A progressive increase in cardiovascular risk assessed by coronary angiography in non-diabetic patients at sub-diabetic glucose levels

<p>Abstract</p> <p>Objective</p> <p>Diabetes mellitus type 2 (DM2) is a risk factor for coronary heart disease (CHD). While there is a clear correlation of fasting blood glucose (FBG) and 2 h post-challenge blood glucose values (2h-BG) with microvascular complications, the risk for CHD conferred by glucose dysregulation antecedent to DM2 is less clear. Therefore, we investigated associations of FBG and 2h-BG values with the prevalence of CHD assessed by coronary angiography as the most sensitive diagnostic tool.</p> <p>Research Design and Methods</p> <p>Coronary angiography was performed in 1394 patients without known DM. Capillary blood glucose was analyzed before and 2 h after an oral glucose tolerance test. Associations between FBG as well as 2h-BG levels and the risk for CHD were assessed by logistic regression analysis.</p> <p>Results</p> <p>1064 (75%) of patients were diagnosed with CHD. 204 (15%) were diagnosed with so far unknown DM2, 274 (20%) with isolated impaired fasting glucose (IFG), 188 (13%) with isolated impaired glucose tolerance (IGT) and 282 (20%) with both, IGT and IFG. We found a continuous increase in the risk for CHD with fasting and post-challenge blood glucose values even in the subdiabetic range. This correlation did however not suggest clear cut-off values. The increase in risk for CHD reached statistical significance at FBG levels of > 120 mg/dl (Odds Ratio of 2.7 [1.3-5.6] and 2h-BG levels > 140 mg/dl (141-160 mg/dl OR 1.8 [1.1-2.9], which was however lost after adjusting for age, sex and BMI.</p> <p>Conclusions</p> <p>In our study population we found a continuous increased risk for CHD at fasting and 2h-BG levels in the sub-diabetic glucose range, but no clear cut-off values for cardiovascular risk.</p

Emergent Trion-Phonon Coupling in Atomically-Reconstructed MoSe2_2-WSe2_2 Heterobilayers

In low-temperature resonant Raman experiments on MoSe$_2$-WSe$_2$ heterobilayers, we identify a hybrid interlayer shear mode (HSM) with an energy, close to the interlayer shear mode (SM) of the heterobilayers, but with a much broader, asymmetric lineshape. The HSM shows a pronounced resonance with the intralayer hybrid trions (HX$^-$) of the MoSe$_2$ and WSe$_2$ layers, only. No resonance with the neutral intralayer excitons is found. First-principles calculations reveal a strong coupling of Q-valley states, which are delocalized over both layers and participate in the HX$^-$, with the SM. This emerging trion-phonon coupling may be relevant for experiments on gate-controlled heterobilayers.Comment: 6 pages, 3 figure

Evaluation of a peer coach-led intervention to improve pain symptoms (ECLIPSE): Rationale, study design, methods, and sample characteristics

Chronic pain is prevalent, costly, and a leading cause of disability. Pain self-management (i.e., employing self-management strategies including behavioral modifications) is an effective, evidence-based treatment. However, implementation and delivery of a pain self-management model is challenging because of time and resources. Peer supported pain self-management offers a promising approach to implementing pain self-management programs using fewer clinical resources. Evaluation of a Peer Coach-Led Intervention for the Improvement of Pain Symptoms (ECLIPSE) is a randomized controlled trial testing effectiveness of peer coach-delivered pain self-management intervention versus controls receiving a class on pain and pain self-management. ECLIPSE is a Hybrid Type 1 study testing effectiveness while examining implementation factors. ECLIPSE enrolled 215 veterans randomly assigned to the peer coaching (N = 120) or control (N = 95) arm. The peer coaching intervention lasts 6 months, with patient-peer coach pairs instructed to talk twice per month. Coaches attend initial training, are provided a detailed training manual, and attend monthly booster sessions. Outcomes are assessed at baseline, 6 months, and 9 months. The primary outcome is overall pain (intensity and interference), measured by the Brief Pain Inventory (BPI). Secondary outcomes are self-efficacy, social support, pain catastrophizing, patient activation, health-related quality of life, and health care utilization. To maximize implementation potential of pain self-management, innovative delivery methods are needed that do not require additional resources from healthcare teams. A novel and promising approach is a peer-coaching model, in which patients who are successfully managing their pain offer information, ongoing support, and advice to other patients with pain

Disrupting the HDAC6-ubiquitin interaction impairs infection by influenza and Zika virus and cellular stress pathways.

The deacetylase HDAC6 has tandem catalytic domains and a zinc finger domain (ZnF) binding ubiquitin (Ub). While the catalytic domain has an antiviral effect, the ZnF facilitates influenza A virus (IAV) infection and cellular stress responses. By recruiting Ub via the ZnF, HDAC6 promotes the formation of aggresomes and stress granules (SGs), dynamic structures associated with pathologies such as neurodegeneration. IAV subverts the aggresome/HDAC6 pathway to facilitate capsid uncoating during early infection. To target this pathway, we generate designed ankyrin repeat proteins (DARPins) binding the ZnF; one of these prevents interaction with Ub in vitro and in cells. Crystallographic analysis shows that it blocks the ZnF pocket where Ub engages. Conditional expression of this DARPin reversibly impairs infection by IAV and Zika virus; moreover, SGs and aggresomes are downregulated. These results validate the HDAC6 ZnF as an attractive target for drug discovery

Disrupting the HDAC6-ubiquitin interaction impairs infection by influenza and Zika virus and cellular stress pathways

The deacetylase HDAC6 has tandem catalytic domains and a zinc finger domain (ZnF) binding ubiquitin (Ub). While the catalytic domain has an antiviral effect, the ZnF facilitates influenza A virus (IAV) infection and cellular stress responses. By recruiting Ub via the ZnF, HDAC6 promotes the formation of aggresomes and stress granules (SGs), dynamic structures associated with pathologies such as neurodegeneration. IAV subverts the aggresome/HDAC6 pathway to facilitate capsid uncoating during early infection. To target this pathway, we generate designed ankyrin repeat proteins (DARPins) binding the ZnF; one of these prevents interaction with Ub in vitro and in cells. Crystallographic analysis shows that it blocks the ZnF pocket where Ub engages. Conditional expression of this DARPin reversibly impairs infection by IAV and Zika virus; moreover, SGs and aggresomes are downregulated. These results validate the HDAC6 ZnF as an attractive target for drug discovery

Digitale Teilhabe

Das Themenheft Digitale Teilhabe beschäftigt sich zentral mit den Potentialen der Nutzung der neuen Informations- und Kommunikationstechnologien durch benachteiligte Menschen. Im Leitartikel wird der Versuch unternommen, mögliche theoretische Anknüpfungspunkte und Forschungsfragen für weitere Studien- und Forschungsarbeiten in dem noch jungen Themenfeld der Digitalen Teilhabe zu identifizieren. Hierzu wird zunächst das zugrunde liegende Verständnis von Behinderung/Benachteiligung diskutiert und inklusive (Medien-)Bildung als Teil der Persönlichkeitsbildung skizziert. In verschiedenen Diskursen bzw. Disziplinen werden dann theoretische Anknüpfungspunkte für weitere Forschungsarbeiten benannt. Die Idee für das Themenheft ist im Rahmen des Projekts "Begleitforschung im PIKSL-Labor" des Zentrums für Planung und Evaluation Sozialer Dienste der Uni Siegen (ZPE) entstanden. Das PIKSL-Projekt zielt darauf ab, Menschen mit Behinderungen moderne Kommunikationstechnologien zugänglich zu machen, um ihnen Teilhabemöglichkeiten zu erleichtern und zugleich die personale Abhängigkeit von professioneller Unterstützung zu reduzieren. Der inter- und transdisziplinäre Ansatz von PIKSL wird durch die Vielfalt der Artikel in dem Heft deutlich: Digitale Teilhabe wird nicht alleine aus (medien-)pädagogischer bzw. sozialwissenschaftlicher Perspektive betrachtet. Die Besonderheit liegt in der Kooperation unterschiedlicher Disziplinen wie Soziale Arbeit, Kunst und Webdesign

Planning and Development of Social Services for Persons with Disabilities

Soziale Dienste zur Unterstützung von Menschen mit Behinderungen haben sich in den letzten Jahren dynamisch entwickelt und unterliegen auch aktuell einem erheblichen Veränderungsdruck. Die Forschungsarbeiten, die in diesem Band versammelt sind, haben die Entwicklung hin zu einer inklusionsorientierten Unterstützung in zahlreichen Projekten auf unterschiedlichen Ebenen aktiv begleitet.Social services to support persons with disabilities have developed dynamically in recent years and are currently subject to considerable pressure to change. The research work collected in this volume has actively accompanied the development towards inclusion-oriented support in numerous projects at different levels

Acute mental stress drives vascular inflammation and promotes plaque destabilization in mouse atherosclerosis

Publisher Copyright: © 2021 The Author(s). Published by Oxford University Press on behalf of the European Society of Cardiology.Aims: Mental stress substantially contributes to the initiation and progression of human disease, including cardiovascular conditions. We aim to investigate the underlying mechanisms of these contributions since they remain largely unclear. Methods and results: Here, we show in humans and mice that leucocytes deplete rapidly from the blood after a single episode of acute mental stress. Using cell-tracking experiments in animal models of acute mental stress, we found that stress exposure leads to prompt uptake of inflammatory leucocytes from the blood to distinct tissues including heart, lung, skin, and, if present, atherosclerotic plaques. Mechanistically, we found that acute stress enhances leucocyte influx into mouse atherosclerotic plaques by modulating endothelial cells. Specifically, acute stress increases adhesion molecule expression and chemokine release through locally derived norepinephrine. Either chemical or surgical disruption of norepinephrine signalling diminished stress-induced leucocyte migration into mouse atherosclerotic plaques. Conclusion: Our data show that acute mental stress rapidly amplifies inflammatory leucocyte expansion inside mouse atherosclerotic lesions and promotes plaque vulnerability.publishersversionPeer reviewe