Is there decreasing public interest in renal transplantation? A Google trends TM analysis

Background and objectives: Renal transplantation is the preferred form of renal replacement therapy for the majority of patients with end stage renal disease (ESRD). The Internet is a key tool for people seeking healthcare-related information. This current work explored the interest in kidney transplantation based on Internet search queries using Google TrendsTM. Design, setting, participants, and measurements: We performed a Google TrendsTM search with the search term “kidney transplantation” between 2004 (year of inception) and 2018. We retrieved and analyzed data on the worldwide trend as well as data from the United Network for Organ Sharing (UNOS), the Organización Nacional de Trasplantes (ONT), the Eurotransplant area, and the National Health Service (NHS) Transplant Register. Google TrendsTM indices were investigated and compared to the numbers of performed kidney transplants, which were extracted from the respective official websites of UNOS, ONT, Eurotransplant, and the NHS. Results: During an investigational period of 15 years, there was a significant decrease of the worldwide Google TrendsTM index from 76.3 to 25.4, corresponding to an absolute reduction of −50.9% and a relative reduction by −66.7%. The trend was even more pronounced for the UNOS area (−75.2%), while in the same time period the number of transplanted kidneys in the UNOS area increased by 21.9%. Events of public interest had an impact on the search queries in the year of occurrence, as shown by an increase in the Google TrendsTM index by 39.2% in the year 2005 in Austria when a person of public interest received his second live donor kidney transplant. Conclusions: This study indicates a decreased public interest in kidney transplantation. There is a clear need to raise public awareness, since transplantation represents the best form of renal replacement therapy for patients with ESRD. Information should be provided on social media, with a special focus on readability and equitable access, as well as on web pages

Modulation of Liver Inflammation and Fibrosis by Interleukin-37

Background and Aims: Chronic inflammation induces liver fibrosis, cirrhosis and potentially liver cancer. Kupffer cells modulate hepatic stellate cells by secreting immunologically active proteins as TGF-beta. TGF-beta promotes liver fibrosis via the activation of Sma- and Mad-related protein 3. IL-37 broadly suppresses innate and adaptive immune responses. Intracellular IL-37 interacts with Smad3. We hypothesize that IL-37 downregulates the activation of hepatic Kupffer and stellate cells and interferes with the TGF-beta signaling cascade to modulate liver fibrogenesis. Methods: The role of IL-37 on liver inflammation and fibrogenesis was assessed in three mouse models as well as isolated Kupffer- and stellate cells. Serum IL-37 was tested by ELISA in a clinical cohort and correlated with liver disease severity. Results: Transgene expression of IL-37 in mice extends survival, reduces hepatic damage, expression of early markers of fibrosis and histologically assessed liver fibrosis after bile duct ligation. IL-37tg mice were protected against CCl4-induced liver inflammation. Colitis-associated liver inflammation and fibrosis was less severe in IL-10 knockout IL-37tg mice. Spontaneous and LPS/TGF-beta-induced cytokine release and profibrogenic gene expression was lower in HSC and KC isolated from IL-37tg mice and IL-37 overexpressing, IL-1 beta stimulated human LX-2 stellate cells. However, administration of recombinant human IL-37 did not modulate fibrosis pathways after BDL in mice, LX2 cells or murine HSCs. In a large clinical cohort, we observed a positive correlation of serum IL-37 levels with disease severity in liver cirrhosis. Conclusions: Predominantly intracellular IL-37 downregulates liver inflammation and fibrosis. The correlation of serum IL-37 with disease severity in cirrhosis suggests its potential as a novel target modulating the course of liver fibrosis

Non-alcoholic fatty liver disease and COVID-19 susceptibility and outcomes: a Korean nationwide cohort

Background- Evidence for the association between underlying non-alcoholic fatty liver disease (NAFLD), the risk of testing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive, and the clinical consequences of coronavirus disease 2019 (COVID-19) is controversial and scarce. We aimed to investigate the association between the presence of NAFLD and the risk of SARS-CoV-2 infectivity and COVID-19-related outcomes. Methods- We used the population-based, nationwide cohort in South Korea linked with the general health examination records between January 1, 2018 and July 30, 2020. Data for 212,768 adults older than 20 years who underwent SARS-CoV-2 testing from January 1 to May 30, 2020, were obtained. The presence of NAFLDs was defined using three definitions, namely hepatic steatosis index (HSI), fatty liver index (FLI), and claims-based definition. The outcomes were SARS-CoV-2 test positive, COVID-19 severe illness, and related death. Results- Among 74,244 adults who completed the general health examination, there were 2,251 (3.0%) who were SARS-CoV-2 positive, 438 (0.6%) with severe COVID-19 illness, and 45 (0.06%) COVID-19-related deaths. After exposure-driven propensity score matching, patients with pre-existing HSI-NAFLD, FLI-NAFLD, or claims-based NAFLD had an 11–23% increased risk of SARS-CoV-2 infection (HSI-NAFLD 95% confidence interval [CI], 1–28%; FLI-NAFLD 95% CI, 2–27%; and claims-based NAFLD 95% CI, 2–31%) and a 35–41% increased risk of severe COVID-19 illness (HSI-NAFLD 95% CI, 8–83%; FLI-NAFLD 95% CI, 5–71%; and claims-based NAFLD 95% CI, 1–92%). These associations are more evident as liver fibrosis advanced (based on the BARD scoring system). Similar patterns were observed in several sensitivity analyses including the full-unmatched cohort. Conclusion- Patients with pre-existing NAFLDs have a higher likelihood of testing SARS-CoV-2 positive and severe COVID-19 illness; this association was more evident in patients with NAFLD with advanced fibrosis. Our results suggest that extra attention should be given to the management of patients with NAFLD during the COVID-19 pandemic

Estimation of global case fatality rate of coronavirus disease 2019 (COVID-19) using meta-analyses: Comparison between calendar date and days since the outbreak of the first confirmed case

Objective: Since the outbreak of the coronavirus disease 2019 (COVID-19) in December of 2019 in China, the estimation of the pandemic’s case fatality rate (CFR) has been the focus and interest of many stakeholders. In this manuscript, we prove that the method of using the cumulative CFR is static and does not reflect the trend according to the daily change per unit of time. Methods: A proportion meta-analysis was carried out on CFR in every country reporting COVID-19 cases. Based on the results, we performed a meta-analysis for global COVID-19 CFR. Each analysis was performed on two different calculations of CFR: according to calendar date and according to days since the outbreak of the first confirmed case. We thus explored an innovative and original calculation of CFR concurrently based on the date of the first confirmed case as well as on a daily basis. Results: For the first time, we showed that using meta-analyses, according to calendar date and days since the outbreak of the first confirmed case were different. Conclusion: We propose that CFR according to days since the outbreak of the first confirmed case might be a better predictor of the current CFR of COVID-19 and its kinetics

Establishment and characterization of a new human pancreatic adenocarcinoma cell line with high metastatic potential to the lung

<p>Abstract</p> <p>Background</p> <p>Pancreatic cancer is still associated with devastating prognosis. Real progress in treatment options has still not been achieved. Therefore new models are urgently needed to investigate this deadly disease. As a part of this process we have established and characterized a new human pancreatic cancer cell line.</p> <p>Methods</p> <p>The newly established pancreatic cancer cell line PaCa 5061 was characterized for its morphology, growth rate, chromosomal analysis and mutational analysis of the K-<it>ras</it>, EGFR and p53 genes. Gene-amplification and RNA expression profiles were obtained using an Affymetrix microarray, and overexpression was validated by IHC analysis. Tumorigenicity and spontaneous metastasis formation of PaCa 5061 cells were analyzed in pfp^-/-/rag2^-/-mice. Sensitivity towards chemotherapy was analysed by MTT assay.</p> <p>Results</p> <p>PaCa 5061 cells grew as an adhering monolayer with a doubling time ranging from 30 to 48 hours. M-FISH analyses showed a hypertriploid complex karyotype with multiple numerical and unbalanced structural aberrations. Numerous genes were overexpressed, some of which have previously been implicated in pancreatic adenocarcinoma (GATA6, IGFBP3, IGFBP6), while others were detected for the first time (MEMO1, RIOK3). Specifically highly overexpressed genes (fold change > 10) were identified as EGFR, MUC4, CEACAM1, CEACAM5 and CEACAM6. Subcutaneous transplantation of PaCa 5061 into pfp^-/-/rag2^-/-mice resulted in formation of primary tumors and spontaneous lung metastasis.</p> <p>Conclusion</p> <p>The established PaCa 5061 cell line and its injection into pfp^-/-/rag2^-/-mice can be used as a new model for studying various aspects of the biology of human pancreatic cancer and potential treatment approaches for the disease.</p

A gut bacterial signature in blood and liver tissue characterizes cirrhosis and hepatocellular carcinoma

BackgroundHCC is the leading cause of cancer in chronic liver disease. A growing body of experimental mouse models supports the notion that gut-resident and liver-resident microbes control hepatic immune responses and, thereby, crucially contribute to liver tumorigenesis. However, a comprehensive characterization of the intestinal microbiome in fueling the transition from chronic liver disease to HCC in humans is currently missing.MethodsHere, we profiled the fecal, blood, and liver tissue microbiome of patients with HCC by 16S rRNA sequencing and compared profiles to nonmalignant cirrhotic and noncirrhotic NAFLD patients.ResultsWe report a distinct bacterial profile, defined from 16S rRNA gene sequences, with reduced α-and β-diversity in the feces of patients with HCC and cirrhosis compared to NAFLD. Patients with HCC and cirrhosis exhibited an increased proportion of fecal bacterial gene signatures in the blood and liver compared to NAFLD. Differential analysis of the relative abundance of bacterial genera identified an increased abundance of Ruminococcaceae and Bacteroidaceae in blood and liver tissue from both HCC and cirrhosis patients compared to NAFLD. Fecal samples from cirrhosis and HCC patients both showed a reduced abundance for several taxa, including short-chain fatty acid-producing genera, such as Blautia and Agathobacter. Using paired 16S rRNA and transcriptome sequencing, we identified a direct association between gut bacterial genus abundance and host transcriptome response within the liver tissue.ConclusionsOur study indicates perturbations of the intestinal and liver-resident microbiome as a critical determinant of patients with cirrhosis and HCC

Dietary lipids fuel GPX4-restricted enteritis resembling Crohn’s disease

Abstract: The increased incidence of inflammatory bowel disease (IBD) has become a global phenomenon that could be related to adoption of a Western life-style. Westernization of dietary habits is partly characterized by enrichment with the ω-6 polyunsaturated fatty acid (PUFA) arachidonic acid (AA), which entails risk for developing IBD. Glutathione peroxidase 4 (GPX4) protects against lipid peroxidation (LPO) and cell death termed ferroptosis. We report that small intestinal epithelial cells (IECs) in Crohn’s disease (CD) exhibit impaired GPX4 activity and signs of LPO. PUFAs and specifically AA trigger a cytokine response of IECs which is restricted by GPX4. While GPX4 does not control AA metabolism, cytokine production is governed by similar mechanisms as ferroptosis. A PUFA-enriched Western diet triggers focal granuloma-like neutrophilic enteritis in mice that lack one allele of Gpx4 in IECs. Our study identifies dietary PUFAs as a trigger of GPX4-restricted mucosal inflammation phenocopying aspects of human CD

Review of solar energetic particle models

Solar Energetic Particle (SEP) events are interesting from a scientific perspective as they are the product of a broad set of physical processes from the corona out through the extent of the heliosphere, and provide insight into processes of particle acceleration and transport that are widely applicable in astrophysics. From the operations perspective, SEP events pose a radiation hazard for aviation, electronics in space, and human space exploration, in particular for missions outside of the Earth’s protective magnetosphere including to the Moon and Mars. Thus, it is critical to improve the scientific understanding of SEP events and use this understanding to develop and improve SEP forecasting capabilities to support operations. Many SEP models exist or are in development using a wide variety of approaches and with differing goals. These include computationally intensive physics-based models, fast and light empirical models, machine learning-based models, and mixed-model approaches. The aim of this paper is to summarize all of the SEP models currently developed in the scientific community, including a description of model approach, inputs and outputs, free parameters, and any published validations or comparisons with data.</p

"...dans toute affaire criminelle, le point faible, c'est la femme."

Im Rahmen dieser Arbeit sollte untersucht werden, wie die Veränderung der Rechte der Frauen im zwanzigsten Jahrhundert in der Literatur Eingang gefunden hat. Diese Entwicklung wurde im Genre des Kriminalromans untersucht, der zu Beginn sehr stark von Stereotypen geprägt war, aber im Laufe der letzten Jahrzehnte immer mehr diversifizierte Frauenbilder hervorgebracht hat. Die beiden Autoren Léo Malet (der seine Reihe Les Nouveaux Mystères de Paris um den Detektiv Nestor Burma in den fünfziger Jahren schrieb) und Fred Vargas (die seit den achtziger Jahren ihre Reihe zum Kommissar Jean-Baptiste Adamsberg veröffentlicht) wurden einer Vergleichsstudie unterzogen, wobei auf die theoretischen Abhandlungen von Jean-Louis Dufays, Stéréotype et lecture, und Nathalie Heinich, États de femme, zurückgegriffen wurde. Zusammenfassend kann gesagt werden, dass die beiden Autoren im Großen und Ganzen ähnliche Frauenfiguren verwendet haben, die typischen Schuldige und Opfer, aber auch die Geliebte oder die helfende Sekretärin sind vorhanden. Es gibt bei Beiden aber auch ungewöhnlich Figuren, wie die bevorzugten Prostituierten oder die beiden älteren Damen, die alleine die Unschuld des Kommissars beweisen. Allerdings sind dies Ausreißer-Fälle, die dem Gesamtbild nicht widersprechen, dass Frauen auch heutzutage im Kriminalroman noch stereotyp dargestellt werden.In this paper, we wanted to match the evolution of women’s rights in the second part of the last century and their depiction in fictional texts. The detective novel seemed a good genre, because it too has lived an evolution in the last decades, and especially concerning the role of women, wanting to describe stronger feminine figures. We chose two french authors: Léo Malet (who published in the fifties) and Fred Vargas, whose first novel was published in 1986. Comparing the depiction of women in their novels would lead us to examine if women are really treated differently by contemporary authors, or if the stereotypes used in the fifties still applied, which was our original hypothesis. The first part of our paper was dedicated to draw up the notion of (gender) stereotypes and their impact on reading, and then determine the roles of women in fictional texts and more specifically in detective fiction. In the second part, we analyzed and compared the roles women got allocated from both authors and could conclude that their depiction in detective fiction did not really change over the last decades, at least not in Fred Vargas’ novels

Transmission of oral microbiota to the biliary tract during endoscopic retrograde cholangiography

Abstract Background Endoscopic retrograde cholangiography (ERC) possesses a translocation risk of microbes to the biliary system. We studied bile contamination during ERC and its impact on patients’ outcome in a real-life-situation. Methods Ninety-nine ERCs were analyzed and microbial samples were taken from the throat before and from bile during ERC and from irrigation fluid of the duodenoscope before and after ERC. Results 91.2% of cholangitis patients had detectable microbes in the bile (sensitivity 91%), but the same was true for 86.2% in the non-cholangitis group. Bacteroides fragilis (p=0.015) was significantly associated with cholangitis. In 41.7% of ERCs with contaminated endoscopes these microbes were found in the bile after the procedure. Analysis of duodenoscopes’ irrigation liquid after ERC matched the microbial bile analysis of these patients in 78.8%. Identical microbial species were in throat and in bile samples of the same ERC in 33% of all cases and in 45% in the non-cholangitis group. Transmission of microbes to the biliary tract did not result in more frequent cholangitis, longer hospital stays, or worse outcome. Conclusions During ERC bile samples are regularly contaminated with microbes of the oral cavity but it did not affect clinical outcome