The Research Institute at Nationwide Children's Hospital

About: The Research Institute at Nationwide Children's Hospital is a based out in . It is known for research contribution in the topics: Poison control & Population. The organization has 1743 authors who have published 2372 publications receiving 72781 citations.

An interferon-inducible neutrophil-driven blood transcriptional signature in human tuberculosis

Abstract: Tuberculosis (TB), caused by infection with Mycobacterium tuberculosis, is a major cause of morbidity and mortality worldwide. Efforts to control it are hampered by difficulties with diagnosis, prevention and treatment. Most people infected with M. tuberculosis remain asymptomatic, termed latent TB, with a 10% lifetime risk of developing active TB disease. Current tests, however, cannot identify which individuals will develop disease. The immune response to M. tuberculosis is complex and incompletely characterized, hindering development of new diagnostics, therapies and vaccines. Here we identify a whole-blood 393 transcript signature for active TB in intermediate and high-burden settings, correlating with radiological extent of disease and reverting to that of healthy controls after treatment. A subset of patients with latent TB had signatures similar to those in patients with active TB. We also identify a specific 86-transcript signature that discriminates active TB from other inflammatory and infectious diseases. Modular and pathway analysis revealed that the TB signature was dominated by a neutrophil-driven interferon (IFN)-inducible gene profile, consisting of both IFN-gamma and type I IFN-alphabeta signalling. Comparison with transcriptional signatures in purified cells and flow cytometric analysis suggest that this TB signature reflects changes in cellular composition and altered gene expression. Although an IFN-inducible signature was also observed in whole blood of patients with systemic lupus erythematosus (SLE), their complete modular signature differed from TB, with increased abundance of plasma cell transcripts. Our studies demonstrate a hitherto underappreciated role of type I IFN-alphabeta signalling in the pathogenesis of TB, which has implications for vaccine and therapeutic development. Our study also provides a broad range of transcriptional biomarkers with potential as diagnostic and prognostic tools to combat the TB epidemic.

Intravascular AAV9 preferentially targets neonatal neurons and adult astrocytes

Abstract: Delivery of genes to the brain and spinal cord across the blood-brain barrier (BBB) has not yet been achieved. Here we show that adeno-associated virus (AAV) 9 injected intravenously bypasses the BBB and efficiently targets cells of the central nervous system (CNS). Injection of AAV9-GFP into neonatal mice through the facial vein results in extensive transduction of dorsal root ganglia and motor neurons throughout the spinal cord and widespread transduction of neurons throughout the brain, including the neocortex, hippocampus and cerebellum. In adult mice, tail vein injection of AAV9-GFP leads to robust transduction of astrocytes throughout the entire CNS, with limited neuronal transduction. This approach may enable the development of gene therapies for a range of neurodegenerative diseases, such as spinal muscular atrophy, through targeting of motor neurons, and amyotrophic lateral sclerosis, through targeting of astrocytes. It may also be useful for rapid postnatal genetic manipulations in basic neuroscience studies.

Epidemiology of Concussions Among United States High School Athletes in 20 Sports

Abstract: Background: In the United States (US), an estimated 300,000 sports-related concussions occur annually. Among individuals 15 to 24 years of age, sports are second only to motor vehicle crashes as the leading cause of concussions.Purpose: To investigate the epidemiology of concussions in high school athletes by comparing rates and patterns of concussion among 20 sports.Study Design: Descriptive epidemiology study.Methods: Using an Internet-based data collection tool, RIO, certified athletic trainers from a large, nationally disperse sample of US high schools reported athlete exposure and injury data for 20 sports during the 2008-2010 academic years.Results: During the study period, 1936 concussions were reported during 7,780,064 athlete-exposures (AEs) for an overall injury rate of 2.5 per 10,000 AEs. The injury rate was higher in competition (6.4) than practice (1.1) (rate ratio [RR], 5.7; 95% confidence interval [CI], 5.2-6.3). The majority of concussions resulted from participation in football (47.1%, n ...

Astrocytes from familial and sporadic ALS patients are toxic to motor neurons

Abstract: Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease, with astrocytes implicated as contributing substantially to motor neuron death in familial (F)ALS. However, the proposed role of astrocytes in the pathology of ALS derives in part from rodent models of FALS based upon dominant mutations within the superoxide dismutase 1 (SOD1) gene, which account for 90% of ALS patients, remains to be established. Using astrocytes generated from postmortem tissue from both FALS and SALS patients, we show that astrocytes derived from both patient groups are similarly toxic to motor neurons. We also demonstrate that SOD1 is a viable target for SALS, as its knockdown significantly attenuates astrocyte-mediated toxicity toward motor neurons. Our data highlight astrocytes as a non-cell autonomous component in SALS and provide an in vitro model system to investigate common disease mechanisms and evaluate potential therapies for SALS and FALS.