Pediatric and adult Out-of-Hospital cardiac arrest incidence within and near public schools in British Columbia: Missed opportunities for Systematic AED deployment strategies.

BACKGROUND: Systematic automated external defibrillator(AED) placement in schools may improve pediatric out-of-hospital cardiac arrest(OHCA) survival. To estimate their utility, we identified school-located pediatric and adult OHCAs to estimate the potential utilization of school-located AEDs. Further, we identified all OHCAs within an AED-retrievable distance of the school by walking, biking, and driving. METHODS: We used prospectively collected data from the British Columbia(BC) Cardiac Arrest Registry(2013-2020), and geo-plotted all OHCAs and schools(n = 824) in BC. We identified adult and pediatric(age < 18 years) OHCAs occurring in schools, as well as nearby OHCAs for which a school-based externally-placed AED could be retrieved by a bystander prior to emergency medical system(EMS) arrival. RESULTS: Of 16,409 OHCAs overall in the study period, 28.6 % occurred during school hours. There were 301 pediatric OHCAs. 5(1.7 %) occurred in schools, of whom 2(40 %) survived to hospital discharge. Among both children and adults, 28(0.17 %) occurred in schools(0.0042/school/year), of whom 21(75 %) received bystander resuscitation, 4(14 %) had a bystander AED applied, and 14(50 %) survived to hospital discharge. For each AED, an average of 0.29 OHCAs/year(95 % CI 0.21-0.37), 0.93 OHCAs/year(95 % CI 0.69-1.56) and 1.69 OHCAs/year(95 % CI 1.21-2.89) would be within the potential retrieval distance of a school-located AED by pedestrian, cyclist and automobile retrieval, respectively, using the median EMS response times. CONCLUSION: While school-located OHCAs were uncommon, outcomes were favourable. 11.1% to 60.9% of all OHCAs occur within an AED-retrievable distance to a school, depending on retrieval method. Accessible external school-located AEDs may improve OHCA outcomes of school children and in the surrounding community.

Modified expression of the ADAMTS enzymes and tissue inhibitor of metalloproteinases 3 during human intervertebral disc degeneration.

OBJECTIVE: Intervertebral disc degeneration is linked to loss of extracellular matrix (ECM), particularly the early loss of aggrecan. A group of metalloproteinases called aggrecanases are important mediators of aggrecan turnover. The present study was undertaken to investigate the expression of the recognized aggrecanases and their inhibitor, tissue inhibitor of metalloproteinases 3 (TIMP-3), in human intervertebral disc tissue. METHODS: Twenty-four nondegenerated and 30 degenerated disc samples were analyzed for absolute messenger RNA (mRNA) copy number of ADAMTS 1, 4, 5, 8, 9, and 15 and TIMP-3 by real-time reverse transcription-polymerase chain reaction. Thirty-six formalin-fixed embedded intervertebral disc samples of varying grades of degeneration were used for immunohistochemical analyses. In addition, samples from 8 subjects were analyzed for the presence of matrix metalloproteinase (MMP)- and aggrecanase-generated aggrecan products. RESULTS: Messenger RNA for all the aggrecanases other than ADAMTS-8 was identified in intervertebral disc tissue, as was mRNA for TIMP-3. Levels of mRNA expression of ADAMTS 1, 4, 5, and 15 were significantly increased in degenerated tissue compared with nondegenerated tissue. All these aggrecanases and TIMP-3 were also detected immunohistochemically in disc tissue, and numbers of nucleus pulposus cells staining positive for ADAMTS 4, 5, 9, and 15 were significantly increased in degenerated tissue compared with nondegenerated tissue. Aggrecan breakdown products generated by MMP and aggrecanase activities were also detected in intervertebral disc tissue. CONCLUSION: The aggrecanases ADAMTS 1, 4, 5, 9, and 15 may contribute to the changes occurring in the ECM during intervertebral disc degeneration. Targeting these enzymes may be a possible future therapeutic strategy for the prevention of intervertebral disc degeneration and its associated morbidity.

Retrovirally mediated correction of bone marrow-derived mesenchymal stem cells from patients with mucopolysaccharidosis type I.

We have investigated the utility of bone marrow-derived mesenchymal stem cells (MSCs) as targets for gene therapy of the autosomal recessive disorder mucopolysaccharidosis type IH (MPS-IH, Hurler syndrome). Cultures of MSCs were initially exposed to a green fluorescent protein-expressing retrovirus. Green fluorescent protein-positive cells maintained their proliferative and differentiation capacity. Next we used a vector encoding alpha-L-iduronidase (IDUA), the enzyme that is defective in MPS-IH. Following transduction, MPS-IH MSCs expressed high levels of IDUA and secreted supernormal levels of this enzyme into the extracellular medium. Exogenous IDUA expression led to a normalization of glycosaminoglycan storage in MPS-IH cells, as evidenced by a dramatic decrease in the amount of (35)SO(4) sequestered within the heparan sulfate and dermatan sulfate compartments of these cells. Finally, gene-modified MSCs were able to cross-correct the enzyme defect in untransduced MPS-IH fibroblasts via protein transfer.