Urokinase receptor cleavage and shedding: occurrence and consequences.

The urokinase-type plasminogen activator receptor (uPAR), is a multifunctional protein with an impressive range of distinct, but overlapping functions in the process of tissue remodelling and cell migration: 1) uPAR regulates extracellular proteolysis by promoting plasminogen activation; 2) uPAR regulates cell adhesion as an adhesion receptor for vitronectin and by its capacity to modulate integrin function; 3) uPAR regulates cell migration as a signal transduction molecule and by its intrinsic chemotactic activity. In this thesis I have analysed the consequences, and occurrence, of uPAR cleavage and shedding. In chapter 3 I analyse the structural requirements for uPAR to promote cellular adhesion to vitronectin. I demonstrate that cell surface expression of intact uPAR is necessary and sufficient to promote binding of the myeloid cell line 32D to vitronectin. In this cell system the uPAR mediated cell binding does not lead to cell spreading and does not require integrin activation. In chapter 4 I demonstrate that the chemotactic activity of uPAR maps to the linker region which connects the first and second domain of uPAR. This chemotactic epitope (the SRSRY motif) is required and sufficient for the chemotactic activity of soluble uPAR fragments and appears to induce signalling similar to that induced by uPAR ligands such as uPA. In chapter 5 I show that uPAR and the uPAR fragments Dl and D2D3 are indeed generated on the cell surface and released to the surroundings by several different cell types. In chapter 6 I describe and characterise the presence of soluble uPAR and uPAR fragments in vivo. I demonstrate that suPAR as well as the suPAR fragments Dl and D2D3 are present in human urine. Using mice xenografted with human model tumours I demonstrate that the tumour tissue is a source of urinary suPAR antigen and that the suPAR fragment pattern in urine correlates with uPAR cleavage in the tumour tissue

"Everything just seems much more right in nature":how veterans with post-traumatic stress disorder experience nature-based activities in a forest therapy garden

Available evidence shows that an increasing number of soldiers are seeking help for post-traumatic stress disorder. The post-traumatic stress disorder condition has big emotional and psychological consequences for the individual, his/her family and the society. Little research has been done to explore the impact of nature-based therapy for veterans with post-traumatic stress disorder although there is a growing amount of evidence pointing towards positive outcome. This qualitative study aims to achieve a deeper understanding of this relationship from the veteran’s perspective. Eight Danish veterans participated in a 10-week nature-based therapy. Qualitative interviews were conducted and analysed using the interpretative phenomenological method. The results indicated that the veterans have achieved tools to use in stressful situations and experienced an improvement in their post-traumatic stress disorder symptoms

A Diagnostic Post-Occupancy Evaluation of the Nacadia® Therapy Garden

The design of the Nacadia® therapy garden is based on a model for evidence-based health design in landscape architecture (EBHDL). One element of the model is a diagnostic post-occupancy evaluation (DPOE), which has not previously been fully developed. The present study develops a generic DPOE for therapy gardens, with a focus on studying the effects of the design on patients’ health outcomes. This is done in order to identify successes and failures in the design. By means of a triangulation approach, the DPOE employs a mixture of methods, and data is interpreted corroborating. The aim of the present study is to apply the DPOE to the Nacadia® therapy garden. The results of the DPOE suggest that the design of the Nacadia® therapy garden fulfills its stated aims and objectives. The overall environment of the Nacadia ® therapy garden was experienced as protective and safe, and successfully incorporated the various elements of the nature-based therapy programme. The participants encountered meaningful spaces and activities which suited their current physical and mental capabilities, and the health outcome measured by EQ-VAS (self-estimated general health) indicated a significant increase. Some design failures were identified, of which visual exposure was the most noteworthy. The DPOE model presented appears to be efficient but would nonetheless profit from being validated by other cases

<i>AHRR </i>(cg05575921) methylation extent of leukocyte DNA and lung cancer survival

<div><p>Background</p><p>Prior studies have shown that <i>AHRR</i> (cg05575921) hypomethylation may be a marker of smoking, lung cancer risk and potentially lung cancer survival (in some lung cancer subtypes). It is unknown if <i>AHRR</i> (cg05575921) hypomethylation is associated with reduced survival among lung cancer patients.</p><p>Methods</p><p>In bisulfite treated leukocyte DNA from 465 lung cancer patients from the Copenhagen prospective lung cancer study, we measured <i>AHRR</i> (cg05575921) methylation. 380 died during max follow-up of 4.4 years. Cox proportional hazard models were used to analyze survival as a function of <i>AHRR</i> (cg05575921) methylation.</p><p>Results</p><p>We observed the expected inverse correlation between cumulative smoking and <i>AHRR</i> methylation, as methylation (%) decreased (Coefficient -0.03; 95% confidence interval, -0.04- -0.02, p = 8.6x10^-15) for every pack-year. Cumulative smoking > 60 pack-years was associated with reduced survival (hazard ratio and 95% confidence interval 1.48; 1.05–2.09), however, <i>AHRR</i> (cg05575921) methylation was not associated with survival when adjusted for sex, body mass index, smoking status, ethnicity, performance status, TNM Classification, and histology type of lung cancer.</p><p>Conclusion</p><p><i>AHRR</i> (cg05575921) methylation is linked to smoking but does not provide independent prognostic information in lung cancer patients.</p></div

Exploring the capability of wireless near infrared spectroscopy as a portable seizure detection device for epilepsy patients

AbstractPurposeNear infrared spectroscopy (NIRS) has proved useful in measuring significant hemodynamic changes in the brain during epileptic seizures. The advance of NIRS-technology into wireless and portable devices raises the possibility of using the NIRS-technology for portable seizure detection.MethodsThis study used NIRS to measure changes in oxygenated (HbO), deoxygenated (HbR), and total hemoglobin (HbT) at left and right side of the frontal lobe in 33 patients with epilepsy undergoing long-term video-EEG monitoring. Fifteen patients had 34 focal seizures (20 temporal-, 11 frontal-, 2 parietal-lobe, one unspecific) recorded and analyzed with NIRS. Twelve parameters consisting of maximum increase and decrease changes of HbO, HbR and HbT during seizures (1min before- to 3min after seizure-onset) for left and right side, were compared with the patients’ own non-seizure periods (a 2-h period and a 30-min exercise-period). In both non-seizure periods a 4min moving windows with maximum overlapping were applied to find non-seizure maxima of the 12 parameters. Detection was defined as positive when seizure maximum change exceeded non-seizure maximum change.ResultsWhen analyzing the 12 parameters separately the positive seizure detection was in the range of 6–24%. The increase in hemodynamics was in general better at detecting seizures (15–24%) than the decrease in hemodynamics (6–18%) (P=0.02).ConclusionNIRS did not seem to be a suitable technology for generic seizure detection given the device, settings, and methods used in this study. There are still several challenges to overcome before the NIRS-technology can be used as a home-monitoring seizure detection device