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Miranda C.J.,The Research Institute at Nationwide Childrens Hospital
Nature Medicine | Year: 2016

Astrocytes isolated from individuals with amyotrophic lateral sclerosis (ALS) are toxic to motor neurons (MNs) and play a non–cell autonomous role in disease pathogenesis. The mechanisms underlying the susceptibility of MNs to cell death remain unclear. Here we report that astrocytes derived from either mice bearing mutations in genes associated with ALS or human subjects with ALS reduce the expression of major histocompatibility complex class I (MHCI) molecules on MNs; reduced MHCI expression makes these MNs susceptible to astrocyte-induced cell death. Increasing MHCI expression on MNs increases survival and motor performance in a mouse model of ALS and protects MNs against astrocyte toxicity. Overexpression of a single MHCI molecule, HLA-F, protects human MNs from ALS astrocyte–mediated toxicity, whereas knockdown of its receptor, the killer cell immunoglobulin-like receptor KIR3DL2, on human astrocytes results in enhanced MN death. Thus, our data indicate that, in ALS, loss of MHCI expression on MNs renders them more vulnerable to astrocyte-mediated toxicity. © 2016 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. Source


Bartlett C.W.,The Research Institute at Nationwide Childrens Hospital
BMC bioinformatics | Year: 2012

In 2011, the IEEE VisWeek conferences inaugurated a symposium on Biological Data Visualization. Like other domain-oriented Vis symposia, this symposium's purpose was to explore the unique characteristics and requirements of visualization within the domain, and to enhance both the Visualization and Bio/Life-Sciences communities by pushing Biological data sets and domain understanding into the Visualization community, and well-informed Visualization solutions back to the Biological community. Amongst several other activities, the BioVis symposium created a data analysis and visualization contest. Unlike many contests in other venues, where the purpose is primarily to allow entrants to demonstrate tour-de-force programming skills on sample problems with known solutions, the BioVis contest was intended to whet the participants' appetites for a tremendously challenging biological domain, and simultaneously produce viable tools for a biological grand challenge domain with no extant solutions. For this purpose expression Quantitative Trait Locus (eQTL) data analysis was selected. In the BioVis 2011 contest, we provided contestants with a synthetic eQTL data set containing real biological variation, as well as a spiked-in gene expression interaction network influenced by single nucleotide polymorphism (SNP) DNA variation and a hypothetical disease model. Contestants were asked to elucidate the pattern of SNPs and interactions that predicted an individual's disease state. 9 teams competed in the contest using a mixture of methods, some analytical and others through visual exploratory methods. Independent panels of visualization and biological experts judged entries. Awards were given for each panel's favorite entry, and an overall best entry agreed upon by both panels. Three special mention awards were given for particularly innovative and useful aspects of those entries. And further recognition was given to entries that correctly answered a bonus question about how a proposed "gene therapy" change to a SNP might change an individual's disease status, which served as a calibration for each approaches' applicability to a typical domain question. In the future, BioVis will continue the data analysis and visualization contest, maintaining the philosophy of providing new challenging questions in open-ended and dramatically underserved Bio/Life Sciences domains. Source


O'Brien S.H.,The Research Institute at Nationwide Childrens Hospital
Hematology / the Education Program of the American Society of Hematology. American Society of Hematology. Education Program | Year: 2012

Given the commonality of bleeding symptoms in the general population and the diagnostic limitations of available laboratory testing for mild bleeding disorders, there has been increasing interest in a more precise quantification of bleeding symptoms. The Vicenza bleeding score (and its successor, Molecular and Clinical Markers for the Diagnosis and Management of Type 1 von Willebrand disease [MCMDM-1 VWD]) and its pediatric counterpart, the Pediatric Bleeding Questionnaire, are validated research tools that have demonstrated their ability to discriminate between healthy subjects and those with VWD. These instruments collect data regarding both the presence and severity of a variety of bleeding symptoms and generate a bleeding score by summing the severity of all symptoms reported by a subject. More recent work demonstrates the promise of these tools as a diagnostic aid in the evaluation of patients with a suspected inherited mild bleeding disorder, as well as the development of a condensed score with increased clinical applicability. This review focuses on the development of these bleeding assessment tools, recent publications applying and refining these instruments, and current limitations of bleeding scores. Needed research studies and potential clinical applications of bleeding scores are also discussed. The ultimate goal would be for bleeding scores to be integrated with the results of standardized laboratory testing to allow for a universal diagnostic approach to patients with suspected bleeding disorders. Source


Chisolm D.J.,The Research Institute at Nationwide Childrens Hospital
Telemedicine journal and e-health : the official journal of the American Telemedicine Association | Year: 2011

This study measured health literacy in a population of teens in treatment for asthma or diabetes and tested the association between health literacy and willingness to use online health resources. About 180 patients aged 13-18 years treated for asthma or diabetes in specialty care clinics completed assessments of demographic characteristics, health literacy, and Internet access and use. Teens were provided a resource page listing selected publically available health-related Web sites and asked about perceived ease of use, perceived usefulness, and intent to use the listed Web sites. The relationship between demographic characteristics, health literacy, and online health information use was tested using chi-squared or Fisher's exact test. Predictors of intent to use resource page Web sites were assessed using bivariate and multivariate ordinal logistic regression. About 92% of participants had adequate health literacy. Over 50% of participants had previously searched online for health information. Older age was the only significant predictor of health information search. Most teens (79%) reported intent to use at least one Web site from the resource page at least occasionally within the next 3 months. Higher health literacy (odds ratio [OR]=6.24, p<0.01) and stronger perceived usefulness (OR=1.74, p=0.01) were associated with greater intent for regular use, after controlling for demographic and Internet access variables. Teens with lower health literacy searched online for health information as often as peers with higher literacy, but were less likely to express the intent to use recommended sites. Belief in the usefulness of a Web site is the strongest attitudinal predictor of intended future use. Source


Patent
The Research Institute At Nationwide Childrens Hospital and Ohio State Innovation Foundation | Date: 2014-03-12

A medical testing apparatus and method of use for for penetrating a patients tissue with an agent, the apparatus comprises an arcuate rail having spaced first and second sides supported by upper and lower arcuate surfaces and an arcuate handle having first and second ends extending from the upper surface of the arcuate rail. A plurality of tips extend substantially from and normally outward as the lower arcuate surface. The plurality of tips comprises alternating blunt tips and reed tips.

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