Experimental treatment modalities for osteosarcoma: Preclinical studies on virotherapy, chemotherapy and small molecule therapy

Kaspers, G.J.L. [Promotor]Wuisman, P.I.J.M. [Promotor]Beusechem, V.W. van [Copromotor]Carette, J. [Copromotor

A longitudinal study on the persistence of Livestock Associated-MRSA in swine herds

In recent years, a new type of MRSA, now called livestock-associated MRSA (LA-MRSA), belonging to the clonal complex (CC) 398, has globally emerged in swine world wide. Aim of this study was to gain more insight into the persistence of LA-MRSA in different types of pig farms over a period of two years. To investigate this, 15 MRSA-positive herds from a previous study were selected; an additional pig farm was selected because this one was found to be positive with a human MRSA-strain. Starting in September 2009, five dust samples were collected every two months. Samples were analysed for MRSA and spa-typing was done to confirm that MRSA isolates belonged to CC398 and to gain insight into persistence of strains within a farm. Three herds were positive on all sampling occasions and were consistently contaminated with LA-MRSA. In the remaining herds, occasionally no positive dust samples were found at some sampling moments. The predominating spa -types were t011 and t108. A maximum of 5 different spa-types were found in two herds, with 3 different spa-types present in one sampling, indicating multiple introductions. These results show that LA-MRSA remains present on a pig farm over a long period. Most likely, transmission within the herd occurs after initial introduction, and an endemic situation seems to be the endpoint. The relatively low sensitivity of dust sampling compared to sampling of animals, the small sample size and lack of strict standardization of dust sampling might explain occasional negative samplings in overall positive herds. However, a true change of a positive MRSA-status to a negative status, followed by re-introduction cannot be ruled out in our study design

Transmission and quantification of verocytotoxin-producing Escherichia coli O157 in dairy cattle and calves

Data from a field study of 14 months duration in a naturally colonized dairy herd and data from an experiment with calves were used to quantify transmission of verocytotoxin-producing Escherichia coli (VTEC O157) in cattle. For the latter, two groups of 10 calves were randomly assigned and put out in one of two pastures. From each group, five animals were experimentally inoculated with 109 c.f.u. O157 VTEC and, considered infectious, put back in their group. Each of the susceptible contact calves became positive within 6 days of being reunited. The estimate of the basic reproduction ratio (R0) in the experiment was 7·3 (95% CI 3·92¿11·5), indicating that each infectious calf will infect seven other calves on average during an assumed infectious period of 28 days in a fully susceptible population. The R0 among dairy cows appeared to be about 10 times lower (0·70, 95% CI 0·48¿1·04). After the transmission experiment, six contact-infected animals that were shedding continuously during the experiment were housed in a tie stall during winter. After 40 days, all six tested negative for O157 VTEC. In June, after a period of 34 weeks in which the heifers remained negative, they were put out in a clean and isolated pasture to observe whether they started shedding again. On each pasture that was infected with O157 VTEC during the transmission experiment the previous summer, newly purchased susceptible calves were placed. None of the heifers or calves started shedding during 14 weeks, indicating that both the heifers and the previously contaminated pasture did not function as reservoir of O157 VTE

Prevalentie van angst en agressie in de Nederlandse populatie Rottweilers

Om de mate van angst en agressie bij Rottweilers vast te stellen zijn in deze pilotstudy de volgende onderzoeksvragen beantwoord: - Wat is de prevalentie van angst en agressie in de Nederlandse populatie van zowel raszuivere Rottweilers als look-a-likes?; - Is er verschil in de prevalentie van angst en agressie tussen de populatie raszuivere Rottweilers en de populatie look-a-likes

Роль международной мобильности ученых на разных этапах истории науки Украины

В статье освещается эволюция международного сотрудничества ученых Украины с зарубежными исследователями. Продемонстрировано огромное влияние стажировки отечественных ученых в крупнейших научных центрах мира, совместных исследований с зарубежными исследователями для становления науки в Украине, развития сети научных учреждений и высших учебных заведений. Охарактеризовано основные тенденции международного сотрудничества ученых Национальной академии наук и миграции научных работников в последние десятилетия.У статті висвітлюється еволюція міжнародного співробітництва вчених України з зарубіжними дослідниками. Продемонстровано величезний вплив стажування вітчизняних учених у найбільших наукових центрах світу, спільних досліджень із зарубіжними дослідниками для становлення науки в Україні, розвитку мережі наукових установ та вищих навчальних закладів. Охарактеризовано основні тенденції міжнародної співпраці вчених Національної академії наук України та міграції наукових працівників в останні десятиліття.Evolution of the international cooperation of Ukrainian scientists with foreign researchers is emphasized. The great impact from probation of national scientists at largest research centers across the globe, joint research with foreign partners on establishing the science system in Ukraine and building up the network of research institutions and higher education establishments is shown. Main tendencies in the international cooperation of scientists from the National Academy of Sciences of Ukraine and scientists’ migration in the latest decades

Photoemission and x-ray absorption studies of valence states in (Ni,Zn,Fe,Ti)3_{3}O4_{4} thin films exhibiting photo-induced magnetization

By means of photoemission and x-ray absorption spectroscopy, we have studied the electronic structure of (Ni,Zn,Fe,Ti)$_{3}$O$_{4}$ thin films, which exhibits a cluster glass behavior with a spin-freezing temperature $T_f$ of $\sim 230$ K and photo-induced magnetization (PIM) below $T_f$. The Ni and Zn ions were found to be in the divalent states. Most of the Fe and Ti ions in the thin films were trivalent (Fe$^{3+}$) and tetravalent (Ti$^{4+}$), respectively. While Ti doping did not affect the valence states of the Ni and Zn ions, a small amount of Fe$^{2+}$ ions increased with Ti concentration, consistent with the proposed charge-transfer mechanism of PIM.Comment: 4 pages, 4 figure

Eimeria species occurrence varies between geographic regions and poultry production systems and may influence parasite genetic diversity

Coccidiosis is one of the biggest challenges faced by the global poultry industry. Recent studies have highlighted the ubiquitous distribution of all Eimeria species which can cause this disease in chickens, but intriguingly revealed a regional divide in genetic diversity and population structure for at least one species, Eimeria tenella. The drivers associated with such distinct geographic variation are unclear, but may impact on the occurrence and extent of resistance to anticoccidial drugs and future subunit vaccines. India is one of the largest poultry producers in the world and includes a transition between E. tenella populations defined by high and low genetic diversity. The aim of this study was to identify risk factors associated with the prevalence of Eimeria species defined by high and low pathogenicity in northern and southern states of India, and seek to understand factors which vary between the regions as possible drivers for differential genetic variation. Faecal samples and data relating to farm characteristics and management were collected from 107 farms from northern India and 133 farms from southern India. Faecal samples were analysed using microscopy and PCR to identify Eimeria occurrence. Multiple correspondence analysis was applied to transform correlated putative risk factors into a smaller number of synthetic uncorrelated factors. Hierarchical cluster analysis was used to identify poultry farm typologies, revealing three distinct clusters in the studied regions. The association between clusters and presence of Eimeria species was assessed by logistic regression. The study found that large-scale broiler farms in the north were at greatest risk of harbouring any Eimeria species and a larger proportion of such farms were positive for E. necatrix, the most pathogenic species. Comparison revealed a more even distribution for E. tenella across production systems in south India, but with a lower overall occurrence. Such a polarised region- and system-specific distribution may contribute to the different levels of genetic diversity observed previously in India and may influence parasite population structure across much of Asia and Africa. The findings of the study can be used to prioritise target farms to launch and optimise appropriate anticoccidial strategies for long-term control

Off the beaten track:Studies on deep brain stimulation for obsessive-compulsive disorder

The overall aim of this thesis was to study the effects of deep brain stimulation (DBS) in patients with refractory obsessive-compulsive disorder (OCD). First, we evaluated the current standard of DBS for patients with treatment-refractory OCD. For this, we investigated effectiveness and adverse effects of DBS in a naturalistic, clinical setting. In addition, we looked at long-term outcomes of DBS in patients with OCD, including on quality of life and functioning. The second goal of this thesis was to improve patient selection by identifying predictors of response to DBS, and by addressing specific co-morbidities that may affect clinical outcome. At last, DBS is a treatment that consists of 3 phases; implantation of the electrodes, modulation of the effect by optimizing electrode settings and consolidation of results on the long term. In the third part of this thesis we conducted studies that focused on how to advance these three phases. We investigated (I) a technique to improve electrode targeting, (II) a new stimulation paradigm (cyclic DBS) aimed to reduce adverse effects, by performing a randomized controlled clinical trial, and (III) the additional effects cognitive behavioral therapy to consolidate clinical outcomes. Ultimately, the goal was to improve the overall results of DBS for OCD and add to the academic discussion about the place of DBS in the treatment of OCD

Intravenous administration of the conditionally replicative adenovirus Ad5-Delta24RGD induces regression of osteosarcoma lung metastases

<p>Abstract</p> <p>Metastatic osteosarcoma (OS) has a very poor prognosis. New treatments are therefore wanted. The conditionally replicative adenovirus Ad5-Δ24RGD has shown promising anti-tumor effects on local cancers, including OS. The purpose of this study was to determine whether intravenous administration of Ad5-Δ24RGD could suppress growth of human OS lung metastases. Mice bearing SaOs-lm7 OS lung metastases were treated with Ad5-Δ24RGD at weeks 1, 2 and 3 or weeks 5, 6 and 7 after tumor cell injection. Virus treatment at weeks 1–3 did not cause a statistically significant effect on lung weight and total body weight. However, the number of macroscopic lung tumor nodules was reduced from a median of >158 in PBS-treated control mice to 58 in Ad5-Δ24RGD-treated mice (p = 0.15). Moreover, mice treated at weeks 5–7 showed a significantly reduced lung weight (decrease of tumor mass, p < 0.05), a significantly increased body weight gain (decrease of disease symptoms, p < 0.005) and a reduced number of macroscopic lung tumor nodules (median 60 versus > 149, p = 0.12) compared to PBS treated control animals. Adenovirus hexon expression was detected in lung tumor nodules at sacrifice three weeks after the last intravenous adenovirus administration, suggesting ongoing viral infection. These findings suggest that systemic administration of Ad5-Δ24RGD might be a promising new treatment strategy for metastatic osteosarcoma.</p