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Abstract After publication of our article 1, we realized the need for posting a correction note in order to prevent i) overinterpretation of some results by the readers and ii) concerns about potentially unintended misguidance by the authors.

Abstract Background In damaged organs tissue repair and replacement of cells by connective tissue provokes a response of fibroblasts to cellular stress factors such as hypoxia. MicroRNAs (miRNA) are small non-coding RNA molecules which bind to their mRNA targets which eventually lead to repression of translation. Whether the response of fibroblasts to stress factors also involves the miRNA system is largely unknown. Results By miRNA profiling we identified down-regulation of miRNA-449a/b expression in hypoxic fibroblasts. Specific miRNA inhibitors and mimics showed direct evidence for targeting the serine protease inhibitor (serpin) protein (SERPINE1; plasminogen activator inhibitor-1, PAI-1) by miRNA-449a/b leading to SERPINE1 mRNA and protein up- and down-regulation, respectively. SERPINE1 expression in vivo could be located predominantly in areas of fibrosis and remodeling. Conclusions Our study offers serious lines of evidence for a novel hypoxia-dependent mechanism involving hypoxia-induced decrease of clustered miRNA-449a/b, hypoxia-induced amplification of concomitant increase of targeted SERPINE1 (PAI-1) and its overexpression in tissues showing a hypoxic environment.

Abstract Background The effect of additional treatment strategies with antineoplastic agents on intraperitoneal tumor stimulating interleukin levels are unclear. Taurolidine and Povidone-iodine have been mainly used for abdominal lavage in Germany and Europe. Methods In the settings of a multicentre (three University Hospitals) prospective randomized controlled trial 120 patients were randomly allocated to receive either 0.5% taurolidine/2,500 IU heparin (TRD) or 0.25% povidone-iodine (control) intraperitoneally for resectable colorectal, gastric or pancreatic cancers. Due to the fact that IL-1beta (produced by macrophages) is preoperatively indifferent in various gastrointestinal cancer types our major outcome criterion was the perioperative (overall) level of IL-1beta in peritoneal fluid. Results Cytokine values were significantly lower after TRD lavage for IL-1beta, IL-6, and IL-10. Perioperative complications did not differ. The median follow-up was 50.0 months. The overall mortality rate (28 vs. 25, p = 0.36), the cancer-related death rate (17 vs. 19, p = .2), the local recurrence rate (7 vs. 12, p = .16), the distant metastasis rate (13 vs. 18, p = 0.2) as well as the time to relapse were not statistically significant different. Conclusion Reduced cytokine levels might explain a short term antitumorigenic intraperitoneal effect of TRD. But, this study analyzed different types of cancer. Therefore, we set up a multicentre randomized trial in patients undergoing curative colorectal cancer resection. Trial registration ISRCTN66478538

Long-term and continuous observations of mesospheric/lower thermospheric winds are rare, but they are important to investigate climatological changes at these altitudes on time scales of several years, covering a solar cycle and longer. Such long time series are a natural heritage of the mesosphere/lower thermosphere climate, and they are valuable to compare climate models or long term runs of general circulation models (GCMs). Here we present a climatological comparison of wind observations from six meteor radars at two conjugate latitudes to validate the corresponding mean winds and atmospheric diurnal and semidiurnal tides from three GCMs, namely Ground-to-Topside Model of Atmosphere and Ionosphere for Aeronomy (GAIA), Whole Atmosphere Community Climate Model Extension (Specified Dynamics) (WACCM-X(SD)) and Upper Atmosphere ICOsahedral Non-hydrostatic (UA-ICON) model. Our results indicate that there are interhemispheric differences in the seasonal characteristics of the diurnal and semidiurnal tide. There also are some differences in the mean wind climatologies of the models and the observations. Our results indicate that GAIA shows a reasonable agreement with the meteor radar observations during the winter season, whereas WACCM-X(SD) shows a better agreement with the radars for the hemispheric zonal summer wind reversal, which is more consistent with the meteor radar observations. The free running UA-ICON tends to show similar winds and tides compared to WACCM-X(SD). [ABSTRACT FROM AUTHOR]

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Abstract Objective We sought to evaluate the impact of different antineoplastic treatment methods on systolic and diastolic myocardial function, and the feasibility estimation of regional deformation parameters with non-Doppler 2D echocardiography in rats. Background The optimal method for quantitative assessment of global and regional ventricular function in rats and the impact of complex oncological multimodal therapy on left- and right-ventricular function in rats remains unclear. Methods 90 rats after subperitoneal implantation of syngenetic colonic carcinoma cells underwent different onclogical treatment methods and were diveded into one control group and five treatment groups (with 15 rats in each group): group 1 = control group (without operation and without medication), group 2 = operation group without additional therapy, group 3 = combination of operation and photodynamic therapy, group 4 = operation in combination with hyperthermic intraoperative peritoneal chemotherapy with mitomycine, and group 5 = operation in combination with hyperthermic intraoperative peritoneal chemotherapy with gemcitabine, group 6 = operation in combination with taurolidin i.p. instillation. Echocardiographic examination with estimation of wall thickness, diameters, left ventricular fractional shortening, ejection fraction, early and late diastolic transmitral and myocardial velocities, radial and circumferential strain were performed 3–4 days after therapy. Results There was an increase of LVEDD and LVESD in all groups after the follow-up period (P = 0.0037). Other LV dimensions, FS and EF as well as diastolic mitral filling parameters measured by echocardiography were not significantly affected by the different treatments. Values for right ventricular dimensions and function remained unchanged, whereas circumferential 2D strain of the inferior wall was slightly, but significantly reduced under the treatment (-18.1 ± 2.5 before and -16.2 ± 2.9 % after treatment; P = 0.001) without differences between the single treatment groups. Conclusion It is feasible to assess dimensions, global function, and regional contractility with echocardiography in rats under different oncological therapy. The deformation was decreased under overall treatment without influence by one specific therapy. Therefore, deformation assessment with non-Doppler 2D strain echocardiography is more sensitive than conventional echocardiography for assessing myocardial dysfunction in rats under oncological treatment.

Abstract Background Castleman's disease is a rare lymphoproliferative syndrome. Its etiology and pathogenesis are unclear. The disease can be occasionally associated with a paraneoplastic pemphigus (PNP), an autoimmune mucocutaneous disorder commonly seen in neoplasms of lymphocytic origin. Case presentation We present a case of a 63-year old male patient who was referred for surgical treatment of a lately diagnosed retroperitoneal pelvic mass. The patient had been already treated for two years due to progressive diffuse cutaneous lesions histologically consistent with lichen ruber verucosus and pemphigus vulgaris. Intraoperatively a highly vascularized solid mass occupying the small pelvis was resected after meticulous vascular ligation and hemostasis. After surgery and following immunosuppressive treatment a clear remission of the skin lesions was observed. Conclusion Castleman's tumor should be always suspected when a retroperitoneal mass is combined with PNP. In a review of the literature we found 37 additional cases. Complete surgical resection of the tumor can be curative in most of the cases.

Abstract Background Taurolidine (TRD) is a novel agent with multimodal antineoplastic effects. We present the case of a tumor remission after intravenous administration of taurolidine in a patient with gastric cancer re-recurrence. Case presentation A 58 years old male patient suffering from a gastric adenocarcinoma was submitted to partial gastrectomy and partial liver resection (pT2, pN1, pM1L (liver segment 2), N0, V0). 24 months later a local recurrence was diagnosed and the patient was reoperated. Postoperatively the patient underwent a palliative chemotherapy with eloxatin, FU, and leucovorin. A subsequent CT-revealed a liver metastasis and a recurrence adjacent to the hepatic artery. After successful radiofrequency ablation of the liver metastasis the patient was intravenously treated with 2% taurolidine. The patient endured the therapy well and no toxicity was observed. CT-scans revealed a stable disease without a tumor progression or metastatic spread. After 39 cycles the patient was submitted to left nephrectomy due to primary urothelial carcinoma and died 2 days later due to myocardial infarction. Postmortem histology of the esophageal-jejunal anastomosis and liver revealed complete remission of the known metastasized gastric adenocarcinoma. Conclusion The intravenous treatment with 2% taurolidine led to a histological remission of the tumor growth without any toxicity for the patient.

Observations of upper mesosphere/lower thermosphere (MLT) wind have been performed at Collm (51.3 ∘ N, 13.0 ∘ E) and Kazan (56 ∘ N, 49 ∘ E), using two SKiYMET all-sky meteor radars with similar configuration. Daily vertical profiles of mean winds and tidal amplitudes have been constructed from hourly horizontal winds. We analyse the response of mean winds and tidal amplitudes to geomagnetic disturbances. To this end, we compare winds and amplitudes for very quiet (Ap ≤ 5) and unsettled/disturbed (Ap ≥ 20) geomagnetic conditions. Zonal winds in both the mesosphere and lower thermosphere are weaker during disturbed conditions for both summer and winter. The summer equatorward meridional wind jet is weaker for disturbed geomagnetic conditions. Tendencies for geomagnetic effects on mean winds over Collm and Kazan qualitatively agree during most of the year. For the diurnal tide, amplitudes in summer are smaller in the mesosphere and greater in the lower thermosphere, but no clear tendency is seen for winter. Semidiurnal tidal amplitudes increase during geomagnetic active days in summer and winter. Terdiurnal amplitudes are slightly reduced in the mesosphere during disturbed days, but no clear effect is visible for the lower thermosphere. Overall, while there is a noticeable effect of geomagnetic variability on the mean wind, the effect on tidal amplitudes, except for the semidiurnal tide, is relatively small and partly different over Collm and Kazan. [ABSTRACT FROM AUTHOR]

In recent years, multistatic specular meteor radars (SMRs) have been introduced to study the Mesosphere and Lower Thermosphere (MLT) dynamics. In this paper, the statistics of mesoscale MLT power spectra are explored through observations from a campaign using the SIMONe (Spread-spectrum Interferometric Multistatic meteor radar Observing Network) approach conducted in northern Germany in 2018 (hereafter SIMONe 2018). The seven-day SIMONe 2018 comprised of fourteen multistatic SMR links and allows to build a substantial database of specular meteor trail events, collecting more than one hundred thousand detections per day within a geographic area of ~ 500 km x 500 km. The two methods we propose to obtain the power spectra in frequency range are (1) Wind field Correlation Function Inversion (WCFI), which utilizes two-point correlations of specular meteor observations, and (2) Mean Wind Estimation (MWE), which determines the MLT winds and gradients from specular meteor observations. Monte Carlo simulations of a gravity wave spectral model were implemented to validate and compare both methods. The simulation analyses suggest that the WCFI is the viable option among them to study the second-order statistics of the MLT winds that helps to capture the energy of small-scale wind fluctuations. Characterization of the spectral slope at different MLT altitudes has been conducted on the SIMONe 2018, and it provides evidence that gravity waves with periods smaller than seven hours and greater than two hours are dominated by waves with horizontal wavelength significantly larger than 500 km, which might be associated to secondary gravity waves. We believe that the presented methods can help us bridge the observational gap between large and small-scale mesospheric wind fluctuations and also improve the capabilities of SMRs. [ABSTRACT FROM AUTHOR]

Implementing a nonlinear whole atmosphere gravity wave (GW) parameterization into the Middle and Upper Atmosphere Model extending to the lower thermosphere (160 km), we study the response of the atmosphere in terms of the circulation patterns, temperature distribution, and migrating terdiurnal solar tide activity to the upward propagating small-scale internal GWs originating in the lower atmosphere. We perform three test simulations for the Northern Hemisphere winter con5 ditions in order to assess the effects of variations in the initial GW spectrum on the dynamics of the mesosphere and lower thermosphere. We find that the overall strength of the source level momentum flux has a comparatively small impact on zonal mean dynamics. The tails of the GW source level spectrum, however, are crucial for the lower thermosphere dynamics. With respect to the terdiurnal tide, we find a strong dependence of tidal amplitude on the induced GW drag, generally being larger when GW drag is increased. [ABSTRACT FROM AUTHOR]