Elliott E.,Pediatric Cardiothoracic Surgery |
Hardy C.,Northwestern University |
Sullivan C.,Childrens Memorial Research Center |
Backer C.L.,Pediatric Cardiothoracic Surgery
Pediatric Critical Care Medicine | Year: 2011
OBJECTIVES:: To determine whether the implementation of a standardized handover protocol could reduce the number of errors occurring during patient transitions from the operating room to the intensive care unit. DESIGN:: Prospective, interventional study. SETTING:: Pediatric cardiac intensive care unit. SUBJECTS:: Seventy-nine patient handovers in patients transitioning from the operating room to the cardiac intensive care unit after congenital cardiac surgery. INTERVENTIONS:: A preintervention assessment of patient handovers was obtained by direct observation using a standardized checklist. A teamwork-driven handover process and protocol was developed using traditional and novel quality-improvement techniques. The postimplementation observational assessment of handovers was performed using the same preintervention assessment tool. Preintervention and postintervention data metrics were analyzed and compared. MEASUREMENTS AND MAIN RESULTS:: Forty-one and 38 observations were performed in the preintervention and postintervention periods, respectively. Protocol implementation improved key areas of the handover process. Technical errors per handover were reduced from 6.24 to 1.52 (p < .0001), and critical verbal handoff information omissions were reduced from 6.33 to 2.38 (p < .0001) per handover. There was no change in duration of either the verbal handoff briefing or the overall handover process. Caregivers noted improvement in teamwork and handoff content received after the intervention. CONCLUSIONS:: A formal, structured handover process for pediatric patients transitioning to the intensive care unit after cardiac surgery can reduce medical errors that occur during the admission process and improve teamwork among caregivers. Copyright © 2011 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.
Barry K.A.,Feinberg Cardiovascular Research Institute |
Schultz K.M.,Feinberg Cardiovascular Research Institute |
Payne C.J.,Childrens Memorial Research Center |
McGarry T.J.,Feinberg Cardiovascular Research Institute
Developmental Biology | Year: 2012
Spermatogonial stem cells divide throughout life, maintaining their own population and giving rise to differentiated gametes. The unstable regulatory protein Geminin is thought to be one of the factors that determine whether stem cells continue to divide or terminally differentiate. Geminin regulates the extent of DNA replication and is thought to maintain cells in an undifferentiated state by inhibiting various transcription factors and chromatin remodeling proteins. To examine how Geminin might regulate spermatogenesis, we developed two conditional mouse models in which the Geminin gene (Gmnn) is deleted from either spermatogonia or meiotic spermatocytes. Deleting Geminin from spermatogonia causes complete sterility in male mice. Gmnn(-/-) spermatogonia disappear during the initial wave of mitotic proliferation that occurs during the first week of life. Gmnn(-/-) spermatogonia exhibit more double-stranded DNA breaks than control cells, consistent with a defect in DNA replication. They maintain expression of genes associated with the undifferentiated state and do not prematurely express genes characteristic of more differentiated spermatogonia. In contrast, deleting Geminin from spermatocytes does not disrupt meiosis or the differentiation of spermatids into mature sperm. In females, Geminin is not required for meiosis, oocyte differentiation, or fertility after the embryonic period of mitotic proliferation has ceased. We conclude that Geminin is absolutely required for mitotic proliferation of spermatogonia but does not regulate their differentiation. Our results suggest that Geminin maintains replication fidelity during the mitotic phase of spermatogenesis, ensuring the precise duplication of genetic information for transmission to the next generation. © 2012 Elsevier Inc.
Kluppel M.,Northwestern University |
Kluppel M.,Childrens Memorial Research Center
Molecular and Cellular Biochemistry | Year: 2011
Proteoglycans carrying chondroitin sulfate side chains have been shown to fulfill important biological functions in development, disease, and signaling. One area of considerable interest is the functional importance of chondroitin sulfates as inhibitors of the regeneration of axonal projections in the mammalian central nervous system. In animal models of spinal cord injury, injections of the enzyme Chondroitinase ABC from the bacterium Proteus vulgaris into the lesion site leads to degradation of chondroitin sulfates, and promotes axonal regeneration and significant functional recovery. Here, a mammalian expression system of an epitope-tagged Chondroitinase ABC protein is described. It is demonstrated that the addition of a eukaryotic secretion signal sequence to the N-terminus of the bacterial Chondroitinase ABC sequence allowed secretion, but interfered with function of the secreted enzyme. In contrast, expression of the Chondroitinase ABC gene without N-terminal eukaryotic secretion sequence or bacterial hydrophobic leader sequence led to efficient secretion of a biologically active Chondroitinase ABC protein from both immortalized and primary cells. Moreover, the C-terminal epitope tag could be utilized to follow expression of this protein. This novel Chondroitinase ABC gene is a valuable tool for a better understanding of the in vivo roles of chondroitin sulfates in mammalian development and disease, as well as in gene therapy approaches, including the treatment of spinal chord injuries. © 2011 Springer Science+Business Media, LLC.
Hendrickson P.G.,Childrens Memorial Research Center |
Silliker M.E.,DePaul University
Current Genetics | Year: 2010
Similarity searches with Didymium iridis mitochondrial genomic DNA identified six possible ribosomal protein-coding regions, however, each region contained stop codons that would need to be removed by RNA editing to produce functional transcripts. RT-PCR was used to amplify these regions from total RNA for cloning and sequencing. Six functional transcripts were verified for the following ribosomal protein genes: rpS12, rpS7, rpL2, rpS19, rpS3, and rpL16. The editing events observed, such as single C and U nucleotide insertions and a dinucleotide insertion, were consistent with previously observed editing patterns seen in D. iridis. Additionally, a new form of insertional editing, a single A insertion, was observed in a conserved region of the rpL16 gene. While the majority of codons created by editing specify hydrophobic amino acids, a greater proportion of the codons created in these hydrophilic ribosomal proteins called for positively charged amino acids in comparison to the previously characterized hydrophobic respiratory protein genes. This first report of edited soluble mitochondrial ribosomal proteins in myxomycetes expands upon the RNA editing patterns previously seen; there was: a greater proportion of created codons specifying positively charged amino acids, a shift in the codon position edited, and the insertion of single A nucleotides. © 2010 Springer-Verlag.
Ostrowski R.A.,Loyola University Chicago |
Sullivan C.L.,Childrens Memorial Research Center |
Morgan G.A.,Childrens Memorial Research Center |
Pachman L.M.,Northwestern University
Arthritis and Rheumatism | Year: 2010
Objective. To determine the association of normal numbers of end row loops (ERLs) in nailfold capillaries at the time of diagnosis of juvenile dermatomyositis (DM) with clinical findings in untreated children with the disease and to identify predictors of the development of decreased numbers of ERLs. Methods. Clinical and laboratory data from 80 untreated children with juvenile DM were collected. ERL numbers were recorded at the time of diagnosis and at 24 months and 36 months thereafter. The 12 children who had normal ERLs at diagnosis were compared with the remaining 68 children. Outcomes included the duration of untreated disease, the duration of treatment with immunosuppressive medications, family medical history, Disease Activity Score (DAS) for juvenile DM, creatinine phosphokinase level, aldolase level, absolute number of CD3-CD56+/16+ natural killer cells, and von Willebrand factor antigen level. Crosssectional and longitudinal analyses were performed. Results. At diagnosis, children with normal ERLs had a shorter duration of untreated disease (P = 0.03) and a lower skin DAS (P = 0.045). Over time, an increased likelihood of having decreased numbers of ERLs was associated with a longer duration of untreated disease and with a higher skin DAS. Conclusion. The presence of a normal number of ERLs in juvenile DM appears to be associated with a shorter duration of symptoms and may be a useful indicator of disease chronicity in the newly diagnosed child. Normal ERLs is also associated with a lower skin DAS. The lack of association between normal ERLs and other variables indicates that normal findings on nailfold capillaroscopy should not be used as justification to delay immunosuppressive therapy in children with typical symptoms of juvenile DM. © 2010, American College of Rheumatology.