Type 1 diabetes and cardiovascular disease

The presence of cardiovascular disease (CVD) in Type 1 diabetes largely impairs life expectancy. Hyperglycemia leading to an increase in oxidative stress is considered to be the key pathophysiological factor of both micro- and macrovascular complications. In Type 1 diabetes, the presence of coronary calcifications is also related to coronary artery disease. Cardiac autonomic neuropathy, which significantly impairs myocardial function and blood flow, also enhances cardiac abnormalities. Also hypoglycemic episodes are considered to adversely influence cardiac performance. Intensive insulin therapy has been demonstrated to reduce the occurrence and progression of both micro- and macrovascular complications. This has been evidenced by the Diabetes Control and Complications Trial (DCCT) / Epidemiology of Diabetes Interventions and Complications (EDIC) study. The concept of a metabolic memory emerged based on the results of the study, which established that intensified insulin therapy is the standard of treatment of Type 1 diabetes. Future therapies may also include glucagon-like peptide (GLP)-based treatment therapies. Pilot studies with GLP-1-analogues have been shown to reduce insulin requirements

Characterization and Application of Hard X-Ray Betatron Radiation Generated by Relativistic Electrons from a Laser-Wakefield Accelerator

The necessity for compact table-top x-ray sources with higher brightness, shorter wavelength and shorter pulse duration has led to the development of complementary sources based on laser-plasma accelerators, in contrast to conventional accelerators. Relativistic interaction of short-pulse lasers with underdense plasmas results in acceleration of electrons and in consequence in the emission of spatially coherent radiation, which is known in the literature as betatron radiation. In this article we report on our recent results in the rapidly developing field of secondary x-ray radiation generated by high-energy electron pulses. The betatron radiation is characterized with a novel setup allowing to measure the energy, the spatial energy distribution in the far-field of the beam and the source size in a single laser shot. Furthermore, the polarization state is measured for each laser shot. In this way the emitted betatron x-rays can be used as a non-invasive diagnostic tool to retrieve very subtle information of the electron dynamics within the plasma wave. Parallel to the experimental work, 3D particle-in-cell simulations were performed, proved to be in good agreement with the experimental results.Comment: 38 pages, 19 figures, submitted to the Journal of Plasma Physic

The nephrological perspective on SGLT-2 inhibitors in type 1 diabetes

Prevalence of type 1 diabetes mellitus (T1DM) is globally continuously increasing. T1DM is accompanied by a high risk of developing cardiovascular and renal comorbidities and is one of the leading causes of end-stage renal disease (ESRD). However, current therapeutic approaches for chronic and/or diabetic kidney disease (CKD/DKD) existed for a long time, and offer room for improvement, particularly in T1DM. In 2019, the European Medicines Agency (EMA) approved a first sodium/glucose co-transporter 2 inhibitor (SGLT-2i) and a first dual SGLT-1/-2i to improve glycaemic control, as an adjunctive treatment to insulin in persons with T1DM and a body mass index >27 kg/m(2). Of note, SGLT-1/2is and SGLT-2is are not approved by the Food and Drug Administration (FDA) as an adjunct treatment in T1DM, nor approved for the treatment of CKD or DKD by EMA and FDA. SGLT is have shown to mediate different renoprotective effects in type 2 diabetes mellitus in corresponding cardiovascular and renal outcome trials. First efficacy trials offer insights into potential positive effects on renal function and kidney disease of SGLTis in T1DM. This review summarizes and discusses latest available data on SGLT inhibition and provides an update on the nephrological perspective on SGLTis, specifically in T1DM. (c) 2020 Published by Elsevier B.V.Peer reviewe

Krüppel-like factor 8 (KLF8) is expressed in gliomas of different WHO grades and is essential for tumor cell proliferation.

Krüppel-like factor 8 (KLF8) has only recently been identified to be involved in tumor cell proliferation and invasion of several different tumor entities like renal cell carcinoma, hepatocellular carcinoma and breast cancer. In the present study, we show for the first time the expression of KLF8 in gliomas of different WHO grades and its functional impact on glioma cell proliferation. In order to get information about KLF8-mRNA regulation qPCR was performed and did not reveal any significant difference in samples (n = 10 each) of non-neoplastic brain (NNB), low-grade gliomas (LGG, WHO°II) and glioblastomas (GBM, WHO°IV). Immunohistochemistry of tissue samples (n = 7 LGG, 11 AA and 12 GBM) did not show any significant difference in the fraction of KLF8-immunopositive cells of all analyzed cells in LGG (87%), AA (80%) or GBM (89%). Tissue samples from cerebral breast cancer metastasis, meningiomas but also non-neoplastic brain demonstrated comparable relative cell counts as well. Moreover, there was no correlation between KLF8 expression and the expression pattern of the assumed proliferation marker Ki67, which showed high variability between different tumor grade (9% (LGG), 6% (AA) and 15% (GBM) of Ki67-immunopositive cells). Densitometric analysis of Western blotting revealed that the relative amount of KLF8-protein did also not differ between the highly aggressive and proliferative GBM (1.05) compared to LGG (0.93; p<0.05, studens t-test). As demonstrated for some other non-glial cancer entities, KLF8-knockdown by shRNA in U87-MG cells confirmed its functional relevance, leading to an almost complete loss of tumor cell proliferation. Selective blocking of KLF8 might represent a novel anti-proliferative treatment strategy for malignant gliomas. Yet, its simultaneous expression in non-proliferating tissues could hamper this approach

Soziale Bildungsungleichheit in Österreichs Schulen: Kontinuitäten und Wandel zwischen 2012 und 2022

Dieser Beitrag analysiert die Entstehung und Entwicklung von Bildungsungleichheiten in Österreichs Schulen zwischen 2012 und 2022. Dabei stehen Veränderungen der Bildungspartizipation in den letzten drei Jahren im Fokus der empirischen Betrachtung, indem die Folgen der coronabedingten Schulschließungen und der gegenwärtigen Teuerungskrise für Ungleichheitsmuster untersucht werden. Der zweite Teil dieses Beitrags beschreibt darauf bezogene bildungspolitische Reformmaßnahmen im letzten Jahrzehnt sowie im Kontext der jüngsten Krisenbewältigung. Abschließend werden diese Entwicklungsstränge zusammengeführt und die sich daraus ergebenden Herausforderungen für die gegenwärtige Bildungspolitik diskutiert. Drei wesentliche Erkenntnisse dieses Beitrags sind: Bereits vor den jüngsten Krisenentwicklungen lassen sich für Österreich deutliche und persistente Bildungsungleichheiten nach sozialer Herkunft zeigen. Ungünstigere Voraussetzungen für Schüler:innen haben sich im Krisenkontext verstärkt und Bildungsungleichheiten im österreichischen Schulsystem weiter erhöht. Trotz bildungspolitischer Bekundung von Chancengleichheit werden Maßnahmen zur nachhaltigen Überwindung sozialer Ungleichheit im Schulsystem in der bildungspolitischen Praxis nicht bzw. nicht mit entscheidendem Nachdruck verfolgt.This chapter analyses origins and developments of educational inequalities in the Austrian school system between 2012 and 2022. In particular, we analyze the educational participation of pupils from different socioeconomic backgrounds within the last three years, paying special attention to the role of school closures during the Corona pandemic as well as the current inflation crisis. The second part of this chapter describes governmental policies regarding this question over this period. Finally, both strands are brought together in an outlook on the persistent challenges for the field of education policy and potential answers to reduce educational inequalities in the Austrian school system. Three key findings of this chapter are: Even before the recent crisis, strong and persistent social educational inequalities have characterized the Austrian school system. In the crisis context, however, socioeconomic disadvantages of pupils have intensified, leading to a further increase in educational inequalities in the Austrian school system. Despite being an often-cited goal, in practice, policy measures to overcome social inequalities in the school system are not pursued and implemented with sufficient emphasis

Hippocampal EUD in primarily irradiated glioblastoma patients

Background: Radiation delivery for malignant brain tumors is gradually becoming more precise. Particularly the possibilities of sparing adjacent normal structures such as the hippocampus are increasing. To determine its radiation exposure more exactly, the equivalent uniform dose (EUD) of the hippocampus was compared with further treatment parameters. This way sparing options could be found. Methods: From the database of the University hospital of Munich 61 glioblastoma patients were selected who received primary radiotherapy in 2011. General data about the etiology, treatment course, survival of the patients and dose parameters were retrieved. Results: In a linear regression analysis the side of the tumor (left hippocampus: p < 0.001/right hippocampus: p = 0.009) and its temporal location (left hippocampus: p = 0.015/right hippocampus: p = 0.033) were identified as factors with a significant influence on the EUD of the respective hippocampus. Besides this, the size of the planning target volume (PTV) and the EUD of the hippocampus correlated significantly (p = 0.027;Pearson correlation = 0.291). The median PTV size of the tumor in the right hemisphere was 386.1 ml (range 131.2-910.7 ml), and in the left hemisphere 291.3 ml (range 146.0-588.9 ml) (Kruskal-Wallis test: p = 0.048). A dose quartile analysis showed that 31 patients had a high dose exposure of the hippocampus on one side while having a moderate dose exposure in the other side. Conclusions: The radiation exposure of the respective hippocampus is dependent on the side where the tumor is located as well as on whether it is temporally located. The exposure of the contralateral hippocampus is further dependent on multiple additional factors - nevertheless a reasonable protection seems to be possible in about half of all cases

Report from the 5th cardiovascular outcome trial (CVOT) summit

The 5th Cardiovascular Outcome Trial (CVOT) Summit was held in Munich on October 24th-25th, 2019. As in previous years, this summit served as a reference meeting for in-depth discussions on the topic of recently completed and presented CVOTs. This year, focus was placed on the CVOTs CAROLINA, CREDENCE, DAPA-HF, REWIND, and PIONEER-6. Trial implications for diabetes management and the impact on new treatment algorithms were highlighted for diabetologists, cardiologists, endocrinologists, nephrologists, and general practitioners. Discussions evolved from CVOTs to additional therapy options for heart failure (ARNI), knowledge gained for the treatment and prevention of heart failure and diabetic kidney disease in populations with and without diabetes, particularly using SGLT-2 inhibitors and GLP-1 receptor agonists. Furthermore, the ever increasing impact of CVOTs and substances tested for primary prevention and primary care was discussed. The 6th Cardiovascular Outcome Trial Summit will be held in Munich on October 29th-30th, 2020 (https://www.cvot.org)

Report from the CVOT Summit 2020:new cardiovascular and renal outcomes

The 6th Cardiovascular Outcome Trial (CVOT) Summit "Cardiovascular and Renal Outcomes 2020" was the first to be held virtually on October 29-30, 2020. As in previous years, this summit served as reference meeting for in-depth discussions on the topic of recently completed and presented major outcome trials. This year, focus was placed on the outcomes of VERTIS-CV, EMPEROR-Reduced, DAPA- CKD, and FIDELIO-DKD. Trial implications for diabetes management and the impact on new treatment algorithms were highlighted for diabetologists, cardiologists, endocrinologists, nephrologists, and general practitioners. Discussion evolved from major outcome trials using SGLT-2 inhibitors for treatment and prevention of heart failure and chronic kidney disease in people with and without diabetes, to additional therapy options for chronic kidney disease with a novel mineralocorticoid receptor antagonist. Furthermore, challenges in diabetes management like COVID-19 and obesity, as well as novel treatment strategies and guidelines, were discussed. The 7th Cardiovascular Outcome Trial Summit will be held virtually on November, 18-19, 2021 (http://www.cvot.org)