Impact of COVID-19 on gynaecological patient care: results of patient's survey with 327 patients.

PURPOSE: The pandemic SARS-CoV-2 poses new and unprecedented challenges for health care systems on a national and global level. Although the current situation has been going on for more than 1 year, there is limited data on the impact of the pandemic on general hospital and medical practice care. This survey captures the perspective of patients with gynaecological diseases of this impact. METHODS: Using a paper-based questionnaire, 327 patients were asked about medical care and their experiences during the pandemic at the University Hospital Bonn and the University Hospital Charité Berlin. The study was performed from the 1st June to 30th September 2020. RESULTS: A total of 327 patients participated in the study: 156 stated to have been tested for coronavirus, and 1 patient reported a positive test. 41.3% of the patients felt insecure about the current situation, 30.4% were concerned about the risk of infection during the hospital stay. The pandemic-specific measures in hospitals and medical practices unsettled 6.8% of patients. 18.1% of patients feared that their gynaecological disease would not be treated adequately due to the pandemic. 55.7% of patients reported that their confidence in their physicians has increased during the pandemic. CONCLUSION: The results show that patients' confidence in the healthcare system and the physicians acting significantly increased during the COVID-19 crisis. Transparent and comprehensive information policy regarding actions and restrictions within the COVID-19 crisis eases patients concerns and improves patients' confidence in their physicians, which is crucial for a successful treatment's outcome.

Metabolic activation and toxicological evaluation of polychlorinated biphenyls in Drosophila melanogaster.

Degradation of polychlorinated biphenyls (PCBs) is initiated by cytochrome P450 (CYP) enzymes and includes PCB oxidation to OH-metabolites, which often display a higher toxicity than their parental compounds. In search of an animal model reflecting PCB metabolism and toxicity, we tested Drosophila melanogaster, a well-known model system for genetics and human disease. Feeding Drosophila with lower chlorinated (LC) PCB congeners 28, 52 or 101 resulted in the detection of a human-like pattern of respective OH-metabolites in fly lysates. Feeding flies high PCB 28 concentrations caused lethality. Thus we silenced selected CYPs via RNA interference and analyzed the effect on PCB 28-derived metabolite formation by assaying 3-OH-2',4,4'-trichlorobiphenyl (3-OHCB 28) and 3'-OH-4',4,6'-trichlorobiphenyl (3'-OHCB 28) in fly lysates. We identified several drosophila CYPs (dCYPs) whose knockdown reduced PCB 28-derived OH-metabolites and suppressed PCB 28 induced lethality including dCYP1A2. Following in vitro analysis using a liver-like CYP-cocktail, containing human orthologues of dCYP1A2, we confirm human CYP1A2 as a PCB 28 metabolizing enzyme. PCB 28-induced mortality in flies was accompanied by locomotor impairment, a common phenotype of neurodegenerative disorders. Along this line, we show PCB 28-initiated caspase activation in differentiated fly neurons. This suggested the loss of neurons through apoptosis. Our findings in flies are congruent with observation in human exposed to high PCB levels. In plasma samples of PCB exposed humans, levels of the neurofilament light chain increase after LC-PCB exposure, indicating neuronal damage. In summary our findings demonstrate parallels between Drosophila and the human systems with respect to CYP mediated metabolism and PCB mediated neurotoxicity.

[Influence of culture and religion on the treatment of cancer patients]. / Einfluss von Kultur und Religion auf die Therapie von Krebspatienten.

Religion, which is one of the most important sources of human identity, has so far hardly been taken into account in the clinic. In the largely secularized society of Germany, this has played a highly subordinate role. Currently, however, the development towards a multireligious society is emerging, which will also be reflected in everyday medical care. Disease and mortality in patients can affect different cultural-religious spheres. Although distinction between cultural and religious aspects is possible, it is not necessary for clinical practice. In the situation of oncological therapy, questions may arise which must be answered differently in the religions Christianity, Judaism and Islam and which should be taken into account when selecting therapy. The consideration of cultural-religious rules can intensify the patient's acceptance, but it can also impair it in case of disregard. Such peculiarities can be the separation into male and female spheres or the restriction of certain auxiliary substances or drugs (blood products, narcotics). Kübler-Ross's phase model is suitable for determining where cultural-religious sensitivities should be taken into account in the phases of disease and how cultural-religious offerings can benefit the course of therapy. Due to large individual, regional, cultural and confessional differences, no systematic catalogue of procedures can be provided here. However, knowledge of such differences, more sensitive interaction with patients and their families and cooperation with hospital pastors can strengthen the relationship of trust between doctor and patient and thus improve the conditions for successful oncological therapy. These aspects should not be underestimated when treating people of other faiths in Germany's secular society.

[Cold atmospheric plasma for the treatment of urological tumors]. / Kaltes atmosphärisches Plasma für die urologische Tumortherapie.

Cold atmospheric plasma (CAP) is a highly reactive ionized physical state consisting of electrically charged particles, radicals and photons as well as electromagnetic radiation. Due to the high energy and reactivity of plasma components, physical plasmas are also referred to as the 4th aggregate state. In biological systems, CAP promotes antimicrobial, immunomodulatory, anti-inflammatory, and wound-healing effects. Moreover, CAP bears antineoplastic properties which may be applied as a potential intraoperative option in the treatment of wound and resection margins during surgery of urological tumors. Some properties such as the penetration depth in various biological tissues, the effect on physiological healthy tissue, and the molecular mode of action regarding signalling and effector pathways are the subject of further investigation. CAP treatment effectively attenuates malignant cell growth. As an intraoperative application, CAP may represent a promising option particularly for the treatment of tissue regions that are close to critical structures (e. g., nerves, adjacent organs). The present review article summarizes the current status of CAP-related studies in the field of urological oncology.

[Systemic immune checkpoint inhibition : A promising treatment for urological tumors?] / Systemische Immuncheckpoint-Inhibition : Eine vielversprechende Therapie urologischer Tumoren?

Improved understanding of the immunomodulatory interactions between tumor cells and immune cells has led to new and promising systemic therapeutic approaches in the first- and second-line therapy of urological tumors. Particularly in the case of urothelial carcinoma, for the first time in 20 years, checkpoint inhibitors (PD-1 and PDL-1 inhibitors) provide well-tolerated therapy that achieves response rates of >20% that can be sustained over the long term. This review explains the approach of immunotherapy and summarizes the current phase III clinical situation on urothelial carcinoma and renal cell carcinoma. The current immunomodulatory therapeutic approaches for prostate cancer are discussed. Finally, we highlight new immunomodulatory therapeutic approaches in basic research.

Virucide properties of cold atmospheric plasma for future clinical applications.

Cold atmospheric plasma (CAP) has been repeatedly identified to bear powerful microbicidal efficacy on bacteria including multidrug resistant organisms and fungi on non-living surfaces, in biofilms as well as on contaminated and infected tissues. CAP furthermore was found to stimulate wound healing in chronic wounds and exerted anti-neoplastic effects on numerous tumor entities. Thus, CAP represents a promising medical tool for many clinical and therapeutic issues. Studies about CAP effects on virus particles recently were in arrears, but to date increasingly move into the focus of interest. Apparently, CAP treatment is followed by a promising virus inactivation and contributes to tissue regeneration. Here we review the current state of science concerning the so far investigated CAP effects on different virus species and virus-associated disorders. J. Med. Virol. 89:952-959, 2017. © 2017 Wiley Periodicals, Inc.

Jump in the fire--heat shock proteins and their impact on ovarian cancer therapy.

Ovarian cancer (OC) is a major problem in gynecological oncology. Options for diagnosis and treatment of advanced stages and thus for patient prognosis have not been improved substantially over the past decades. Heat shock proteins (HSP) are characterized as stress-induced molecular chaperones performing cell survival factor functions. In cancer cells, various crucial and clinically important cell responses are vitally influenced and modulated by HSPs, e.g., cell growth and treatment resistance. Despite the limited knowledge on HSPs in OC progression, their roles as biomarkers, prognostic factors and their drug target properties appears promising for future clinical applications and therapeutic approaches.

[Transforming growth factor ß in prostate cancer: cellular effects and basic molecular mechanisms]. / "Transforming growth factor ß" im Prostatakarzinom : Zelluläre Wirkungen und molekulare Grundlagen.

The multifunctional cytokine transforming growth factor ß (TGFß) plays a dual role in prostate cancer (PCa), cell growth and tumorigenesis, reflected by its opposing properties of anti-oncogenic (e.g. growth inhibition and apoptosis) and pro-oncogenic effects (e.g. proliferation, cell motility and remodelling of the microenvironment). In the later stages of PCa, TGFß loses anti-proliferative and thereby tumor-suppressive functions and shifts to a tumorigenic phenotype, mainly initiated by cross-talk between TGFß signalling and other proliferation signal transduction pathways, such as mitogen-activated protein kinase (MAPK) and androgen receptor (AR) signalling. Although TGFß plays an important role in tumor progression little is known about the underlying effects of TGFß in the molecular pathology of PCa.

Furin cleavage of bacterial expressed glutathione-S-transferase-pro-transforming growth factor beta1 fusion protein in vitro.

To investigate the processing of transforming growth factor beta1 (TGFbeta1) pro-protein by furin protease we expressed a GST-pro-TGFbeta1 fusion protein in bacteria. Analysis of the furin digestion pattern revealed the liberation of 12.5 kDa TGFbeta1 monomers. There was no evidence for cleavage of an alternative furin site within the pro-protein.

Cometabolic ring fission of dibenzofuran by Gram-negative and Gram-positive biphenyl-utilizing bacteria.

Thirty-five strains of soil bacteria were grown with biphenyl (BP) and tested for their capacity to cooxidize dibenzofuran (DBF). During metabolism of DBF, the culture medium of 17 strains changed from colorless to orange, indicating a meta-cleavage pathway of DBF degradation. The ring cleavage product of these isolates was shown to be 2-hydroxy-4-(3'-oxo-3' H-benzofuran-2'-yliden)but-2-enoic acid (HOBB). The strain SBUG 271, studied in detail and identified as Rhodococcus erythropolis, degraded DBF via 1,2-dihydroxydibenzofuran. The ensuing meta-cleavage yielded HOBB and salicylic acid. In addition, the four monohydroxylated monomers of DBF and two metabolites, which were not further characterized, were detected. Thus, our results demonstrate that the metabolic mechanism involves lateral dioxygenation of DBF followed by meta-cleavage and occurs in Gram-negative as well as in Gram-positive BP-degrading bacteria.

Chimeric bovine respiratory syncytial virus with attachment and fusion glycoproteins replaced by bovine parainfluenza virus type 3 hemagglutinin-neuraminidase and fusion proteins.

Chimeric bovine respiratory syncytial viruses (BRSV) expressing glycoproteins of bovine parainfluenza virus type 3 (BPIV-3) instead of BRSV glycoproteins were generated from cDNA. In the BRSV antigenome cDNA, the open reading frames of the major BRSV glycoproteins, attachment protein G and fusion protein F, were replaced individually or together by those of the BPIV-3 hemagglutinin-neuraminidase (HN) and/or fusion (F) glycoproteins. Recombinant virus could not be recovered from cDNA when the BRSV F open reading frame was replaced by the BPIV-3 F open reading frame. However, cDNA recovery of the chimeric virus rBRSV-HNF, with both glycoproteins replaced simultaneously, and of the chimeric virus rBRSV-HN, with the BRSV G protein replaced by BPIV-3 HN, was successful. The replication rates of both chimeras were similar to that of standard rBRSV. Moreover, rBRSV-HNF was neutralized by antibodies specific for BPIV-3, but not by antibodies specific to BRSV, demonstrating that the BRSV glycoproteins can be functionally replaced by BPIV-3 glycoproteins. In contrast, rBRSV-HN was neutralized by BRSV-specific antisera, but not by BPIV-3 specific sera, showing that infection of rBRSV-HN is mediated by BRSV F. Hemadsorption of cells infected with rBRSV-HNF and rBRSV-HN proved that BPIV-3 HN protein expressed by rBRSV is functional. Colocalization of the BPIV-3 glycoproteins with BRSV M protein was demonstrated by confocal laser scan microscopy. Moreover, protein analysis revealed that the BPIV-3 glycoproteins were present in chimeric virions. Taken together, these data indicate that the heterologous glycoproteins were not only expressed but were incorporated into the envelope of recombinant BRSV. Thus, the envelope glycoproteins derived from a member of the Respirovirus genus can together functionally replace their homologs in a Pneumovirus background.