Retaining a viable workforce: a critical challenge for nursing

Nursing is facing a crisis nationally and internationall, with Australia, the United States, New Zealand, Canada, the United Kingdom and Western Europe experiencing critical shortages of nurses. Problems with recruitment, retention and an ageing workforce means that attempts to ensure a viable nursing workforce must be placed at the top of the professional agenda. Strategies currently used to manage the crisis, such as overseas recruitment, are not sustainable and are ethically dubious. The demographic timebomb is ticking and up to half the current nursing workforce will reach retirement age by 2020. It is vital that there are adequate numbers of skilled and qualified nurses to take their places. Nursing and nurses are facing unprecedented challenges and pressures in the workplace. Job satisfaction is threatened as nurses are pressured to do more with less, Nursing productivity has increased phenomenally over the past ten years in response to increased demands and decreasing numbers of staff. The nursing workplace has disturbingly high levels of occupational violence, and many nurses operate within a culture of blame and scapegoating. There is evidence that organizational change is imposed upon nurses with little or no consultation and the literature reveals that this has a direct and negative effect on job satisfaction and on retention of nurses. This paper explores some of the critical issues that nursing must confront to be successful in establishing and maintaining a vigorous, dynamic and viable workforce.     

采用蛋白指纹图谱技术筛选大肠癌肝转移特异性相关蛋白

目的:应用表面增强激光解析电离飞行时间质谱技术从大肠癌及大肠癌肝转移患者中筛选出大肠癌肝转移患者血清特异性相关蛋白。方法:实验于2005-07/2006-09分别在南方医院消化中心实验室与解放军第一五○医院实验室完成。应用美国CipherGen公司IMAC3(ImmobilizedMetalAffinityCapture,金属亲和表面)芯片和蛋白芯片仪检测44例大肠癌患者及36例大肠癌肝转移患者血清中的蛋白质相对含量。设定所有血清样本检测的蛋白质相对分子质量区间在1500～20000。利用PBSⅡ型蛋白质芯片阅读仪对IMAC3芯片进行检测,所得到的蛋白质以波谱的形式表示。采用BiomarkerWizard软件对2组血清在相同质荷比的蛋白质含量数据进行方差分析,将分析所得到的含量有显著性差异(P<0.05)的蛋白质建立数据库,导入BiomarkerPattern智能统计分析软件,选择相应条件,对其进行分组统计,从而得到能够正确分组的特异性蛋白标志物并构建大肠癌肝转移的诊断模型。采用酶联免疫法检测相同血清标本中的CEA水平,与构建的诊断模型在大肠癌肝转移诊断中作比较。结果:①44例大肠癌患者与36例大肠癌肝转移患者的血清蛋白质在质荷比为2685.64～11813间有16个蛋白质含量有显著差异。②大肠癌组在质荷比为5909处的蛋白质的相对含量高于大肠癌肝转移组[(30.1±9.6)%,(14.5±10.4)%,P≤0.01]。③其中44例大肠癌患者中有38例患者被正确分组,36例大肠癌肝转移患者被正确识别,准确率为92.5%(74/80),灵敏度和特异性分别为100%(36/36),86.4%(38/44)。结论:表面增强激光解析电离飞行时间质谱技术快速、准确、灵敏度、特异性高,通过蛋白芯片仪发现的特异性相关蛋白,有望成为大肠癌肝转移诊断中有应用价值的临床检测指标。     

Accumulation of premutagenic DNA lesions in mice defective in removal of oxidative base damage

DNA damage generated by oxidant byproducts of cellular metabolism has been proposed as a key factor in cancer and aging. Oxygen free radicals cause predominantly base damage in DNA, and the most frequent mutagenic base lesion is 7,8-dihydro-8-oxoguanine (8-oxoG). This altered base can pair with A as well as C residues, leading to a greatly increased frequency of spontaneous G.C-->T.A transversion mutations in repair-deficient bacterial and yeast cells. Eukaryotic cells use a specific DNA glycosylase, the product of the OGG1 gene, to excise 8-oxoG from DNA. To assess the role of the mammalian enzyme in repair of DNA damage and prevention of carcinogenesis, we have generated homozygous ogg1(-/-) null mice. These animals are viable but accumulate abnormal levels of 8-oxoG in their genomes. Despite this increase in potentially miscoding DNA lesions, OGG1-deficient mice exhibit only a moderately, but significantly, elevated spontaneous mutation rate in nonproliferative tissues, do not develop malignancies, and show no marked pathological changes. Extracts of ogg1 null mouse tissues cannot excise the damaged base, but there is significant slow removal in vivo from proliferating cells. These findings suggest that in the absence of the DNA glycosylase, and in apparent contrast to bacterial and yeast cells, an alternative repair pathway functions to minimize the effects of an increased load of 8-oxoG in the genome and maintain a low endogenous mutation frequency.     

Human fetal bone marrow early progenitors for T, B, and myeloid cells are found exclusively in the population expressing high levels of CD34

Experimentation on human stem cells is hampered by the relative paucity of this population and by the lack of assays identifying multilineage differentiation, particularly along the lymphoid lineages. In our current study, phenotypic analysis of low-density fetal bone marrow cells showed two distinct populations of CD34+ cells: those expressing a high density of CD34 antigen on their surface (CD34hi) and those expressing an intermediate level of CD34 antigen (CD34lo). Multiple tissues were used to characterize the in vitro and in vivo potential of these subsets and showed that only CD34hi cells support long-term B lymphopoiesis and myelopoiesis in vitro and mediate T, B, and myeloid repopulation of human tissues implanted into SCID mice. CD34lo cells repeatedly failed to provide long-term hematopoietic activity in vivo or in vitro. These results indicate that a simple fractionation based on well-defined CD34 antigen levels can be used to reproducibly isolate cells highly enriched for in vivo long-term repopulating activity and for multipotent progenitors, including T- and B-cell precursors. Additionally, given the limited variability in the results and the high correlation between in vitro and in vivo hematopoietic potential, we propose that the CD34hi population contains virtually all of the stem cell activity in fetal bone marrow and therefore is the population of choice for future studies in hematopoietic stem cell development and gene therapy.     

Bioactive alkaloids of frog skin: combinatorial bioprospecting reveals that pumiliotoxins have an arthropod source

Nearly 500 alkaloids have been detected in skin extracts from frogs of the family Dendrobatidae. All seem to have been sequestered unchanged into skin glands from alkaloid-containing arthropods. Ants, beetles, and millipedes seem to be the source of decahydroquinolines, certain izidines, coccinellines, and spiropyrrolizidine oximes. But the dietary source for a major group of frog-skin alkaloids, namely the pumiliotoxins (PTXs), alloPTXs, and homoPTXs, remained a mystery. In hopes of revealing an arthropod source for the PTX group, small arthropods were collected from eight different sites on a Panamanian island, where the dendrobatid frog (Dendrobates pumilio) was known to contain high levels of two PTXs. The mixed arthropod collections from several sites, each representing up to 20 arthropod taxa, contained PTX 307A and/or alloPTX 323B. In addition, the mixed arthropod collections from several sites contained a 5,8-disubstituted indolizidine (205A or 235B), representing another class of alkaloids previously unknown from an arthropod. An ant alkaloid, decahydroquinoline 195A, was detected in the mixed arthropod collections from several sites. Thus, "combinatorial bioprospecting" demonstrates that further collection and analysis of individual taxa of leaf-litter arthropods should reveal the taxa from which PTXs, alloPTXs, and 5,8-disubstituted indolizidines are derived.     

Valine-alanine manganese superoxide dismutase polymorphism is not associated with alcohol-induced oxidative stress or liver fibrosis

The role of genetic factors in the pathogenesis of alcohol-induced liver disease (ALD) is receiving increasing attention. Recently, it has been reported that homozygosity for a valine to alanine substitution in the mitochondrial targeting sequence of manganese superoxide dismutase (Mn-SOD) represents a risk factor for severe ALD. Because this mutation is postulated to modify enzyme transport into mitochondria, we have sought confirmatory evidence of this association in a larger group of patients and investigated whether this polymorphism might influence alcohol-induced oxidative stress. Genotyping for the valine-alanine (Val-Ala) polymorphism of the Mn-SOD gene in 281 patients with advanced ALD (cirrhosis/fibrosis) and 218 drinkers without liver disease showed no differences in either the heterozygote (55% vs. 50%) or the homozygote (19% vs. 23%) frequency for the alanine allele. By measuring the titers of circulating antibodies against oxidized cardiolipin (OX-CL) and malondialdehyde (MDA) or hydroxy-ethyl radical (HER) adducts as markers of oxidative stress, we found a significant increase in ALD patients compared with healthy controls. However, the carriers of the alanine Mn-SOD allele had titers of anti-MDA, anti-HER, and anti-OX-CL IgG comparable with heterozygotes and patients homozygous for the valine allele. Similarly, the frequency of subjects with antibody titers above the 95th percentile of controls was not increased among homozygotes for the alanine Mn-SOD allele. In conclusion, in our population Val-Ala polymorphism in Mn-SOD influences neither susceptibility to alcohol-induced liver fibrosis nor alcohol-induced oxidative stress.     

Serum soluble interleukin-2 receptor is associated with clinical and pathologic disease status in hairy cell leukemia.

Hairy cell leukemia is a chronic lymphoproliferative disorder of B-cell lineage, whose malignant cells express the interleukin-2 (IL-2) receptor. A soluble form of the IL-2 receptor is released by these cells in culture, and the sera of patients with hairy cell leukemia contain elevated levels of this soluble receptor. Four hundred twenty-seven serum samples from 101 patients were analyzed for soluble IL-2 receptor (sIL-2R). The clinical status of patients appeared to be associated with the serum level of sIL-2R. The hairy cell index (a measure of tumor cell burden) was correlated with the square root of the serum sIL-2R level (r = .77). Improved clinical status was associated with decreasing serum sIL-2R levels, whereas disease relapse was associated with increasing levels. Notably, every patient who responded to therapy had a decline in serum sIL-2R level, and every patient with disease progression had an increase in serum sIL-2R level. This phenomenon was observed for several different treatments, including standard-dose interferon, low-dose interferon, and deoxycoformycin. The predictive reliability of this test is currently being prospectively evaluated.