Recent advances in experimental testing and computational modelling for characterisation of mechanical properties of biomaterials and biological cells

Biomaterials and biological cells possess a number of different properties; amongst them, mechanical properties are extremely important in studies and applications about tissue engineering, design and development of implants, surgical tools and medical devices for treatments and diagnosis of diseases. Changes in mechanical properties such as a stiffness of cells are often the signs of changes in cell physiology or diseases in tissues; and studying these changes can lead to the development of devices for early disease detection and new drug delivery mechanisms. This paper presents advances in recent years in experimental testing and computational modelling for characterisation of mechanical properties of biomaterials and biological cells, in which the presented research projects and related studies were mainly implemented by research groups in the UK. The recent important findings as well as research directions and challenges are emphasised and discussed, to open channels for research collaborations in development of cost-effective medical diagnosis and treatment solutions

Persönlichkeitsentwicklung und Leistungsbereitschaft junger Arbeiter in Jugendbrigaden

Es werden zusammenfassende Auswertungen von empirischen Untersuchungen zu den Jugendbrigaden in der DDR gegeben. Behandelt werden Leistungsmotivation, Einstellung zum wissenschaftlich-technischen Fortschritt, Beteiligung und Einstellung zur MMM ("Messe der Meister von morgen"), FDJ-Aktivitäten, Freizeit sowie Probleme der Förderung und Bildung von Jugendbrigaden. Hintergrund der Untersuchungen war die Situation, daß es mit den geburtenschwachen Jahrgängen immer schwieriger wurde, Jugendbrigaden in dem gewünschten Ausmaß zu erhalten. Es wird kritisiert, daß Jugendbrigaden vielerorts "formalistischer Selbstzweck" geworden seien und sie daher ungeeignet seien, die Leistungsbereitschaft zu stimulieren oder politisches Verantwortungsgefühl zu fördern. (psz

Ectopic internal carotid artery presenting as an oropharyngeal mass

Ectopic internal carotid artery (ICA) is a very rare variation. The major congenital abnormalities of the ICA can be classified as agenesis, aplasia and hypoplasia, and they can be unilateral or bilateral. Anomalies of the neck artery may be vascular neoplasms or ectopic position. Carotid angiograms provide absolute confirmation of an aberrant carotid artery, while EcoColorDoppler (ECD) gives also important information about the evaluation of carotid vassels. Nevertheless Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) of the neck provide spatial information about the adjacent pharyngeal anatomy and are less invasive than angiogram. Injuries to the ICA during simple pharyngeal surgical procedures can be catastrophic due to the risk of massive bleeding. We report a case of a 56 year-old male patient suffering from dysphagia associated with aberrant ICA manifesting itself as a pulsative protruding of the left lateral wall of the oropharynx

Multi-detector row computed tomography (MDCT) and magnetic resonance imaging (MRI) in the evaluation of the mandibular invasion by squamous cell carcinomas (SCC) of the oral cavity. Correlation with pathological data

<p>Abstract</p> <p>Background</p> <p>To retrospectively compare the diagnostic accuracy of magnetic resonance imaging (MRI) and multidetector-row computed tomography (MDCT) in the assessment of the mandibular invasion by squamous cell carcinoma (SCC) having histopathological exams as standard of reference.</p> <p>Materials and methods</p> <p>Institutional review board approval with a waiver of informed patient consent was obtained. Of the 147 patients selected from our database who underwent surgical excision of a tumour arising into the oral cavity, thirty-six patients (26 men, 10 women; mean age, 56 years; range, 30-75 years) with hystologically proven SCC who performed both a preoperative MRI and MDCT, composed our final study population.</p> <p>Images were qualitatively analyzed in consensus by two expert radiologist in head and neck imaging. Sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) were assessed for both MRI and MDCT.</p> <p>Differences in sensitivity, specificity, positive and negative predictive values were calculated at a statistical significance of p < .05.</p> <p>Results</p> <p>The sensitivity, the specificity and the accuracy of MRI and MDCT in the detection of the mandibular involvement were respectively 93%, 82%, 86% and 79%, 82%, 81%, while the positive predictive value (PPV) and negative predictive value (NPV) were respectively 76%, 95% and 73%, 86%. There wasn't any statistically significant difference in overall diagnostic accuracy between MRI and MDCT in the evaluation of mandibular tumour invasion (p > .05).</p> <p>Conclusion</p> <p>MRI showed to have a higher sensitivity compare to MDCT in the assessment of mandibular involvement from SCC arising in the oral cavity although none statistically significant differences were noted.</p

Potential drug interactions and duplicate prescriptions among ambulatory cancer patients: a prevalence study using an advanced screening method

<p>Abstract</p> <p>Background</p> <p>The pharmacotherapeutic treatment of patients with cancer is generally associated with multiple side-effects. Drug interactions and duplicate prescriptions between anti-cancer drugs or interactions with medication to treat comorbidity can reinforce or intensify side-effects.</p> <p>The aim of the present study is to gain more insight into the prevalence of drug interactions and duplicate prescriptions among patients being treated in the outpatient day care departments for oncology and hematological illnesses. For the first time the prevalence of drug interactions with OTC-drugs in cancer patients will be studied. Possible risk factors for the occurrence of these drug-related problems will also be studied.</p> <p>Methods/Design</p> <p>A multicenter cross-sectional observational study of the epidemiology of drug interactions and duplicate prescriptions is performed among all oncology and hemato-oncology patients treated with systemic anti-cancer drugs at the oncology and hematology outpatient day care department of the VU University medical center and the Zaans Medical Center.</p> <p>Discussion</p> <p>In this article the prevalence of potential drug interactions in outpatient day-care patients treated with anti-cancer agents is studied using a novel more extensive screening method. If this study shows a high prevalence of drug interactions clinical pharmacists and oncologists must collaborate to develop a pharmaceutical screening programme, including an automated electronic warning system, to support drug prescribing for ambulatory cancer patient. This programme could minimize the occurrence of drug related problems such as drug interactions and duplicate prescriptions, thereby increasing quality of life.</p> <p>Trial registration</p> <p>This study is registered, number NTR2238.</p

Potential Impact of Benzodiazepine Use on the Rate of Hip Fractures in Five Large European Countries and the United States

Benzodiazepine use increases the risk of falls and has been associated with an increased risk of hip fractures. Our aim was to estimate the possible population impact of the use of benzodiazepines on the rate of hip fracture in France, Germany, Italy, Spain, the United Kingdom, and the United States. We conducted a literature review to estimate the pooled relative risk (RR) for hip fractures and use of benzodiazepines. Prevalence rates of benzodiazepine use in 2009 were calculated for each country using the IMS MIDAS database and three public databases in Denmark, the Netherlands, and Norway. Both the RR and prevalence rates were used for calculation of population attributable risks (PARs) of hip fractures associated with benzodiazepine use. The literature review showed an increased risk of hip fractures in benzodiazepine users (RR = 1.4, 95 % CI 1.2–1.6). Rate of benzodiazepine use showed considerable differences between countries, ranging from 4.7 % to 22.3 % of population ever in a 1-year period. These are reflected in results for the PARs; estimated attributions of benzodiazepines to the rate of hip fractures were 1.8 %, 95 % CI 1.1–2.6 (Germany); 2.0 %, 95 % CI 1.2–2.8 (United Kingdom); 5.2 %, 95 % CI 3.2–7.3 (Italy); 7.4 %, 95 % CI 4.5–10.0 (France); 8.0 %, 95 % CI 4.9–11.0 (United States); and 8.2 %, 95 % CI 5.1–12.0 (Spain). PAR estimates suggest that the potential attribution of benzodiazepine use on the population rate of hip fractures in the five specified European countries and the United States varies between 1.8 % and 8.2 %. During the next phase of the IMI-PROTECT study, a comparison with individual patient data will show whether this approach is valid

Sustained Delivery of Activated Rho GTPases and BDNF Promotes Axon Growth in CSPG-Rich Regions Following Spinal Cord Injury

Background: Spinal cord injury (SCI) often results in permanent functional loss. This physical trauma leads to secondary events, such as the deposition of inhibitory chondroitin sulfate proteoglycan (CSPG) within astroglial scar tissue at the lesion. Methodology/Principal Findings: We examined whether local delivery of constitutively active (CA) Rho GTPases, Cdc42 and Rac1 to the lesion site alleviated CSPG-mediated inhibition of regenerating axons. A dorsal over-hemisection lesion was created in the rat spinal cord and the resulting cavity was conformally filled with an in situ gelling hydrogel combined with lipid microtubes that slowly released constitutively active (CA) Cdc42, Rac1, or Brain-derived neurotrophic factor (BDNF). Treatment with BDNF, CA-Cdc42, or CA-Rac1 reduced the number of GFAP-positive astrocytes, as well as CSPG deposition, at the interface of the implanted hydrogel and host tissue. Neurofilament 160kDa positively stained axons traversed the glial scar extensively, entering the hydrogel-filled cavity in the treatments with BDNF and CA-Rho GTPases. The treated animals had a higher percentage of axons from the corticospinal tract that traversed the CSPG-rich regions located proximal to the lesion site. Conclusion: Local delivery of CA-Cdc42, CA-Rac1, and BDNF may have a significant therapeutic role in overcoming CSPGmediate

[Cost]effectiveness of withdrawal of fall-risk increasing drugs versus conservative treatment in older fallers: design of a multicenter randomized controlled trial (IMPROveFALL-study)

Background: Fall incidents represent an increasing public health problem in aging societies worldwide. A major risk factor for falls is the use of fall-risk increasing drugs. The primary aim of the study is to compare the effect of a structured medication assessment including the withdrawal of fall-risk increasing drugs on the number of new falls versus 'care as usual' in older adults presenting at the Emergency Department after a fall. Methods/Design. A prospective, multi-center, randomized controlled trial will be conducted in hospitals in the Netherlands. Persons aged 65 years who visit the Emergency Department due to a fall are invited to participate in this trial. All patients receive a full geriatric assessment at the research outpatient clinic. Patients are randomized between a structured medication assessment including withdrawal of fall-risk increasing drugs and 'care as usual'. A 3-monthly falls calendar is used for assessing the number of falls, fallers and associated injuries over a one-year follow-up period. Measurements will be at three, six, nine, and twelve months and include functional outcome, healthcare consumption, socio-demographic characteristics, and clinical information. After twelve months a second visit to the research outpatient clinic will be performed, and adherence to the new medication regimen in the intervention group will be measured. The primary outcome will be the incidence of new falls. Secondary outcome measurements are possible health effects of medication withdrawal, health-related quality of life (Short Form-12 and EuroQol-5D), costs, and cost-effectiveness of the intervention. Data will be analyzed using an intention-to-treat analysis. Discussion. The successful completion of this trial will provide evidence on the effectiveness of withdrawal of fall-risk increasing drugs in older patients as a method for falls reduction. Trial Registration. The trial is registered in the Netherlands Trial Register (NTR1593)

Assessing the Permeability of Engineered Capillary Networks in a 3D Culture

Many pathologies are characterized by poor blood vessel growth and reduced nutrient delivery to the surrounding tissue, introducing a need for tissue engineered blood vessels. Our lab has developed a 3D co-culture method to grow interconnected networks of pericyte-invested capillaries, which can anastamose with host vasculature following implantation to restore blood flow to ischemic tissues. However, if the engineered vessels contain endothelial cells (ECs) that are misaligned or contain wide junctional gaps, they may function improperly and behave more like the pathologic vessels that nourish tumors. The purpose of this study was to test the resistance to permeability of these networks in vitro, grown with different stromal cell types, as a metric of vessel functionality. A fluorescent dextran tracer was used to visualize transport across the endothelium and the pixel intensity was quantified using a customized MATLAB algorithm. In fibroblast-EC co-cultures, the dextran tracer easily penetrated through the vessel wall and permeability was high through the first 5 days of culture, indicative of vessel immaturity. Beyond day 5, dextran accumulated at the periphery of the vessel, with very little transported across the endothelium. Quantitatively, permeability dropped from initial levels of 61% to 39% after 7 days, and to 7% after 2 weeks. When ECs were co-cultured with bone marrow-derived mesenchymal stem cells (MSCs) or adipose-derived stem cells (AdSCs), much tighter control of permeability was achieved. Relative to the EC-fibroblast co-cultures, permeabilities were reduced 41% for the EC-MSC co-cultures and 50% for the EC-AdSC co-cultures after 3 days of culture. By day 14, these permeabilities decreased by 68% and 77% over the EC-fibroblast cultures. Co-cultures containing stem cells exhibit elevated VE-cadherin levels and more prominent EC-EC junctional complexes when compared to cultures containing fibroblasts. These data suggest the stromal cell identity influences the functionality and physiologic relevance of engineered capillary networks