This study aimed to investigate the microRNA (miRNA) profile in prostate carcinoma tissue by microarray analysis and RT‐qPCR, to clarify associations of miRNA expression with clinicopathologic data ...and to evaluate the potential of miRNAs as diagnostic and prognostic markers. Matched tumor and adjacent normal tissues were obtained from 76 radical prostatectomy specimens. Twenty‐four tissue pairs were analyzed using human miRNA microarrays for 470 human miRNAs. Differentially expressed miRNAs were validated by TaqMan RT‐qPCR using all 76 tissue pairs. The diagnostic potential of miRNAs was calculated by receiver operating characteristics analyses. The prognostic value was assessed in terms of biochemical recurrence using Kaplan–Meier and Cox regression analyses. Fifteen differentially expressed miRNAs were identified with concordant fold‐changes by microarray and RT‐qPCR analyses. Ten microRNAs (hsa‐miR‐16, hsa‐miR‐31, hsa‐miR‐125b, hsa‐miR‐145, hsa‐miR‐149, hsa‐miR‐181b, hsa‐miR‐184, hsa‐miR‐205, hsa‐miR‐221, hsa‐miR‐222) were downregulated and 5 miRNAs (hsa‐miR‐96, hsa‐miR‐182, hsa‐miR‐182*, hsa‐miR‐183, hsa‐375) were upregulated. Expression of 5 miRNAs correlated with Gleason score or pathological tumor stage. Already 2 microRNAs classified up to 84% of malignant and nonmalignant samples correctly. Expression of hsa‐miR‐96 was associated with cancer recurrence after radical prostatectomy and that prognostic information was confirmed by an independent tumor sample set from 79 patients. That was shown with hsa‐miR‐96 and the Gleason score as final variables in the Cox models build in the 2 patient sets investigated. Thus, differential miRNAs in prostate cancer are useful diagnostic and prognostic indicators. This study provides a solid basis for further functional analyses of miRNAs in prostate cancer.
Bladder cancer is a common cancer in the Western world. The current prognosticators such as tumor grade, stage, size, and multifocality do not accurately reflect the clinical outcome. It is of ...clinical interest to identify biomarkers that could improve diagnostic and/or prognostic predictions. The objectives of this study were to identify deregulated miRNAs in bladder cancer samples and evaluate their potential as diagnostic and prognostic biomarkers. We screened 723 miRNAs by microarray and selected a subset of 15 distinctively deregulated miRNAs for further validation by real-time quantitative RT-(q)PCR. Seven miRNAs (miR-20a, miR-106b, miR-130b, miR-141, miR-200a, miR-200a*, and miR-205) were found to be up-regulated and eight miRNAs (miR-100, miR-125b, miR-130a, miR-139-5p, miR-145*, miR-199a-3p, miR-214, and miR-222) were found to be down-regulated in malignant bladder tissue samples compared to healthy tissue. Four miRNAs that have already been described in the literature (miR-141, miR-199a-3p, miR-205, and miR-214) were significantly differentially expressed between nonmuscle-invasive and muscle-invasive bladder cancer. Furthermore, real-time RT-qPCR of all miRNAs provided high overall correct classification (>75%) of bladder cancer diagnosis. Two miRNAs (miR-141 and miR-205) were associated with overall survival time. The verification of tumor-specific miRNA expression profile, together with the observed association of miR-141 and miR-205 expression with overall survival, underline the potential of miRNAs to function as diagnostic and/or prognostic markers of bladder cancer.
Design Things Binder, Thomas; Michelis, Giorgio De; Ehn, Pelle ...
09/2011
eBook, Book
Design Things offers an innovative view of design thinking and design practice, envisioning ways to combine creative design with a participatory approach encompassing aesthetic and democratic ...practices and values. The authors of Design Things look at design practice as a mode of inquiry that involves people, space, artifacts, materials, and aesthetic experience, following the process of transformation from a design concept to a thing. Design Things, which grew out of the Atelier (Architecture and Technology for Inspirational Living) research project, goes beyond the making of a single object to view design projects as sociomaterial assemblies of humans and artifacts--"design things." The book offers both theoretical and practical perspectives, providing empirical support for the authors' conceptual framework with field projects, case studies, and examples from professional practice. The authors examine the dynamics of the design process; the multiple transformations of the object of design; metamorphing, performing, and taking place as design strategies; the concept of the design space as "emerging landscapes"; the relation between design and use; and the design of controversial things.
MicroRNAs are short single‐stranded RNAs that are associated with gene regulation at the transcriptional and translational level. Changes in their expression were found in a variety of human cancers. ...Only few data are available on microRNAs in clear cell renal cell carcinoma (ccRCC). We performed genome‐wide expression profiling of microRNAs using microarray analysis and quantification of specific microRNAs by TaqMan real‐time RT‐PCR. Matched malignant and non‐malignant tissue samples from two independent sets of 12 and 72 ccRCC were profiled. The microarray‐based experiments identified 13 over‐expressed and 20 down‐regulated microRNAs in malignant samples. Expression in ccRCC tissue samples compared with matched non‐malignant samples measured by RT‐PCR was increased on average by 2.7‐ to 23‐fold for the hsa‐miR‐16, −452*, −224, −155 and −210, but decreased by 4.8‐ to 138‐fold for hsa‐miR‐200b, −363, −429, −200c, −514 and −141. No significant associations between these differentially expressed microRNAs and the clinico‐pathological factors tumour stage, tumour grade and survival rate were found. Nevertheless, malignant and non‐malignant tissue could clearly be differentiated by their microRNA profile. A combination of miR‐141 and miR‐155 resulted in a 97% overall correct classification of samples. The presented differential microRNA pattern provides a solid basis for further validation, including functional studies.
Reverse transcription quantitative real-time PCR (RT-qPCR) is widely used in microRNA (miRNA) expression studies on cancer. To compensate for the analytical variability produced by the multiple steps ...of the method, relative quantification of the measured miRNAs is required, which is based on normalization to endogenous reference genes. No study has been performed so far on reference miRNAs for normalization of miRNA expression in urothelial carcinoma. The aim of this study was to identify suitable reference miRNAs for miRNA expression studies by RT-qPCR in urothelial carcinoma.
Candidate reference miRNAs were selected from 24 urothelial carcinoma and normal bladder tissue samples by miRNA microarrays. The usefulness of these candidate reference miRNAs together with the commonly for normalization purposes used small nuclear RNAs RNU6B, RNU48, and Z30 were thereafter validated by RT-qPCR in 58 tissue samples and analyzed by the algorithms geNorm, NormFinder, and BestKeeper.
Based on the miRNA microarray data, a total of 16 miRNAs were identified as putative reference genes. After validation by RT-qPCR, miR-101, miR-125a-5p, miR-148b, miR-151-5p, miR-181a, miR-181b, miR-29c, miR-324-3p, miR-424, miR-874, RNU6B, RNU48, and Z30 were used for geNorm, NormFinder, and BestKeeper analyses that gave different combinations of recommended reference genes for normalization.
The present study provided the first systematic analysis for identifying suitable reference miRNAs for miRNA expression studies of urothelial carcinoma by RT-qPCR. Different combinations of reference genes resulted in reliable expression data for both strongly and less strongly altered miRNAs. Notably, RNU6B, which is the most frequently used reference gene for miRNA studies, gave inaccurate normalization. The combination of four (miR-101, miR-125a-5p, miR-148b, and miR-151-5p) or three (miR-148b, miR-181b, and miR-874,) reference miRNAs is recommended for normalization.
MicroRNAs (miRNAs) play a pivotal role in cancerogenesis and cancer progression, but their specific role in the metastasis of clear cell renal cell carcinomas (ccRCC) is still limited. Based on ...microRNA microarray analyses from normal and cancerous samples of ccRCC specimens and from bone metastases of ccRCC patients, we identified a set of 57 differentially expressed microRNAs between these three sample groups of ccRCC. A selected panel of 33 miRNAs was subsequently validated by RT-qPCR on total 57 samples. Then, 30 of the 33 examined miRNAs were confirmed to be deregulated. A stepwise down-regulation of miRNA expression from normal, over primary tumor to metastatic tissue samples, was found to be typical. A total of 23 miRNAs (miR-10b/-19a/-19b/-20a/-29a/-29b/-29c/-100/-101/-126/-127/-130/-141/-143/-145/-148a/-192/-194/-200c/-210/-215/-370/-514) were down-regulated in metastatic tissue samples compared with normal tissue. This down-regulated expression in metastatic tissue in comparison with primary tumor tissue was also present in 21 miRNAs. In cell culture experiments with 5-aza-2'-deoxycytidine and trichostatin A, epigenetic modifications were shown as one reason of this down-regulation. The altered miRNA profiles, comprising newly identified metastasis-associated miRNAs, termed metastamir and the predicted miRNA-target interactions together with the significant correlations of miRNAs that were either lost or newly appeared in the studied sample groups, afford a solid basis for further functional analyses of individual miRNAs in RCC metastatic progression.
Posttraumatic TNF-alpha signaling may be one of the factors responsible for pain and hyperalgesia in complex regional pain syndromes (CRPS). In order to further specify the role of TNF-alpha we ...investigated tissue (skin) and serum concentrations in three different patient groups: patients with osteoarthritis and planned surgery, with acute traumatic upper limb bone fracture waiting for surgery, and with CRPS I. Thirty patients (10 in each group) were recruited. Mean CRPS duration was 36.1 ± 8.1 weeks (range 8- 90 weeks). Skin punch biopsies were taken at the beginning of the surgery in osteoarthritis and fracture patients and from the affected side in CRPS patients. Blood samples were taken before the respective procedures. Skin and serum TNF-alpha levels were quantified by ELISA. Compared to patients with osteoarthritis, skin TNF-alpha was significantly elevated in CRPS (p<0.001) and fracture patients (p<0.04). Skin TNF-alpha in CRPS patients was higher than in patients with acute bone fracture (p<0.02). In contrast, serum TNF-alpha values were the same in osteoarthritis and CRPS, and lower in fracture patients (p<0.03). Our results indicate a local but not systemic increase of TNF-alpha in CRPS patients. This increase persists for months after limb trauma and may offer the opportunity for targeted treatment.
The paper explores what exactly it is that users participate in when being involved in participatory design (PD), relating this discussion to the CSCW perspective on collaborative design work. We ...argue that a focus on decision-making in design is necessary for understanding participation in design. Referring to Schön we see design as involving creating choices, selecting among them, concretizing choices and evaluating the choices. We discuss how these kinds of activities have played out in four PD projects that we have participated in. Furthermore, we show that the decisions are interlinked, and discuss the notion of decision linkages. We emphasize the design result as the most important part of PD. Finally, participation is discussed as the sharing of power, asking what the perspective of power and decision-making adds to the understanding of design practices.
The present study evaluates complete supra-annular bioprostheses in patients with an aortic annulus of 18 to 23 mm in diameter.
Aortic valve replacement in patients with small aortic annulus using ...stented bioprostheses is often associated with unsatisfactory hemodynamic results and high incidence of patient-prosthesis mismatch.
Between February 2000 and January 2004, 156 patients with aortic valve disease and an aortic annulus of 18 to 23 mm in diameter received the stented bovine Soprano (Sorin Biomedica Cardio, Saluggia, Italy) (n = 18), Perimount (Edwards Lifesciences, Irvine, California) (n = 52), Perimount Magna (Edwards Lifesciences) (n = 42), or the stented porcine Mosaic (Medtronic Inc., Minneapolis, Minnesota) (n = 44) bioprostheses. Intraoperatively, the surgeon measured the aortic annulus diameter by inserting a hegar dilator. Thus, postoperative hemodynamic results could be referred to the patient’s aortic annulus diameter instead of referring the results to the labeled valve size. This allows for objective comparisons between different valve types.
There was no significant difference in hemodynamic results between the different valve types in patients with an aortic annulus 18 to 20 mm. In patients with an annulus 21 to 23 mm, the Magna was significantly superior to the other investigated devices in mean pressure gradient, effective orifice area, and incidence of patient-prosthesis mismatch. There was no significant difference between the complete supra-annular bioprostheses Mosaic and Soprano and the intra-supra-annular Perimount valve.
In patients with an aortic annulus of 18 to 20 mm in diameter, hemodynamic performance is independent of the implanted stented valve type and the annular position. Root enlargement or stentless valves may be beneficial alternatives. Patients with annulus diameter 21 to 23 mm benefit from the Magna in complete supra-annular position leading to superior hemodynamic results.
Objective Aortic valve replacement in patients with a small aortic annulus is often associated with increased pressure gradients. For this reason, prostheses for completely supra-annular placement ...have been developed. To evaluate the potential benefit of this design, the present study compared the effectiveness of 1 intra–supra-annular bioprosthesis and 3 completely supra-annular bioprostheses in patients with an aortic annulus diameter of 23 mm or less. Methods Between August 2000 and December 2004, each of 192 patients requiring aortic valve replacement with an intraoperatively measured aortic annulus diameter of 23 mm or less received one of the following bioprostheses: the stented bovine Sorin Soprano bioprosthesis (n = 28) (Sorin Group, Saluggia, Italy), the Carpentier–Edwards Perimount bioprosthesis (n = 50) (Edwards Lifesciences, Irvine, Calif), the Carpentier–Edwards Perimount Magna bioprosthesis (n = 70) (Edwards Lifesciences), or the stented porcine Medtronic Mosaic (n = 44) (Medtronic Inc, Minneapolis, Minn) bioprosthesis. After 6 months, hemodynamic data at rest and during exercise were obtained by echocardiography in 142 patients. Results The pericardial valves showed lower mean systolic pressure gradients, larger effective orifice areas and indices, and superior effective orifice fractions than did the porcine valve ( P < .05) (Carpentier–Edwards Perimount: 10.9 ± 3.6 mm Hg, 1.59 ± 0.41 cm2 , 0.9 ± 0.25 cm2 /m2 , 41.9% ± 9.6%; Carpentier–Edwards Perimount Magna 10.1 ± 3.8 mm Hg, 1.64 ± 0.38 cm2 , 0.93 ± 0.22 cm2 /m2 , 45.1% ± 10.2%; Sorin Soprano 13.5 ± 5.0 mm Hg, 1.64 ± 0.32 cm2 , 0.92 ± 0.15 cm2 /m2 , 45.8% ± 9.0%; vs Medtronic Mosaic 15.5 ± 5.2 mm Hg, 1.31 ± 0.42 cm2 , 0.75 ± 0.24 cm2 /m2 , 35.2% ± 10.0%, respectively). The lowest mean systolic pressure gradients were found after the implantation of the Carpentier–Edwards Perimount Magna. Effective orifice areas, indices, and fractions of the pericardial valves did not show significant differences. Conclusions In patients with small aortic roots, transvalvular gradients and effective orifice area showed a tendency to superior results in pericardial valves compared with the porcine bioprosthesis. However, the completely supra-annular design does not necessarily lead to superior hemodynamic results compared with the intra–supra-annular position.
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