Untersuchungen zur gewebsspezifischen Expression von ASB10 in der Maus – Eine Reportergenanalyse

Hintergrund: Bei ASB10 handelt es sich um ein möglicherweise mit dem Glaukom assoziiertes Gen. Die Funktion von ASB10 liegt vermutlich in der Ubiquitinierung eines spezifischen Substrates, somit ist es Bestandteil zellulärer Abbauprozesse. In dieser Arbeit soll die Expression von ASB10 im Versuchsorganismus Maus (adult und embryonal) dargestellt werden. Methoden: Es wurde eine ASB10+/--Mauslinie verwendet, bei welcher eine promotergesteuerte LacZ-Kassette in das ASB10-Gen eingeschoben wurde. Somit konnte die Genexpression mittels einer LacZ-Färbung von Gefrierschnitten der einzelnen Organe sichtbar gemacht werden. Zudem wurden Kaiserschnitte von trächtigen Mäusen und anschließend LacZ-Färbungen der Embryonen durchgeführt, um die Expression von ASB10 im embryonalen Stadium zu zeigen. Ergebnisse: Es zeigte sich eine nahezu ubiquitäre Expression von ASB10 im embryonalen sowie im adulten Organismus der Maus. Die Intensität der durchgeführten LacZ-Färbung zeigt eine deutliche Varianz zwischen den einzelnen Organen, am stärksten ausgeprägt ist sie in Myokard, Nierenparenchym und Nervengewebe, kaum bis gar nicht vorhanden ist die Färbung in Skelettmuskulatur, Thymus- und Leberparenchym, die weiteren Organe zeigen eine intermediäre Intensität der Färbung. Dies kann sowohl auf eine unterschiedliche Expression von ASB10 in den einzelnen Organen als auch auf eine unterschiedliche Verteilung des Substrates bzw. der Substrate von ASB10 zurückzuführen sein. Zudem zeigte sich auch bei Genotypisierung der Embryonen kein homozygoter ASB10-/--Genotyp, sodass von einer Letalität der homozygoten ASB10-Defizienz in einem frühen embryonalen Stadium ausgegangen werden muss. Schlussfolgerung: Die gezeigte ubiquitäre Expression von ASB10 steht im Einklang mit der Hypothese, dass ASB10 an der Ubiquitinierung und damit an zellulären Abbauprozessen beteiligt ist. Bezüglich der Bedeutung von ASB10 als ein mit dem Glaukom assoziiertes Gen kann durch die Ergebnisse der vorliegenden Arbeit jedoch noch keine präzise Aussage getroffen werden

Risk factors for bladder neck contracture after transurethral resection of the prostate

Introduction Transurethral resection of the prostate (TURP) is the most frequently used treatment of benign prostate hyperplasia with a prostate volume of <80 mL. A long-term complication is bladder neck contracture (BNC). The aim of the present study was to identify the risk factors for BNC formation after TURP. Methods We conducted a retrospective analysis of all TURP primary procedures which were performed at one academic institution between 2013 and 2018. All patients were analyzed and compared with regard to postoperative formation of a BNC requiring further therapy. Uni- and multivariable logistic regression analyses (MVAs) were performed to identify possible risk factors for BNC development. Results We included 1368 patients in this analysis. Out of these, 88 patients (6.4%) developed BNC requiring further surgical therapy. The following factors showed a statistically significant association with BNC development: smaller preoperative prostate volume (p = 0.001), lower resected prostate weight (p = 0.004), lower preoperative levels of prostate-specific antigen (PSA, p < 0.001), shorter duration of the surgery (p = 0.027), secondary transurethral intervention (due to urinary retention or gross hematuria) during inpatient stay (p = 0.018), positive (≥100  CFU/mL) preoperative urine culture (p = 0.010), and urethral stricture (US) formation requiring direct visual internal urethrotomy (DVIU) postoperatively after TURP (p < 0.001), in particular membranous (p = 0.046) and bulbar (p < 0.001) strictures. Preoperative antibiotic treatment showed a protective effect (p = 0.042). Histopathological findings of prostate cancer (PCA) in the resected prostate tissue were more frequent among patients who did not develop BNC (p = 0.049). On MVA, smaller preoperative prostate volume (p = 0.046), positive preoperative urine culture (p = 0.021), and US requiring DVIU after TURP (p < 0.001) were identified as independent predictors for BNC development. Conclusion BNC is a relevant long-term complication after TURP. In particular, patients with a smaller prostate should be thoroughly informed about this complication

Ureteroplasty with buccal mucosa graft without omental wrap: an effective method to treat ureteral strictures

Purpose Successful treatment options for ureteral strictures are limited. Surgical options such as ileal interposition and kidney autotransplantation are difficult and associated with morbidity and complications. Techniques such as Boari flap and psoas hitch are limited to distal strictures. Only limited case studies on the success of open buccal mucosa graft (BMG) ureteroplasty exist to this date. The purpose of this study was to evaluate the success of open BMG ureteroplasty without omental wrap. Methods In this single-center retrospective study between July 2020 and January 2023, we included 14 consecutive patients with ureteric strictures who were treated with open BMG ureteroplasty without omental wrap. The primary outcome was the success of open BMG ureteroplasty. Further endpoints were complications and hospital readmission. Outcome variables were assessed by clinical examination, kidney sonography, and patient anamnesis. Results Out of 14 patients, 13 were stricture and ectasia-free without a double-J stent at a median follow-up of 15 months (success rate 93%). No complications were observed at the donor site, and the complication rate overall was low with 3 out of 14 patients (21%) having mild-to-medium complications. Conclusions Open BMG ureteroplasty without omental wrap is a successful and feasible technique for ureteric stricture repair

Search of the Orion spur for continuous gravitational waves using a loosely coherent algorithm on data from LIGO interferometers

We report results of a wideband search for periodic gravitational waves from isolated neutron stars within the Orion spur towards both the inner and outer regions of our Galaxy. As gravitational waves interact very weakly with matter, the search is unimpeded by dust and concentrations of stars. One search disk (A) is 6.87° in diameter and centered on 20h10m54.71s+33°33′25.29′′, and the other (B) is 7.45° in diameter and centered on 8h35m20.61s-46°49′25.151′′. We explored the frequency range of 50-1500 Hz and frequency derivative from 0 to -5×10-9 Hz/s. A multistage, loosely coherent search program allowed probing more deeply than before in these two regions, while increasing coherence length with every stage. Rigorous follow-up parameters have winnowed the initial coincidence set to only 70 candidates, to be examined manually. None of those 70 candidates proved to be consistent with an isolated gravitational-wave emitter, and 95% confidence level upper limits were placed on continuous-wave strain amplitudes. Near 169 Hz we achieve our lowest 95% C.L. upper limit on the worst-case linearly polarized strain amplitude h0 of 6.3×10-25, while at the high end of our frequency range we achieve a worst-case upper limit of 3.4×10-24 for all polarizations and sky locations. © 2016 American Physical Society

First low frequency all-sky search for continuous gravitational wave signals

In this paper we present the results of the first low frequency all-sky search of continuous gravitational wave signals conducted on Virgo VSR2 and VSR4 data. The search covered the full sky, a frequency range between 20 and 128 Hz with a range of spin-down between −1.0×10−10 and +1.5×10−11  Hz/s, and was based on a hierarchical approach. The starting point was a set of short fast Fourier transforms, of length 8192 s, built from the calibrated strain data. Aggressive data cleaning, in both the time and frequency domains, has been done in order to remove, as much as possible, the effect of disturbances of instrumental origin. On each data set a number of candidates has been selected, using the FrequencyHough transform in an incoherent step. Only coincident candidates among VSR2 and VSR4 have been examined in order to strongly reduce the false alarm probability, and the most significant candidates have been selected. The criteria we have used for candidate selection and for the coincidence step greatly reduce the harmful effect of large instrumental artifacts. Selected candidates have been subject to a follow-up by constructing a new set of longer fast Fourier transforms followed by a further incoherent analysis, still based on the FrequencyHough transform. No evidence for continuous gravitational wave signals was found, and therefore we have set a population-based joint VSR2-VSR4 90% confidence level upper limit on the dimensionless gravitational wave strain in the frequency range between 20 and 128 Hz. This is the first all-sky search for continuous gravitational waves conducted, on data of ground-based interferometric detectors, at frequencies below 50 Hz. We set upper limits in the range between about 10−24 and 2×10−23 at most frequencies. Our upper limits on signal strain show an improvement of up to a factor of ∼2 with respect to the results of previous all-sky searches at frequencies below 80 H

Search of the Orion spur for continuous gravitational waves using a loosely coherent algorithm on data from LIGO interferometers

We report results of a wideband search for periodic gravitational waves from isolated neutron stars within the Orion spur towards both the inner and outer regions of our Galaxy. As gravitational waves interact very weakly with matter, the search is unimpeded by dust and concentrations of stars. One search disk (A) is 6.87° in diameter and centered on 20[superscript h]10[superscript m]54.71[superscript s] + 33°33[superscript ′]25.29[superscript ′′], and the other (B) is 7.45° in diameter and centered on 8[superscript h]35[superscript m]20.61[superscript s] - 46°49[superscript ′]25.151[superscript ′′]. We explored the frequency range of 50–1500 Hz and frequency derivative from 0 to -5 × 10[superscript -9]  Hz/s. A multistage, loosely coherent search program allowed probing more deeply than before in these two regions, while increasing coherence length with every stage. Rigorous follow-up parameters have winnowed the initial coincidence set to only 70 candidates, to be examined manually. None of those 70 candidates proved to be consistent with an isolated gravitational-wave emitter, and 95% confidence level upper limits were placed on continuous-wave strain amplitudes. Near 169 Hz we achieve our lowest 95% C.L. upper limit on the worst-case linearly polarized strain amplitude h[subscript 0] of 6.3 × 10[superscript -25], while at the high end of our frequency range we achieve a worst-case upper limit of 3.4 × 10[superscript -24] for all polarizations and sky locations.National Science Foundation (U.S.)United States. National Aeronautics and Space AdministrationCarnegie TrustDavid & Lucile Packard FoundationAlfred P. Sloan Foundatio

Search of the Orion spur for continuous gravitational waves using a loosely coherent algorithm on data from LIGO interferometers

We report results of a wideband search for periodic gravitational waves from isolated neutron stars within the Orion spur towards both the inner and outer regions of our Galaxy. As gravitational waves interact very weakly with matter, the search is unimpeded by dust and concentrations of stars. One search disk (A) is 6.87° in diameter and centered on 20[superscript h]10[superscript m]54.71[superscript s] + 33°33[superscript ′]25.29[superscript ′′], and the other (B) is 7.45° in diameter and centered on 8[superscript h]35[superscript m]20.61[superscript s] - 46°49[superscript ′]25.151[superscript ′′]. We explored the frequency range of 50–1500 Hz and frequency derivative from 0 to -5 × 10[superscript -9]  Hz/s. A multistage, loosely coherent search program allowed probing more deeply than before in these two regions, while increasing coherence length with every stage. Rigorous follow-up parameters have winnowed the initial coincidence set to only 70 candidates, to be examined manually. None of those 70 candidates proved to be consistent with an isolated gravitational-wave emitter, and 95% confidence level upper limits were placed on continuous-wave strain amplitudes. Near 169 Hz we achieve our lowest 95% C.L. upper limit on the worst-case linearly polarized strain amplitude h[subscript 0] of 6.3 × 10[superscript -25], while at the high end of our frequency range we achieve a worst-case upper limit of 3.4 × 10[superscript -24] for all polarizations and sky locations.National Science Foundation (U.S.)United States. National Aeronautics and Space AdministrationCarnegie TrustDavid & Lucile Packard FoundationAlfred P. Sloan Foundatio

Epidemiology and therapy of symptomatic lymphoceles after robot-assisted radical prostatectomy (RARP)

Background: Lymphoceles are a common postoperative complication after radical prostatectomy with pelvic lymphadenectomy. Therapeutic options include cannulation and drainage (CD), drainage and instillation (DI), or laparoscopic fenestration (LF). The aim of this study was to investigate the epidemiology of symptomatic lymphoceles (SLC) and evaluate the treatment options. Methods: We retrospectively analysed all patients who underwent robot-assisted radical prostatectomy (RARP) at our clinic from January 1, 2014 to December 31, 2018. All documented lymphoceles of these patients were recorded and analysed with regard to symptoms, possible infection and the treatment option (or options) chosen. Results: We were able to include all 1,029 patients who underwent RARP in the aforementioned period of time. Of these, 18.1% were diagnosed with a lymphocele either when discharged or when readmitted and 6.9% experienced an SLC requiring treatment. Thirteen-point-seven percent of patients readmitted with SLC showed an accompanying thrombosis. Due to recurring or bilateral SLCs receiving different treatment options for each side, there was a total of 115 SLCs treated. CD was carried out in 102 cases. Twenty-point six percent of patients were sufficiently treated this way, the rest required further treatment or experienced recurrences not requiring further treatment. DI was carried out in 56 cases. Of those patients, 46.4% were sufficiently treated. LF was carried out in 54 cases (either after CD, or after DI, or primarily). Of those patients, 98.1% were treated sufficiently. LF had a statistically significant higher success rate compared to CD and DI (P<0.001 respectively). Conclusions: The study confirmed the significance of SLC as a common complication after RARP. LF turned out to be the most effective treatment option for SLC, while CD as well as DI have not been proven effective

High BMI, Aggressive Tumours and Long Console Time Are Independent Predictive Factors for Symptomatic Lymphocele Formation after Robot-Assisted Radical Prostatectomy and Pelvic Lymph Node Dissection

Introduction: Lymphocele (LC) formation is a common complication which may cause severe symptoms after robot-assisted radical prostatovesiculectomy (RARP) with concomitant pelvic lymph node dissection (PLND). Compared to open radical prostatectomy, the amount of data on potential risk factors for LC formation is still limited. The aim of the present study was to identify risk factors for symptomatic LC formation (sLC) after RARP with PLND. Methods: We used the data of a prospective multicentre series of 232 RARP patients which were treated between March 2017 and December 2017. The primary endpoint was the presence of sLC within 90 days. Asymptomatic LC (aLC) formation was also recorded. We evaluated clinical, perioperative, and histopathological criteria and compared their distribution in patients with and without post-operative sLC. Uni- and multivariable logistic regression analyses (MVAs) were performed to identify potential predictors for LC formation. Regarding the influence of patients’ BMI, 2 models were calculated: BMI continuously (model 1) and BMI dichotomized with cut-off 30 kg/m2 (WHO definition, model 2). Results: Post-operative sLC was present in 21 patients (9.1%), while aLC was detected in 49 patients (21.1%) 90 days after RARP with PLND. Patients with sLC showed higher median baseline PSA levels (9.8 vs. 8.1 ng/mL), higher prevalence of obesity (BMI >30; 42.9 vs. 19.9%), and longer median console time (180 vs. 165 min) compared to patients without sLC. On MVA higher BMI {model 1: OR 1.145 (confidence interval [CI] 1.025–1.278); model 2: OR 2.761 (1.045–7.296)}, longer console time (model 1: OR 1.013 [1.005–1.021]; model 2: OR 1.013 [1.005–1.020]) and an ISUP grade ≥3 (model 1: OR 3.247 [1.182–8.917]; model 2: OR 2.791 [1.050–7.423]) were identified as independent predictors for sLC development. Conclusion: Patients with aggressive tumours and higher BMI should be informed about a potentially increased risk for sLC formation. In case of a long console time, a close and regular follow-up should be considered to check for LC development

Search of the Orion spur for continuous gravitational waves using a loosely coherent algorithm on data from LIGO interferometers

We report results of a wideband search for periodic gravitational waves from isolated neutron stars within the Orion spur towards both the inner and outer regions of our Galaxy. As gravitational waves interact very weakly with matter, the search is unimpeded by dust and concentrations of stars. One search disk (A) is 6.87° in diameter and centered on 20h10m54.71s+33°33′25.29′′, and the other (B) is 7.45° in diameter and centered on 8h35m20.61s−46°49′25.151′′. We explored the frequency range of 50–1500 Hz and frequency derivative from 0 to −5×10−9  Hz/s. A multistage, loosely coherent search program allowed probing more deeply than before in these two regions, while increasing coherence length with every stage. Rigorous follow-up parameters have winnowed the initial coincidence set to only 70 candidates, to be examined manually. None of those 70 candidates proved to be consistent with an isolated gravitational-wave emitter, and 95% confidence level upper limits were placed on continuous-wave strain amplitudes. Near 169 Hz we achieve our lowest 95% C.L. upper limit on the worst-case linearly polarized strain amplitude h0 of 6.3×10−25, while at the high end of our frequency range we achieve a worst-case upper limit of 3.4×10−24 for all polarizations and sky locations