Autologous Cell Therapies for Bone Tissue Regeneration

The healing potential of bone is sufficient to restore simple fractures, which are generally treated by standard conservative or surgical therapy. However, in some cases, reparative osteogenesis does not result in structural and functional recovery of the bone. Extended bone defects following trauma or cancer resection or non-unions of fractures may require more sophisticated treatment. In these cases, bone grafting procedures, segmental bone transport, distraction osteogenesis or biomaterials are applied for reconstruction

Comparative effectiveness of loop diuretics on mortality in the treatment of patients with chronic heart failure – a multicenter propensity score matched analysis

Background: Loop diuretics are given to the majority of patients with chronic heart failure (HF). Whether the different pharmacological properties of the three guideline-recommended loop diuretics result in differential effects on survival is unknown. Methods: 6293 patients with chronic HF using either bumetanide, furosemide or torasemide were identified in three European HF registries. Patients were individually matched on both the respective propensity scores for receipt of the individual drug and dose-equivalents thereof. Results: During a follow-up of 35,038 patient-years, 652 (53.7%), 2179 (51.9%), and 268 (30.4%) patients died amongst those prescribed bumetanide, furosemide, and torasemide, respectively. In univariable analyses of the general sample, bumetanide and furosemide were both associated with higher mortality as compared with torasemide treatment (HR 1.50, 95% CI 1.31–1.73, p < 0.001, and HR 1.34, CI 1.18–1.52, p < 0.001, respectively). Mortality was higher in bumetanide users when compared to furosemide users (HR 1.11, 95% CI 1.02–1.20, p = 0.01). However, there was no significant association between loop diuretic choice and all-cause mortality in any of the matched samples (bumetanide vs. furosemide, HR 1.03, 95% CI 0.93–1.14, p = 0.53; bumetanide vs. torasemide, HR 0.98, 95% CI 0.78–1.24, p = 0.89; furosemide vs. torasemide, HR 1.02, 95% CI 0.84–1.24, p = 0.82). The results were confirmed in subgroup analyses with respect to age, sex, left ventricular ejection fraction, NYHA functional class, cause of HF, rhythm, and systolic blood pressure. Conclusions: In patients with HF, mortality is not affected by the choice of individual loop diuretics

Facile access to potent antiviral quinazoline heterocycles with fluorescence properties via merging metal-free domino reactions

Most of the known approved drugs comprise functionalized heterocyclic compounds as subunits. Among them, non-fluorescent quinazolines with four different substitution patterns are found in a variety of clinically used pharmaceuticals, while 4,5,7,8-substituted quinazolines and those displaying their own specific fluorescence, favourable for cellular uptake visualization, have not been described so far. Here we report the development of a one-pot synthetic strategy to access these 4,5,7,8-substituted quinazolines, which are fluorescent and feature strong antiviral properties (EC$_{50}$ down to 0.6±0.1 μM) against human cytomegalovirus (HCMV). Merging multistep domino processes in one-pot under fully metal-free conditions leads to sustainable, maximum efficient and high-yielding organic synthesis. Furthermore, generation of artesunic acid–quinazoline hybrids and their application against HCMV (EC$_{50}$ down to 0.1±0.0 μM) is demonstrated. Fluorescence of new antiviral hybrids and quinazolines has potential applications in molecular imaging in drug development and mechanistic studies, avoiding requirement of linkage to external fluorescent markers

Covalent binding of heparin to functionalized PET materials for improved haemocompatibility

The hemocompatibility of vascular grafts made from poly(ethylene terephthalate) (PET) is insufficient due to the rapid adhesion and activation of blood platelets that occur upon incubation with whole blood. PET polymer was treated with NHx radicals created by passing ammonia through gaseous plasma formed by a microwave discharge, which allowed for functionalization with amino groups. X-ray photoelectron spectroscopy characterization using derivatization with 4-chlorobenzaldehyde indicated that approximately 4% of the –NH2 groups were associated with the PET surface after treatment with the gaseous radicals. The functionalized polymers were coated with an ultra-thin layer of heparin and incubated with fresh blood. The free-hemoglobin technique, which is based on the haemolysis of erythrocytes, indicated improved hemocompatibility, which was confirmed by imaging the samples using confocal optical microscopy. A significant decrease in number of adhered platelets was observed on such samples. Proliferation of both human umbilical vein endothelial cells and human microvascular endothelial cells was enhanced on treated polymers, especially after a few hours of cell seeding. Thus, the technique represents a promising substitute for wet-chemical modification of PET materials prior to coating with heparin

Psychometrische Überprüfung eines Klinikkultur-Fragebogens (KKF-15)

Zunehmend wird in der Gesundheitsversorgung erkannt, dass organisationale Merkmale wie die Klinikkultur den Behandlungserfolg beeinflussen. Da kein deutschsprachiger Fragebogen zur Erfassung von diesem Aspekt in der Gesundheitsversorgung existierte, wurde angelehnt an die „Kurzskala zur Erfassung der Unternehmenskultur (KUK)” der Klinikkultur-Fragebogen (KKF-15) entwickelt. Ziel dieser Arbeit ist die Evaluierung des Klinikkultur-Fragebogens sowohl auf der Item- als auch der Skalenebene. Verschiedene Itemkonfigurationen wurden an einer Stichprobe von 272 Mitarbeitern mittels einer strukturanalytischen Modellierung überprüft. Dabei zeigte sich für die drei- und vierfaktorielle Struktur die beste Passung, so dass die vierfaktorielle Lösung analog der KUK ausgewählt wurde. Die hohe Interkorrelation zwischen den beiden Faktoren ‚Zusammenarbeit’ und ‚Führung’ erfordert einen Faktor zweiter Ordnung ‘Interaktion’. Die Reliabilität war für alle Skalen gut und die Konstruktvalidität des Fragebogens wurde belegt. Weitere vertiefende Untersuchungen stehen noch aus. </jats:p

Covalent Binding of Heparin to Functionalized PET Materials for Improved Haemocompatibility

The hemocompatibility of vascular grafts made from poly(ethylene terephthalate) (PET) is insufficient due to the rapid adhesion and activation of blood platelets that occur upon incubation with whole blood. PET polymer was treated with NHx radicals created by passing ammonia through gaseous plasma formed by a microwave discharge, which allowed for functionalization with amino groups. X-ray photoelectron spectroscopy characterization using derivatization with 4-chlorobenzaldehyde indicated that approximately 4% of the –NH2 groups were associated with the PET surface after treatment with the gaseous radicals. The functionalized polymers were coated with an ultra-thin layer of heparin and incubated with fresh blood. The free-hemoglobin technique, which is based on the haemolysis of erythrocytes, indicated improved hemocompatibility, which was confirmed by imaging the samples using confocal optical microscopy. A significant decrease in number of adhered platelets was observed on such samples. Proliferation of both human umbilical vein endothelial cells and human microvascular endothelial cells was enhanced on treated polymers, especially after a few hours of cell seeding. Thus, the technique represents a promising substitute for wet-chemical modification of PET materials prior to coating with heparin

3-Dimensional Porous Nanocomposite Scaffolds Based on Cellulose Nanofibers for Cartilage Tissue Engineering

Fully bio-based three-dimensional porous scaffold for cartilage repair was prepared via freeze-drying where cellulose nanofibers, which were cytocompatible, were used as mechanical reinforcement (70-90 wt%) in a matrix of gelatin and chitosan (9:1) and crosslinked using genipin. Morphology studies showed that the scaffolds had interconnected pores with favorable pore diameters (< 250 μm) for cell growth. Compression modulus of the scaffolds (1-3 MPa) at room conditions was in the range for natural cartilage and decreased significantly (0.03-0.05 MPa) in phosphate buffered saline (PBS) at 37°C. The high PBS uptake shown by the scaffolds (< 3000 wt%) was attributed to liquid trapped in the pores during immersion in PBS. Furthermore, the scaffolds showed good cytocompatibility towards chondrocytes, which attached and proliferated properly. The scaffolds are considered to have potential in cartilage tissue engineering due to high porosity (≈ 95%) and good mechanical performance that promote cell attachment and extracellular matrix (ECM) production.Validerad; 2016; Nivå 2; 20140922 (narnas

Design and evaluation of an IPE module at the beginning of professional training in medicine, nursing, and physiotherapy

Aim: Interprofessional education (IPE) is a central feature of modern education in the health care professions. Despite this, empirically founded and systematically structured IPE courses are absent from many curricula. To answer the WHO’s call for improved interprofessional collaboration in the health care system, a seminar was designed, implemented and evaluated. The target group consisted of students beginning nursing and medical studies (first and second semesters) and physiotherapy students (first year of training).The aim was to develop a basic IPE module focusing not only on the demands placed by academia and politics, but also the interests of the target group. This module was evaluated on the basis of the modified four-level Kirkpatrick approach.Method: Based on focus group interviews analyzed qualitatively using Mayring’s content analysis, it was possible to define five learning objectives and develop four practice-oriented modules. The seminar was then implemented and evaluated using written pre- and post-seminar evaluations and group discussions.Results: Analysis confirmed the success of the IPE concept in that the seminar was positively rated by attendees not only in terms of their immediate reactions, but also attitude, knowledge and skills according to Kirkpatrick.Conclusion: In the future, it is intended to offer the IPE module on a permanent basis and assess the competencies acquired in the seminar using observation. Courses to ensure sustained learning outcomes would also be desirable