238 research outputs found

    A closer look at ARSA activity in a patient with metachromatic leukodystrophy.

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    Metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal storage disease mainly caused by a deficiency of arylsulfatase A activity. The typical clinical course of patients with the late infantile form includes a regression in motor skills with progression to dysphagia, seizures, hypotonia and death. We present a case of a 4-year-old female with rapidly progressive developmental regression with loss of motor milestones, spasticity and dysphagia. MRI showed volume loss and markedly abnormal deep white matter. Enzymatic testing in one laboratory showed arylsulfatase A activity in their normal range. However, extraction of urine showed a large increase in sulfatide excretion in a second laboratory. Measurement of arylsulfatase A in that laboratory showed a partial decrease in arylsulfatase A activity measured under typical conditions (about 37% of the normal mean). When the concentration of substrate in the assay was lowered to one quarter of that normally used, this individual had activity \u3c10% of controls. The patient was found to be homozygous for an unusual missense mutation in the arylsulfatase A gene confirming the diagnosis of MLD. This case illustrates the importance of careful biochemical and molecular testing for MLD if there is suspicion of this diagnosis

    Ethno-Religious Conflict In Northern Ireland

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    The Troubles, is an ethno-religious conflict within Northern Ireland that occurred from 1968 to 1998. During this conflict, the constitutional status of Northern Ireland was questioned—will it remain with the United Kingdom or finally become a united Ireland? Many scholars in political science discuss the roots of this conflict as an ethnic divide, citing anti-Irish discrimination and the perpetuation of ethnic stereotypes for centuries. However, scholars within this field fail to acknowledge the strong religious identities and anti-Catholicism. Without divulging and understanding each identities’ religious beliefs, scholars fail to understand how each identity sees not only themselves, but also others. I argue that the Troubles is not an ethno-national conflict, but an ethno-religious conflict that promoted two extreme forms of nationalism--the same pattern that has been present for centuries. The presence of paramilitary groups and discrimination within the political system divided these two groups even further. The Good Friday Agreement in 1998 led to the official end of the conflict, and promoted peace and stability in Northern Ireland. With the recent controversy of the United Kingdom leaving the European Union, the question of Northern Ireland’s constitutional status is back on the table

    Increasing the reliability of fully automated surveillance for central line–associated bloodstream infections

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    OBJECTIVETo increase reliability of the algorithm used in our fully automated electronic surveillance system by adding rules to better identify bloodstream infections secondary to other hospital-acquired infections.METHODSIntensive care unit (ICU) patients with positive blood cultures were reviewed. Central line–associated bloodstream infection (CLABSI) determinations were based on 2 sources: routine surveillance by infection preventionists, and fully automated surveillance. Discrepancies between the 2 sources were evaluated to determine root causes. Secondary infection sites were identified in most discrepant cases. New rules to identify secondary sites were added to the algorithm and applied to this ICU population and a non-ICU population. Sensitivity, specificity, predictive values, and kappa were calculated for the new models.RESULTSOf 643 positive ICU blood cultures reviewed, 68 (10.6%) were identified as central line–associated bloodstream infections by fully automated electronic surveillance, whereas 38 (5.9%) were confirmed by routine surveillance. New rules were tested to identify organisms as central line–associated bloodstream infections if they did not meet one, or a combination of, the following: (I) matching organisms (by genus and species) cultured from any other site; (II) any organisms cultured from sterile site; (III) any organisms cultured from skin/wound; (IV) any organisms cultured from respiratory tract. The best-fit model included new rules I and II when applied to positive blood cultures in an ICU population. However, they didn’t improve performance of the algorithm when applied to positive blood cultures in a non-ICU population.CONCLUSIONElectronic surveillance system algorithms may need adjustment for specific populations.Infect. Control Hosp. Epidemiol. 2015;36(12):1396–1400</jats:sec

    What is translational research? Background, concepts, and a definition

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    Author version made available here in accordance with publisher copyright policy.This discussion paper aims to offer an overview and working definition of translational research, appropriate to health. Methods: Using scholarly and applied literature, the paper first identifies key challenges in achieving evidence-based policy and practice. It highlights international policy interest in new approaches to evidence translation and the barriers to achieving sound evidence translation. The paper offers an explicit definition of translational research and explains why it is important to have such a definition. It then elaborates on this definition by identifying and exploring seven distinctive research practices that could be associated with translational research. Findings and conclusions: Translational research is research with a sense of place. Its defining feature is excellence in evidence for a specific context or sphere of action, whether that is health policy for the World Health Organisation or service design for a local non-government organisation. If research is to be translated at all, it needs to be meaningful to many specific contexts, including small and regional contexts. The best promise that translational research offers is of exciting new techniques to achieve rigour and systemacy for such localised ‘real world’ policy, service and practice contexts

    Directed Trans-Differentiation of Thymus Cells into Parathyroid-Like Cells Without Genetic Manipulation

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    Replacement of a diseased organ with an autologously derived tissue is an ideal therapy for some medical problems. However, it is difficult to recreate many adult human tissues in vitro due to the functionally necessary architecture of most organs and the lack of understanding of methods to direct the development of the organ of interest. The parathyroid gland is ideal for in vitro organ development because this gland is relatively simple, is transplantable, and is commonly affected by a surgical complication rather than an autoimmune disease. We have investigated thymus as a source of autologous endoderm and parathyroid-like precursor cells. Human thymus cells were treated with a differentiation protocol we developed with human embryonic stem cells (The Bingham Protocol) that utilizes timed exposures to Activin A and soluble Sonic hedgehog (Shh). We incrementally changed the protocol to optimize the differentiation of the thymus cells into parathyroid-like cells. The final protocol used 50-ng/mL Activin A and 100-ng/mL Shh over 13 weeks. The differentiated cells expressed the parathyroid markers parathyroid hormone (PTH), calcium sensing receptor, chemokine receptor type-4 (CXCR4), and chorian-specific transcription factor (GCM2) as measured by reverse transcription-polymerase chain reaction and PTH enzyme-linked immunosorbent assay. Cultured thymus cells without Activin A or Shh exposure did not secrete PTH nor express similar markers. The differentiated cells released PTH, which was suppressed in response to increased calcium concentration. The chemically differentiated cells did not form tumors in immune-compromised mice. Our protocol recreated cells with markers of parathyroid tissue that responded as parathyroid cells to physiologic stimuli. This approach is a further step toward a strategy to restore parathyroid function using autologous cells that were directed to differentiate by nongenetic in vitro manipulation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90464/1/ten-2Etec-2E2011-2E0170.pd

    Differentiation of Human Embryonic Stem Cells to a Parathyroid-Like Phenotype

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    Iatrogenic hypoparathyroidism is the most common complication of cervical endocrine surgery. Current management is limited and palliative. As the molecular steps in parathyroid development have been defined, they may be replicable in vitro, with a goal of cellular replacement therapy. Human embryonic stem cell (hESC) lines were investigated as a model for parathyroid regeneration in vitro. BG01 was selected as a model based on expression of genes of interest in embryoid bodies (EBs). Established strategies for mouse embryonic stem cell differentiation into definitive endoderm were modified and extended to maximize the expression of definitive markers of parathyroid development. The optimal approach included the use of Activin A at 100 ng/mL with BG01 cells grown on murine embryonic fibroblasts for 5 days under conditions of increasing serum concentration. After 5 days, the cells were allowed to mature further in tissue culture without murine fibroblasts but with continuous Activin A. Our strategy produced differentiated cell cultures that expressed intermediate markers of endoderm and parathyroid development (CXCR4, EYA1, Six1, and Pax1), as well as markers of committed parathyroid precursors or developed parathyroid glands (glial cell missing-2 [Gcm2], CCL21, calcium sensing receptor [CaSR], and parathyroid hormone [PTH]). We further characterized the cells by testing conditioned medium from various time points in our differentiation scheme for the presence of PTH. We found that by keeping the cells in culture 2 weeks after the withdrawal of Activin A, the cells were able to produce PTH. Further in vivo work will be needed to demonstrate proper functionality of the cells developed in this way.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78132/1/scd.2008.0337.pd
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