemia.

Acute leukemia characterized by chromosomal rearrangements requires additional molecular disruptions to develop into full-blown malignancy, yet the cooperative mechanisms remain elusive. Using whole-genome sequencing of a pair of monozygotic twins discordant for MLL (also called KMT2A) gene-rearranged leukemia, we identified a transforming MLL-NRIP3 fusion gene and biallelic mutations in SETD2 (encoding a histone H3K36 methyltransferase). Moreover, loss-of-function point mutations in SETD2 were recurrent (6.

Cord blood biomarkers of vascular endothelial growth (VEGF and sFlt-1) and postnatal growth: a preterm birth cohort study.

Background: Preterm infants are at risk for postnatal growth failure (PGF). Identification of biomarkers that are associated with neonatal growth may help reduce PGF and associated long-term morbidity.

Objective: To investigate the associations between cord blood vascular endothelial growth factor (VEGF) and its soluble receptor (sFlt-1) with birth weight (BW) and postnatal growth in premature infants.

Age-Dependent Association between Protein Expression of the Embryonic Stem Cell Marker Cripto-1 and Survival of Glioblastoma Patients.

Exploring the re-emergence of embryonic signaling pathways may reveal important information for cancer biology. Nodal is a transforming growth factor-β (TGF-β)-related morphogen that plays a critical role during embryonic development. Nodal signaling is regulated by the Cripto-1 co-receptor and another TGF-β member, Lefty.

Targeting alpha-synuclein with a microRNA-embedded silencing vector in the rat substantia nigra: positive and negative effects.

Background: Alpha-synuclein (SNCA) downregulation shows therapeutic potential for synucleinopathies, including Parkinson's disease (PD). Previously we showed that human (h)SNCA gene silencing using a short hairpin (sh)RNA in rat substantia nigra (SN) protects against a hSNCA-induced forelimb deficit, but not dopamine (DA) neuron loss. Furthermore, the shRNA increases cell death in vitro, but the same target sequence embedded in a microRNA30 transcript (mir30-hSNCA) does not.