2-Amino-4-aryl-5-oxo-4,5-dihydropyrano[3,2-c]chromene-3-carbonitriles with Microtubule-Disruptive, Centrosome-Declustering, and Antiangiogenic Effects in vitro and in vivo

A series of fifteen 2‐amino‐4‐aryl‐5‐oxo‐4,5‐dihydropyrano[3,2‐c]chromene‐3‐carbonitriles (1 a–o) were synthesized via a three‐component reaction of 4‐hydroxycoumarin, malononitrile, and diversely substituted benzaldehydes or pyridine carbaldehydes. The compounds were tested for anticancer activities against a panel of eight human tumor cell lines. A few derivatives with high antiproliferative activities and different cancer cell specificity were identified and investigated for their modes of action. They led to microtubule disruption, centrosome de‐clustering and G2/M cell cycle arrest in 518 A2 melanoma cells. They also showed anti‐angiogenic effects in vitro and in vivo

Rectum separation in patients with cervical cancer for treatment planning in primary chemo-radiation

PURPOSE: To proof feasibility of hydrogel application in patients with advanced cervical cancer undergoing chemo-radiation in order to reduce rectal toxicity from external beam radiation as well as brachytherapy. MATERIAL AND METHODS: Under transrectal sonographic guidance five patients with proven cervical cancer underwent hydro gel (20 cc) instillation into the tip of rectovaginal septum adherent to posterior part of the visible cervical tumor. Five days after this procedure all patients underwent T2 weighted transversal and sagittal MRI for brachytherapy planning. MRI protocol included T2 weighted fast spin echo (FSE) imaging in sagittal, coronal and para-axial orientation using an 1.5 Tesla MRI. Separation of anterior rectal wall and cervix was documented. RESULTS: Hydrogel application was uneventful in all patients and no toxicity was reported. Separation ranged from 7 to 26 mm in width (median 10 mm). The length of the separation varied between 18 and 38 mm (median 32 mm). In all patients displacement was seen in the posterior vaginal fornix, and/or at the deepest part of uterine cervix depending on the extension of the cul-de-sac in correlation to the posterior wall of the uterus. In patients with bulky tumor and/or deep (vaginal) extend of peritoneal cavity tumour was seen mainly cranial from the rectovaginal space and therefore above the hydrogeI application. Only in the extra-peritoneal (lower) part of the cervix a good separation could be achieved between the rectum and cervix. CONCLUSION: Hydrgel instillation in patients with cervial cancer undergoing chemoradiation is safe and feasible. Because of the loose tissue of the cul-de-sac and its intra- and extraperitoneal part, hydrogel instillation of 20 cc did not result in a sufficient separation of the cervix from anterior wall

A Worker-Like Female of Myrmica sabuleti (Meinert, 1861) (Hymenoptera: Formicidae: Myrmicinae) in a Pitfall Trap with Five Mermithids (Nematoda: Mermithidae) Protruding from the Gaster

A worker-like female of Myrmica sabuleti (Meinert, 1861), pitfall-trapped near Jena, Germany, in late summer 2016, was infested by five postparasitic juvenile mermithids. They poked out of the ant´s gaster as a trail of seven filaments of various lengths. Apart from its swollen gaster, the ant differed from conspecifics in several morphometric parameters. Using both morphological and molecular techniques, the parasite family Mermithidae was confirmed. Our stray find raises multiple questions concerning the genus and species identity of the parasite, its biology, and the infestation rate of the host ant population. More mermithid awareness by the various researchers working with Myrmica will help, but directed fieldwork, experimental life-history research, and molecular studies are needed to emancipate progress in ant-mermithid research from serendipity

Platelet G i protein Gα i2 is an essential mediator of thrombo-inflammatory organ damage in mice

Platelets are crucial for hemostasis and thrombosis and exacerbate tissue injury following ischemia and reperfusion. Important regulators of platelet function are G proteins controlled by seven transmembrane receptors. The Gi protein Gα(i2) mediates platelet activation in vitro, but its in vivo role in hemostasis, arterial thrombosis, and postischemic infarct progression remains to be determined. Here we show that mice lacking Gα(i2) exhibit prolonged tail-bleeding times and markedly impaired thrombus formation and stability in different models of arterial thrombosis. We thus generated mice selectively lacking Gα(i2) in megakaryocytes and platelets (Gna(i2)(fl/fl)/PF4-Cre mice) and found bleeding defects comparable to those in global Gα(i2)-deficient mice. To examine the impact of platelet Gα(i2) in postischemic thrombo-inflammatory infarct progression, Gna(i2)(fl/fl)/PF4-Cre mice were subjected to experimental models of cerebral and myocardial ischemia/reperfusion injury. In the model of transient middle cerebral artery occlusion stroke Gna(i2)(fl/fl)/PF4-Cre mice developed significantly smaller brain infarcts and fewer neurological deficits than littermate controls. Following myocardial ischemia, Gna(i2)(fl/fl)/PF4-Cre mice showed dramatically reduced reperfusion injury which correlated with diminished formation of the ADP-dependent platelet neutrophil complex. In conclusion, our data provide definitive evidence that platelet Gα(i2) not only controls hemostatic and thrombotic responses but also is critical for the development of ischemia/reperfusion injury in vivo.Fil: Devanathan, Vasudharani. University of Tübingen; AlemaniaFil: Hagedorn, Ina. University Hospital; AlemaniaFil: Köhler, David. University of Tübingen; AlemaniaFil: Pexa, Katja. Universitat Dusseldorf; AlemaniaFil: Cherpokova, Deya. University Hospital; AlemaniaFil: Kraft, Peter. Universität Würzburg; AlemaniaFil: Singh, Madhurendra. Universitat Dusseldorf; AlemaniaFil: Rosenberger, Peter. University of Tübingen; AlemaniaFil: Stoll, Guido. Universität Würzburg; AlemaniaFil: Birnbaumer, Lutz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Research Triangle Park; AlemaniaFil: Piekorz, Roland P.. Universitat Dusseldorf; AlemaniaFil: Beer-Hammer, Sandra. University of Tübingen; AlemaniaFil: Nieswandt, Bernhard. University Hospital; AlemaniaFil: Nürnberg, Bernd. University of Tübingen; Alemani

Early Continence and Extravasation After Open Retropubic Radical Prostatectomy – Interrupted vs Continuous Suturing for Vesicourethral Anastomosis

Purpose: To compare running suture (RS) and interrupted suture (IS) of vesicourethral anastomosis (VUA) during open retropubic radical prostatectomy (RRP) on early urinary continence and extravasation. Patients and methods: Single center analysis of 211 patients who underwent RRP performed by a single surgeon during 2008 to 2017 was retrospectively analyzed. For VUA, we used the standard interrupted suture technique (n=100) with a 3-0 PDS suture. The RS (n=111) was performed with 12-bite suture using 3-0 PDS. The primary endpoints were extravasation and early continence. Demographic and peri-operative data were collected and analyzed using Pearson's chi-square, t-Test and Mann-Whitney U-test. A binary logistic regression analysis was carried out to explore predictors that affected early continence after catheter removal. Results: The rates of early urinary incontinence (UI) were 7.7% vs 42.2% (p<0.001). The duration of catheterization and hospitalization was significantly shorter in the interrupted group (4 days vs 5 days, p<0.001 and 5 days vs 6 days, p<0.001). The groups did not differ significantly in body mass index or prostate volume. There were older patients and higher PSA levels in the group with RS technique. No significant difference was found in the postoperative extravasation rates between both groups (13.5% vs 12%, p=0.742). Conclusion: Running vesicourethral anastomosis increased the rate of early urinary incontinence. Both anastomosis techniques provided a similar rate of postoperative urine extravasation. VUA should only be one of the many criteria that must be considered for the preservation of urinary continence of patients after RRP

Employment effects of innovations over the business cycle : firm-level evidence from European countries

A growing literature investigates how firms’ innovation input reacts to changes in the business cycle. However, so far there is no evidence whether there is cyclicality in the effects of innovation on firm performance as well. In this paper, we investigate the employment effects of innovations over the business cycle. Our analysis employs a large data set of manufacturing firms from 26 European countries over the period from 1998 to 2010. Using the structural model of Harrison et al. (2014), our empirical analysis reveals four important findings: First, the net effect of product innovation on employment growth is pro-cyclical. It turns out to be positive in all business cycle phases except for the recession. Second, product innovators are more resilient to recessions than non-product innovators. Even during recessions they are able to substitute demand losses from old products by demand gains of new products to a substantial degree. As a result their net employment losses are significantly lower in recessions than those of non-product innovators. Third, we only find resilience for SMEs but not for large firms. Fourth, process and organizational innovations displace labor primarily during upturn and downturn periods

Innovation, creative destruction and structural change : firm-level evidence from European Countries

The shift of employment from lower to higher productive firms is an important driver for structural change and industry dynamics. We investigate this reallocation in terms of employment gains and losses from innovation. New employment created by product innovation may be offset by employment losses in related products, known as ‘cannibalisation’ or ‘business stealing’ effects in the literature, by employment losses from process and organisational innovation and by general productivity increases. The paper investigates this effect empirically with a large dataset from the European Community Innovation Survey (CIS). We find that employment gains and losses increase with technology intensity of the sector. High-technology manufacturing shows the strongest employment gains and losses from innovation, followed by knowledge-intensive services, low-technology manufacturing and less knowledge-intensive services. The net contribution of innovation to employment growth is mostly positive, an exception being manufacturing industries in recession periods

Strategy for use of herbicides in regions of water conservation

In Niedersachsen lassen sich zunehmend Abbauprodukte einiger Rapsherbizide im Grundwasser nachweisen. Dabei handelt es sich vorrangig um nicht relevante Metabolite. Um den Wirkstoffeintrag in wassersensiblen Gebieten zu reduzieren, werden in Feldversuchen der Landwirtschaftskammer Niedersachsen verschiedene Herbizidstrategien geprüft. Aufgrund neuerer Zulassungen der letzten Jahre besteht inzwischen die Möglichkeit, auch im Winterraps Unkräuter gezielt im Nachauflauf zu bekämpfen, bei gleichzeitigem Verzicht auf den Wirkstoff Metazachlor. Mit dem ausschließlichen Einsatz von Herbiziden im Nachauflauf ist eine gezielte Unkrautbekämpfung unter Berücksichtigung von Schadensschwellen möglich. Zusätzlich wird eine Wirkstoffrotation empfohlen. Verfahren zur mechanischen Unkrautbekämpfung in Winterraps werden aktuell auf ihre Praktikabilität geprüft.In Lower-Saxony an increasing number of degradation products from herbicides that are used for weed control in winter oil seed rape can be found in the groundwater. These are predominantly non relevant metabolic intermediates. To decrease the input of active ingredients to groundwater in endangered zones field trials for different herbicides strategies were carried out by the Agricultural Chamber Lower Saxony. As a result of new admissions for crop protection products it is possible to control weeds in oil seed rape after sproud without using Metazachlor-products. After rising of the plants it is possible to use selective herbicides for controlling the weeds while paying attention to the damage threshold of the weeds. Additionally it is recommended to change active substances in the used products. The practicality of mechanical weed control is currently examined