Surgical reconstruction of the left main coronary artery with patch-angioplasty

<p>Abstract</p> <p>Background</p> <p>Conventional coronary artery bypass grafting (CABG) has been established as the treatment of choice for left main coronary artery (LMCA) stenosis However, the conventional grafting provides a retrograde perfusion to extensive myocardial area and leads prospectively to competitive flow of the non-occluded coronaries thus consuming the grafts. Surgical reconstruction of the LMCA with patch-angioplasty is an alternative method that eliminates these drawbacks.</p> <p>Methods</p> <p>Between February 1997 and July 2007, 37 patients with isolated LMCA stenosis were referred for surgical ostial reconstruction. In 27 patients (73%) surgical angioplasties have been performed. All patients were followed up clinically and with transesophageal echocardiography (TEE) and coronary angiography when required.</p> <p>Results</p> <p>In 10 patients (27%) a LMCA stenosis could not be confirmed. There were no early mortality or perioperative myocardial infarctions. The postoperative course was uneventful in all patients. In 25 patients, TEE demonstrated a wide open main stem flow pattern one to six months after reconstruction of the left main coronary artery with one patch mild aneurysmal dilated.</p> <p>Conclusions</p> <p>The surgical reconstruction with patch-angioplasty is a safe and effective method for the treatment of proximal and middle LMCA stenosis. Almost one third of the study group had no really LMCA stenosis: antegrade flow pattern remained sustained and the arterial grafts have been spared. In the cases of unclear or suspected LMCA stenosis, cardio-CT can be performed to unmask catheter-induced coronary spasm as the underlying reason for isolated LMCA stenosis.</p

Perceived economic self‑sufficiency: a countryand generation‑comparative approach

We thank Michael Camasso and Radha Jagannathan as well as Asimina Christoforou, Gerbert Kraaykamp, Fay Makantasi, Tiziana Nazio, Kyriakos Pierrakakis, Jacqueline O’Reilly and Jan van Deth for their contribution to the CUPESSE project (Seventh Framework Programme; Grant Agreement No. 61325). CUPESSE received additional funding from the Mannheim Centre for European Social Research (MZES) and the Field of Focus 4 “Self-Regulation and Regulation: Individuals and Organisations” at Heidelberg University. We further acknowledge helpful comments on this article by two anonymous reviewers. Julian Rossello provided valuable research assistance.Electronic supplementary material The online version of this article (https ://doi.org/10.1057/ s4130 4-018-0186-3) contains supplementary material, which is available to authorized users.Existing datasets provided by statistical agencies (e.g. Eurostat) show that the economic and financial crisis that unfolded in 2008 significantly impacted the lives and livelihoods of young people across Europe. Taking these official statistics as a starting point, the collaborative research project “Cultural Pathways to Economic Self-Sufficiency and Entrepreneurship in Europe” (CUPESSE) generated new survey data on the economic and social situation of young Europeans (18–35 years). The CUPESSE dataset allows for country-comparative assessments of young people’s perceptions about their socio-economic situation. Furthermore, the dataset includes a variety of indicators examining the socio-economic situation of both young adults and their parents. In this data article, we introduce the CUPESSE dataset to political and social scientists in an attempt to spark a debate on the measurements, patterns and mechanisms of intergenerational transmission of economic self-sufficiency as well as its political implications.CUPESSE project (Seventh Framework Programme; Grant Agreement No. 61325

Transcriptional and Post-Transcriptional Regulation of SPAST, the Gene Most Frequently Mutated in Hereditary Spastic Paraplegia

Hereditary spastic paraplegias (HSPs) comprise a group of neurodegenerative disorders that are characterized by progressive spasticity of the lower extremities, due to axonal degeneration in the corticospinal motor tracts. HSPs are genetically heterogeneous and show autosomal dominant inheritance in ∼70–80% of cases, with additional cases being recessive or X-linked. The most common type of HSP is SPG4 with mutations in the SPAST gene, encoding spastin, which occurs in 40% of dominantly inherited cases and in ∼10% of sporadic cases. Both loss-of-function and dominant-negative mutation mechanisms have been described for SPG4, suggesting that precise or stoichiometric levels of spastin are necessary for biological function. Therefore, we hypothesized that regulatory mechanisms controlling expression of SPAST are important determinants of spastin biology, and if altered, could contribute to the development and progression of the disease. To examine the transcriptional and post-transcriptional regulation of SPAST, we used molecular phylogenetic methods to identify conserved sequences for putative transcription factor binding sites and miRNA targeting motifs in the SPAST promoter and 3′-UTR, respectively. By a variety of molecular methods, we demonstrate that SPAST transcription is positively regulated by NRF1 and SOX11. Furthermore, we show that miR-96 and miR-182 negatively regulate SPAST by effects on mRNA stability and protein level. These transcriptional and miRNA regulatory mechanisms provide new functional targets for mutation screening and therapeutic targeting in HSP

NEK1 variants confer susceptibility to amyotrophic lateral sclerosis

To identify genetic factors contributing to amyotrophic lateral sclerosis (ALS), we conducted whole-exome analyses of 1,022 index familial ALS (FALS) cases and 7,315 controls. In a new screening strategy, we performed gene-burden analyses trained with established ALS genes and identified a significant association between loss-of-function (LOF) NEK1 variants and FALS risk. Independently, autozygosity mapping for an isolated community in the Netherlands identified a NEK1 p.Arg261His variant as a candidate risk factor. Replication analyses of sporadic ALS (SALS) cases and independent control cohorts confirmed significant disease association for both p.Arg261His (10,589 samples analyzed) and NEK1 LOF variants (3,362 samples analyzed). In total, we observed NEK1 risk variants in nearly 3% of ALS cases. NEK1 has been linked to several cellular functions, including cilia formation, DNA-damage response, microtubule stability, neuronal morphology and axonal polarity. Our results provide new and important insights into ALS etiopathogenesis and genetic etiology

Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

Web-based infectious disease surveillance systems and public health perspectives: a systematic review

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Abstract Background Emerging and re-emerging infectious diseases are a significant public health concern, and early detection and immediate response is crucial for disease control. These challenges have led to the need for new approaches and technologies to reinforce the capacity of traditional surveillance systems for detecting emerging infectious diseases. In the last few years, the availability of novel web-based data sources has contributed substantially to infectious disease surveillance. This study explores the burgeoning field of web-based infectious disease surveillance systems by examining their current status, importance, and potential challenges. Methods A systematic review framework was applied to the search, screening, and analysis of web-based infectious disease surveillance systems. We searched PubMed, Web of Science, and Embase databases to extensively review the English literature published between 2000 and 2015. Eleven surveillance systems were chosen for evaluation according to their high frequency of application. Relevant terms, including newly coined terms, development and classification of the surveillance systems, and various characteristics associated with the systems were studied. Results Based on a detailed and informative review of the 11 web-based infectious disease surveillance systems, it was evident that these systems exhibited clear strengths, as compared to traditional surveillance systems, but with some limitations yet to be overcome. The major strengths of the newly emerging surveillance systems are that they are intuitive, adaptable, low-cost, and operated in real-time, all of which are necessary features of an effective public health tool. The most apparent potential challenges of the web-based systems are those of inaccurate interpretation and prediction of health status, and privacy issues, based on an individuals internet activity. Conclusion Despite being in a nascent stage with further modification needed, web-based surveillance systems have evolved to complement traditional national surveillance systems. This review highlights ways in which the strengths of existing systems can be maintained and weaknesses alleviated to implement optimal web surveillance systems