Die Theologische Realenzyklopädie (TRE) als moderne Fachenzyklopädie repräsentiert in 36 Textbänden (1976–2004) den Wissensstand der theologischen Forschung im Ganzen. Mehr als eine Generation von ...Wissenschaftlerinnen und Wissenschaftlern haben an ihr mitgearbeitet und in mehr als 2.500 Artikeln (auf mehr als 28.000 Textseiten) auf höchstem fachwissenschaftlichem Niveau das einzigartige, international ausgerichtete Nachschlagewerk zu einem Dokument der Wissenschaftsgeschichte gemacht. Die TRE ist ein unverzichtbares Hilfsmittel für Forschung, Studium und Lehre vor allem der Theologie, aber auch ihrer angrenzenden Fachgebiete wie Geschichte, Philosophie, Judaistik, Religionswissenschaften. Die TRE ist auch als 3-teilige Studienausgabe in Paperback veröffentlicht worden. Aaron - Katechismuspredigt (17 Bände) Katechumenat/Katechumenen - Publizistik/Presse (10 Bände) Pürstinger - Zypern (9 Bände) Gesamtregister (Bibelstellen, Orte, Sachen, Namen: 2 Bände) Weiterhin ist die TRE als Datenbank Theologische Realenzyklopädie Online erhältlich.
Die Theologische Realenzyklopädie (TRE) als moderne Fachenzyklopädie repräsentiert in 36 Textbänden (1976–2004) den Wissensstand der theologischen Forschung im Ganzen. Mehr als eine Generation von ...Wissenschaftlerinnen und Wissenschaftlern haben an ihr mitgearbeitet und in mehr als 2.500 Artikeln (auf mehr als 28.000 Textseiten) auf höchstem fachwissenschaftlichem Niveau das einzigartige, international ausgerichtete Nachschlagewerk zu einem Dokument der Wissenschaftsgeschichte gemacht. Die TRE ist ein unverzichtbares Hilfsmittel für Forschung, Studium und Lehre vor allem der Theologie, aber auch ihrer angrenzenden Fachgebiete wie Geschichte, Philosophie, Judaistik, Religionswissenschaften. Die TRE ist auch als 3-teilige Studienausgabe in Paperback veröffentlicht worden. Aaron - Katechismuspredigt (17 Bände) Katechumenat/Katechumenen - Publizistik/Presse (10 Bände) Pürstinger - Zypern (9 Bände) Gesamtregister (Bibelstellen, Orte, Sachen, Namen: 2 Bände) Weiterhin ist die TRE als Datenbank Theologische Realenzyklopädie Online erhältlich.
Die Theologische Realenzyklopädie (TRE) als moderne Fachenzyklopädie repräsentiert in 36 Textbänden (1976–2004) den Wissensstand der theologischen Forschung im Ganzen. Mehr als eine Generation von ...Wissenschaftlerinnen und Wissenschaftlern haben an ihr mitgearbeitet und in mehr als 2.500 Artikeln (auf mehr als 28.000 Textseiten) auf höchstem fachwissenschaftlichem Niveau das einzigartige, international ausgerichtete Nachschlagewerk zu einem Dokument der Wissenschaftsgeschichte gemacht. Die TRE ist ein unverzichtbares Hilfsmittel für Forschung, Studium und Lehre vor allem der Theologie, aber auch ihrer angrenzenden Fachgebiete wie Geschichte, Philosophie, Judaistik, Religionswissenschaften. Die TRE ist auch als 3-teilige Studienausgabe in Paperback veröffentlicht worden. Aaron - Katechismuspredigt (17 Bände) Katechumenat/Katechumenen - Publizistik/Presse (10 Bände) Pürstinger - Zypern (9 Bände) Gesamtregister (Bibelstellen, Orte, Sachen, Namen: 2 Bände) Weiterhin ist die TRE als Datenbank Theologische Realenzyklopädie Online erhältlich.
The functional contribution of myofibroblasts in fibrosis is not well understood. Using a new genetic mouse model to track and isolate myofibroblasts, we performed gene expression profiling followed ...by biological validation to identify HE4 (encoding human epididymis protein 4, also known as WAP 4-disulfide core domain-2 or Wfdc2) as the most upregulated gene in fibrosis-associated myofibroblasts. The HE4 gene encodes for a putative serine protease inhibitor that is upregulated in human and mouse fibrotic kidneys and is elevated in the serum of patients with kidney fibrosis. HE4 suppresses the activity of multiple proteases, including serine proteases and matrix metalloproteinases, and specifically inhibits their capacity to degrade type I collagen. In particular, we identified two serine proteases, Prss35 and Prss23, as HE4 targets with functional relevance in kidney fibrosis. Administration of HE4-neutralizing antibodies accelerated collagen I degradation and inhibited fibrosis in three different mouse models of renal disease. Collectively these studies suggest that HE4 is a potential biomarker of renal fibrosis and a new therapeutic target.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Fibrogenesis is a pathological wound repair process that fails to cease, even when the initial insult has been removed. Fibroblasts are principal mediators of fibrosis, and fibroblasts from fibrotic ...tissues fail to return to their quiescent stage, including when cultured in vitro. In a search for underlying molecular mechanisms, we hypothesized that this perpetuation of fibrogenesis is caused by epigenetic modifications. We demonstrate here that hypermethylation of RASAL1, encoding an inhibitor of the Ras oncoprotein, is associated with the perpetuation of fibroblast activation and fibrogenesis in the kidney. RASAL1 hypermethylation is mediated by the methyltransferase Dnmt1 in renal fibrogenesis, and kidney fibrosis is ameliorated in Dnmt1(+/-) heterozygous mice. These studies demonstrate that epigenetic modifications may provide a molecular basis for perpetuated fibroblast activation and fibrogenesis in the kidney.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Central venous catheter (CVC) placement is a standard procedure in critical care. Ultrasound guidance during placement is recommended by current guidelines, but there is no consensus on the best ...method for evaluating the correct CVC tip position. Recently, the "rapid atrial swirl sign" (RASS) has been investigated in a limited number of studies.
We performed a prospective diagnostic accuracy study of focused echocardiography for the evaluation of CVC tip position in our medical ICU and IMC units.
We performed a prospective diagnostic accuracy study in 100 patients admitted to the Intensive Care Unit and Intermediate Care Unit at our center. The first 10 subjects were assessed by one staff physician investigator (reference cohort), the remaining 90 patients by different residents (test cohort). All patients received a post-procedural chest radiograph (CXR) as gold standard. CVC placement was assessed with focused echocardiography performed by residents after a short training session. A rapid opacification of the right atrium (RASS) after injection of 10 mL of normal saline was regarded as "positive", flush after more than two seconds was defined as "delayed", no flush was a "negative" test result.
Overall sensitivity of the RASS was 100% (95% CI 73.54-100%), specificity was 94.32% (CI 87.24-98.13%). Positive and negative predictive values were 70.59% (CI 44.04-89.09%) and 100% (CI 95.65-100%), respectively. Median time for echocardiographic testing was 5 minutes (1-28) in the whole cohort, CXRs were available after 49.5 minutes (13-254). Interrater agreement of the RASS was 0.77 (Cohen's kappa), Measurement of CVC tip position was not different between two observers. Test characteristics were similar among differently experienced residents.
Presence of the RASS by focused echocardiography showed excellent sensitivity and specificity and was equally performed by residents after minimal training. In patients with a positive RASS, routine CXR can be safely omitted, reducing time, costs and radiation exposure. A negative RASS should lead to a search for misplaced catheters.
The study was registered with www.clinicaltrials.gov (NCT02661607).
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Methylation of CpG island promoters is an epigenetic event that can effectively silence transcription over multiple cell generations. Hypermethylation of the Rasal1 promoter contributes to activation ...of fibroblasts and progression of kidney fibrosis. Here, we explored whether such causative hypermethylation could be reversed through endogenous mechanisms and whether such reversal of hypermethylation is a constituent of the antifibrotic activity of bone morphogenic protein 7 (BMP7). We show that successful inhibition of experimental kidney fibrosis through administration of BMP7 associates with normalization of Rasal1 promoter hypermethylation. Furthermore, this reversal of pathologic hypermethylation was achieved specifically through Tet3-mediated hydroxymethylation. Collectively, our findings reveal a new mechanism that may be exploited to facilitate therapeutic DNA demethylation to reverse kidney fibrosis.
Acute kidney injury (AKI) and progressive chronic kidney disease (CKD) are intrinsically tied syndromes. In this regard, the acutely injured kidney often does not achieve its full regenerative ...capacity and AKI directly transitions into progressive CKD associated with tubulointerstitial fibrosis. Underlying mechanisms of such AKI-to-CKD progression are still incompletely understood and specific therapeutic interventions are still elusive. Because epigenetic modifications play a role in maintaining tissue fibrosis, we used a murine model of ischemia-reperfusion injury to determine whether aberrant promoter methylation of RASAL1 contributes causally to the switch between physiological regeneration and tubulointerstitial fibrogenesis, a hallmark of AKI-to-CKD progression. It is known that the antihypertensive drug hydralazine has demethylating activity, and that its optimum demethylating activity occurs at concentrations below blood pressure–lowering doses. Administration of low-dose hydralazine effectively induced expression of hydroxylase TET3, which catalyzed RASAL1 hydroxymethylation and subsequent RASAL1 promoter demethylation. Hydralazine-induced CpG promoter demethylation subsequently attenuated renal fibrosis and preserved excretory renal function independent of its blood pressure–lowering effects. In comparison, RASAL1 demethylation and inhibition of tubulointerstitial fibrosis was not detected upon administration of the angiotensin-converting enzyme inhibitor Ramipril in this model. Thus, RASAL1 promoter methylation and subsequent transcriptional RASAL1 suppression plays a causal role in AKI-to-CKD progression.
Thrombophilic risk factors (TRFs) occur rather frequently in hemodialysis (HD) patients. However, little is known about their significance in HD patients, besides their potential impact on ...arteriovenous (AV) access failure, with varying results. We examined the effects of a wide variety of TRFs on both early AV fistula occlusion and survival among HD patients in long-term follow-up.
In this single-center, observational study, 70 consecutive HD patients from our dialysis center were examined with respect to shunt occlusion within the first 2 years after fistula creation and patient survival in a long-term follow-up (at least 16 years). We examined the presence of factor V, prothrombin, and MTHFR mutations using real-time fluorescence polymerase chain reaction. Furthermore, antithrombin (AT), protein C, protein S, and antiphospholipid antibodies (APL-Abs) were assessed.
Among the 70 patients, 32 had MTHFR mutations, 10 had heterozygous factor V Leiden mutations, 4 had prothrombin mutations, 4 had protein S deficiency, 2 had protein C deficiency, 9 had AT deficiency, and 14 had APL-Abs. 40 patients had shunt occlusion. TRFs were associated with a significantly increased risk for shunt thrombosis (P<0.02). Kaplan-Meier analysis with a log-rank test revealed significantly shorter survival in HD patients with TRFs (P<0.02). Cox regression analysis showed that the presence of TRFs (P<0.05; hazard ratio, 1.94; 95% CI: 1.07-3.56), but not early shunt occlusion, was associated with short patient survival.
TRFs in hemodialysis patients have a strong impact on patient survival and early AV fistula failure; however, patient survival is not significantly affected by early shunt occlusion.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This is the second part of a two-part paper on the application of computer-aided diagnosis to diffuse optical tomography (DOT) for diagnosing rheumatoid arthritis (RA). A comprehensive analysis of ...techniques for the classification of DOT images of proximal interphalangeal joints of subjects with and without RA is presented. A method for extracting heuristic features from DOT images was presented in Part 1. The ability of five classification algorithms to accurately label each DOT image as belonging to a subject with or without RA is analyzed here. The algorithms of interest are the k-nearest-neighbors, linear and quadratic discriminant analysis, self-organizing maps, and support vector machines (SVM). With a polynomial SVM classifier, we achieve 100.0% sensitivity and 97.8% specificity. Lower bounds for these results (at 95.0% confidence level) are 96.4% and 93.8%, respectively. Image features most predictive of RA are from the spatial variation of optical properties and the absolute range in feature values. The optimal classifiers are low-dimensional combinations (<7 features). These results underscore the high potential for DOT to become a clinically useful diagnostic tool and warrant larger prospective clinical trials to conclusively demonstrate the ultimate clinical utility of this approach.
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