numbers of double-sorted HSC from Npm1 þ / þ and Npm1 þ /À mice (CD45.1 þ CD45.2 þ ) were transplanted into lethally irradiated C57BL/6 (CD45.2) recipients together with competitor cells (CD45.2). Short-term (2 months) and long-term (4 months) competitive repopulating capability was studied by monitoring peripheral blood donor chimerism of recipient mice by flow cytometry. Mice transplanted with Npm1 þ /À HSC exhibited markedly lower engraftment than the recipients of Npm1 þ / þ HSC as measured by total chimerism (threefold; Figure 2a, Po0.03). The percentage total and myeloid chimerism in individual transplanted mice did not differ significantly at 2 and 4 months (data not shown). We also quantified donor chimerism in the bone marrow of the recipient mice 4 months after transplantation (Figure 2b). Similar to the results in the peripheral blood, the competitive repopulating ability of the HSC from Npm1 þ /À mice was significantly reduced (8.5-fold; Figure 2b, Po0.02) in the bone marrow of the recipient mice. Although the engraftment potential of Npm1 þ /À HSC was reduced, we did not observe any effects on the composition of donor-derived mature hematopoietic cells in the peripheral blood of recipient mice (Supplementary Figure 5). Thus, the level of NPM1 expression has a direct effect on HSC repopulating ability in vivo, but has no effect on hematopoietic fate commitment.In summary, our Npm1 þ /À mouse model indicates that NPM1 has a role in maintaining HSC number and in preserving the functional integrity of these cells in the context of competitive transplantation. However, it does not appear to have a role in regulating HSC differentiation. Npm1 haploinsufficiency did not result in significant alterations in mature blood cell numbers or significant dysplasia in our mice. These results are at some variance with a previous report, in which Npm1 heterozygosity was associated with an MDS-like phenotype in older (6-10 months) mice. 4 We cannot completely exclude the possibility that the different techniques used to generate these mutant mice may explain the differences in our results; however, both models are associated with homozygous null embryonic lethality as well as decreased Npm1 mRNA (data not shown) and protein levels in Npm1 þ /À mice. Our study did use mice in which the targeted Npm1 allele was functionally eliminated by a single-gene trap event in the NPM1 locus between exons 7 and 8 (genetic background 129/SvEvBrd  C57BL/6J), whereas in the previous study exons 2-7 were replaced by green fluorescent protein cassette introducing the stop codon after exon 2 (genetic background 129/Sv  C57BL/6). Minor genetic variability between the two different substrains used in these studies (129/Sv vs 129/SvEvBrd) might also influence their respective phenotypes. 7 Although we have no definitive explanation for the difference in phenotypes, only our study directly assessed HSC function. We speculate that the increased number of HSC in Npm þ /À mice could be an important early step in myeloid pathogenesis, as thes...
Introduction Scald injuries affect many vulnerable populations. We know that there is a relationship between time and temperature as to severity of injury. When one of the authors had their residential hot water heater replaced, it was set to an uncomfortable temperature, 134oF, until adjusted to a safe level. This highlighted the possibility of catastrophic injury from a simple household function like washing hands or taking a bath. As a result, we have undertaken efforts to assess locations where burn team members and their families are potentially exposed to excessively hot water and educate them as to methods to measure their water temperature and maintain it at safe levels. Temperature differences between 120oF and 130oF mean the difference between injury in minutes to seconds. Methods Using a Taylor Market Digital Candy Thermometer, the tap is run at maximum hot water for 2 minutes. With water still running, a volume of approximately one liter is collected and the thermometer is immediately immersed in the water with the temperature recorded once stable. Data was recorded at a variety of locations, including residential (of care team), hotels, and around a variety of taps through the hospital. Results Twenty sites were measured for water temperature. The average temperature recorded was 114.1oF, with a median temperature recorded 110.9oF. There were three recordings of water temperature greater than 120oF, with the highest recorded at 132.9oF. All of these sites were immediately informed of the risks and appropriate measures taken to adjust water sources to an appropriate temperature. Conclusions We as burn care professionals know what acceptable water temperatures are for taps in our personal spaces. Despite that it is possible that hazardous conditions can exist. Many areas of society are looking for the guidance of health care providers, and we need to start in our own homes to make that environment safe, and then take that message to our relatives and community. Applicability of Research to Practice This is a real world demonstration of the need to verify safety in our own homes and then take that message of prevention to vulnerable populations.
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