Students' Perspectives on Learning Practical Nursing Skills: A Focus Group Study in Norway.

Practical nursing skills are complex and involve technical, theoretical, and practical aspects, caring perspectives adjusted to both patient and circumstances, as well as ethical and moral considerations. Patients' length of stay in hospitals is decreasing, and more advanced patient treatment is conducted in primary healthcare settings. Hence, education and nursing skills need adjustment in line with the rapidly evolving field of practice. Studies emphasize a need to uncover whether the technical aspect of nursing skills, in general, is challenging in students' learning. The aim of this study was to explore students' perspectives on practical nursing skills and how they can best learn these. Three focus group interviews were conducted with registered nurse students and intellectual disability nurse students in their last semester (n = 11). Conventional, inductive content analysis in line with recommendations from Hsieh and Shannon was used to analyze the data. Two main categories with subcategories were identified: (1) the content of practical skills, with subcategories (a) human-to-human relations, (b) organizational competence, and (c) technical mastering and (2) building competence, with subcategories (a) need for supervision, (b) planning the learning situations, and (c) relevance for practice. Students experienced that practical skills did not only include technical aspects but also the ability to establish a relationship to the patient and to organize their working day. Supervising was assumed as essential both when training in the simulation center and in clinical placement, as well as planning of the training, respectively. Students experienced that some skills learned in the university college were less relevant in clinical practice and that certain skills were difficult to perform in practice due to the type of clinical placement. Hence, there is a need to review the approach to and content of practical nursing skills' learning in healthcare undergraduate programs, to prepare students for clinical practice, and to ensure that they build the competence needed in healthcare services.

A link between inflammation and metastasis: serum amyloid A1 and A3 induce metastasis, and are targets of metastasis-inducing S100A4.

S100A4 is implicated in metastasis and chronic inflammation, but its function remains uncertain. Here we establish an S100A4-dependent link between inflammation and metastatic tumor progression. We found that the acute-phase response proteins serum amyloid A (SAA) 1 and SAA3 are transcriptional targets of S100A4 via Toll-like receptor 4 (TLR4)/nuclear factor-κB signaling. SAA proteins stimulated the transcription of RANTES (regulated upon activation normal T-cell expressed and presumably secreted), G-CSF (granulocyte-colony-stimulating factor) and MMP2 (matrix metalloproteinase 2), MMP3, MMP9 and MMP13. We have also shown for the first time that SAA stimulate their own transcription as well as that of proinflammatory S100A8 and S100A9 proteins. Moreover, they strongly enhanced tumor cell adhesion to fibronectin, and stimulated migration and invasion of human and mouse tumor cells. Intravenously injected S100A4 protein induced expression of SAA proteins and cytokines in an organ-specific manner. In a breast cancer animal model, ectopic expression of SAA1 or SAA3 in tumor cells potently promoted widespread metastasis formation accompanied by a massive infiltration of immune cells. Furthermore, coordinate expression of S100A4 and SAA in tumor samples from colorectal carcinoma patients significantly correlated with reduced overall survival. These data show that SAA proteins are effectors for the metastasis-promoting functions of S100A4, and serve as a link between inflammation and tumor progression.

Introducing T-shaped managers. Knowledge management's next generation.

Most companies do a poor job of capitalizing on the wealth of expertise scattered across their organizations. That's because they tend to rely on centralized knowledge-management systems and technologies. But such systems are really only good at distributing explicit knowledge, the kind that can be captured and codified for general use. They're not very good at transferring implicit knowledge, the kind needed to generate new insights and creative ways of tackling business problems or opportunities. The authors suggest another approach, something they call T-shaped management, which requires executives to share knowledge freely across their organization (the horizontal part of the "T"), while remaining fiercely committed to their individual business unit's performance (the vertical part). A few companies are starting to use this approach, and one--BP Amoco--has been especially successful. From BP's experience, the authors have gleaned five ways that T-shaped managers help companies capitalize on their inherent knowledge. They increase efficiency by transferring best practices. They improve the quality of decision making companywide. They grow revenues through shared expertise. They develop new business opportunities through the cross-pollination of ideas. And they make bold strategic moves possible by delivering well-coordinated implementation. All that takes time, and BP's managers have had to learn how to balance that time against the attention they must pay to their own units. The authors suggest, however, that it's worth the effort to find such a balance to more fully realize the immense value of the knowledge lying idle within so many companies.

Networked incubators. Hothouses of the new economy.

Business incubators such as Hotbank, CMGI, and Idealab! are a booming industry. Offering office space, funding, and basic services to start-ups, these organizations have become the hottest way to nurture and grow fledgling businesses. But are incubators a fleeting phenomenon born of an overheated stock market, or are they an important and lasting way of creating value and wealth in the new economy? The authors argue that one type of incubator, called a networked incubator, represents a fundamentally new and enduring organizational model uniquely suited to growing businesses in the Internet economy. It shares certain features with other incubators--mainly, it fosters a spirit of entrepreneurship and offers economies of scale. But its key distinguishing feature is its ability to give start-ups preferential access to a network of potential partners. Such incubators institutionalize their networking--they have systems in place to encourage networking, helping start-ups, for example, to meet with potential business allies. That doesn't mean incubatees get preferential treatment; it means only that they have built-in access to partnerships that might not have existed without the incubator. Even with this advantage, however, networked incubators can easily follow the road to ruin. To avoid failure, they must create a portfolio of companies and advisers that their incubatees can leverage. That can be done by strategically investing in portfolio firms and by enlisting a large set of business allies. It can also be done by establishing connections and relationships that are anchored more to the incubator than to particular individuals.

What's your strategy for managing knowledge?

The rise of the computer and the increasing importance of intellectual assets have compelled executives to examine the knowledge underlying their businesses and how it is used. Because knowledge management as a conscious practice is so young, however, executives have lacked models to use as guides. To help fill that gap, the authors recently studied knowledge management practices at management consulting firms, health care providers, and computer manufacturers. They found two very different knowledge management strategies in place. In companies that sell relatively standardized products that fill common needs, knowledge is carefully codified and stored in databases, where it can be accessed and used--over and over again--by anyone in the organization. The authors call this the codification strategy. In companies that provide highly customized solutions to unique problems, knowledge is shared mainly through person-to-person contacts; the chief purpose of computers is to help people communicate. They call this the personalization strategy. A company's choice of knowledge management strategy is not arbitrary--it must be driven by the company's competitive strategy. Emphasizing the wrong approach or trying to pursue both can quickly undermine a business. The authors warn that knowledge management should not be isolated in a functional department like HR or IT. They emphasize that the benefits are greatest--to both the company and its customers--when a CEO and other general managers actively choose one of the approaches as a primary strategy.

Perineal hernia repair using gracilis myocutaneous flap.

Perineal hernia formation is an infrequent but well-recognized complication of major pelvic surgery. Various methods of perineal reconstruction have been reported. This report describes one technique of perineal hernia repair using a unilateral gracilis myocutaneous flap. The gracilis myocutaneous flap provides well-vascularized tissue that is useful in many situations requiring reconstruction of the pelvis and perineum, especially when the area has been irradiated.

The sequence, crystal structure determination and refinement of two crystal forms of lipase B from Candida antarctica.

BACKGROUND: Lipases constitute a family of enzymes that hydrolyze triglycerides. They occur in many organisms and display a wide variety of substrate specificities. In recent years, much progress has been made towards explaining the mechanism of these enzymes and their ability to hydrolyze their substrates at an oil-water interface. RESULTS: We have determined the DNA and amino acid sequences for lipase B from the yeast Candida antarctica. The primary sequence has no significant homology to any other known lipase and deviates from the consensus sequence around the active site serine that is found in other lipases. We have determined the crystal structure of this enzyme using multiple isomorphous replacement methods for two crystal forms. Models for the orthorhombic and monoclinic crystal forms of the enzyme have been refined to 1.55 A and 2.1 A resolution, respectively. Lipase B is an alpha/beta type protein that has many features in common with previously determined lipase structures and other related enzymes. In the monoclinic crystal form, lipid-like molecules, most likely beta-octyl glucoside, can be seen close to the active site. The behaviour of these lipid molecules in the crystal structure has been studied at different pH values. CONCLUSION: The structure of Candida antarctica lipase B shows that the enzyme has a Ser-His-Asp catalytic triad in its active site. The structure appears to be in an 'open' conformation with a rather restricted entrance to the active site. We believe that this accounts for the substrate specificity and high degree of stereospecificity of this lipase.

[Renal insufficiency in myelomatosis. Causes and treatment]. / Nyreinsufficiens ved myelomatose. Arsager og behandling.

Renal failure is a frequent complication in multiple myeloma and it is present in about 50% of patients with newly-diagnosed multiple myeloma. Renal failure at the time of diagnosis has earlier been associated with a bad prognosis, but a better prognostic factor is the response to chemotherapy. In general, it is important to distinguish between 1) renal insufficiency at the time of diagnosis, 2) acute renal insufficiency and 3) chronic renal insufficiency developing during the course of the disease. The patients in the first two groups are treated with intensive therapy which is long-lasting (median four to six weeks). The improved function of the kidney is correlated to an improved survival. Patients developing chronic renal insufficiency late in the course of the disease should receive palliative therapy. The most important factors that provoke acute renal insufficiency are dehydration, hypercalcaemia and/or infection, but renal insufficiency is also provoked by the use of nephrotoxic drugs, hyperuricaemia and/or hyperviscosity. Chronic renal insufficiency is provoked by deposits of light chains, infiltration by plasma cells or deposits of amyloid. The treatment consists of elimination of the provoking factors and start of chemotherapy.

[Daily single-dose aminoglycoside administration. Therapeutic and economic benefits]. / Aminoglykosidadministration én gang i døgnet. En terapeutisk og øokonomisk gevinst.

Aminoglycosides are among the most active antimicrobial agents against Gram-negative infections, but they also share the potential for oto- and nephrotoxicity. Animal studies have shown that dosing aminoglycosides once daily is more efficient and less nephrotoxic than the conventional multiple daily dosing regimens. Pharmacokinetic and microbiological data support this finding. Clinical trials confirm that once-daily dosing is more efficient and less toxic than multiple daily dosing. The two most important risk factors for nephrotoxicity seem to be the duration of aminoglycoside treatment and high trough levels of aminoglycoside. Netilmicin and amikacin are the drugs most often used in clinical trials of once-daily dosing regimens. Recommendations for once-daily dosing of netilmicin are given.

Cerebral pharmacodynamics of physostigmine in Alzheimer's disease investigated using single-photon computerised tomography.

The effects of physostigmine on patterns of rCBF in patients with pre-senile Alzheimer's disease were studied using 99mTc-labelled HMPAO SPECT. Regional CBF increased in the left cortex relative to right, with the most significant effect in left frontal and higher frontal regions. Measures of regional brain function, such as SPECT, are an important complement to psychological test batteries in understanding the effects in brain of putative antidementia drugs. SPECT brain imaging could extend our understanding of the action of psychotropic drugs in other major psychiatric illnesses.

A novel aspartyl protease allowing KEX2-independent MF alpha propheromone processing in yeast.

Mutants of Saccharomyces cerevisiae which lack the KEX2-encoded endopeptidase are unable to process proteolytically the mating factor alpha (MF alpha) propheromone produced from the chromosomal MF alpha 1 and MF alpha 2 genes (Julius et al., 1983). Overproduction of pheromone precursor from multiple, plasmid-borne MF alpha genes did, however, lead to the production of active MF alpha peptides in the absence of the KEX2 gene product. S. cerevisiae therefore must possess an alternative processing enzyme. The cleavage site of this enzyme appeared identical to that of the KEX2-encoded endopeptidase. To identify the gene responsible for the alternative processing, we have isolated clones which allowed production of mature MF alpha in a kex2-disrupted strain even from the chromosomal MF alpha genes. The gene isolated in this way was shown also to be essential for the KEX2-independent processing of propheromone overproduced from plasmid-borne MF alpha 1. The amino acid sequence deduced from the gene shows extensive homology to a number of aspartyl proteases including the PEP4 and BAR1 gene products from S. cerevisiae. In contrast to the BAR1 gene product, the novel aspartyl protease (YAP3 for Yeast Aspartyl Protease 3) contains a C-terminal serine/threonine-rich sequence and potential transmembrane domain similar to those found in the KEX2 gene product. The corresponding gene YAP3 was located to chromosome XII. The normal physiological role of the YAP3 gene product is not known. Strains disrupted in YAP3 are both viable and able to process the mating factor a precursor.

Competitive expression of two heterologous genes inserted into one plasmid in Saccharomyces cerevisiae.

Plasmids were constructed which contained two expression units encoding single-chain insulin precursors. Surprisingly, the total amount of insulin precursor produced was similar to that produced from plasmids containing a single expression unit. In this system, therefore, two expression cassettes can be brought to compete for the limited ability of the yeast cell for synthesis and secretion. Using genes encoding B(1-29)-A(1-21) and B(1-29)-Ala-Ala-Lys-A-(1-21), the slightly different precursors could be quantified individually after separation by high-performance liquid chromatography from the culture supernatant. The two-cassette system allowed a sensitive and well controlled comparison of parameters important for optimal expression of a heterologous gene in Saccharomyces cerevisiae. The system was used to compare two promoter constructions and also to evaluate the position of expression cassettes in the plasmid. Finally the codon usage in the gene to be expressed was found to influence its ability to compete for expression.

Monomeric insulins obtained by protein engineering and their medical implications.

The use of insulin as an injected therapeutic agent for the treatment of diabetes has been one of the outstanding successes of modern medicine. The therapy has, however, had its associated problems, not least because injection of insulin does not lead to normal diurnal concentrations of insulin in the blood. This is especially true at meal times when absorption from subcutaneous tissue is too slow to mimic the normal rapid increments of insulin in the blood. In the neutral solutions used for therapy, insulin is mostly assembled as zinc-containing hexamers and this self-association, which under normal physiological circumstances functions to facilitate proinsulin transport, conversion and intracellular storage, may limit the rate of absorption. We now report that it is possible, by single amino-acid substitutions, to make insulins which are essentially monomeric at pharmaceutical concentrations (0.6 mM) and which have largely preserved their biological activity. These monomeric insulins are absorbed two to three times faster after subcutaneous injection than the present rapid-acting insulins. They are therefore capable of giving diabetic patients a more physiological plasma insulin profile at the time of meal consumption.

Soluble, prolonged-acting insulin derivatives. II. Degree of protraction and crystallizability of insulins substituted in positions A17, B8, B13, B27 and B30.

It has previously been found that insulins, to which positive charge has been added by substitutions in position B30, thus raising the isoelectric point towards pH 7, had a prolonged action when injected as slightly acidic solutions because such derivatives crystallize very readily upon neutralization. Positive charge has now been added by substituting the B13 and A17 glutamic acid residues with glutamines and B27 threonine with lysine or arginine. These substitutions were introduced by site-specific mutagenesis in a gene coding for a single-chain insulin precursor. By tryptic transpeptidation the single-chain precursors were transformed to the double-chain insulin structure, concomitantly with incorporation of residue B30. Thus insulins combining B13 glutamine, A17 glutamine and B27 lysine or arginine with B30 threonine, threonine amide or lysine amide were synthesized. The time course of blood glucose lowering effect and the absorption were studied after subcutaneous injection in rabbits and pigs. The prolonged action of B30-substituted insulins was markedly enhanced by B27 lysine or arginine substitutions and by B13 glutamine. The B27 residue is located on the surface of the hexamer, so a basic residue in this position presumably promotes the packing of hexamers at neutral pH. The B13 residues cluster in the centre of the hexamer. When the electrostatic repulsive forces from six glutamic acid residues are abolished by substitution with glutamine, a stabilization of the hexamer can be envisaged.(ABSTRACT TRUNCATED AT 250 WORDS)

Secretion of human insulin by a transformed yeast cell.

A yeast expression plasmid encoding a mini-proinsulin molecule was constructed and transformed into Saccharomyces cerevisiae. The plasmid encoded the sequence: B-Arg-Arg-Leu-Gln-Lys-Arg-A in which B represents the B-chain (30 amino acid residues) and A represents the A-chain (21 amino acid residues) of human insulin. The secreted peptides were shown to be a mixture of human insulin and des(B-30)human insulin. Thus, correct disulphide bridges can be established in proinsulin-like molecules devoid of a normal C-peptide region. Furthermore, the specificity of the yeast processing enzymes is so similar to the proinsulin converting enzymes in the human pancreatic beta-cell that it allows the processing of the mini-proinsulin to insulin.

The secretion of glucagon by transformed yeast strains.

Saccharomyces cerevisiae strains were transformed with plasmids coding for modified mating factor alpha 1 leader sequences followed by glucagon. Glucagon-containing peptides which were secreted into the fermentation broth were isolated and their amino acid sequences determined. The yeast strain transformed with the sequence coding for the complete mating factor alpha 1 leader sequence preceding the glucagon gene (MT556) secreted glucagon plus glucagon extended at its N-terminal by parts of the leader sequence. The yeast strain transformed with the sequence coding for a truncated mating factor alpha 1 leader sequence before the glucagon gene (MT615) secreted glucagon. These observations suggest that S. cerevisiae is a suitable vehicle for the efficient expression of plasmids coding for polypeptides similar to glucagon (e.g. VIP, secretin, GIP).

Secretion and processing of insulin precursors in yeast.

A series of dibasic insulin precursors including proinsulin was expressed and secreted from Saccharomyces cerevisiae. Recombinant plasmids were constructed to encode fusion proteins consisting of a modified mating factor alpha 1 leader sequence and an insulin precursor. The leader sequence serves to direct the fusion protein into the secretory pathway of the cell and to expose it to the Lys-Arg processing enzyme system. The secreted peptides were purified from the fermentation broth and characterized by sequencing and amino acid analysis. Processing at one or both dibasic sequences was shown in proinsulin and in other insulin precursors containing a short spacer peptide in place of the C peptide. In contrast, no processing was observed in the absence of a spacer peptide in the insulin precursor molecule, e.g., B-Lys-Arg-A (where A and B are the A and B chain of human proinsulin, respectively). This type of single-chain insulin precursors isolated from such constructions could be enzymatically converted into insulin by treatment with trypsin and carboxypeptidase B. The above results suggest that the C-peptide region of proinsulin serves to direct the trypsin-like converting enzyme to process at the two dibasic sequences. We propose that in hormone precursors in general the spacer peptides serve to expose dibasic sequences for processing.

Two different types of intervening sequences in the glucoamylase gene from Aspergillus niger.

One single glucoamylase gene could be identified in the chromosomal DNA of Aspergillus niger by Southern blot analysis. This glucoamylase gene was isolated from a genomic library of A. niger DNA. The glucoamylase gene is situated on a 2.5-kb EcoRI-EcoRV fragment and contains five intervening sequences in the coding region. One 169-bp intron is involved in differential mRNA processing leading to the two different glucoamylase enzymes G1 and G2; the other four introns are all very small ranging from 55 to 75 bp in length. One intron has a significant homology to the coding region which immediately follows, and it contains the internal conserved sequence TACTAAC, which is also found in yeast chromosomal gene introns, and is thought to participate in mRNA splicing. Two transcription initiation sites and a typical eukaryotic promoter region with TATAAT and CAAT boxes are located upstream from the gene.

Rescue of mitomycin C- or psoralen-inactivated Micrococcus radiodurans by additional exposure to radiation or alkylating agents.

The processing of damaged DNA was altered in a mitomycin C-sensitive mutant (mtcA) of Micrococcus radiodurans. Even though the mutant retained resistance to 254-nm UV radiation, it did not, in contrast to the wild-type strain, show any excessive DNA degradation or cell death when incubated with chloramphenicol after sublethal doses of either UV light or mitomycin C. The results suggest the constitutive synthesis of an enzyme system responsible for wild-type proficiency in the repair of mitomycin C-induced damage. An alternative system able to repair damage caused by mitomycin C was demonstrated in the mtcA background. In this strain, additional damage inflicted upon the cellular DNA effected a massive rescue of cells previously inactivated by mitomycin C. Rescue was provoked by ionizing radiation, by UV light, or by simple alkylating agents. Cells treated with psoralen plus near-UV radiation could be rescued only when inactivation was due primarily to psoralen-DNA interstrand cross-links rather than to monoadducts. The rescue of inactivated cells was prevented in the presence of chloramphenicol. These results can be interpreted most readily in terms of an alternative repair system able to overcome DNA interstrand cross-links produced by mitomycin C or psoralen plus near-UV light, but induced only by the more abundant number of damages produced by radiation or simple alkylating agents.