Actions of Competence in Occupational Therapy Practice: A phenomenological study of practice in narrative form

This study examined the phenomenon ?what are occupational therapists doing when they feel competent?. Data were provided by eleven occupational therapists who narrated clinical cases in which they had felt themselves to be competent. The empirical phenomenological psychological (EPP) method was used to analyse and interpret the data. The result revealed that on a general level the experience of feeling competent as an occupational therapist derived from achieving results in the rehabilitation project that were satisfying for both participants (the therapist and the client). The strategies for accomplishing this were related to the empathic competence of the therapists. This competence involved interpreting clinical situations as well as understanding the relationship between motive, meaning, decision and time. Further it involved bringing objects, in the form of adaptations, technical aids, structures, simplifications or compensations, into the clinical situation. These abilities together had a great impact on the therapeutic outcome by shaping the clients' lifeworld to make it richer and more active.     

The Nonhematopoietic Effects of Erythropoietin in Skin Regeneration and Repair: From Basic Research to Clinical Use

Erythropoietin (EPO) is the main regulator of red blood cell production but there exists also a variety of nonhematopoietic properties. More recent data show that EPO is also associated with the protection of tissues suffering from ischemia and reperfusion injury as well as with improved regeneration in various organ systems, in particular the skin. This review highlights the mechanisms of EPO in the different stages of wound healing and the reparative processes in the skin emphasizing pathophysiological mechanisms and potential clinical applications. There is clear evidence that EPO effectively influences all wound‐healing phases in a dose‐dependent manner. This includes inflammation, tissue, and blood vessel formation as well as the remodeling of the wound. The molecular mechanism is predominantly based on an increased expression of the endothelial and inducible nitric oxide (NO) synthase with a consecutive rapid supply of NO as well as an increased content of vascular endothelial growth factor (VEGF) in the wound. The improved understanding of the functions and regulatory mechanisms of EPO in the context of wound‐healing problems and ischemia/reperfusion injury, especially during flap surgery, may lead to new considerations of this growth hormone for its regular clinical application in patients.     

Leukocyte adhesion deficiency II patients with a dual defect of the GDP-fucose transporter

Leukocyte adhesion deficiency II (LAD II) is a rare congenital disease caused by defective fucosylation leading to immuno-deficiency and psychomotor retardation. We have previously identified the genetic defect of LAD II in a patient whose Golgi GDP-fucose transporter (GFTP) bears a single amino acid exchange that renders this protein nonfunctional but correctly localized to the Golgi. We now report a novel dual defect by which a truncated GFTP causes the disease in a new LAD II patient. We show that the truncation renders this GFTP unable to localize to the Golgi, the compartment where it is required. Furthermore, the missing part of the GFTP can be dissected into 2 regions, one that is needed for Golgi localization and one that is additionally required for the function of the GFTP. We investigated the subcellular localization of all known defective GFTPs allowing us to divide all genetically analyzed LAD II patients into 2 groups, one in which single amino acid exchanges in the GFTP impair its function but not its subcellular localization, and another group with a dual defect in function and Golgi expression of the GFTP due to the absence of 2 important molecular regions.     

In vivo regulation of inducible no synthase in immune-mediated liver injury in mice

Inducible nitric oxide synthase (iNOS) has been shown to play an important role in the development of liver injury. iNOS deficiency protects mice from hemorrhage/resuscitation as well as from cytokine-mediated liver injury, for example, after administration of concanavalin A (con A). Here we investigated the in vivo effects of tumor necrosis factor (TNF)-alpha and/or interferon (IFN)-gamma, two mediators of con A-induced liver injury, the TNF receptor (TNFR) usage leading to iNOS expression, and its connection with nuclear factor kappaB (NF-kappaB) activation. In conclusion, iNOS expression in vivo is dependent on both TNF-alpha and IFN-gamma. Although con A-induced liver injury depends on both TNFR1 and TNFR2, TNF-dependent iNOS expression is mediated exclusively by TNFR1 and requires NF-kappaB activation.     

Spinal cord stimulation for refractory angina pectoris: a retrospective analysis of efficacy and cost-benefit

BACKGROUND: Patients with refractory angina pectoris have severe symptoms despite optimal medication, but are not suitable for revascularisation. Spinal cord stimulation (SCS) has been used for treating refractory angina pectoris since 1985. The efficacy of SCS has been proven by randomised controlled trials and follow-up studies have shown that SCS is a safe treatment. The objective of the current study was to retrospectively analyse the clinical outcomes and cost-benefit of SCS in patients with refractory angina pectoris. METHODS: Eighteen months after SCS implantation, the effects on Canadian Cardiovascular Society (CCS) functional level and acute symptom relief of 24 patients with permanent SCS were analysed by review of medical records. Nineteen of these 24 patients were able to report their anginal frequency, nitroglycerin consumption and subjective perception on physical activity and quality of life. RESULTS: Angina frequency decreased from a median of 14.0 to 2.3 attacks/week (p < 0.01). Nitroglycerin intake decreased from a median of 27.5 to 1.5 doses/week (p < 0.01). Canadian Cardiovascular Society angina class improved from a median of three to two (p < 0.001). During a three-year period before SCS implantation, the hospitalisation rate and duration related to coronary artery disease increased progressively. The duration of hospitalisation increased from a median of three to 10 days/patient/year. In the year after SCS implantation the duration of hospitalisation decreased to a median of 0 day/patient/year (p < 0.001). The cost of hospital care due to coronary artery disease decreased significantly thereafter. The total cost of SCS procedure was recovered within 16 months after implantation, which is less than 40% of the device life span. CONCLUSIONS: This retrospective study indicates that SCS treatment alleviates angina symptoms and improves quality of life. The treatment is also effective in preventing hospitalisations and saving costs in hospital care. A prospective study is warranted to confirm the current observations.     

Compound library development guided by protein structure similarity clustering and natural product structure

To identify biologically relevant and drug-like protein ligands for medicinal chemistry and chemical biology research the grouping of proteins according to evolutionary relationships and conservation of molecular recognition is an established method. We propose to employ structure similarity clustering of the ligand-sensing cores of protein domains (PSSC) in conjunction with natural product guided compound library development as a synergistic approach for the identification of biologically prevalidated ligands with high fidelity. This is supported by the concepts that (i) in nature spatial structure is more conserved than amino acid sequence, (ii) the number of fold types characteristic for all protein domains is limited, and (iii) the underlying frameworks of natural product classes with multiple biological activities provide evolutionarily selected starting points in structural space. On the basis of domain core similarity considerations and irrespective of sequence similarity, Cdc25A phosphatase, acetylcholinesterase, and 11beta-hydroxysteroid dehydrogenases type 1 and type 2 were grouped into a similarity cluster. A 147-member compound collection derived from the naturally occurring Cdc25A inhibitor dysidiolide yielded potent and selective inhibitors of the other members of the similarity cluster with a hit rate of 2-3%. Protein structure similarity clustering may provide an experimental opportunity to identify supersites in proteins.