Cardiac arrhythmias mimicking primary neurological disorders: a difficult diagnostic situation

Cardiac arrhythmias can present with the signs and symptoms of a seizure disorder. This potentially life–threatening underlying cause of non–febrile seizures should be recognized early, since successful specific treatment is possible. The purpose of this retrospective study was to examine common features in such patients. Over a period of 25 years, eight patients were initially treated for up to 5 years at our institution for a seizure disorder until dysrhythmia as the underlying cause of the seizures was disclosed. The main symptom was drop attacks coinciding with physical activity or emotional stress. Convulsions were only rarely observed. In five of the eight patients the underlying disorder was the long–QT–syndrome (Romano–Ward syndrome). In one patient intermittent complete atrioventricular block was found, another patient showed ventricular tachydysrhythmia of unknown etiology and the last patient suffered from hypertrophic cardiomyopathy.     

The Local Matrix Distribution and the Functional Development of Tissue Engineered Cartilage,a Finite Element Study

Assessment of the functionality of tissue engineered cartilage constructs is hampered by the lack of correlation between global measurements of extra cellular matrix constituents and the global mechanical properties. Based on patterns of matrix deposition around individual cells, it has been hypothesized previously, that mechanical functionality arises when contact occurs between zones of matrix associated with individual cells. The objective of this study is to determine whether the local distribution of newly synthesized extracellular matrix components contributes to the evolution of the mechanical properties of tissue engineered cartilage constructs. A computational homogenization approach was adopted, based on the concept of a periodic representative volume element. Local transport and immobilization of newly synthesized matrix components were described. Mechanical properties were taken dependent on the local matrix concentration and subsequently the global aggregate modulus and hydraulic permeability were derived. The transport parameters were varied to assess the effect of the evolving matrix distribution during culture. The results indicate that the overall stiffness and permeability are to a large extent insensitive to differences in local matrix distribution. This emphasizes the need for caution in the visual interpretation of tissue functionality from histology and underlines the importance of complementary measurements of the matrixs intrinsic molecular organization.     

Design of scaffolds for blood vessel tissue engineering using a multi-layering electrospinning technique

Aiming to develop a scaffold architecture mimicking morphological and mechanically that of a blood vessel, a sequential multi-layering electrospinning (ME) was performed on a rotating mandrel-type collector. A bi-layered tubular scaffold composed of a stiff and oriented PLA outside fibrous layer and a pliable and randomly oriented PCL fibrous inner layer (PLA/PCL) was fabricated. Control over the level of fibre orientation of the different layers was achieved through the rotation speed of the collector. The structural and mechanical properties of the scaffolds were examined using scanning electron microscopy (SEM) and tensile testing. To assess their capability to support cell attachment, proliferation and migration, 3T3 mouse fibroblasts and later human venous myofibroblasts (HVS) were cultured, expanded and seeded on the scaffolds. In both cases, the cell-polymer constructs were cultured under static conditions for up to 4 weeks. Environmental-scanning electron microscopy (SEM), confocal laser scanning microscopy (CLSM), histological examination and biochemical assays for cell proliferation (DNA) and extracellular matrix production (collagen and glycosaminoglycans) were performed. The findings suggest the feasibility of ME to design scaffolds with a hierarchical organization through a layer-by-layer process and control over fibre orientation. The resulting scaffolds achieved the desirable levels of pliability (elastic up to 10% strain) and proved to be capable to promote cell growth and proliferation. The electrospun PLA/PCL bi-layered tube presents appropriate characteristics to be considered a candidate scaffold for blood vessel tissue engineering.     

Relation between Hypofractionated Radiotherapy,Toxicity and Outcome in Early Breast Cancer

To compare adjuvant conventional radiotherapy (C‐RT) to hypofractionated schedule (HF‐RT) in early breast cancer. Between May 2012 and September 2015, 120 patients were included in the analysis. All patients underwent conservative surgery and adjuvant RT. RT was delivered in C‐RT (50 Gy; 2 Gy/fr) or HF‐RT (42.5 Gy; 2.66 Gy/fr), followed by a tumor bed boost (10 Gy; 2 Gy/fr). RT‐induced toxicity was recorded and compared between groups. Toxicity results were graded according to the Common Terminology Criteria for Adverse Events guidelines. A multivariate analysis was performed of the factors associated with acute toxicity onset. Mild acute skin toxicity was observed in 71.7% of patients. No grade 4 toxicity was observed. From the multivariate analysis, Breast volume and RT fractionation significantly affected acute radiation‐related toxicity. No increase in late toxic effects has been reported between C‐RT and HF‐RT schedules. Overall, the 2‐year disease free survival was 94.4%. HF‐RT represents a valid adjuvant treatment option in early breast cancer patients, without negative impact on acute and late radiation sequelae, as well as tumor control.     

The influence of endothelial cells on the ECM composition of 3D engineered cardiovascular constructs

Tissue engineering of small diameter (<5 mm) blood vessels is a promising approach to develop viable alternatives for autologous vascular grafts. Development of a functional, adherent, shear resisting endothelial cell (EC) layer is one of the major issues limiting the successful application of these tissue engineered grafts. The goal of the present study was to create a confluent EC layer on a rectangular 3D cardiovascular construct using human venous cells and to determine the influence of this layer on the extracellular matrix composition and mechanical properties of the constructs. Rectangular cardiovascular constructs were created by seeding myofibroblasts (MFs) on poly(glycolic acid) poly-4-hydroxybutyrate scaffolds using fibrin gel. After 3 or 4 weeks, ECs were seeded and co-cultured using EGM-2 medium for 2 or 1 week, respectively. A confluent EC layer could be created and maintained for up to 2 weeks. The EGM-2 medium lowered the collagen production by MFs, resulting in weaker constructs, especially in the 2 week cultured constructs. Co-culturing with ECs slightly reduced the collagen content, but had no additional affect on the mechanical performance. A confluent endothelial layer was created on 3D human cardiovascular constructs. The layer was co-cultured for 1 and 2 weeks. Although, the collagen production of the MFs was slightly lowered, co-culturing ECs for 1 week results in constructs with good mechanical properties and a confluent EC layer.