Elastin production is characteristically turned off during the maturation of elastin-rich organs such as the aorta. MicroRNAs (miRNAs) are small regulatory RNAs that down-regulate target mRNAs by binding to miRNA regulatory elements (MREs) typically located in the 3′ UTR. Here we show a striking up-regulation of miR-29 and miR-15 family miRNAs during murine aortic development with commensurate down-regulation of targets including elastin and other extracellular matrix (ECM) genes. There were a total of 14 MREs for miR-29 in the coding sequences (CDS) and 3′ UTR of elastin, which was highly significant, and up to 22 miR-29 MREs were found in the CDS of multiple ECM genes including several collagens. This overrepresentation was conserved throughout mammalian evolution. Luciferase reporter assays showed synergistic effects of miR-29 and miR-15 family miRNAs on 3′ UTR and coding-sequence elastin constructs. Our results demonstrate that multiple miR-29 and miR-15 family MREs are characteristic for some ECM genes and suggest that miR-29 and miR-15 family miRNAs are involved in the down-regulation of elastin in the adult aorta.

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Our findings suggest that mgR/mgR mice could be a useful model to study aortic abnormalities in segments other than the ascending aorta in order to understand the molecular mechanisms of aortic disease in Marfan syndrome.

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Background: Peer-assisted learning is well established in medical education; however, peer tutors rarely act as assessors for the OSCE. In the compulsory, near-peer teaching programme covering basic medical skills at the University of Heidelberg, peer tutors serve as assessors on a formative OSCE. This study aimed to investigate the feasibility and acceptance of peer assessors and to survey the perceived advantages and disadvantages of their use. Methods: In 2016 and 2017 all OSCE peer assessors (third to sixth-year medical students) and all of the peerassessed students in 2017 (second-year-medical students) were invited to participate in a survey. Both groups were asked to complete a tablet-based questionnaire immediately after the OSCE. Peer assessors were asked to rate eight statements and the peer-assessed students to rate seven statements on a five-point Likert scale. Both were asked to comment on the advantages and disadvantages of peer-assessors. Results: Overall, 74 of 76 peer assessors and 307 of 308 peer-assessed students participated in the study. 94% (67/74) of peer assessors and 90% (276/307) of the peer-assessed group thought that it is important to have peer tutors as assessors. Of the peer assessors, 92% (68/74) felt confident in giving structured feedback during the OSCE and 66% (49/74) felt they had improved their teaching skills. Of the peer-assessed students, 99% (306/307) were satisfied with their peers as OSCE assessors and 96% (292/307) considered the peer feedback during the OSCE as helpful. The participants mentioned structural benefits, such as lower costs, and suggested the quality of the OSCE was higher due to the use of peer assessors. The use of peer assessors was found to be beneficial for the learners in the form of highquality feedback and an overall reduction in stress. Furthermore, the use of peer assessors was found to be beneficial for the peer assessors (improved teaching and clinical skills). Conclusion: From a learner's perspective, the use of peer assessors for a formative OSCE that is part of a near-peer teaching program aimed at junior medical students is favourable for all. A broad implementation of peer assessment in the formative OSCE should be encouraged to investigate effects on quality and stress-reduction.

Marfan syndrome is characterized by high expression of matrix metalloproteinases (MMPs) in aortic smooth muscle cells (AoSMCs) associated with medial elastolysis and aortic root aneurysm. We aimed to reduce aortic elastolysis through decrease of MMP expression with decoy oligodeoxynucleotides (dODNs) neutralizing the transcription factor activating factor-1 (AP-1). AP-1 abundance in nuclear extracts as well as MMP-2 and MMP-9 expression were significantly increased in isolated mAoSMC of mgR/mgR Marfan mice compared to wild-type cells. Exposure to AP-1 neutralizing dODNs resulted in a significant reduction of basal and interleukin-1β-stimulated MMP expression and activity in mAoSMCs. Moreover, increased migration and formation of superoxide radical anions was substantially decreased in mAoSMCs by AP-1 dODN treatment. Aortic grafts from donor Marfan mice were treated with AP-1- dODN ex vivo and implanted as infrarenal aortic interposition grafts in mgR/mgR mice. Pretreatment of aortic grafts with AP-1 dODN led to reduced elastolysis, macrophage infiltration, and MMP activity. Permeability of the endothelial monolayer was increased for dODN in mgR/mgR aortae with observed loss of tight junction proteins ZO-1 and occludin, enabling dODN to reach the tunica media. Targeting AP-1 activity offers a new potential strategy to treat the vascular phenotype associated with Marfan syndrome.

Pseudoaneurysms and patch aneurysms are life-threatening late complications after thoracoabdominal aortic aneurysm (TAAA) repair. We treated four patients who presented with a pseudoaneurysm or patch aneurysm involving the descending thoracic portion of a previously implanted TAAA graft. In each patient, stent grafts were placed within the existing graft to cover the aneurysm endoluminally. All patients recovered without major complications, and computed tomography performed after a mean follow-up of 51.5 ± 19.7 months showed that the repairs remained intact.

Background: Providing end of life care (EoLC) is an important aspect of primary care, which reduces the risk of hospital admission for most patients. However, general practitioners (GPs) seem to have low confidence in their ability to provide EoLC. Little is known about an adequate volume and kind of training in EoLC among GP trainees. Methods: We performed a before-after comparison in all postgraduate GP trainees who were registered in the vocational training program (KWBW VerbundweiterbildungPLUS). They were offered participation within a two-day seminar focussing on palliative care in 2017. Those who attended the seminar (intervention group I) completed a paper-based questionnaire directly before the intervention (T 1) and 6 months after (T 2). None-attendees (group C) were also asked to fill out the questionnaire once. The questionnaire covered previous experiences in palliative care, self-assessment of competencies in EoLC in the organisation of patient care as well as in control of symptoms, attitudes towards death and caring for dying patients and questions about GPs' role in EoLC. Results: In total, 294 GP trainees (I: n = 219; C: n = 75) participated in the study. Of those, more than 90% had previously gained experience in EoLC mainly during vocational training in the hospital rotation. Around a third had previously gained competencies in EoLC in medical school. Between groups I (T 1) and C no significant differences were observed in socio-demographic characteristics, pre-existing experience or overall expertise. At T 2, 75% of participants of group I declared they have extended their competencies in EoLC after the intervention and 70% classified the intervention as helpful or very helpful. Overall, they rated their competencies significantly higher than at T 1 (p < 0.01). In detail, competencies in organisation of EoLC and competencies in handling of symptoms significantly improved (p < 0.01). Due to the intervention, 66% could reflect their attitudes towards dying, death and grief and 18% changed their attitudes. Group I highlighted palliative care as one of GPs tasks (Likert 4.47/5, SD 0.75). Conclusions: The intervention fostered personal competencies, understanding and self-confidence in EoLC among GP trainees. This is crucial for the aim to broadly provide EoLC.