Der Vergleich zwischen früher und verzögerter systemischen Behandlung von Ratten nach ischämischen Schlaganfall mit Candesartan

Ziele: In vorherigen Studien konnten durch die ausschließliche Blockade von AT1-Rezeptoren im Gehirn mittels direkter intracerebroventikulärer Injektion eines AT1-Rezeptorantagonisten die Folgen eines Schlaganfalles deutlich vermindert werden. Diese Untersuchungen verdeutlichen die Bedeutung des zentralen Renin-Angiotensin-Systems beim Schlaganfall. Weitere Studien belegen, dass der AT1-Rezeptorantagonist Candesartan in der Lage ist, die Blut-Hirn-Schranke in ausreichendem Maße zu passieren, um effizient AT1-Rezeptoren im Gehirn zu blockieren. Konsequenterweise konnte durch eine systemische Vorbehandlung mit diesem Antagonisten eine Reduktion der Infarktgröße und Verbesserung des neurologischen Defizits bei Ratten nach fokaler zerebraler Ischämie beobachtet werden. In der aktuellen Studie wurde untersucht, ob die neuroprotektiven Effekte von Candesartan auch nach einem akuten Schlaganfall zu beobachten sind. Es wurden die Effekte einer hochdosierten Candesartan Behandlung mit Beginn 3 h und 24 h nach fokal zerebraler Ischämie bei der normotensiven Ratte untersucht. Aufbau und Methoden: Die zerebrale Ischämie wurde durch eine 90-minütige Okklusion der Arteria Cerebri media (middle cerebral artery occlusion = MCAO) mit nachfolgender Reperfusion induziert. Der zerebrale Blutfluss wurde mittels Laser Doppler Flußmetrie aufgezeichnet. Es wurden nur Tiere mit einer Reduktion des zerebralen Blutflusses von mehr als 75% während der Okklusionperiode in die Studie aufgenommen. Die Behandlung mit Candesartan erfolgte 3 h oder 24 h nach Beginn der MCAO. Im Anschluss wurden die Tiere mit der gleichen Dosierung in den darauf folgenden 2 oder 7 Tagen weiter behandelt. Kontrolltiere erhielten eine Trägerlösung. Candesartan wurde subkutan mit einer Dosis von 3,0 mg/kg verabreicht. In dieser Dosierung hemmt Candesartan effektiv die AT1-Rezeptoren im Gehirn und senkt den Blutdruck. Die Ratten wurden täglich, unter Benutzung von zwei verschiedenen Wertungssystemen, auf ihre neurologischen Defizite untersucht. Die Gehirne der Ratten wurden nach 2 und 7 Behandlungstagen entnommen und das Infarktvolumen mittels Cresylviolett-Färbung von Serienschnitten ermittelt. Apoptose und Entzündungsreaktion wurden mittels immunhistologischer Färbung mit TUNEL sowie aktivierter Mikroglia detektiert. Ergebnisse: Die Vehikeltiere zeigten 24 h und 48 h nach MCAO deutliche neurologische Defizite. Der neurologische Status verbesserte sich allmählich in der darauffolgenden siebentägigen Periode. Durch einen frühen Beginn der Behandlung mit Candesartan (3 h nach MCAO) konnte eine Verbesserung des neurologische Defizits, aber keine Reduktion der Infarktgröße gemessen werden. Nach spätem Beginn der Behandlung mit Candesartan (24 h nach MCAO) wurde kein Effekt auf das neurologische Defizit oder das Infarktvolumen beobachtet. Es ist anzunehmen, dass die Dosierung 3 mg/kg aufgrund der gemessenen Senkung des Blutdruckes in der Phase der Reperfusion zu keiner Reduktion des Infarktvolumens geführt hat. Jedoch zeigte sich eine signifikant geringe Detektion apoptotischer Prozesse nach Behandlung mit Candesartan. Eine geringere Invasion inflammatorischer Zellen konnte nur 7 Tage nach MCAO beobachtet werden. Schlussfolgerung: Die durchgeführte Studie zeigt, dass nur bei frühem Beginn, aber nicht bei verzögertem Beginn der systemischen Therapie mit Candesartan der neurologische Status nach fokaler Ischämie verbessert wurde. Aufgrund der akuten Behandlung mit Candesartan in der gewählten Dosierung war der Antagonist vermutlich nicht in der Lage, die zerebrovaskuläre Autoregulation auf ein niedrigeres Druckniveau zu führen, um eine adäquate Perfusion des Gehirn zu gewährleisten. Das Ausmaß der neurologischen Beeinträchtigung korrelierte nicht immer mit dem Infarktvolumen

Changes in gynecologic and breast cancer diagnoses during the first wave of the COVID-19 pandemic: analysis from a tertiary academic gyneco-oncological center in Germany

PURPOSE With the beginning of 2021, the world has been suffering from the COVID-19 pandemic for more than 1 year. More and more, we are able to evaluate side effects of the pandemic in the healthcare sector. A negative impact on cancer diagnoses is one of them. Careful observation of trends in an academic gyneco-oncological context appears important to identify potential negative developments. METHODS We analyzed the case number of gynecologic and breast cancer diagnoses in the period from January to June 2020 compared to 2019 and during the period of the first general German lockdown (March 22nd until May 5th 2020). Patients were characterized by age, tumor type, FIGO or TNM stage and presence of symptoms at initial hospital presentation. RESULTS The frequency of newly diagnosed gynecologic and breast cancer cases from beginning of January until end of June changed by - 10% and by - 12% during the lockdown in 2020 compared to 2019. In both periods, reduction of breast cancer cases was relatively larger than decrease of gynecologic cancers. Moreover, median patient age decreased. For the first half of 2020, we found a shift towards higher tumor stages (N+/M1 or FIGO III-IV). During the lockdown period, the appearance of tumor-associated symptoms at diagnosis increased by about 12%. CONCLUSION This analysis illustrates the anticipated general decrease in diagnoses of primary cancers during the lockdown periods in 2020 due to COVID-19 pandemic for gynecologic and breast cancer cases

Increased risk for thromboembolic events from combination of a gynecologic malignancy with severe acute respiratory syndrome coronavirus 2 infection: a case report

Purpose During the severe acute respiratory syndrome coronavirus 2 pandemic, several patient groups are at particular risk. Mortality is higher among cancer patients and may be increased further by thromboembolic events, which are more common in coronavirus 2019 patients according to recent publications. We discuss the association of gynecologic malignancies, Severe acute respiratory syndrome coronavirus 2, and thromboembolism by reporting a case study and summarizing available literature. Case report A 71-year-old Caucasian patient with ovarian cancer receiving first-line chemotherapy was diagnosed with deep vein thrombosis and pulmonary embolism. Routine screening revealed infection with severe acute respiratory syndrome coronavirus 2 in absence of specific symptoms. After uneventful recovery, oncologic treatment could be continued a few weeks later. Methods We performed a systematic review of the literature on PubMed following Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. The search included articles ahead of print, published between 1 December 2019 and 1 June 2020. Cross-searches were conducted on all relevant articles. Results We identified five articles meeting the defined criteria, including two retrospective studies, a review, a position paper, as well as a letter to the editor. Conclusion Cancer patients infected with severe acute respiratory syndrome coronavirus 2 have a relatively poor outcome, which may partially be due to a higher rate of thromboembolic events. Thromboprophylaxis is recommended, and scoring systems are helpful in early detection. In cancer patients with severe acute respiratory syndrome coronavirus 2, individual risk for thromboembolic events should be taken into account when considering interruption versus continuation of antitumoral therapy. However, further data and studies are required

Testing the effect of individual scent compounds on pollinator attraction in nature using quasi-isogenic Capsella lines

Premise Floral scent, usually consisting of multiple compounds, is a complex trait, and its role in pollinator attraction has received increasing attention. However, disentangling the effect of individual floral scent compounds is difficult due to the complexity of isolating the effect of single compounds by traditional methods. Methods Using available quasi-isogenic lines (qILs) that were generated as part of the original mapping of the floral scent volatile-related loci CNL1 (benzaldehyde) and TPS2 (β-ocimene) in Capsella, we generated four genotypes that should only differ in these two compounds. Plants of the four genotypes were introduced into a common garden outside the natural range of C. rubella or C. grandiflora, with individuals of a self-compatible C. grandiflora line as pollen donors, whose different genetic background facilitates the detection of outcrossing events. Visitors to flowers of all five genotypes were compared, and the seeds set during the common-garden period were collected for high-throughput amplicon-based sequencing to estimate their outcrossing rates. Results Benzaldehyde and β-ocimene emissions were detected in the floral scent of corresponding genotypes. While some pollinator groups showed specific visitation preferences depending on scent compounds, the outcrossing rates in seeds did not vary among the four scent-manipulated genotypes. Conclusions The scent-manipulated Capsella materials constructed using qILs provide a powerful system to study the ecological effects of individual floral scent compounds under largely natural environments. In Capsella, individual benzaldehyde and β-ocimene emission may act as attractants for different types of pollinators

Initial results for dual constellation dual-frequency multipath models

This paper presents an update of the ongoing work to develop dual frequency dual constellation airborne multipath models for Galileo E1, E5a and GPS L1 and GPS L5 in the frame of the project DUFMAN (Dual Frequency Multipath Models for Aviation) funded by the European Commission. The goal of this activity is to support the development and implementation of airborne GNSS-based navigation solutions, such as Advanced Receiver Autonomous Integrity Monitoring (ARAIM), dual-frequency multiconstellation Satellite Based Augmentation System (SBAS) and dual-frequency multi-constellation Ground based Augmentation System (GBAS). Previous work described the methodology proposed to derive the airborne multipath models and presented preliminary multipath models obtained from an experimental installation. In this paper we present the initial results obtained from flight campaigns conducted within DUFMAN on Airbus commercial aircraft. The measurements are collected from prototypes of dual-frequency multi-constellation avionics receiver and the antenna installed on the aircraft has been selected to meet at best the current dual-frequency dual-constellation antenna requirements. In addition to the initial results obtained from avionics hardware, the impact of the different receiver correlator spacing and bandwidth is investigated and discussed

Treatment of Early Breast Cancer Patients: Evidence, Controversies, Consensus: Focusing on Systemic Therapy - German Experts' Opinions for the 16th International St. Gallen Consensus Conference (Vienna 2019)

A German working group of leading breast cancer experts have discussed the votes at the International St. Gallen Consensus Conference in Vienna for the treatment of primary breast cancer with regard to the German AGO (Ar-beitsgemeinschaft Gynakologische Onkologie) recommendations for clinical practice in Germany. Three of the German breast cancer experts were also members of this year's St. Gallen panel. Comparing the St. Gallen recommendations with the annually updated treatment recommendations of the Gynecological Oncology Working Group (AGO Mamma 2019) and the German S3 Guideline is useful, because the recommendations of the St. Gallen panel are based on expert opinions of different countries and disciplines. The focus of this article is on systemic therapy. The motto of this year's 16th St. Gallen Consensus Conference was Estimating the magnitude of clinical benefit. The rationale behind this motto is that, for every treatment decision, a benefit-risk assessment must be taken into consideration for each patient

Final results on airborne multipath models for dualconstellation dual-frequency aviation applications

This paper proposes DFMC airborne multipath models and antenna error models derived from measurement and supported by simulations. Based on the data evaluated, new multipath models (including the contribution from the antenna) for Galileo E1 and GPS L1 and Galileo E5a and GPS L5 are discussed. Furthermore, a model for the Ionosphere-Free combination of the signals is proposed