Albumin-heparin matrices loaded with growth factor as substrates for endothelial cell seeding

The research described in this thesis is focused on the synthesis and evaluation of a vascular graft coating consisting of albumin and the anticoagulant heparin (alb-hep conjugate), which may fulfill the above mentioned requirements. Previous research demonstrated that coating of surfaces with alb-hep conjugates improves blood compatibility of graft surfaces. Moreover, a number of adhesive proteins such as cellular fibronectin have binding sites for heparin, and may therefore mediate the binding of ECs to the alb-hep conjugate coating. In the present model study, polystyrene is modified by gas plasma treatment to generate chemical groups at the surface which are used to covalently immobilize the alb-hep conjugate. The coupling chemistry and the stability of the coatings have been investigated. Subsequently, this substrate (either with or without added fibronectin) was tested for its capability to allow adherence and proliferation of ECs. Moreover, the effect of basic fibroblast growth factor (bFGF), loaded onto surface-immobilized alb-hep conjugate, on the proliferation of seeded ECs has been studied. Next, blood compatibility of surfaces coated with alb-hep conjugate is reported, as well as the effect of seeded ECs on platelet deposition to these substrates. In addition, blood compatibility of crosslinked gels of albumin and heparin, adhesion and proliferation of ECs on these substrates, as well as the effect of seeded ECs on platelet deposition have been investigated. Finally, the isolation and characterization of microvascular ECs from adipose tissue are reported, as well as their culture on surface-immobilized alb-hep conjugate

Ibn Al-Jazzar On Sexual Diseases

First published in 1997. Routledge is an imprint of Taylor & Francis, an informa company

Ibn Al-Jazzar On Fevers

First published in 2000. Routledge is an imprint of Taylor & Francis, an informa company

Quantifying “Pillarization”:Extracting Political History from Large Databases of Digitized Media Collections

We analyzed long-term dynamic developments in newspaper content in connection with the process of pillar- ization (the segmentation of Dutch society and politics along religious/ideological cleavages) over the period 1918– 1967. One of the main characteristics of the historical debate on this phenomenon is an alleged close connection of political and media organizations on personnel, organizational and content-driven levels. In the political commu- nication debate, this raises the question about the relationship between ‘politization of media’ and ‘mediatization of politics’. Our preliminary study shows how patterns in the interactive relation between politics and newspapers can be further unraveled, by analyzing data based on the digitized newspaper collection of the Royal Dutch Library and related digitized political historical sources (parliament, parties, biographical material). In particular, it shows differences between Socialist and Catholic approaches towards the pillarized culture of “the other” and themselves. Whereas the Socialist pillar mainly focused on the politics and socio-economics of both their own and other groups, we find that the Catholic pillar was more inclined towards cultural and organizational self-reference

Meten van verzuilde politiek in de media:Een digitale benadering van katholieke en sociaaldemocratische dagbladen, 1918-1967

Sinds het einde van de vorige eeuw houden mediahistorici zich meer bezig met de manier waarop media-inhoud tot stand is gekomen en welke betekenis dat heeft gehad voor publieksgroepen en maatschappelijk-politieke realiteiten. In dit artikel wordt gepoogd deze benadering te combineren met digital history, aan de hand van het verzuilingsdebat en gebruik makend van de digitale krantencollectie van de Koninklijke Bibliotheek van Nederland. Enerzijds wordt onderzocht in hoeverre de veronderstelde ideologische gebondenheid van dagbladen in de jaren 1918-1967 zichtbaar wordt in de hoeveelheid kopij waarmee katholieke en sociaaldemocratische kranten over politiek hebben bericht en hoe verschillen daarin te verklaren zijn. Anderzijds wordt door het testen van kwantitatieve methoden uit de digital humanities geprobeerd een bijdrage te leveren aan digitale bronnenkritiek voor historisch onderzoek. Since the end of the last century media historians have taken an interest in researching the origins and development of media content and its significance for audiences and socio-political realities. This article seeks to combine this approach with digital history. It does so by focusing on the pillarisation debate and by utilising the digital newspaper collection of the National Library of the Netherlands. On the one hand, this article investigates to what extent the ideological background of the Catholic and Social Democratic press is actually reflected in the number of newspaper articles reporting on politics written between 1918-1967, and how any differences can be explained. On the other hand, by testing quantitative methods from the digital humanities, the article attempts to contribute to digital source criticism for historical research

Daily fluctuations of negative affect are only weakly associated with tremor symptoms in functional and organic tremor patients

BACKGROUND: There is a long-standing research history on the presumed psychological origin of functional movement disorders. Most studies do not address the heterogeneity in functional movement disorders and do not distinguish between risk factors, causes and consequences. We studied the associations between negative affect and objective as well as subjective symptom levels in patients with functional and organic tremor. METHODS: Thirty-three patients with a functional (14) or organic tremor (19) completed a web-based diary on subjective symptom burden and negative affect, five times a day for 30 days (total number of observations = 4759). During the same period, the participants wore an accelerometer to objectively record tremor. Vector autoregressive modelling was used to determine the time-lagged and contemporaneous associations between negative affect and objective/subjective tremor symptoms, both on an individual and a group level. RESULTS: In contrast to previous literature, patients with a functional or organic tremor showed a weak contemporaneous association between negative affect and objective/subjective tremor symptoms (on average r = 0.038 and 0.174 respectively). Time-lagged associations between negative affect and objective/subjective tremor symptoms were mixed in effect and direction and only present in a subset of patients, with no differences between patients with functional or organic tremor. CONCLUSIONS: Negative affect is only weakly associated with objective/subjective tremor symptoms, both on the contemporaneous and time-lagged associations, and these associations were mainly similar between patients with functional or organic tremor. These results argue against a strong influence of daily stress on tremor symptoms in patients with a functional or organic tremor

A comparison of treatment allocation and survival between younger and older patients with HER2-overexpressing de novo metastatic breast cancer

Introduction: There have been several developments in the treatment of HER2-overexpressing metastatic breast cancer. However, pivotal trials mainly included younger and healthier patients, resulting in a lack of information about the benefits and harms of treatment for most older patients. The aim of this study was to provide an overview of the differences in treatment allocation and survival outcomes over time between younger and older patients with HER2-overexpressing metastatic breast cancer. Materials and Methods: All patients from the Netherlands Cancer Registry with de novo metastatic breast cancer between 2005 and 2021 were included. Patients were divided into three age groups: &lt;65, 65–74, and ≥ 75 years. Changes in treatment allocation were graphically depicted over time. Cox proportional hazard models were used to calculate overall survival and Poisson models for relative survival. Results: Overall, 2,722 patients were included. Between 2005 and 2021, the use of targeted therapy as first-line treatment increased for all age groups (&lt;65 years from 33.8% to 90.6%, p &lt; 0.001; 65–74 years from 29.2% to 86.5%, p = 0.001; ≥75 years from 4.3% to 55.8%, p &lt; 0.001). Use of chemotherapy as first-line treatment also increased for all age groups (&lt;65 years from 73.5% to 89.8%, p &lt; 0.001; 65–74 years from 50.0% to 78.4%, p = 0.01; ≥75 years from 8.7% to 37.2%, p = 0.04). Although not statistically significant, the use of endocrine therapy, both as monotherapy and in combination with targeted therapy in the first line, decreased (&lt;65 years 19.1% to 5.5%, p &lt; 0.001; 65–74 years 25.0% to 13.5%, p = 0.03; ≥75 years 65.2% to 37.2%, p = 0.16). Changes in relative and overall survival were similar and improved in all age groups, but most in the youngest age group (relative excess risk [RER] 0.93, 95% confidence interval [CI] 0.91–0.94 per year, p &lt; 0.001), and least in patients ≥75 (RER 0.96, 95% CI 0.93–0.98 per year, p = 0.001). Discussion: The use of first-line chemotherapy and targeted therapy increased in all age groups, while the use of endocrine therapy decreased over time. Nevertheless, the uptake of chemotherapy and targeted therapies was substantially slower in the oldest age group. Overall survival and relative survival improved for all age groups, but these improvements were smaller in the older age groups.</p

Presence of HIF-1 and related genes in normal mucosa, adenomas and carcinomas of the colorectum

Expression of the transcription factor hypoxia-inducible factor 1 (HIF-1), which plays a key role in cellular adaptation to hypoxia, was investigated in normal colorectal mucosa (ten), adenomas (61), and carcinomas (23). Tissue samples were analyzed for HIF-1α, its upstream regulators, von Hippel–Lindau factor, AKT, and mammalian target of rapamycin (mTOR) and its downstream targets glucose transporter 1 (GLUT1), carbonic anhydrase IX, stromal-cell-derived factor 1 (SDF-1) by immunohistochemistry. In normal colorectal mucosa, HIF-1α was observed in almost all nuclei of surface epithelial cells, probably secondary to a gradient of oxygenation, as indicated by pimonidazole staining. The same staining pattern was present in 87% of adenomas. In carcinomas, HIF-1α was present predominantly around areas of necrosis (78%). Active AKT and mTOR, were present in all adenomas, carcinomas, and in normal colorectal mucosa. GLUT1 and SDF-1 were present in the normal surface epithelium of all adenoma cases, whereas in the carcinoma GLUT1 was located around necrotic regions and SDF-1 was present in all epithelial cells. In conclusion, HIF-1α appears to be physiologically expressed in the upper part of the colorectal mucosa. The present observations support that upregulation of HIF-1α and its downstream targets GLUT1 and SDF-1 in colorectal adenomas and carcinomas may be due to hypoxia, in close interaction with an active phosphatidylinositol 3-kinases–AKT–mTOR pathway