Natural products against acute respiratory infections: Strategies and lessons learned

Under embargo until: 11.10.2020Ethnopharmacological relevance: A wide variety of traditional herbal remedies have been used throughout history for the treatment of symptoms related to acute respiratory infections (ARIs). Aim of the review: The present work provides a timely overview of natural products affecting the most common pathogens involved in ARIs, in particular influenza viruses and rhinoviruses as well as bacteria involved in co-infections, their molecular targets, their role in drug discovery, and the current portfolio of available naturally derived anti-ARI drugs. Materials and methods: Literature of the last ten years was evaluated for natural products active against influenza viruses and rhinoviruses. The collected bioactive agents were further investigated for reported activities against ARI-relevant bacteria, and analysed for the chemical space they cover in relation to currently known natural products and approved drugs. Results: An overview of (i) natural compounds active in target-based and/or phenotypic assays relevant to ARIs, (ii) extracts, and (iii) in vivo data are provided, offering not only a starting point for further in-depth phytochemical and antimicrobial studies, but also revealing insights into the most relevant anti-ARI scaffolds and compound classes. Investigations of the chemical space of bioactive natural products based on principal component analysis show that many of these compounds are drug-like. However, some bioactive natural products are substantially larger and have more polar groups than most approved drugs. A workflow with various strategies for the discovery of novel antiviral agents is suggested, thereby evaluating the merit of in silico techniques, the use of complementary assays, and the relevance of ethnopharmacological knowledge on the exploration of the therapeutic potential of natural products. Conclusions: The longstanding ethnopharmacological tradition of natural remedies against ARIs highlights their therapeutic impact and remains a highly valuable selection criterion for natural materials to be investigated in the search for novel anti-ARI acting concepts. We observe a tendency towards assaying for broad-spectrum antivirals and antibacterials mainly discovered in interdisciplinary academic settings, and ascertain a clear demand for more translational studies to strengthen efforts for the development of effective and safe therapeutic agents for patients suffering from ARIs.acceptedVersio

Aura versus Dialogue. Displaying Nazi Objects in the Exhibition "Disposing of Hitler: Out of the Cellar, Into the Museum"

What should we do with the remnants of Nazism? Should we dispose of them? Is it acceptable to sell them at a flea market or on the internet? At what point does memory become nostalgia, or even illegal neo-Nazi activity? Objects related to Nazism get discovered in various places and contexts – whether in one’s own basement, at flea markets or an online portal, in the estate of relatives or even in the trash. Even if one’s own family history is not entangled with the Nazi regime, such finds trigger feelings ranging from shame to detachment and even fascination. The exhibition "Disposing of Hitler. Out of the Cellar, Into the Museum", House of Austrian History ("Hitler entsorgen. Vom Keller ins Museum", Haus der Geschichte Österreich) asks about the social responsibility in dealing with relics of Nazism and explores the question of how these things can strengthen democratic consciousness in the present. What should we do with the remnants of Nazism? Should we dispose of them? Is it acceptable to sell them at a flea market or on the internet? At what point does memory become nostalgia, or even illegal neo-Nazi activity? Objects related to Nazism get discovered in various places and contexts – whether in one’s own basement, at flea markets or an online portal, in the estate of relatives or even in the trash. Even if one’s own family history is not entangled with the Nazi regime, such finds trigger feelings ranging from shame to detachment and even fascination. The exhibition "Disposing of Hitler. Out of the Cellar, Into the Museum", House of Austrian History ("Hitler entsorgen. Vom Keller ins Museum", Haus der Geschichte Österreich) asks about the social responsibility in dealing with relics of Nazism and explores the question of how these things can strengthen democratic consciousness in the present.&nbsp

Correlation of bioactive marker compounds of an orally applied Morus alba root bark extract with toxicity and efficacy in BALB/c mice

Introduction: In traditional Chinese medicine, the root bark of Morus alba L. is used to treat respiratory infections. Recently, anti-inflammatory and multiple anti-infective activities (against influenza viruses, corona virus 2, S. aureus , and S. pneumoniae ) were shown in vitro for a standardized root bark extract from M . alba (MA60). Sanggenons C and D were identified as major active constituents of MA60. The aim of the present preclinical study was to evaluate, whether these findings are transferable to an in vivo setting. Methods: MA60 was orally administered to female BALB/c mice to determine 1) the maximum tolerated dose (MTD) in an acute toxicity study and 2) its anti-influenza virus and anti-inflammatory effects in an efficacy study. A further aim was to evaluate whether there is a correlation between the obtained results and the amount of sanggenons C and D in serum and tissues. For the quantitation of the marker compounds sanggenons C and D in serum and tissue samples an UPLC-ESI-MS method was developed and validated. Results: In our study setting, the MTD was reached at 100 mg/kg. In the efficacy study, the treatment effects were moderate. Dose-dependent quantities of sanggenon C in serum and sanggenon D in liver samples were detected. Only very low concentrations of sanggenons C and D were determined in lung samples and none of these compounds was found in spleen samples. There was no compound accumulation when MA60 was administered repeatedly. Discussion: The herein determined low serum concentration after oral application once daily encourages the use of an alternative application route like intravenous, inhalation or intranasal administration and/or multiple dosing in further trials. The established method for the quantitation of the marker sanggenon compounds in tissue samples serves as a basis to determine pharmacokinetic parameters such as their bioavailability in future studies

Aura versus Dialogue. Displaying Nazi Objects in the Exhibition "Disposing of Hitler: Out of the Cellar, Into the Museum"

What should we do with the remnants of Nazism? Should we dispose of them? Is it acceptable to sell them at a flea market or on the internet? At what point does memory become nostalgia, or even illegal neo-Nazi activity? Objects related to Nazism get discovered in various places and contexts – whether in one’s own basement, at flea markets or an online portal, in the estate of relatives or even in the trash. Even if one’s own family history is not entangled with the Nazi regime, such finds trigger feelings ranging from shame to detachment and even fascination. The exhibition "Disposing of Hitler. Out of the Cellar, Into the Museum", House of Austrian History ("Hitler entsorgen. Vom Keller ins Museum", Haus der Geschichte Österreich) asks about the social responsibility in dealing with relics of Nazism and explores the question of how these things can strengthen democratic consciousness in the present.

Pancreatic resection for intraductal papillary mucinous neoplasm– a thirteen-year single center experience

BACKGROUND: The purpose of this study is to review our results for pancreatic resection in patients with intraductal papillary mucinous neoplasm (IPMN) with and without associated carcinoma. METHODS: A total of 54 patients undergoing pancreatic resection for IPMN in a single university surgical center (Medical University of Graz) were reviewed retrospectively. Their survival rates were compared to those of patients with pancreatic ductal adenocarcinoma. RESULTS: Twenty-four patients exhibit non-invasive IPMN and thirty patients invasive IPMN with associated carcinoma. The mean age is 67 (+/-11) years, 43 % female. Surgical strategies include classical or pylorus-preserving Whipple procedure (n = 30), distal (n = 13) or total pancreatectomy (n = 11), and additional portal venous resection in three patients (n = 3). Median intensive care stay is three days (range 1 – 87), median in hospital stay is 23 days (range 7 – 87). Thirty-day mortality is 3.7 %. Median follow up is 42 months (range 0 – 127). One-, five- and ten-year overall actuarial survival is 87 %; 84 % and 51 % respectively. Median overall survival is 120 months. Patients with non-invasive IPMN have significantly better survival than patients with invasive IPMN and IPMN-associated carcinoma (p < 0.008). In the subgroup of invasive IPMN with associated carcinoma, a positive nodal state, perineural invasion as well as lymphovascular infiltration are associated with poor outcome (p < 0.0001; <0.0001 and =0.001, respectively). Elevated CA 19-9(>37 U/l) as well as elevated lipase (>60 U/l) serum levels are associated with unfavorable outcome (p = 0.009 and 0.018; respectively). Patients operated for pancreatic ductal adenocarcinoma show significantly shorter long-term survival than patients with IPMN associated carcinoma (p = 0.001). CONCLUSIONS: Long-term outcome after pancreatic resection for non-invasive IPMN is excellent. Outcome after resection for invasive IPMN with invasive carcinoma is significantly better than for pancreatic ductal adenocarcinoma. In low- and intermediate risk IPMN with no clear indication for immediate surgical resection, a watchful waiting strategy should be evaluated carefully against surgical treatment individually for each patient

COVID-19: Is There Evidence for the Use of Herbal Medicines as Adjuvant Symptomatic Therapy?

Background: Current recommendations for the self-management of SARS-Cov-2 disease (COVID-19) include self-isolation, rest, hydration, and the use of NSAID in case of high fever only. It is expected that many patients will add other symptomatic/adjuvant treatments, such as herbal medicines. Aims: To provide a benefits/risks assessment of selected herbal medicines traditionally indicated for “respiratory diseases” within the current frame of the COVID-19 pandemic as an adjuvant treatment. Method: The plant selection was primarily based on species listed by the WHO and EMA, but some other herbal remedies were considered due to their widespread use in respiratory conditions. Preclinical and clinical data on their efficacy and safety were collected from authoritative sources. The target population were adults with early and mild flu symptoms without underlying conditions. These were evaluated according to a modified PrOACT-URL method with paracetamol, ibuprofen, and codeine as reference drugs. The benefits/risks balance of the treatments was classified as positive, promising, negative, and unknown. Results: A total of 39 herbal medicines were identified as very likely to appeal to the COVID-19 patient. According to our method, the benefits/risks assessment of the herbal medicines was found to be positive in 5 cases (Althaea officinalis, Commiphora molmol, Glycyrrhiza glabra, Hedera helix, and Sambucus nigra), promising in 12 cases (Allium sativum, Andrographis paniculata, Echinacea angustifolia, Echinacea purpurea, Eucalyptus globulus essential oil, Justicia pectoralis, Magnolia officinalis, Mikania glomerata, Pelargonium sidoides, Pimpinella anisum, Salix sp, Zingiber officinale), and unknown for the rest. On the same grounds, only ibuprofen resulted promising, but we could not find compelling evidence to endorse the use of paracetamol and/or codeine. Conclusions: Our work suggests that several herbal medicines have safety margins superior to those of reference drugs and enough levels of evidence to start a clinical discussion about their potential use as adjuvants in the treatment of early/mild common flu in otherwise healthy adults within the context of COVID-19. While these herbal medicines will not cure or prevent the flu, they may both improve general patient well-being and offer them an opportunity to personalize the therapeutic approaches

Eine "populistische Lektion". Emotionssensible Perspektiven für die politische Bildung

Der vorliegende Beitrag beschäftigt sich mit der Instrumentalisierung von Emotionen als Strategie rechtspopulistischer Politik und zieht daraus Schlüsse für die politische Bildung. Die negative Bewertung von Emotionen oder deren Verdrängung aus dem politischen Diskurs bilden eine Leerstelle im Politischen. Auf Basis der Theorie der Intergruppen-Emotionen zeigt der Beitrag die Funktionen von Emotionen für Identitätsstiftung und Gruppenbildung und die Risiken für eine pluralistische Gesellschaft auf. Der Beitrag plädiert für eine stärkere Thematisierung und kritische Reflexion von Emotionen in der politischen Bildung und stellt Perspektiven für eine emotionssensible politische Bildung dar. (DIPF/Orig.)This article addresses the instrumentalization of emotions as a strategy of right-wing populist politics and draws conclusions concerning civic education. The negative evaluation of emotions or their suppression from the political discourse forms a void in the political discourse. Based on the intergroup-emotions-theory the article shows the functions of emotions for identity building and group formation and the risks for a pluralistic society. The article argues for a stronger thematization and critical reflection of emotions in civic education and outlines perspectives for an emotion-sensitive civic education. (DIPF/Orig.

fünfjährigen

Die Forschungsarbeit befasst sich mit dem subjektiven Erleben von Streitsituationen im Kindergarten von Kindern im Alter von fünf bis sechs Jahren. Im Kontext der Kindheitsforschung nimmt die subjektive Sichtweise der einzelnen Kinder einen aktuellen Stellenwert ein. Aus dieser Perspektive wird das Kind als aktiv handelndes Subjekt ins Zentrum gerückt und gilt nicht mehr lediglich als „auszubildender“ Mensch. Dadurch können neue Erkenntnisse über die Lebenswelt der Kinder, sowie für pädagogisches Handeln gewonnen werden. Die vorliegende Masterarbeit fokussiert dabei auf zentrale Themen des Konflikts, und erforscht dabei das Erleben von Streitsituationen, die damit verbundenen Empfindungen, sowie mögliche Lösungsstrategien von Mädchen und Buben. Vor dem Hintergrund einer theoretischen Abhandlung zu emotionalen und sozialen Entwicklungsverläufen von Kindern, werden Themen wie emotionale Kompetenzen, die Entwicklung von Moral, die Perspektivenübernahme, sowie Bildungsprozesse und Lernsituationen von Kindern, mit besonderem Fokus auf das kindliche Spiel, diskutiert. Der daraus abgeleitete Forschungsfokus wird anhand von qualitativen Interviews mit neun Kindern in einem Kindergartenumfeld untersucht. Die Ergebnisse dieser Interviews weisen darauf hin, dass Streit für die befragten Kinder zumeist als physischer Konflikt wahrgenommen wird und verbale Konflikte noch nicht als Streit empfunden werden. Die gesellschaftliche Konfliktlösungsstrategie des „Entschuldigens“ war den Kindern zwar bekannt, die dahinterstehenden Gründe konnten allerdings nicht unbedingt nachvollzogen werden. Methodisch zeigte sich, dass Kinder in diesem Alter besonders bei generellen Aussagen ausführlicher antworten, im Vergleich zur Rekonstruktion von konkreten Vorfällen. Die daraus resultierenden Konsequenzen für den Umgang mit Konfliktsituationen im Kindergarten und die pädagogische Rolle werden im letzten Teil mit Bezug zu den Forschungsergebnissen behandelt.The present study deals with the childrens’ subjective perception of conflict situations in kindergarten. The subjective viewpoint of children is in particular important in the context of current childhood studies. From this perspective a child is conceptualized as an actively acting subject and not just as a person that has to be formed. Based on this perspective new insights can be gained on the experienced world of children, as well as on educational and pedagogic behavior. The master thesis focuses on central topics of conflict such as their subjective experience, the related feelings and possible conflict resolution strategies of children. The thesis features a theoretical discussion of the emotional and social development of children, dealing with topics like emotional competences, development of morality, the ability to take other perspectives, educational processes and learning situations of children, in particular with focus on child’s play. In order to study the thereby derived research questions, qualitative interviews with nine children are conducted in the surrounding of a kindergarten.The results indicate that the questioned children perceive conflict mostly as physical dispute, while verbal arguments tend not to be regarded as conflict. Apologizing, as a socially accepted form of behavior, was a known resolution strategy. However children were not able to name the rationale behind the behavior. A further insight was that children in the age of five and six years were in principle able to answer to general questions, but had troubles reconstructing concrete incidences. In the last part of the thesis, the resulting consequences for the practical handling of conflict situations in kindergarten and in particular the role of the pedagogue are discussed with reference to the research results.vorgelegt von Langeder Katrin Bakk. phil.Zusammenfassungen in Deutsch und EnglischAbweichender Titel laut Übersetzung der VerfasserinMasterarbeit Karl-Franzens-Universität Graz 2015 1.68