Effect of eplerenone on extracellular cardiac matrix biomarkers in patients with acute ST-elevation myocardial infarction without heart failure: insights from the randomized double-blind REMINDER Study

Objective: Aldosterone stimulates cardiac collagen synthesis. Circulating biomarkers of collagen turnover provide a useful tool for the assessment of cardiac remodeling in patients with an acute myocardial infarction (MI).  Methods: The REMINDER trial assessed the effect of eplerenone in patients with an acute ST-elevation Myocardial Infarction (STEMI) without known heart failure (HF), when initiated within 24 h of symptom onset. The primary outcome was almost totally (>90%) driven by natriuretic peptide (NP) thresholds after 1-month post-MI (it also included a composite of cardiovascular death or re-hospitalization or new onset HF or sustained ventricular tachycardia or fibrillation or LVEF ≤40% after 1-month post-MI). This secondary analysis aims to assess the extracellular matrix marker (ECMM) levels with regards to: (1) patients` characteristics; (2) determinants; (3) and eplerenone effect.  Results: Serum levels of ECMM were measured in 526 (52%) of the 1012 patients enrolled in the REMINDER trial. Patients with procollagen type III N-terminal propeptide (PIIINP) above the median were older and had worse renal function (p < 0.05). Worse renal function was associated with increased levels of PIIINP (standardized β ≈ 0.20, p < 0.05). Eplerenone reduced PIIINP when the levels of this biomarker were above the median of 3.9 ng/mL (0.13 ± 1.48 vs. -0.37 ± 1.56 ng/mL, p = 0.008). Higher levels of PIIINP were independently associated with higher proportion of NP above the prespecified thresholds (HR = 1.95, 95% CI 1.16-3.29, p = 0.012).  Conclusions: Eplerenone effectively reduces PIIINP levels when baseline values were above the median. Eplerenone may limit ECMM formation in post-MI without HF

A Motor Function for the DEAD-Box RNA Helicase, Gemin3, in Drosophila

The survival motor neuron (SMN) protein, the determining factor for spinal muscular atrophy (SMA), is complexed with a group of proteins in human cells. Gemin3 is the only RNA helicase in the SMN complex. Here, we report the identification of Drosophila melanogaster Gemin3 and investigate its function in vivo. Like in vertebrates, Gemin3 physically interacts with SMN in Drosophila. Loss of function of gemin3 results in lethality at larval and/or prepupal stages. Before they die, gemin3 mutant larvae exhibit declined mobility and expanded neuromuscular junctions. Expression of a dominant-negative transgene and knockdown of Gemin3 in mesoderm cause lethality. A less severe Gemin3 disruption in developing muscles leads to flightless adults and flight muscle degeneration. Our findings suggest that Drosophila Gemin3 is required for larval development and motor function

Cardiomyocyte Specific Ablation of p53 Is Not Sufficient to Block Doxorubicin Induced Cardiac Fibrosis and Associated Cytoskeletal Changes

Doxorubicin (Dox) is an anthracycline used to effectively treat several forms of cancer. Unfortunately, the use of Dox is limited due to its association with cardiovascular complications which are manifested as acute and chronic cardiotoxicity. The pathophysiological mechanism of Dox induced cardiotoxicity appears to involve increased expression of the tumor suppressor protein p53 in cardiomyocytes, followed by cellular apoptosis. It is not known whether downregulation of p53 expression in cardiomyocytes would result in decreased rates of myocardial fibrosis which occurs in response to cardiomyocyte loss. Further, it is not known whether Dox can induce perivascular necrosis and associated fibrosis in the heart. In this study we measured the effects of acute Dox treatment on myocardial and perivascular apoptosis and fibrosis in a conditional knockout (CKO) mouse model system which harbours inactive p53 alleles specifically in cardiomyocytes. CKO mice treated with a single dose of Dox (20 mg/kg), did not display lower levels of myocardial apoptosis or reactive oxygen and nitrogen species (ROS/RNS) compared to control mice with intact p53 alleles. Interestingly, CKO mice also displayed higher levels of interstitial and perivascular fibrosis compared to controls 3 or 7 days after Dox treatment. Additionally, the decrease in levels of the microtubule protein α-tubulin, which occurs in response to Dox treatment, was not prevented in CKO mice. Overall, these results indicate that selective loss of p53 in cardiomyocytes is not sufficient to prevent Dox induced myocardial ROS/RNS generation, apoptosis, interstitial fibrosis and perivascular fibrosis. Further, these results support a role for p53 independent apoptotic pathways leading to Dox induced myocardial damage and highlight the importance of vascular lesions in Dox induced cardiotoxicity

JournalistInnen als persönliche Marken

Branding von JournalistInnen auf sozialen Medien, das primär der positiven Präsentation und Vermarktung der JournalistInnen selbst, der Medienunternehmen sowie des Journalismus insgesamt dient, findet zahlreicher Studien zufolge zunehmend statt. Die bestehende Forschung konzentriert sich derweil verstärkt auf die Perspektive der JournalistInnen. Die Haltung des Publikums zum digitalen Branding von JournalistInnen wurde bisweilen jedoch kaum empirisch untersucht. Doch gerade in Zeiten der Krise des Journalismus, geprägt durch Image-, Vertrauens- und Glaubwürdigkeitsverluste, schwaches, gesellschaftliches Ansehen, zunehmende Abgrenzungsschwierigkeiten zu neueren InformationsvermittlerInnen, Verluste der Alleinstellung als Gatekeeper und sinkende RezipientInnenzahlen, scheint eine dahingehende wissenschaftliche Auseinandersetzung als essentiell und dringlich. Dieser Forschungslücke nimmt sich die vorliegende Arbeit an und untersucht im Rahmen qualitativer, virtuell durchgeführter Fokusgruppeninterviews, anhand 30 Teilnehmender im Alter von 24 und 39 Jahren (Millennials), welche grundsätzliche Haltung das Publikum zu Branding von JournalistInnen auf sozialen Medien hat, welche Erwartungen sie an JournalistInnen im Umgang mit sozialen Medien haben und welcher Zusammenhang zwischen digitalem, journalistischem Branding und Publikumsimage, Bekannt- und Beliebtheit von JournalistInnen beim Publikum sowie dem journalistischen Rezeptionsverhalten des Publikums besteht. In der Arbeit werden dabei JournalistInnen durchwegs als DarstellerInnen auf öffentlichen Bühnen im Sinne Goffmans Selbstdarstellungstheorie betrachtet. Insgesamt zeigt sich ein weitestgehend positives Stimmungsbild der befragten Millennials gegenüber Branding von JournalistInnen auf sozialen Medien. Dazu trägt vor allem das Kennenlernen der persönlichen Seite von JournalistInnen, zunehmender Dialog und Austausch mit JournalistInnen sowie auch die empfundene Notwendigkeit von digitalem Branding bei JournalistInnen bei. Außerdem werden JournalistInnen durch ihr Branding auf sozialen Medien beim Publikum zumeist als vertrauensvoller, angesehener und einflussreicher erachtet, wofür wiederum vorwiegend eine stärkere Interaktions- und Dialoghaltung, das Gewähren von privaten Einblicken, der Aufbau einer engeren Beziehung mit dem Publikum und das Erlangen eines Markenwerts verantwortlich gemacht wird. Lediglich im Punkto Glaubwürdigkeit dürfte mehr noch die Qualität journalistischer Inhalte als die digitale Vermarktung von JournalistInnen ausschlaggebend sein. Dennoch wird insgesamt eine Tendenz in Richtung eines positiven Zusammenhangs zwischen Branding und Publikumsimage erkennbar. Ebenfalls wird insgesamt ein positiver Zusammenhang zwischen Branding und Bekannt- sowie Beliebtheit deutlich, wobei die Steigerung der Bekanntheit von JournalistInnen durch das Branding auf Social Media von Algorithmen und Filterblasen determiniert sein dürfte. Zudem werden zwar Zuwächse des Wissensstands der Millennials über JournalistInnen in ihrer persönlichen Dimension durch das Branding von JournalistInnen auf sozialen Medien ersichtlich, gleichzeitig bestärkt es oftmals allerdings Abgrenzungsschwierigkeiten zu BloggerInnen und InfluencerInnen. JournalistInnen, die auf sozialen Medien präsent sind, wird des Weiteren Agilität und Fortschrittlichkeit zugeschrieben, was wiederum zur Beliebtheit von JournalistInnen beiträgt. Zusätzlich verhilft das digitale Branding angesichts der meisten Millennials JournalistInnen dabei, dem Verdrängen durch neue AkteurInnen im medialen Umfeld entgegenzuwirken und zugleich ihre eigene Position zu stärken. Zudem werden fast alle Befragten durch das digitale Branding von JournalistInnen zum Konsum journalistischer Inhalte angeregt und der Journalismus dadurch als zugänglicher und nahbarer wahrgenommen, wodurch ebenso ein positiver Zusammenhang zwischen Branding und journalistischem Rezeptionsverhalten festgestellt wird. Insbesondere die zunehmende Sichtbarkeit von journalistischen Beiträgen auf Startseiten, Anreize in Stories oder Beiträgen sowie die Inkludierung von Swipe-Up Links in Stories von JournalistInnen, motiviert Millennials dazu, vermehrt traditionelle, journalistische Inhalte zu rezipieren. Erwartetet wird von JournalistInnen insgesamt ein Mittelweg zwischen Tradition und Modernität bezugnehmend auf Umgangsweisen und Inhalten mit und auf sozialen Medien. Insbesondere wird das Meiden plakativer Werbeeinbindungen auf den Social Media Profilen von JournalistInnen angeraten. Alles in allem kann das Branding von JournalistInnen auf sozialen Medien aus Publikumssicht durchaus als Chance angesehen werden, den negativen Entwicklungen im Journalismus Widerstand zu leisten. Die vorliegende Arbeit liefert zahlreiche Anknüpfungspunkte für weitere Forschungen, welche vor allem in Bezug auf Forschungsdesigns und Stichprobenzusammensetzungen variieren und sich der Überprüfung der hier gewonnenen Erkenntnisse annehmen sollten.According to numerous studies, branding of journalists on social media, which primarily serves the positive presentation and advertising of journalists themselves, media companies and journalism in general, is increasingly occurring. At the moment, existing research is mostly focused on the perspective of journalists. However, the public’s attitude to the digital branding of journalists has hardly been investigated empirically. But especially in times of crisis of journalism, marked by a loss of image, trust, and credibility, weak social reputation, increasing difficulties in distinguishing itself from newer information mediators, losses of the unique position as gatekeepers and declining numbers of recipients, a scientific debate on this issue seems to be essential and urgent. The present paper addresses this research gap, in the context of qualitative, virtual focus group interviews based on 30 participants aged between 24 and 39 years (Millennials), and examines the audience’s attitude towards branding journalists on social media, what expectations they have regarding journalists dealing with social media, and what relationship exists between digital, journalistic branding and the audience image, the awareness and popularity of journalists among the audience, and the journalistic reception behavior of the audience. Throughout the paper, journalists are regarded as actors on public stages in the sense of Goffman’s theory of self-presentation. Overall, the surveyed millennials show a largely positive attitude towards branding journalists on social media. This is mainly due to getting to know the personal side of journalists, increasing dialogue and exchange with journalists, as well as the perceived need for digital branding among journalists. In addition, through their branding on social media, journalists are generally seen as more trustworthy, respected and influential by the audience, which in turn is mainly attributed to stronger interaction and dialogue, the granting of private insights, the development of a closer relationship with the audience and the achievement of a brand value. Only in terms of credibility the quality of journalistic content is probably more decisive than the digital branding of journalists. Nevertheless, there is an overall tendency towards a positive relationship between branding and audience image. A positive relationship is also marked between branding and awareness as well as popularity, whereby the increase in the awareness of journalists through their branding on social media might be determined by algorithms and filter bubbles. In addition, on the one hand, a growth of knowledge about journalists in their personal dimension is shown through the branding of journalists on social media, on the other hand, it demonstrates that it is becoming increasingly hard to differentiate between journalists, bloggers and influencers. Moreover, agility and progressiveness are also attributed to journalists who are present on social media, which in turn contributes to the popularity of journalists. According to millennials, digital branding additionally helps journalists to counteract the repression by new actors in the media environment and strengthens their own position at the same time. Furthermore, almost all respondents are encouraged and stimulated by the digital branding of journalists to consume journalistic content, and thus journalism is perceived as more accessible and approachable, which also points out a positive relationship between branding and journalistic reception behavior. In particular, the increasing visibility of journalistic features on social media start pages, incentives in stories or features as well as the inclusion of swipe-up links in journalists’ stories motivates millennials to receive more traditional journalistic content. Journalists are expected to find a balance between tradition and modernity regarding the content itself as well as dealing with social media in general. Especially, the avoidance of prominent advertising on journalists’ social media profiles is recommended. All in all, from an audience point of view journalistic branding on social media can be definitely seen as an opportunity to resist the negative developments in journalism. The present paper provides numerous starting points for further research, which should mainly vary in terms of research designs and sample compositions and ought to be addressed to the verification of the findings obtained here

MEIS2 Is an Oncogenic Partner in AML1-ETO-Positive AML

Contains fulltext : 159977.pdf (publisher's version ) (Open Access

The Initial Inflammatory Response to Bioactive Implants Is Characterized by NETosis

<div><p>Implants trigger an inflammatory response, which is important for osseointegration. Here we studied neutrophil extracellular trap (NET) release of human neutrophils in response to sandblasted large-grit acid etched (SLA) implants using fluorescent, confocal laser scanning and scanning electron microscopy. Our studies demonstrate that human neutrophils rapidly adhered to SLA surfaces, which triggered histone citrullination and NET release. Further studies showed that albumin or acetylsalicylic acid had no significant effects on the inflammatory response to SLA surfaces. In contrast to bioinert materials, which do not osseointegrate, the bioactivity of SLA surfaces is coupled with the ability to release NETs. Further investigations are necessary for clarifying the role of NETosis for osseointegration.</p></div