During embryonic development, a subset of cells in the mesoderm germ layer are specified as hemato-vascular progenitor cells, which then differentiate into endothelial cells and hematopoietic stem and progenitor cells. In zebrafish, the transcription factor npas4l (cloche) is required for the specification of hemato-vascular progenitor cells. However, it is unclear whether npas4l is the sole factor at the top of the hemato-vascular specification cascade.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2023
The scale and pace of energy infrastructure development required to achieve net-zero greenhouse gas (GHG) emissions are unprecedented, yet our understanding of how to minimize its potential impacts on land and ocean use and natural resources is inadequate. Using high-resolution energy and land-use modeling, we developed spatially explicit scenarios for reaching an economy-wide net-zero GHG target in the western United States by 2050. We found that among net-zero policy cases that vary the rate of transportation and building electrification and use of fossil fuels, nuclear generation, and biomass, the "High Electrification" case, which utilizes electricity generation the most efficiently, had the lowest total land and ocean area requirements (84,000 to 105,000 km vs.
View Article and Find Full Text PDFImportance: Infants with gestational age between 22 0/7 and 23 6/7 weeks (referred to as nano-preterm infants) are at very high risk of adverse outcomes. Noninvasive respiratory support at birth improves outcomes in infants born at 24 0/7 to 27 6/7 weeks' gestational age. Evidence is limited on whether similar benefits of non-invasive respiratory support at birth extend to nano-preterm infants.
View Article and Find Full Text PDFBackground/objectives: Physician-scientists have long been in high demand owing to their role as key drivers of biomedical innovation, but their dwindling prevalence in research and medical communities threatens ongoing progress. As the principal avenue for physician-scientist development, combined MD-PhD training programs and NIH-funded Medical Scientist Training Programs (MSTPs) must address all aspects of career development, including grant writing skills.
Methods: The NIH F-series grants - the F30 grant in particular - model the NIH format of federal funding, and are thus ideal opportunities to acquire biomedical research grant preparation experience.
Among the many academic challenges faced by dual-degree MD-PhD students is access to professional support networks designed to overcome the unique academic and personal barriers to physician-scientist training. In the current study, we hypothesized that regional access to a student MD-PhD conference, termed the Southeastern Medical Scientist Symposium (SEMSS), would enhance medical and/or graduate training by fostering such relationships between physician-scientist trainees, doing so by discussing both the challenges of physician-scientist training and effective strategies to overcome them. In the current study, we used a mixed-methods approach to evaluate the overall usefulness of SEMSS over a ten-year period (2010-2020) to identify key areas of particular benefit to trainees.
View Article and Find Full Text PDFPathogenic variants in KMT2D are typically associated with Kabuki syndrome (KS), a rare multisystem disorder. KS is characterized by facial dysmorphisms, intellectual disability, skeletal and dermatoglyphic differences, and poor growth. Seventy percent of individuals with clinically diagnosed KS have a confirmed pathogenic variant in KMT2D or less commonly KDM6A.
View Article and Find Full Text PDFPediatr Infect Dis J
February 2022
Congenital cytomegalovirus infection is the most common congenital infection. Although most infants with congenital cytomegalovirus infection are asymptomatic at birth, a subset will have readily apparent clinical and/or laboratory manifestations including hepatitis; progression to hepatic failure has not previously been described in term infants who initiated antiviral treatment shortly after birth. We present 2 term infants with congenital cytomegalovirus infection and hepatitis who progressed to hepatic failure despite initial laboratory improvement on therapy.
View Article and Find Full Text PDFObjective: Maternal folate (vitamin B9) status is the largest known modifier of neural tube defect risk, so we evaluated folate-related mechanisms of action for dolutegravir (DTG) developmental toxicity.
Design: Folate receptor 1 (FOLR1) was examined as a target for DTG developmental toxicity using protein and cellular interaction studies and an animal model.
Methods: FOLR1 competitive binding studies were used to test DTG for FOLR1 antagonism.
The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that binds environmental toxicants and regulates gene expression. AHR also regulates developmental processes, like craniofacial development and hematopoiesis, in the absence of environmental exposures. Zebrafish have 3 paralogs of AHR: ahr1a, ahr1b, and ahr2.
View Article and Find Full Text PDFEstrogens act by binding to estrogen receptors alpha and beta (ERα, ERβ), ligand-dependent transcription factors that play crucial roles in sex differentiation, tumor growth and cardiovascular physiology. Estrogens also activate the G protein-coupled estrogen receptor (GPER), however the function of GPER in vivo is less well understood. Here we find that GPER is required for normal heart rate in zebrafish embryos.
View Article and Find Full Text PDFComp Biochem Physiol C Toxicol Pharmacol
June 2018
To study the effects of environmental endocrine disruptor compounds (EDCs) on aquatic animals, embryos and larvae are typically incubated in water containing defined concentrations of EDCs. However, the amount of EDC uptake into the animal is often difficult to determine. Using radiolabeled estradiol ([H]E2), we previously developed a rapid, straightforward assay to measure estradiol uptake from water into zebrafish embryos and larvae.
View Article and Find Full Text PDFZebrafish are a powerful model system to assess the molecular and cellular effects of exposure to toxic chemicals during embryonic development. To study the effects of environmental endocrine disruptors, embryos and larvae are commonly exposed to supraphysiologic concentrations of these compounds in the water, but their bioavailability in zebrafish is largely unknown. One hypothesis is that supraphysiologic concentrations of estrogens in the water are required to achieve physiologic levels in vivo; however, this has not been directly tested.
View Article and Find Full Text PDFStudy Objective: We assess hospital readmission and death within 60 days in older adults admitted from the emergency department (ED) and discharged by an inpatient service within 24 hours.
Methods: This was a retrospective review of ED patients aged 64 years or older, admitted from 2 hospitals (2004 to 2006), who were discharged home within 24 hours. Excluded were in-hospital deaths, observation admissions, transfers to other facilities, patients who left against medical advice, and hospice patients.
Evid Based Complement Alternat Med
June 2009
Static magnetic field (SMF) therapy, applied via a permanent magnet attached to the skin, is used by people worldwide for self-care. Despite a lack of established SMF dosage and treatment regimens, multiple studies are conducted to evaluate SMF therapy effectiveness. Our objectives in conducting this review are to:(i) summarize SMF research conducted in humans; (ii) critically evaluate reporting quality of SMF dosages and treatment parameters and (iii) propose a set of criteria for reporting SMF treatment parameters in future clinical trials.
View Article and Find Full Text PDFThe widespread use of static magnetic field (SMF) therapy as a self-care physical intervention has led to the conduct of numerous randomized controlled trials (RCTs). A recent systematic review of SMF trials for pain reduction concluded that the evidence does not support the use of permanent magnets for pain relief. We argue that this conclusion is unwarranted if the SMF dosage was inadequate or inappropriate for the clinical condition treated.
View Article and Find Full Text PDFThe presence and potential origin of the neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) was determined in cardiac ganglia of the mudpuppy, Necturus maculosus. Although PACAP has been implicated in the regulation of cardiac function in several mammalian species, the presence of this peptide in the autonomic nervous system (ANS) of other species is unclear. Thus, this study is the first to characterize this highly conserved peptide in the ANS of a non-mammalian species.
View Article and Find Full Text PDFThe analysis of food service costs in this article provides an overview of the potential for cost containment of alternative food service systems for facilities ranging in capacity from 100 to 550 beds. This work was conducted mainly with U.S.
View Article and Find Full Text PDFJ Am Pharm Assoc Am Pharm Assoc
April 1960