Sustaining the gains: Reducing unnecessary computed tomography scans in pediatric trauma patients.

Background/purpose: "Pan-scanning" pediatric blunt trauma patients leads to exposure to harmful radiation and increased healthcare costs without improving outcomes. We aimed to reduce computed tomography (CT) scans that are not indicated (NI) by imaging guidelines for injured children.

Methods: In July 2017, our Pediatric Trauma Center prospectively implemented validated imaging guidelines to direct CT imaging for trauma activations and consultations for children younger than 16 years old with blunt traumatic injuries.

Centers for Mendelian Genomics: A decade of facilitating gene discovery.

Purpose: Mendelian disease genomic research has undergone a massive transformation over the past decade. With increasing availability of exome and genome sequencing, the role of Mendelian research has expanded beyond data collection, sequencing, and analysis to worldwide data sharing and collaboration.

Methods: Over the past 10 years, the National Institutes of Health-supported Centers for Mendelian Genomics (CMGs) have played a major role in this research and clinical evolution.

The Glucocorticoid Receptor in Osterix-Expressing Cells Regulates Bone Mass, Bone Marrow Adipose Tissue, and Systemic Metabolism in Female Mice During Aging.

Hallmarks of aging-associated osteoporosis include bone loss, bone marrow adipose tissue (BMAT) expansion, and impaired osteoblast function. Endogenous glucocorticoid levels increase with age, and elevated glucocorticoid signaling, associated with chronic stress and dysregulated metabolism, can have a deleterious effect on bone mass. Canonical glucocorticoid signaling through the glucocorticoid receptor (GR) was recently investigated as a mediator of osteoporosis during the stress of chronic caloric restriction.

A Quality Improvement Approach to Decreasing Postdischarge Acute Care Reuse Among Children With Asthma.

Objectives: To reduce 7-day acute care reuse among children with asthma after discharge from an academic children's hospital by standardizing the delivery of clinical care and patient education.

Methods: A diverse group of stakeholders from our tertiary care children's hospital and local community agencies used quality improvement methods to implement a series of interventions within inpatient, emergency department (ED), and outpatient settings. These interventions were designed to improve admission, inpatient care, and discharge processes for children hospitalized because of asthma and included a focus on (1) resident education, (2) patient access to medication and asthma education, and (3) gaps in existing asthma clinical care pathways in the ED and ICU.

Kynurenine suppresses osteoblastic cell energetics in vitro and osteoblast numbers in vivo.

Aging is a progressive process associated with declining tissue function over time. Kynurenine, an oxidized metabolite of the essential amino acid tryptophan that increases in abundance with age, drives cellular processes of aging and dysfunction in many tissues, and recent work has focused on understanding the pathways involved in the harmful effects of kynurenine on bone. In this study, we sought to investigate the effects of controlled kynurenine administration on osteoblast bioenergetics, in vivo osteoblast abundance, and marrow fat accumulation.

Effect of pharmacist-led task force to reduce opioid prescribing in the emergency department.

Purpose: Results of a study to determine the effect of a pharmacist-led opioid task force on emergency department (ED) opioid use and discharge prescriptions are presented.

Methods: An observational evaluation was conducted at a large tertiary care center (ED volume of 115,000 visits per year) to evaluate selected opioid use outcomes before and after implementation of an ED opioid reduction program by interdisciplinary task force of pharmacists, physicians, and nurses. Volumes of ED opioid orders and discharge prescriptions were evaluated over the entire 25-month study period and during designated 1-month preimplementation and postimplementation periods (January 2017 and January 2018).

MicroRNA-183-5p Increases with Age in Bone-Derived Extracellular Vesicles, Suppresses Bone Marrow Stromal (Stem) Cell Proliferation, and Induces Stem Cell Senescence.

Microvesicle- and exosome-mediated transport of microRNAs (miRNAs) represents a novel cellular and molecular pathway for cell-cell communication. In this study, we tested the hypothesis that these extracellular vesicles (EVs) and their miRNAs might change with age, contributing to age-related stem cell dysfunction. EVs were isolated from the bone marrow interstitial fluid (supernatant) of young (3-4 months) and aged (24-28 months) mice to determine whether the size, concentration, and miRNA profile of EVs were altered with age in vivo.

The aromatic amino acid tryptophan stimulates skeletal muscle IGF1/p70s6k/mTor signaling in vivo and the expression of myogenic genes in vitro.

Objectives: Nutrition plays a key role in the maintenance of muscle and bone mass, and dietary protein deficiency has in particular been associated with catabolism of both muscle and bone tissue. One mechanism thought to link protein deficiency with loss of muscle mass is deficiency in specific amino acids that play a role in muscle metabolism. The aim of this study was to test the hypothesis that the essential amino acid tryptophan, and its metabolite kynurenine, might directly affect muscle metabolism in the setting of protein deficiency.

Caloric restriction and the adipokine leptin alter the SDF-1 signaling axis in bone marrow and in bone marrow derived mesenchymal stem cells.

Growing evidence suggests that the chemokine stromal cell-derived factor-1 (SDF-1) is essential in regulating bone marrow (BM) derived mesenchymal stromal/stem cell (BMSC) survival, and differentiation to either a pro-osteogenic or pro-adipogenic fate. This study investigates the effects of caloric restriction (CR) and leptin on the SDF-1/CXCR4 axis in bone and BM tissues in the context of age-associated bone loss. For in vivo studies, we collected bone, BM cells and BM interstitial fluid from 12 and 20 month-old C57Bl6 mice fed ad-libitum (AL), and 20-month-old mice on long-term CR with, or without, intraperitoneal injection of leptin for 10 days (10 mg/kg).

Selective reduction of fetuses in multiple pregnancies and the law in Australia.

This article considers whether it is lawful in Australia to terminate one or more fetuses in a multiple pregnancy selectively and, if so, under what circumstances. It begins by addressing the preliminary question whether selective reduction is covered by laws relating to abortion and provides a brief outline of the law of abortion in Australian jurisdictions. The article then considers selective reduction of high-order multiple pregnancies, before turning to selective reduction of twin pregnancies in a range of circumstances.

The spectre of court-sanctioned sacrificial separation of teenage conjoined twins against their will.

In a recent decision of the Indian Supreme Court, judges foreshadowed authorising separation of teenage conjoined twins where both would die if not separated but where the operation could save only one. The absence of medical information advising separation precluded such a decision in the case at hand. However, the case raises a number of difficult legal and ethical questions that judges would have to consider before authorising sacrificial separation of these or other non-infant conjoined twins.

Risk of type 1 diabetes progression in islet autoantibody-positive children can be further stratified using expression patterns of multiple genes implicated in peripheral blood lymphocyte activation and function.

There is tremendous scientific and clinical value to further improving the predictive power of autoantibodies because autoantibody-positive (AbP) children have heterogeneous rates of progression to clinical diabetes. This study explored the potential of gene expression profiles as biomarkers for risk stratification among 104 AbP subjects from the Diabetes Autoimmunity Study in the Young (DAISY) using a discovery data set based on microarray and a validation data set based on real-time RT-PCR. The microarray data identified 454 candidate genes with expression levels associated with various type 1 diabetes (T1D) progression rates.

Association of pain score documentation and analgesic use in a pediatric emergency department.

Objectives: This study characterizes the association between pain score documentation and analgesic administration among pediatric emergency department patients.

Methods: This is a secondary analysis of a prospectively collected research database from an academic emergency department. Records of randomly sampled pediatric patients seen between August 2005 and October 2006 were reviewed.

Pharmacokinetics of intravenous lorazepam in pediatric patients with and without status epilepticus.

Objective: To evaluate the single dose pharmacokinetics of an intravenous dose of lorazepam in pediatric patients treated for status epilepticus (SE) or with a history of SE.

Study Design: Ten hospitals in the Pediatric Emergency Care Applied Research Network enlisted patients 3 months to 17 years with convulsive SE (status cohort) or for a traditional pharmacokinetics study (elective cohort). Sparse sampling was used for the status cohort, and intensive sampling was used for the elective cohort.

Separating conjoined twins: a medical and criminal law dilemma.

Surgical separation of conjoined twins that results in the death of one of the twins raises complex moral, ethical and legal issues. Of particular concern is the potential for homicide charges against doctors. In two recent cases, one in England and one in Queensland, judges declared the surgery to be lawful but the legal reasoning employed is problematical and may be difficult to apply to future conjoined twins cases, such as infant twins where one is not fully developed, or where it is proposed to separate adult twins.

Perceived challenges to obtaining informed consent for a time-sensitive emergency department study of pediatric status epilepticus: results of two focus groups.

Objectives: The objective was to describe the perspective of research personnel on issues of informed consent in a time-sensitive clinical study under emergency circumstances.

Methods: The authors convened concurrent focus groups of research staff and investigators involved in a pharmacokinetic study of lorazepam for status epilepticus (SE). Moderators led discussion with open-ended questions on selected issues of parental consent, communication and understanding, patient assent, and comparison to other types of studies.

Widespread genomic signatures of natural selection in hominid evolution.

Selection acting on genomic functional elements can be detected by its indirect effects on population diversity at linked neutral sites. To illuminate the selective forces that shaped hominid evolution, we analyzed the genomic distributions of human polymorphisms and sequence differences among five primate species relative to the locations of conserved sequence features. Neutral sequence diversity in human and ancestral hominid populations is substantially reduced near such features, resulting in a surprisingly large genome average diversity reduction due to selection of 19-26% on the autosomes and 12-40% on the X chromosome.

Use of shotgun proteomics for the identification, confirmation, and correction of C. elegans gene annotations.

We describe a general mass spectrometry-based approach for gene annotation of any organism and demonstrate its effectiveness using the nematode Caenorhabditis elegans. We detected 6779 C. elegans proteins (67,047 peptides), including 384 that, although annotated in WormBase WS150, lacked cDNA or other prior experimental support.

The epidemiology of emergency medical services use by children: an analysis of the National Hospital Ambulatory Medical Care Survey.

Objective: There is an absence of nationally representative data describing pediatric patients who use emergency medical services (EMS) and the factors associated with EMS use by children. This study characterizes pediatric emergency department (ED) visits for which the patient arrived by EMS and identifies factors associated with those visits using a nationally representative database.

Methods: A secondary analysis of the ED component of the 1997-2000 National Hospital Ambulatory Medical Care Survey was performed.

Preferences for EMS transport and pediatric emergency department care.

Objectives: To characterize the reasons pediatric emergency department (PED), patients access emergency medical services (EMS) for transport to the pediatric ED. To describe the acceptability of other modes of transport and alternative sites of care.

Methods: We included a convenience sample of the responsible adults accompanying pediatric patients who arrived via EMS to the PED of an academic medical center.

Stress in fathers of surgical neonatal intensive care unit babies.

The purpose of this study was to identify and measure components of perceived stress in fathers of infants in a surgical neonatal intensive care unit (NICU). The Parent Stressor Scale: Infant Hospitalization (PSS:IH) was used to assess perceived stress in 22 fathers. Paternal stress was highest in the domains of "Parental Role Alteration" and "Infant Appearance and Behavior.

Targeted discovery of novel human exons by comparative genomics.

A complete and accurate set of human protein-coding gene annotations is perhaps the single most important resource for genomic research after the human-genome sequence itself, yet the major gene catalogs remain incomplete and imperfect. Here we describe a genome-wide effort, carried out as part of the Mammalian Gene Collection (MGC) project, to identify human genes not yet in the gene catalogs. Our approach was to produce gene predictions by algorithms that rely on comparative sequence data but do not require direct cDNA evidence, then to test predicted novel genes by RT-PCR.

Characterization and predictive discovery of evolutionarily conserved mammalian alternative promoters.

Recent studies suggest that surprisingly many mammalian genes have alternative promoters (APs); however, their biological roles, and the characteristics that distinguish them from single promoters (SPs), remain poorly understood. We constructed a large data set of evolutionarily conserved promoters, and used it to identify sequence features, functional associations, and expression patterns that differ by promoter type. The four promoter categories CpG-rich APs, CpG-poor APs, CpG-rich SPs, and CpG-poor SPs each show characteristic strengths and patterns of sequence conservation, frequencies of putative transcription-related motifs, and tissue and developmental stage expression preferences.