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En internet farmacia empecé a pedir porque en la farmacia de al lado nunca había deseado surtido de medicamentos comprar cialis Muy cómodo en el uso de la farmacia. Estuvimos en el restaurante a. aquí la tableta con la entrega en el lugar de.
Boekje baco 1516.inddBachelorcongrescommissie 2015 - 2016 Beste studenten en docenten, Namens de Bachelorcongrescommissie heten wij jullie van harte welkom op het vijfde Bachelorcongres van Biomedische Wetenschappen! Het afgelopen halfjaar hebben we ons ingezet om jullie op 29 juni een gevarieerd programma aan te bieden. Het congres zal worden geopend door dr. Jur Koksma, project leider van het REshape center. Naast de jaarlijks terugkerende posterpresentaties, hebben we dit jaar drie gastprekers: Frederike Büchner (epidemioloog), Henk Schallig (parasitoloog) en Lucien Engelen (directeur REshape center). interactive lectures zullen dit jaar opnieuw georganiseerd zijn door de drie onderzoek- sinstituten van het RadboudUMC (RIMLS, RIHS en het Donders Instituut). Via onze website heb je je voorkeur voor één van de interactive lectures gegeven. De derde- jaars Honours studenten, die momenteel in het buitenland een onderzoeksstage doen, zullen in een filmpje vertellen over hun stage-ervaringen. Vandaag zullen de derdejaars BMW-studenten ook hun bachelorstage presenteren in de vorm van een poster. De posterpresentaties zijn uitermate geschikt om de derdejaars studenten inhoudelijke vragen te stellen over hun onderzoek. Daarnaast zijn er highlight-lectures waarin twee studenten hun stage zullen presenteren. Na afloop van de tweede ronde interactive lectures en posterpresentaties is het tijd voor het speeddaten. Hierbij is er gelegenheid om vragen te stellen aan de derdejaars studenten over de ervaringen die ze hebben opgedaan tijdens hun stage. Het congres zal worden afgesloten met een borrel! Dit is bij uitstek een moment om met je medestudenten, studieleiders en docenten de dag na te spreken. Wij wensen jullie veel plezier vandaag! Namens de Bachelorcongrescommissie Biomedische Wetenschappen 2015-2016, Janoe van Hemert, Joyce van der Heijden, Julia van Adrichem, Lieke Heijnen, Manon Gremmen en Pauline de Best Bachelorcongres BMW Paul Smits - Decaan / Vicevoorziter RvB Radboudumc "To have a significant impact on healthcare." Het Radboudumc is een universitair medisch centrum met drie kerntaken: patiëntenzorg, onderwijs en onderzoek. Met deze drie kerntaken werken we aan onze missie: to have a significant impact on healthcare. Voor ons is de mens en zijn kwaliteit van leven het vertrek- en eindpunt. Steeds opnieuw bij alles wat we doen. We bieden onze patiënten topklinische en topreferente zorg en hebben een belangrijke maatschappelijke taak in het vergroten en verspreiden van kennis en kunde. Door onderwijs & opleiding te verzorgen en wetenschap- pelijk onderzoek te doen.
Met onderwijs en onderzoek kunnen we een belangrijke slag slaan om de gezondheidszorg te vernieuwen. Dit is hard nodig om de gezondheidszorg kwalitatief goed, toegankelijk en betaalbaar te houden voor deze en volgende generaties. Onderzoekers en artsen moet- en hierin samenwerken en moeten samen op zoek gaan naar innovatieve oplossingen. De wereld van de wetenschap en de wereld van de praktijk zal hiervoor een belangrijke verbinding moeten aangaan. Alleen dan kunnen we ons doel bereiken.
Dat begint bij nieuwsgierige en gemotiveerde studenten die hieraan een bijdrage willen leveren. Denk bijvoorbeeld aan het innovatieproject, waar onze studenten bedrijven en instellingen adviseren over de toepassing van innovatieve oplossingen. Op deze manier kunnen studenten over hun grenzen heen kijken en de zorg vooruit helpen.
Sta bij het bezoeken van het Bachelorcongres vandaag dan ook eens stil bij de vraag hoe jij de zorg vooruit kan helpen. Hoe jij, met onderzoek en innovatie, je eigen bijdrage kan leveren aan a significant impact on healthcare.
Als decaan en vicevoorzitter van de Raad van Bestuur van het Radboudumc kijk ik met veel belangstelling uit naar deze dag en wens ik iedereen een inspirerend congres toe.
Prof. dr. Paul A.B.M. Smits, decaan / vicevoorzitter Raad van Bestuur Radboudumc Bachelorcongres BMW Henk Schallig en Frederike Büchner Henk Schallig is een parasitoloog, vroeger ontwikkelde hij vaccinaties tegen parasitaire en bacteriele infecties. Momenteel doet hij onderzoek naar de ontwikkelingen en evaluatie van diagnostische middelen, drugs efficacy en resistentie van malaria.
Nu is de heer Schallig vooral bezig met onderzoek naar een goed moleculair diagnostisch systeem voor malaria. Iets wat erg belangrijk is, huidige diagnos- tische systemen zijn namelijk gelimiteerd in het aantal personen wat ze juist detecteren en hebben vaak veel apparatuur nodig wat niet altijd aanwezig is. Het verbeteren van diagnostische testen voor malaria geeft meer controle over ze ziekte, het verlaagd de kans op resistentie wat een grote dreiging is bij de behandeling van malaria. Over malaria en het onderzoek waar de heer Schallig momenteel mee bezig is zal hij op het congres meer vertellen. Frederike Büchner Frederike Büchner, epidemioloog, heeft zelf Biomedische Wetenschappen gestudeerd aan de Radboud Universiteit van Nijmegen en heeft een major gevolg in epidemiologie. Ze heeft haar eindstage gelopen bij het ‘Rijksinstituut voor Volksgezondheid en Milieu' en heeft daar onderzoek gedaan naar de ge- zondheidseffecten van groente en fruit. Op dit moment werkt ze bij de afdeling ‘Public Health en Eerstelijnsgeneeskunde' bij het Leids Universitair Medisch Centrum. Doordat ze hier heeft gestudeerd, is het interessant om haar verhaal te horen en te weten te komen wat ons in de toekomst te wachten staat. Ze gaat vertellen over de verschillende loopbaan mogelijkheden van de studie Biomedische Wetenschappen, onder anderen als epidemioloog.
Bachelorcongres BMW "Stop talking, start doing with Lucien Engelen, directeur van het REshape center for innovation bij het radboud medical center in Nijmegen, wordt ook een ‘disruptive impressionist' genoemd. Hij probeert een toekomst te schetsen van de toekomstige gezond- heidszorg met de tools die nu en in de toekomst aanwezig zullen zijn. Lucien Engelen geeft binnen het Radboud UMC leiding aan het zogeheten REshape-innovatiecentrum, dat mensen, ideeën en technologieën bijeen brengt. De input voor innovatie komt vanuit alle kanten: patiënten en hun families, artsen, verpleegkundigen en de afdeling voor procesverbetering. Een interessante ontwikkeling van het REshape Center is Hereismydata. Samen met Philips en met de hulp van cloudsoftware-aanbieder Salesforce.com is er een persoonlijk gezondheidsdossier ontwikkeld in combinatie met een online community. Het is ook een connectiviteitsplatform voor medische apparatuur, wearables en apps. Dit is een geweldig voorbeeld voor het stimuleren van het betrekken patiënten in het zorgproces Verder heeft Lucien Engelen TED talks gegeven en staat hij bekend als Linke- din INfluencer. Hij staat ook op de lijst van de 30 meest invloedrijke mensen op het gebied van Public Health. Lucien Engelen zal op het Bachelor Congres een interessante lecture geven en de dag afsluiten! Bachelorcongres BMW Highlight Lecture Costs of Sexual Transmitted Infection Services Provided to High Risk Groups in a Community Clinic Setting, Bandung and Indonesia Radboud university medical center, Department for Health Evidence. Route 133.
Co-authors: Dr. A.Y.M. Siregar (Indonesia), Dr. N. Tromp and Dr. R. Baltussen (the Nether- BACKGROUND: In Indonesia, the HIV/AIDS epidemic is highly concentrated among the high risk groups men who have sex with men (MSM), female sex workers (FSW) and transgenders. The idea that having a sexually transmitted infection (STI) is a risk factor for getting HIV has become increasingly accepted since the last decade and is now widely seen as an important force driving the spread of HIV. Against this context, implementing STI services for high risk groups, including counselling, testing, treatment and education, is considered an important and promising HIV reduction programme. Although evidence on the STI services' efficiency is abundant, the costs for implementing and continuing this intervention are not known in Indonesia. However, an insight in the costs is vital for health policy makers.
OBJECTIVE: to assess the costs of STI services (excluding HIV) provided to Key Affected Populations (KAPs) being MSM, FSW and transgenders in Bandung, Indonesia in 2015 from a societal perspective. Results will be used to aid the local AIDS commission Komisi Penanggulangan AIDS (KPA) during their investment decision-making process regarding the funding of HIV interventions and provide policy recommendations.
METHODS: in a 2 month observation period, STI service delivery costs generated by community clinic ‘Klinik Mawar' were estimated on the basis of a micro-costing approach. Non-health care costs were estimated on the basis of a survey among 48 FSW, MSM and transgender STI clients.
RESULTS: in 2015, a total of 677 STI clients visited the clinic. Total annual societal costs of running the STI clinic (Klinik Mawar) equalled 5,864 US$. This comes down to 8.66 US$ per client visit. Patient costs formed 102% of total societal costs, suggesting service cost formed the largest share of total patient costs (44%). Patient costs was followed by clinic costs (39%) and central government costs (3%). CONCLUSION: It can be concluded that Klinik Mawar is getting more independent. In ad- dition, compensation should be considered for travel costs borne by the patient in order to enlarge financial access to the intervention. Furthermore, STI service upscaling scenarios for Bandung are being computed. Future research is needed to determine the effect of the intervention as this information is, in combination with knowledge about the costs, required for priority setting.
Bachelorcongres BMW Highlight Lecture Under-reporting of complementary and alternative drug use in liver disease F.A.C. Berden 1 , G.P.C.A. Netten 1 , W. Kievit 2 , J.P.H. Drenth 1 1 Department of Gastroenterology and Hepatology, Radboud university medical center, Nijmegen, the Netherlands2 Department for Health Evidence, Radboud university medical center, Nijmegen, the Netherlands Complementary and alternative medicine (CAM) encompasses a huge variety of treatments including homeopathy, herbal medications and acupuncture. We hypothe- size that CAM use in liver disease patients is underreported in clinical practice and can lead to relevant pharmacological interactions. The aims of this study were to assess the prevalence and type of CAM use, and experiences with CAM use in liver disease We conducted a cross-sectional survey among the members of the Dutch Liver Patients Association. All members received a questionnaire with 26 questions about demographics, liver disease, frequency and type of, and experiences with CAM use (Survey Monkey). We received 213 completed questionnaires. Mean age of respondents was 55 years (SD 13.5), 64 (30%) respondents were male and main liver diseases were primary sclerosing cholangitis (PSC, n=51, 24%), primary biliary cholangitis (PBC, n=40, 19%), autoimmune hepatitis (AIH, n=39, 19%), PSC PBC AIH overlap syndrome (n=11, 5%), and viral hepatitis (n=16, 8%). A total of 96 patients (43%, 95% confidence interval 36- 50%) reported CAM use; type of CAM was diverse and silymarin was most frequently reported (n=18). Up to 35% of CAM users had not divulged CAM use to their physician. The majority of patients (n=63, 76%) experienced beneficial effects of CAM and 58 patients (71%) would recommend CAM to other patients.
Conclusion: Prevalence of CAM use is high (43%) in liver disease patients and 35% of patients do not report CAM use to their physician. Physicians should actively ask for CAM use because knowledge about CAM use can prevent potential harmful interac- tions with prescribed medication. Keywords: Complementary and Alternative Medication (CAM); Liver disease patients; Silymarin; Drug-drug interactions Bachelorcongres BMW Donders Center for Neuroscience Guillén Fernández - Director "Our research is fundamental in nature, but the insight we provide has already concep- tual impact on healthcare, which we are continuously translating into clinical appli- The universe in your head with 100 billion neurons, each having about 10.000 highly dynamic connections with each other is the biological basis of your cogni- tion, emotion, and behavior. Plastic changes within this fascinating organ, enabling you to remember and adapt to environmental challenges, are the focus of my own research. When affected by neurodegeneration like patients with Alzheimer's dis- ease are, debilitating forgetting is prime symptom. In turn, traumatic memories that are intrusive and resistant to forgetting are prime symptom in anxiety and mood disorders. Thus, neuroplasticity requires an optimal balance in order to be adap- tive. In my research I take an experimental approach probing the system-level underpinnings of such neuroplastic processes and their balance in humans using functional magnetic resonance imaging. However, this type of research is interdis- ciplinary in nature and thus I collaborate closely with clinicians, neurogeneticists, animal behavioral neuroscientists, and computational scientists in providing a mechanistic account for neuroplastic processes like memory formation and consol- idation. The Donders Institute for Brain, Cognition, and Behavior is a cross-cam- pus research facility that provides a perfect platform for this type of interdisciplin- ary research. The Centre for Neuroscience, which I direct, integrates the Donders activities at the science faculty and the Radboudumc. Our research is fundamental in nature, but the insight we provide has already conceptual impact on healthcare, which we are continuously translating into clinical application. In this context it is important to consider that our brain is the most individual organ we have and thus our research focus is on individual differences in brain processes and neuoplasti- city fitting optimally with the strategic goal of the Radboudumc to have a significant impact on personalized healthcare. I hope you share my enthusiasm for probing the biological processes in the universe in your head and how they are impaired in individuals with brain-based ailments.
Bachelorcongres BMW Iris Bevers: Spheres of self regulation strength: Comparing ego depletion by emo-
tion and cognition
WHAT? Self-regulation is described as the individual's ability to gain conscious control over impulses and withhold from short-term attractions which enables the engagement of long-term personal goals. Failures of self-regulation are the core of many personal or societal problems, like substance abuse and obesitas. Because of the great benefits of self-regulation, it's rather surprising that a , major part of the population fails to pursue self-control. This failure can be explained by the limited strength model which suggests that people are provided with a limited capability of self-regulation and each act of self-regulation draws from a limited supply of ‘self-regulatory strength', leaving less available for fol- lowing acts of self-regulation. This phenomenon is defined as ego depletion and extending knowledge about its mechanisms by performing research can be very beneficial for society.
WHY? The aim of this research is to gain insight in the processes underlying ego depletion by com- paring two different tasks which require self-regulation; an emotion regulation task and a cognitive performance task. The accompanying research question is: does regulation of emotional response tendencies or regulation of cognitive response tendencies induce stronger ego depletion? HOW? To answer this question a between subject cross-over design with 60 subjects in total will be used. These 60 subjects are randomly divided in three different groups. One emotional ego depletion group, one cognitive ego depletion group and one control group. Each subject in emotional ego de- pletion group will perform a well-established emotion regulation task, the emotional Stroop test. Each subject of the cognitive ego depletion group will perform the normal variant of the Stroop test. Each subject of the control group will perform a neutral task in which no depletion will take place, a simple word reading task. The data will be analyzed with using 2 three-way between group ANOVAs.
Sophie Jansen: The association between impaired fear extinction in serotonin
transporter knockout rats and epigenetic changes in the amygdala and medial
Background: The risk for post-traumatic stress disorder is increased for those carrying the low allelic variant (short; s) of the serotonin transporter-linked polymorphic region (5-HTTLPR). This variant possible leads to reduced prefrontal control of the amygdala. Previous studies showed that epigenetic mechanisms such as DNA methylation and demethylation are important for the formation and stabilization of fear memory in the prefrontal cortex and amygdala. Expected is that impairment of fear extinction in serotonin transporter knockout (5-HTT- /-) rats is related to changes in DNA methylation and demethylation in these brain regions. This hypothesis will be tested through assessment of overall DNA methylation levels in the amygdala and medial prefron- tal cortex of 5-HTT- /- and wild-type rats that underwent fear extinction and non-extinction, which were only exposed to fear conditioning.
Methods: 5-HTT- /- and wild type Wistar rats were fear conditioned with an auditory conditional stimulus (CS) and a mild foot shock as the unconditional stimulus (US). They were trained with a total of five CS- US pairings. 24 hr after conditioning the rats in the extinction group were exposed to the CS 24 times without the US for 15 minutes. Non-extinction rats will be exposed to the extinction context only. Freezing of the rats was scored. The rats were sacrificed to make coupes of the brain. Brain punches of amygdala, prelimbic and infralimbic cortex will be analyzed to deter- mine the DNA methylation (5-methylcytosine or 5-hydroxymethylcytosine).
Results: 5-HTT knockout rats showed impaired fear extinction compared to wild type rats. Data of methylation in the amygdala and medial prefrontal cortex is not yet available.
Bachelorcongres BMW Mart Munstters: Longitudinal validation of a transgenic rat model for Spinocer-
ebellar ataxia type 17
BACKGROUND: Spinocerebellar ataxia type 17 (SCA17) is a neurodegenerative disease caused by a trinucleotide CAG/CAA expansion in the TBP gene, affecting both brain and muscle tissue with symptoms similar to Huntington's disease. In order to test new treatment options for patients, it is necessary to first generate and validate an animal model that resembles the human symp- toms, as the trinucleotide expansion may have a different effect in rats than in humans. Conse- quently, validation is important so that it is viable to extrapolate towards patients after finding a possible treatment in rats. As the motor deficits in SCA17 make up a major part of its pathogene- sis, a focus on the motor functionality and its decrement is preeminent in validation of the model.
AIM: The aim of this study is to validate a SCA17 transgenic rat model through longitudinal motor METHODS & MATERIALS: Four different motor tests were carried out in Wistar wild type and SCA17 PrP-TBP64 transgenic rats at 3, 6 and 9 months old to assess motor functionality and decrement, namely: CatWalk, BeamWalk, GripStrengthTest and the SinglePelletReachingTask.
RESULTS: Baseline experiments were carried out with 3-month- old rats, still in their presymptom- atic state. In the CatWalk experiment, the most important motor assessment test, the two different genotypes show no overall significant difference at three months old in motor functionality. We hypothesise that the transgenic rats will attain lower scores on the motor tests when they are 6 and 9 months of age, which is supported by SCA17 being a neurodegenerative disease.
Rowanne Steiner: Psychophysical assessment of the peripheral involvement in
the gist of the scene
Background - Visual perception of the surrounding travels from the retina, via the lateral genic- ulate nucleus (LGN), to the primary visual cortex (V1). Traditionally, the V1 is thought to act as a gateway that transfers information to the extrastriate visual cortices and plays a crucial role in generation of a visual percept. However, several anatomically and functionally studies indicate there are also parallel direct pathways from the LGN to the extrastriate cortices, bypassing V1 altogether. An example which supports the idea of parallel pathways is the well-studied "blind- sight" phenomenon in patients with (partial) loss of V1. These lesions causes the loss of visual awareness in the areas corresponding to the retinotopic area that is damaged. However, despite the loss of visual awareness, many of these patients still show visually guided behaviour without visual awareness. We hypothesise that an example of parallel processing is the "gist" phenom- enon, which is the quick extraction (as short as 48 ms) of global information before the details, of a complex visual scene in the healthy brain. In this study we will compare features such as concealment and naturalness for central vision and peripheral vision, to probe the contribution of fast, peripheral visual processing to scene perception. This task may later become incorporated in training for visual rehabilitation of "blindsight" patients, with as a possible result the use of the gist phenomenon in a functional way.
Research Question - Is the scene the gist of scenes due to global feature processing in the Experimental Design - A psychophysical task is developed and piloted. In this task, we use accuracy and speed as outcome measures while varying the stimuli physical properties. This task consists out of categorisation of global or basic-level features after a short scene presentation in the periphery vision and central vision in healthy volunteers.
Bachelorcongres BMW Yara Luijten: Effects of a five-week C-mill training on the posture of SCA pa-
Background: Spinocerebellar ataxia (SCA) is a hereditary, progressive and neurodegenerative disease, which mainly affects the cerebellum. Over 35 genetically different types of SCA have been identified so far. SCA patients fall frequently, due to postural instability and an abnormal gait pattern. Since there is no pharmaceutical treatment available, the preferred therapy is physiother- apy. This is considered to be insufficient, because it is heavily reliant on motor learning and SCA patients are believed to have difficulties with this. Nevertheless, recent literature suggests that SCA patients are still capable of retraining balance and gait. A pilot study was conducted where patients received ten gait adaptability training sessions of one hour over a period of five weeks. These trainings took place on an instrumented treadmill, the C-mill. This treadmill can analyze a person's gait pattern and project visual cues on its surface. Patients were asked to adapt their gait pattern by walking on a narrow or irregular path and to avoid unexpected obstacles last minute, thus training their balance and coordination. This study showed promising results with a significant improvement in obstacle avoidance of the patients. Only, in this pilot study changes in posture were not explored and a group of healthy controls was not included.
Objective: To assess the effects of a five-week C-mill training on the posture of SCA patients compared to healthy controls.
Methods: Twenty SCA patients with the subtype 2, 3, 6, or 14 and seventeen healthy controls, matched for age and sex, each received ten gait adaptability training sessions of one hour over a period of five weeks on the C-mill. In the week before the first training and in the week after the last training, posture was assessed using a device which measures postural sway (SwayStar TM ) during various static and dynamic balance tasks.
Iris van Marwijk: Implicit learning methods for children with cerebral palsy in
AIM: Explicit motor learning places a big demand on working memory. It is assumed that children with cerebral palsy (CP) have poor working memory functioning, therefore explicit motor learning is very difficult for children with CP. Implicit motor learning is characterized by ‘learning by doing' and is therefore easier for children with CP. However, an earlier study showed that 92.2% of the provided instructions by physical education (PE) teachers in their lessons was explicit of nature. Additionally, if a child has a low self-efficacy towards physical activity, it is unlikely that the child will participate in the PE lessons. The aim of this study was to determine whether PE teachers used more implicit motor learning after receiving a manual and to assess if the self-efficacy of the child would increase.
METHODS: Two PE teachers and 12 children, of which 3 had CP participated in this study. Three PE lessons were filmed, and after the first lesson the teachers received a manual about the differ- ent categories of implicit motor learning. The video recordings were analysed via event sampling. The children's self-efficacy was assessed with the Children's Self-perceptions of Adequacy in and Predilection for Physical Activity (CSAPPA) scale. The CSAPPA scale was tested after the first and third PE lesson. To compare the mean CSAPPA score a Wilcoxon Signed Rank Test was performed. RESULTS: The mean CSAPPA score after the first and third lesson was 2.9790 vs. 2.9757 respectively (P = 0.875). The results of the video recordings are not yet known.
CONCLUSION: The results of this study suggest that the children's self-efficacy did not increase. However, more data needs to be collected to draw a final conclusion.
KEYWORDS: Cerebral Palsy, Children, Self-efficacy, Implicit motor learning Bachelorcongres BMW Radboud Institute for Health Sciences Bart Kiemeney - Director "De missie van het Radboud Institute for Health Sciences is om nieuwe ontdekkingen vanuit het biomedisch onderzoek te vertalen naar de klinische praktijk." Handelingen in de kliniek en public health vinden bij voorkeur plaats op basis van "bewijs", niet op basis van gevoel / intuïtie of "ervaring": Evidence Based ipv Eminence Based Practice! In het Rad- boud Institute for Health Sciences (RIHS; www.rihs.nl) richten onderzoekers zich met name op bewijs dat kan worden verkregen met zogenaamd "probabilistisch onderzoek" (ook wel "frequency research" genoemd) binnen de medische wetenschappen. Het gaat dus over onderzoek onder groepen mensen: echte mensen dan wel gesimuleerde mensen in modelsituaties, groepen mensen in de klinische praktijk (patiënten) of in de algemene bevolking. Anders dan bij het meer deterministische onderzoek in het Radboud Institute for Molecular Life Sciences (RIMLS) gaat het in het RIHS dus niet om één of een paar petrischaaltjes, cellijnen of muisjes. Nee, het zijn groepen mensen als object van onderzoek. Via die groepen mensen worden data ("evidence") verkregen over de relatie tussen een determinant en een uit- komst. Indirect wordt daarmee ook inzicht verkregen hóe die relatie werkt. In deterministisch onderzoek probeer je meer direct uit te zoeken hoe iets werkt: mechanistisch onderzoek. In de wetenschap bestaat natuurlijk een duidelijke link tussen het probabilistische (frequentie-) onderzoek en het deterministische (mechanistisch) onderzoek. Onderzoek naar mechanismen zal namelijk altijd gevolgd moeten worden door frequentie-onderzoek (wel gebaseerd op kennis over mechanismen) voordat beleid gemaakt kan worden. Immers, op theorieën of principes alleen kun je wel onderzoek maar geen beleid baseren. Andersom is "frequency research" enerzijds meestal meer waardevol wanneer het gebaseerd is op kennis over mechanismen terwijl het anderzijds vaak nieuwe aanknopingspunten geeft voor mechanis- tisch onderzoek. De beide onderzoeksdomeinen lijken in de praktijk vaak werelden van verschil maar feit is dat ze niet zonder elkaar kunnen. De missie van het RIHS is om nieuwe ontdekkingen vanuit het biomedisch onderzoek te vertalen naar de klinische praktijk. De eerste stap hierin is de vertaling van laboratoriumgegevens en proefdieronderzoek naar de mens in vivo ("proof of concept" studies). In die eerste stap staat het werkingsmechanisme van de interventie vaak centraal ("mechanism- based medicine"). De tweede stap is de vertaling naar "evidence-based medicine". Daarbij moet blijken wat een bepaalde ontdekking werkelijk betekent voor de morbiditeit en mortaliteit van patiënten via het meten van zogenaamde surrogaateindpunten en/ of harde eindpunten. In dit type onderzoek kan de bewijsvo- ering via verschillende epidemiologische methoden worden verkregen, bijvoorbeeld via een retrospectief of prospectief onderzoek, via een "case control study", een cohort studie, een "randomized controlled trial" of een zogenaamde meta-analyse. De derde stap betreft de implementatie van nieuwe inzichten in de klinische praktijk. Onderzoek naar deze laatste stap leert hoe bepaalde richtlijnen en protocollen het beste kunnen worden geïmplementeerd binnen de gezondheidszorg. Het RIHS concentreert zich op onderzoeksmethoden om nieuwe inzichten te vertalen naar de klinische praktijk, en richt zich daarbij op belangrijke ziekten zoals kanker, hart- en vaatziekten, longziekten, reumatische ziekten, neurologische en orthopedische aandoeningen.
Bachelorcongres BMW Maartje van Acht: What is the difference in the MEWS and the outcomes of
the parameters separately, measured by novel smart devices compared to the
nurse measurements and the golden standard?
Background - In every inpatient in the Radboudumc five vital parameters are measured at least three times a day: heart frequency, blood pressure, temperature, respiration rate and the oxygen saturation. These five parameters together with the level of consciousness and the oxygen admin- istration are used to calculate the MEWS (Modified Early Warning Score). Scores higher than 0 indicate the patient is not doing well and a doctor will be alerted. However, this system does have several down sides. Patients are only monitored 3-6 times a day, the parameters are measured by different devices and measuring these parameters is time consuming. To improve the surveil- lance and safety of the patients and to facilitate that patients can participate more, several ‘smart' devices exist. One of these devices is the Viatom's ‘Checkme'. This pocket size device is able to measure the blood pressure, heart rate and oxygen saturation in just 30 seconds. Furthermore, it is also able to measure the temperature in just seconds. The device is now only for personal use, but can perhaps be a great improvement for the patient when used in hospitals. Aim The aim of this study is to investigate the feasibility of the Checkme for determining a patient's health state.
Methods - The investigator will measure patients from the department Intern Medicine two times a day. To create a golden standard, the investigator first will measure the MEWS, precisely following the protocol. After that the MEWS will be calculated using the Checkme. Eventually 3 measure- ments will be compared to each other: the measurements of the nurse, the golden standard (the investigator), and the Checkme.
Results - There are no results yet.
Evelien Been: Development of a stress course to differentiate between mental
stress and physical stress
Background: Chronic stress is a large contributor to impaired health worldwide. Chronic stress leads to several diseases such as asthma, hypertension, coronary artery diseases, peptic ulcers and burn- outs. A way of stress prevention is to make people aware of their high stress levels. A possible solution is via monitoring the heart rate. The heart rate variability (HRV) can be derived from the heart rate. The HRV is the difference between the RR-interval over time. It has been shown that the HRV decreases in as well mental stress as physical stress, but the difference between these two kinds of stress has never been demonstrated.
Aim: The aim of this study is to develop a course that exposes healthy individuals to mental and physical stress, in order to look at possible differences in HRV between these different kinds of stress. When a relation between HRV and the different kind of stress is known, HRV can be moni- tored to increase the awareness of stress.
Method: Healthy subjects follow a course to induce stress. This consists of two mental activities (solving sums and watching a video wearing the google cardboard) and two physical activities (ex- ercising on a cross trainer and bicycle). The heart rate is measured by a Polar chest band and the HealthPatch. The VAS and STAI questionnaires are used to estimate the perceived stress levels after each activity. This data is used to analyse the HRV during the different stressors.
Bachelorcongres BMW Fenna Beeren: Cost-analysis of condom distribution to hotspots in Bandung, Indonesia
BACKGROUND: The HIV/AIDS epidemic in Indonesia is shifting towards the general population. The majority of new infections among the general population occurs among clients of sex workers. Condoms play a key role in reducing the sexual transmission of HIV in Indonesia. However, consistent condom use among Female Sex Workers (FSWs) is barely 35%. KPA Bandung (National AIDS Commission) implemented a condom distribution program to distribute condoms to FSWs in hotspots and make condoms more accessible. To our findings, no data of costs of condom distribution at hotspots in Indonesia is known. Costing analysis of condom distribution at hotspots in Indonesia is necessary to advise KPA on prioritizing interventions and cost reduction.
OBJECTIVE: Estimating the costs of condom distribution to hotspots in Bandung, Indonesia.
METHODS: Interviews with KPA Bandung personnel were used to estimate the costs of the condom distri- bution program of KPA Bandung. Condoms are distributed to 61 hotspots in Bandung. These hotspots are streetbased, community volunteers and beauty salons. A micro-costing approach, distinguishing capital and recurrent costs was used for the estimation. In addition, different (upscaling) scenarios are evaluated and the effects of the program are estimated by interviewing head of hotspots and FSWs.
RESULTS: The unit costs of the condom distribution program are 12,858,053.68 IDR per hotspot. The dis- tributed condoms form the largest cost component (77.5%). Increasing the condom distribution program to all hotspots in Bandung (68 hotspots) will decrease the unit costs with 0.91%. The overall effect of the condom distribution seems positive. Based on interviews with heads of hotspots, the condom use among FSWs increased with 20-80%. In addition, all FSWs indicate an easier access to condoms due to the distribution CONCLUSION: Based on the analysis, the total unit costs of the condom distribution program are 12,858,053.68 IDR per hotspot. Interviews about effectiveness indicate a positive effect, FSWs state that condom use increased. However, they point out that the quality of the condoms is too low. More research is needed to make conclusions about the cost-effectiveness of the programme.
Bronke Boudewijns: The effect of Capitation payment in Ghana's National
Health Insurance Scheme
Background: In 2003 Ghana introduced the National Health Insurance Scheme (NHIS) in order to gain universal health coverage. In recent years the costs of the NHIS have been escalating, partly due to supply and demand side moral hazards. Since 2008 the National Health Insurance Author- ity (NHIA) uses Ghana Diagnosis Related Group (G-DRG) as provider payment method. Because under the G- DRG the cost escalation cannot be halted, a new provider payment method is being piloted in Ashanti region, since 2012. The NHIA implemented capitation payment for primary out- patient services, in which each NHIS member is registered to a care provider of their choice. By allowing providers a fixed budget per registered member, the NHIA hopes to drive down the costs of outpatient care, while maintaining quality of care. Eventually this method is to be rolled out in the entire country. The aim of this study is to evaluate the effect of the new capitation system on health care utilization, and related costs and to see whether this is influenced by demographic, socio economic and health system factors. Methods: To measure the effect of the capitation system, the utilization and costs for both outpa- tient department (OPD) and inpatient department (IPD) of Ashanti region were compared to those of two control regions, Central and Volta, over the years 2010-2014. The costs were cal- culated in US dollars and utilization in number of visits. To make the data from the three regions more comparable, the costs and utilization were divided by the number of NHIS members in that region. Consequently the correlation was measured for health care utilization and costs with urbanization level, poverty headcount, and number of health facilities.
Bachelorcongres BMW Milette Dufour: Fair priority setting in HIV control in low- and middle-income coun-
In 2009, 30 million people infected with Human Immunodifiency Virus (HIV) - which represents 91% of the world's total HIV infected population - lived in Low- and middle income countries (LMICs). As these countries have insufficient funding available to fund all possible interventions aimed at HIV control, priority setting is both inevitable and necessary. Priority setting involves making choices in which inter- ventions to fund. In doing so, decision makers face difficult dilemma's and have to deal with conflicting values and interests of stakeholders.
International guidelines on HIV control provide countries with general guidance on how they can opti- mize HIV control. However, countries still have to make country-specific choices in what interventions they choose to prioritize. As we lack consensus on specific guiding principles that tell countries how to set these priorities, it is argued that we should instead aim for setting these priorities in a fair and legitimate way, by means of organizing fair processes for decision-making. If such fair processes are established, it is argued that outcomes of these processes are also more likely to be accepted as fair and legitimate.
Accountability for reasonableness (A4R) is a framework that promotes four key conditions for priority setting processes to be considered fair and legitimate, namely: i relevance, ii publicity, iii revisability and iv enforcement.
Governments of LMICs report their priority setting choices in a national strategic planning document. The aim of this study is to analyze a selection of these documents in order to answer the question: to what extent do current processes meet the A4R conditions for fair processes. Based on the A4R condi- tions and studies that used the A4R framework to analyze processes, we developed a data- extraction tool, existing of questions related to the A4R conditions. Two independent researchers will analyze the same national strategic planning documents.
Justine Eerden: A direct comparison of the flow-mediated dilation and carotid
artery reactivity test in its ability to detect changes in endothelial function
upon caffeine intake
Introduction - Since endothelial dysfunction is a precursor for atherosclerosis and coronary artery disease, endothelial function is often regarded as a surrogate measure for vascular health. The flow mediated dilation (FMD) test is commonly used as a surrogate marker of vascular health. How- ever, this test is technically challenging. A new test, the carotid artery reactivity test (CAR), may be a good alternative given its simplicity and non-invasive nature. In this study, we examine whether both tests of endothelial function are able to detect the acute impact on vascular health after ingest- ing caffeine: a potent vasoconstricive agent leading to a transient impairment in vascular function.
Methods - FMD and CAR were assessed in participants (n=12) with no history of cardiovascular disease or risk factors. The experiment consisted of two separate days on which they received either caffeinated coffee (170 mg caffeine) or decaffeinated coffee (placebo) (<6 mg caffeine) in randomised order (subjects were blinded). After a 30 minute waiting period, the FMD and CAR were assessed. The FMD represents a hyperaemic flow after occlusion of the brachial artery. The CAR uses a sympathetic stimulus (i.e. ice water) to induce a systemic response. Blood pressure and heart rate were measured continuously. Ultrasound images were analyzed digitally. Main out- come measurements were change in diameter (peak change in percentage) and shear rate. Results - Currently, data of only three participants has been analysed. Mean age participants was 25.7 years (SD±4.7), BMI was 22.2 kg/m² (SD±1.0), and all three participants were male. Caffeine caused an increase in FMD of 6.90%, whilst placebo was associated with an increase of 5.01% in FMD. With CAR, caffeine caused an increase of 7.09%, whilst placebo was associated with an increase of 8.09%.
Conclusion - These data show no significant effect of caffeine on either FMD or CAR.
15 Bachelorcongres BMW Floris Gal: Development of a skin and surface wipe test for the quantification
of dermal exposure and contamination of indoor surfaces of pesticides
Introduction: Pesticides are extensively used in The Netherlands to protect crops, especially in flower and fruit cultivation Pesticides are sprayed over the fields and people living in close vicinity to these fields are concerned about their health. These concerns resulted in a research project to study the exposure of pesticides among residents. The assessment of dermal exposure and contamination of indoor surfaces is part of this research project.
Aim: The aim of this study is to develop and validate a wipe method to assess the dermal expo- sure to pesticides and to assess the contamination of pesticides on indoor surfaces.
Methods: Four different types of wipes were selected for swabbing skin and indoor surfaces i.e. surgical gauze pads, cellulose wipes, paper wipes and Twillwipes. The recovery for nine pesti- cides was determined after spiking the wipes and after spiking different surfaces. In addition, the recovery was determined by using different extraction fluids i.e. methanol, acetone and dichloro- methane. The ethanol:water ratio in the wetting solution was varied from 0% ethanol to 100% ethanol and recoveries were determined. All samples were analysed directly after extraction by Results: Cellulose wipes were excluded prior the first experiment due to practical considerations. Recoveries of surgical gauze pads and Twillwipes were consistently lower compared to paper wipes and . Therefore we selected the paper wipes for further experiments. Dichloromethane showed on average the highest recoveries for all pesticides i.e. 60-100%. Recoveries of 10-60% and 25-65% were reached when spiking skin and trepsa, respectively.
Conclusion: We recommend to use paper wipes wetted with 1:1 ethanol:water to swab skin and trespa. For extraction we recommend dichloromethane as extraction fluid.
Lex Haegens: Identification of phenotypes with different preoperative charac-
teristics in people scheduled for total hip arthroplasty
Recent research has shown that the population of people awaiting total hip arthroplasty (THA) is heterogeneous, with different characteristics regarding aetiology, progression, clinical outcome and response to treatment. In a population of people with osteoarthritis, subgroups with different phenotypes have already been found, and, because osteoarthritis is one of the most common causes of THA, these phenotypes or alternate phenotypes may also be observed for people awaiting THA. Contrary to this heterogeneity, the treatment for these people is homogeneous, i.e., possible phenotypes are not taken into account when choosing treatment for these people. To find out if phenotypes are present in a population of people awaiting THA, a Latent Class Analysis (LCA) was performed with preoperative measurements for physical activity, pain, comor- bidity and bilateral complaints from a dataset of 1200 participants. After the determination of the phenotypes, these found phenotypes were validated using the data from a second database with comparable preoperative measurements. The last step consisted of assessing the difference in clinical outcome between the different phenotypes, using postoperative measurements for length of hospital stay, discharge direction and functional recovery (MILAS).
Characterizing these preoperative phenotypes will help in the development of a more personal- ized treatment and may eventually result in better treatment results, as there is currently still room for improvement on the outcome of THA.
Bachelorcongres BMW Carien Hedeman: The cost-effectiveness of septoplasty versus non-surgical management
in patients with nasal obstruction due to a deviated nasal septum: a modeling study
Background: Septoplasty is a procedure for straightening the septum in patients with nasal obstruction due to a deviated nasal septum. Septoplasty is one of the most performed surgeries at the department of Otorhinolar- yngology. However, the effectiveness of septoplasty is questioned, and scientific evidence is lacking.
Objective: The objective of this study is to model the potential (cost-)effectiveness of septoplasty as compared to non-surgical management in patients with nasal obstruction due to a deviated septum.
Methods: To determine the cost-effectiveness of septoplasty, we developed a decision analytical model. In the model costs and effects are estimated for both septoplasty and a non-surgical management strategy. Effec- tiveness was defined by the ‘satisfaction' of the patients with the outcome and the quality of life of the patients, which corresponds with the daily practice in the clinic. The two strategies were compared in terms of expected mean effects and, mean costs. Furthermore, the needed difference in effect for septoplasty to be cost-effective relative to non-surgical management is determined. Input for the model came from literature and from cost-cal- culations from the Radboudumc. A sensitivity analyses was performed to analyze the impact of the different parameters on the cost difference between septoplasty and non-surgical management. Preliminary Results: The total costs of septoplasty are higher compared to the costs for non-surgical man- agement. Furthermore, the chance of complications is higher after undergoing septoplasty. Existing literature concerning data about the health related quality of life after septoplasty and the costs appears to be scarce and limited.
Conclusion: During the conference we will present the potential gain in QALYs and cost related to both strat- egies, which will help to draw conclusions regarding the potential cost-effectiveness and the influence of the various parameters, which will provide insight in which parameters are key- indicators that should be studied in future trials.
Joyce van Heeswijk: The potential (cost-)effectiveness of a new bone removal
robot in cochlear implant surgery: a modelling study
Background: Cochlear Implantation (CI) has proven to be a promising treatment for patients with se- vere to profound hearing loss. The operation of the current strategy takes several hours during which the surgeon makes an incision behind the ear and drills through the mastoid bone into the middle ear and into the cochlea. Risks of the CI procedure include mastoïditis, meningitis, otitis media (acute of with effusion), shifting of the implanted device requiring resurgery, damage to the facial and chorda tympani nerve and wound infections. A new bone removal robot has been developed with the aim to reduce the operative time, complication rates and to increase the quality and safety of the procedure.
To inform the decision whether or not to further develop the robot, the potential health benefits for the patients and the costs of this robot should be explored in more detail.
Objectives: To assess the potential (cost-)effectiveness of the new bone removal robot in cochlear Methods: A decision-analytic model will be used to evaluate the potential cost-effectiveness of the new bone removal robot. Input for the model are extracted from literature and the cost-calculations from the Radboudumc. Outcome measures that can be used comprise sensitivity to sound, speech perception, speech production, and quality of life. In the model we will compare costs and quali- ty-adjusted life years (QALYs) of the current standard of CI with those of the new robot. First, we will explore the maximum impact of eliminating all complications (headroom analysis). Second, we will model some scenarios with varying complication and operative time reduction. Third, we will estimate the maximum price of the innovation, based on its impact. Results and conclusion: During the confer- ence we will present the potential gain in QALYs and cost related to both strategies, which will help to draw conclusions regarding the potential (cost)-effectiveness of the new bone removal robot.
Bachelorcongres BMW Janne Heijs: The ‘ideal' sitting posture for functional arm tasks
Background: The interaction between the arms and trunk is essential in performing daily tasks. For boys with Duchenne Muscular Dystrophy this interaction can alter due to muscle weakness, limiting the ability to perform activities independently. To increase the autonomy, a supportive de- vice for the trunk is being developed, besides the supportive device for the arm. For the develop- ment, it is important to get insight in the variability of the seated trunk posture.
Objective: What is the variability in the curvature of the spine during the performance of seated functional arm tasks in healthy subjects? Methods: Twenty two healthy participants (6-20 years; 11 boys, 11 girls) were measured. Vicon motion analysis system was used to observe the 3D kinematics. Therefore, markers were placed on the spinous processes of the vertebrae C7, T6, T12, L3 and L5 and on the shoulder, elbow and wrist. The participants performed reaching tasks in the forward direction and towards their dominant side, with and without an additional weight of 500 grams. The statue was placed on eye height and shoulder height, at arm's length and 1.3x arm's length. Furthermore, the participants performed daily tasks, as writing, drinking and replacing an object.
Data analysis: To observe the variability of the curvature of the spine, two angles will be calculat- ed with the law of cosines; the thoracic angle (TA) and the lumbar angle (LA). The differences of TA and LA between the start posture (hands on knees and looking forward) and the task pos- ture (during the task) will be observed to see the alteration of the curvature during a functional arm task. Furthermore, the differences of the curvature of the spine in the task position will be compared between subjects, to determine if there is an ‘ideal' or frequently used posture at which children perform a specific arm task.
Karliene Hoogeweg: REAL-PD study: Streaming Compliance and User Experience in
Large-Scale Wearable Sensors Deployment for Parkinson's Disease
Background: Parkinson's disease (PD) is a chronic and progressive neurodegenerative disorder, caused by the degeneration of dopamine-producing neurons. The disease is characterized by the motor features tremor, bradykinesia, rigidity and postural instability. The expression of clinical symptoms varies between and within people. Currently, most methods for the evaluation of PD symptoms are based on clinical observations in a controlled setting. However, this does not reflect patients' daily lives. Wearable motion sensors can be used to provide objective symptom evaluation in home and community settings. The REAL-PD study is an observational study that investigates the use of wearable sensors to measure Parkinson's symptoms in Objective: To investigate the streaming compliance of the REAL-PD measuring system and to evaluate the patient's experiences with the devices.
Methods: This study included 300 Dutch Parkinson's patients >30 years old. Patients used wearable devices to continuously collect data about day-to- day activity for three months. Additionally, a clinical as- sessment was performed in the follow-up period and a questionnaire at the end of the study. The percentage of time streaming data from the sensor during the follow-up period, streaming compliance, will be used for measuring how well the patients used the system. Descriptive statistics were applied to socio-demographic and compliance data. The system's strengths and weaknesses were assessed using qualitative analysis.
Results: 70% of the included patients were male and the mean age was 63. So far, the mean number of hours streamed data was 1453 and the streaming compliance was 66%. The most common weaknesses mentioned by patients were disconnections between the devices and inaccurate tremor measurements. The medication reminders and the activity feedback are considered to be the system's strengths.
Keywords: Parkinson's disease; Wearable devices; Compliance; User experience Bachelorcongres BMW Lisa van Hoogstraten: Quality of Life and Healthcare for Head and Neck Can-
cer Patients: A Questionnaire-Based Follow-up Study
Objective - Head and neck cancer (HNC) causes a decline in quality of life, due to symptoms and treatment. The change in quality of life, and patients' experiences in quality of healthcare can be analyzed, using patient reported outcomes and patient reported experiences (PROs and PREs). This study evaluates the PROs and PREs of HNC patients, categorized by type of treatment. Patients and Methods A total of 238 participants completed the questionnaires at baseline, 3, 6 and/or 12 months follow-up, yielding scores on the patients' health (functional and symptom scores) and experiences in healthcare. Descriptive analysis and repeated measure ANOVA were performed to compare score differences between treatment groups over time.
Results - Functional and symptom scores show a large diversity in their course over 1 year follow-up. The greatest change in scale scores is seen at 3 months follow-up. PREs address the room for improvement regarding information about- and guidance for the emotional side of the treatment and illness. The PROs are characterized by type of treatment. This study identifies three main types of treatment: radiotherapy (33% of the patients, mean age 62.5±10.89, 71% male), surgery (18% of the patients, mean age 67.5±7.28, 74% male) and chemo radiation (16% of the patients, mean age 58.6±4.81, 80% male).
Conclusions - PROs en PREs of HNC patients are characterized by type of treatment which, in turn, is characterized by e.g. age. These results provide future prospects for HNC patients with similar characteristics, regarding quality of life and experiences in healthcare.
Key words - Head and Neck Cancer, Quality of Life, PRO, PRE, Quality of Healthcare Jip Janssen: Costs of Sexual Transmitted Infection Services Provided to High Risk
Groups in a Community Clinic Setting, Bandung and Indonesia.
BACKGROUND: In Indonesia, the HIV/AIDS epidemic is highly concentrated among the high risk groups men who have sex with men (MSM), female sex workers (FSW) and transgenders. The idea that having a sexually transmitted infection (STI) is a risk factor for getting HIV has become increasingly accepted since the last de- cade and is now widely seen as an important force driving the spread of HIV. Against this context, implement- ing STI services for high risk groups, including counselling, testing, treatment and education, is considered an important and promising HIV reduction programme. Although evidence on the STI services' efficiency is abundant, the costs for implementing and continuing this intervention are not known in Indonesia. However, an insight in the costs is vital for health policy makers.
OBJECTIVE: to assess the costs of STI services (excluding HIV) provided to Key Affected Populations (KAPs) being MSM, FSW and transgenders in Bandung, Indonesia in 2015 from a societal perspective. Results will be used to aid the local AIDS commission Komisi Penanggulangan AIDS (KPA) during their investment deci- sion-making process regarding the funding of HIV interventions and provide policy recommendations.
METHODS: in a 2 month observation period, STI service delivery costs generated by community clinic ‘Klinik Mawar' were estimated on the basis of a micro-costing approach. Non-health care costs were estimated on the basis of a survey among 48 FSW, MSM and transgender STI clients.
RESULTS: in 2015, a total of 677 STI clients visited the clinic. Total annual societal costs of running the STI clinic (Klinik Mawar) equalled 5,864 US$. This comes down to 8.66 US$ per client visit. Patient costs formed 102% of total societal costs, suggesting service cost formed the largest share of total patient costs (44%). Patient costs was followed by clinic costs (39%) and central government costs (3%).
CONCLUSION: It can be concluded that Klinik Mawar is getting more independent. In addition, compensation should be considered for travel costs borne by the patient in order to enlarge financial access to the inter- vention. Furthermore, STI service upscaling scenarios for Bandung are being computed. Future research is needed to determine the effect of the intervention as this information is, in combination with knowledge about the costs, required for priority setting.
Bachelorcongres BMW Sophie Kemper: Cost analysis of religious based HIV/AIDS education
BACKGROUND AND PURPOSE: Sexual risk behavior and preconceptions about HIV/AIDS remain a signifi- cant problem in the fight against HIV/AIDS in Indonesia. Religious based HIV/AIDS education can be used to increase the knowledge of HIV/AIDS in the general population. In this intervention, the imam will educate his/ her visitors about HIV/AIDS, thereby reducing risk behavior and stigma. To allow policy makers to make evi- dence-based decisions about prioritizing between various interventions focused on HIV/AIDS, it is important to calculate the costs of religious based HIV/AIDS education.
METHODS: The costs of this intervention were calculated for the city Bandung, Indonesia over a period of a year from January 2015 until December 2015. The data were collected in April and May 2016. Data about costs were obtained using interviews with experts and records from KPA Bandung (the organization coordinating the intervention). In this intervention, KPA Bandung gave annual trainings to 60 Imams on how to educate visitors about HIV/AIDS. In turn, the Imams will educate their visitors during the religious gathering. The costs were identified from a societal perspective.
RESULTS: The annual societal costs for the religious based HIV/AIDS education is 9710 US$. The annual costs for the visitors of the religious gathering is 440 US$ and the annual costs per mosque is 162 US$. The annual costs for KPA Bandung to conduct this intervention is 470 US$.
CONCLUSIONS: Most of the annual societal costs consist of the building cost for the mosques (38.85%) and the salaries of the Imams (26.16%). These costs are paid by the visitors of the religious gatherings. For KPA Bandung, the highest costs are those of the annual training (1.62%). This is consistent with the time distribution, the annual training about HIV/AIDS education takes up most of the time and effort for KPA Bandung. In order to compare this intervention with other HIV/AIDS interventions, it would be necessary to determine the cost-effec- tiveness of this intervention. Key words: cost analysis, information, communication & education, religious gatherings, HIV/AIDS, Indo- Lindy kregting: The effects of physical activity during pregnancy on birth
weight and gestational age
Background - The American College of Obstetricians and Gynaecologists (ACOG) recommends pregnant women to exercise 30 minutes per day at a moderate intensity on most, if not all, days of the week during the entire pregnancy. However, this recommendation is not met by most of the pregnant women, partly because of fear of consequences for the unborn child. The literature is inconclusive about the effects of physical activity on birth weight and gestational age.
Objective - The aim of this study was to assess whether physical activity during pregnancy influ- ences birth weight and gestational age among offspring of Dutch women.
Methods - This study was embedded in the PRegnancy and Infant DEvelopment (PRIDE) Study, a large prospective cohort study among pregnant women in the Netherlands with data collection through web-based questionnaires. In total, 2476 participants from different Dutch obstetric clinics and midwife practices were included in the statistical analysis. The questionnaires provided data about the outcome variables birth weight and gestational age, physical activity at several points during pregnancy, and multiple potential confounders (e.g. smoking, alcohol consumption and maternal age). The data were analysed with linear and logistic regression analyses using IBM SPSS Statistics 22.
Results - The preliminary analyses showed that preterm birth was less frequent among women with a small amount of low intensity physical activity during the first three months of pregnancy- compared to women without physical activity. However, this effect seemed to decline with increas- ing duration and intensity of physical activity. The analyses for birth weight are still ongoing.
Conclusion - No conclusion can be drawn yet.
Bachelorcongres BMW Sinan Nadi: The role of the Regional Public Health Services in dealing with antimicrobi-
al-resistance in the public health domain
Background: A recent vision document indicates that the exact role of the Regional Public Health Services (RPHS) in the Netherlands in dealing with antimicrobial resistance is not entirely clear. Therefore, the aim of this study is to explore the views and experiences of the Infection Disease Control (IDC) teams of the RPHS on their role as a AMR prevention and control advisor for AMR.
Methods: A qualitative study was conducted to explore views and experiences regarding the role of the RPHS Infection Disease (IDC) Teams concerning antimicrobial resistance. Semi-structured in-depth interviews were held with members of the IDC teams of 9 RPHSs. 21 Interviews were transcribed ad verbatim and we performed thematic content analyses. Different themes were Results: This study shows that members of the IDC Team experience difficulties with defining their exact role concerning MDRO case management; that they have the opinion that expertise regard- ing MDRO prevention and control in nursing homes can be improved; and that they experience that the MDRO status of patients discharged from the hospital is insufficiently communicated to other healthcare professionals.
Conclusions: This study confirms prior findings, and implicates that the RPHS is not exactly sure of their own role. We recommend the development of courses to improve MDRO knowledge among nurses (in nursing homes and RPHS IDC Teams) and that the RPHSs maintain close contact with healthcare network partners in their region. For future policy changes and recommen- dations doubtful themes might serve as fundament for relevant discussions in nearby future.
Glenn Netten: Under-reporting of complementary and alternative drug use in liver disease
INTRODUCTION - Complementary and alternative medicine (CAM) encompasses a huge variety of treatments including homeopathy, herbal medications and acupuncture. We hypothesize that CAM use in liver disease patients is underreported in clinical practice and can lead to relevant pharmacological interactions.
AIMS & METHODS - The aims of this study were to assess the prevalence, types of and beliefs about CAM use in liver disease patients. We conducted a cross-sectional survey among the members of the Dutch Liver Pa- tients Association. All members received a questionnaire through Survey Monkey. The questionnaire included 26 questions about demographics, liver disease, frequency, type, and experiences with CAM use. Results are presented as mean (standard deviation (SD)) and frequencies. Moreover, we performed interviews, until satura- tion was reached, to clarify the perception of physicians about CAM use.
RESULTS - We received 213 completed questionnaires. Mean age of respondents was 55 years (SD 13) and 62 (30%) respondents were male. Main liver diseases were primary sclerosing cholangitis (n=51, 24%) , primairy biliary cholangitis (n=40, 19%), autoimmune hepatitis (n=39, 18%) and PSC-PBC- AIH overlap syndrome (n=11, 5%). A total of 93 46% [95%CI 40-52%] patients reported CAM use; type of CAM was diverse but silymarin was most frequently reported (n=18).Up to 35% of CAM users had not divulged CAM use to their physician. Majority of the physicians handle three conditions for CAM use of liver disease patients: CAM should be used complementary to standard therapy, it should not harm the patient and the physician should know what CONCLUSION - Prevalence of CAM use is high (46%) in liver disease patients and 35% of patients do not report CAM use to their physician. Physicians should actively ask for CAM use because knowledge about CAM use can prevent potential harmful interactions with prescribed medication.
KEYWORDS - Complementary and Alternative Medication (CAM); Liver disease patients; Silymarin; Interaction Bachelorcongres BMW Hilde van Ras: Early screening for depressive symptoms among pregnant women
Introduction: On average 18% of women are depressed during their pregnancy. Unfortunately, the detection of depression in pregnant women is low. Untreated depression among pregnant women can have harmful effects for the mother and child. The Hospital Anxiety and Depression Scale (HADS) and Edinburgh De- pression Scale (EDS) are used as screening tools to detect depression in pregnant women in primary care. The HADS and EDS are long questionnaires and due to the busy obstetric setting there is not always time to complete and interpret these measures. The Patient Health Questionnaire (PHQ-2) exist of only 2 ques- tions, and might be a useful tool to screen for depressive symptoms among pregnant women. However the validity and predictive value of the PHQ-2 have not been assessed in large-scale epidemiological studies. Identifying high risk populations will be an important step in the screening process in early pregnancy, mak- ing it easier to detect women vulnerable for developing depressive symptoms in pregnancy. The aim of this study is to examine whether the PHQ-2 questionnaire is a good screening instrument to use in the beginning of the pregnancy for developing depressive symptoms in a later stage of the pregnancy. We also want to examine which maternal characteristics are associated with a positive score on the PHQ-2 questionnaire to identify high-risk populations.
Methods: Data was used from the PRIDE study, an ongoing prospective cohort study in the Netherlands. Pregnant women completed three web-based questionnaires during pregnancy. To asses depressive symp- toms during pregnancy, the PHQ-2, HADS, and EDS are included in the questionnaires. The questionnaires also included information on maternal demographic characteristics, medical history, pregnancy related char- acteristics, health behaviour in pregnancy, and psychosocial characteristics. The sensitivity, specificity, and kappa are calculated and a ROC curve is made. To identify the high risk population a multivariate logistic regression analyses is performed.
Bo van Santvoort: The association between physical activity and volumetric
mammographic breast density in postmenopausal women.
Background - Around 1 in 7 women will develop breast cancer in their lives. Primary prevention is difficult to realize since most breast cancer risk factors are hard to modify. However, physical activity is a modifiable lifestyle factor which has been shown to reduce the risk of breast cancer. The mechanism by which physical activity reduces the risk of breast cancer potentially involves a decrease in mammographic breast density. The association between mammographic density and physical activity has been examined previously, but the findings were inconsistent. Objective - To evaluate the effect of physical activity on mammographic breast density, assessed with an automated volumetric method, in postmenopausal women.
Methods - This is a cross-sectional study of women who attended the national Dutch breast cancer screening programme in Groningen. A total of 2496 women, aged 50 to 75 years, were included in the study. Information on physical activity and breast cancer risk factors was obtained via a self reported web-based questionnaire. Absolute dense, percentage dense, and non dense volume were estimated using the automated Volpara system. Multivariable linear regression and analysis of covariance were used to assess the association between physical activity and mam- mographic breast density, across Body Mass Indiex (BMI) categories.
Bachelorcongres BMW Anne Siers: The evaluation of the change in heart rate variability in patients
with type 1 Diabetes Mellitus in the course of a hypoglycaemic event.
INTRODUCTION: Hypoglycaemic events are common in patients with type 1 Diabetes Mellitus (DM). Hypoglycaemia, an abnormal low blood glucose level, increases morbidity, mortality, and the costs of medical care. For patients who have developed impaired hypoglycaemic awareness, such events with abnormal low blood sugar levels can be a real problem, due to less or not sensing symptoms, which can eventually lead to impaired brain function and even death.
It is known from literature that heart rate variability (HRV) is significantly decreased in patients with type 1 DM. HRV decreases even further during a hypoglycaemic event. HR refers to the change in time between the R tops of two pulses and is measured in milliseconds. HRV indicates the fluctuations of heart rate around an average heart rate. It seems useful to assess whether there is a significant change in HRV before and during hypoglycaemic events. Eventually, hypoglycaemic events may be predicted, based on the change in HRV, and prevented. AIM: The aim of this study is to investigate whether there is a pattern of change in heart rate vari- ability preceding and during hypoglycaemic events, in patients with type 1 DM.
METHODS: This study is an observational pilot study with type 1 DM adults. Participants will wear the HeathPatch for four days, which measures vital signs continuously. In these four days, vital signs from a hypoglycaemic event will thus be collected by the HealthPatch. Analysis will be per- formed retrospectively with descriptive statistics in SPSS and Kubios.
Balder Stalmeier: Decision making in advanced Parkinson's disease
INTRODUCTION Parkinson's disease (PD) is a progressive neurodegenerative disease. As symptoms worsen, patients may become eligible for one of three advanced treatments. The treatment that is best for a patient heavily depends on their own preferences. Therefore, shared decision making (SDM) between professional and patient is key. In order to develop interventions to improve SDM in this decision, current decision making has to be examined first. Qualitative research by means of focus groups and interviews among patients has already been carried out in this field, but to assess importance and relevance of items mentioned, quantitative research is needed. AIM To quantitatively evaluate patients' current role, their knowledge, their information the factors influencing treatment choice for patients in the decision making process for an ad- vanced treatment option in PD.
METHODS A questionnaire was developed using the items mentioned during the qualitative research. This questionnaire was sent out to patients who had undergone at least one of the advanced treatment options. RESULTS 121 patients filled out the questionnaire. 96% of patients considered an active role important, while only 56% received a role they wanted. Only 40% of patients were familiar with all three treatment options, and 73% of important information subjects were not supplied well DISCUSSION As patients consider it important to have an active role in decision making, they should be able to participate in the decision making to the extent they want. However, the knowl- edge of patients and the information supply to patients are not up to par. Interventions to improve SDM should focus on determining a suitable role for each individual patient and on improving Bachelorcongres BMW Marloes Taken: Bio(Medical) Sciences versus Social Sciences students. More
consumed alcohol but less smoked.
Background: In the Netherlands 30% of all deaths are caused by cancer and 27% by CVD. A large proportion of those cases are caused by an unhealthy lifestyle. To avoid such cases we need to know the trends in lifestyle among different groups in the population. The aim of this study was to give an overview of lifestyle habits among (Bio)Medical Sciences and Social Sciences students focusing on weight, smoking status, alcohol consumption, dietary habits, and physical activity.
Methods: A descriptive survey was carried out among first year Biomedical, Medical & Social Sciences students registered during the 2015/2016 academic year on the Radboud University in Nijmegen. During fall semester a self-reported web-based questionnaire was send to 1104 first year students. The questionnaire included questions about demography, anthropometry, smok- ing status, alcohol consumption, dietary habits and physical activity. We looked at differences between academic discipline and compared lifestyle habits of students with national recommenda- tions for a healthy lifestyle.
Results: Out of 276 respondents, 53 (19%) were male and 223 (81%) were female. 8% of all stu- dents smoked, whereby 10% of Social Sciences and 4% of (Bio)Medical Sciences students. About 85% claimed to be alcohol consumer with more (Bio)Medical Sciences (91%) than Social Scienc- es (73%) students. In total 86% of all students satisfies the norm of a "healthy weight" and 61% vs. 37% of respectively (Bio)Medical sciences and Social Sciences students satisfies the norm "healthy exercising". In terms of dietary habits, students who lived with their family consumed less fruit [p=0.04] and vegetables [p=0.001] compared to students who live away from their family.
Conclusion: In this descriptive study more (Bio)Medical Sciences students reported to consume alcohol, whereas a greater proportion of Social Sciences students smoked.
Agnes Toll: The evaluation of changes in heart rate variability to differentiate
between mental stress and physical stress.
BACKGROUND Stress is defined as the body's psychological and biological responses to exter- nal as well as internal stimuli, such as thoughts and emotions. Stress can be helpful, as it gener- ates an alert state and provides us with a positive survival mechanism. However, repetitive stress, or distress, is associated with illnesses, such as asthma, hypertension, and burn out. Susceptibili- ty to stress differs from person to person, which makes it difficult to diagnose and treat. Last decades much research has been conducted to find a way to explore and measure stress further. Heart rate variability (HRV) is one of the factors which can be used to measure stress. HRV is measured in milliseconds and refers to the change in time between R tops of an ECG signal. It is the heart's ability to adjust to changes in heart rate, which may be caused by stressful events. A high HRV arises in a situation in which a person is relaxed and thus experiences little to no stress. A low HRV, however, is characteristic for being highly stressed. With a low HRV, the body is not able to respond quickly to changes in the heart rate. A low HRV is seen in both physical stress and in mental stress. Recently, wearable devices, which can measure HRV, have been developed. These devices are able to monitor vital parameters like heart rate, temperature, heart rate variability in real time. Wearable devices may help to assess personal stress levels in a non-invasive way.
AIM To assess whether it is possible to differentiate acute mental stress from physical stress with wearable devices that measure HRV. METHOD This study is an observational pilot study. A test course is designed which consists of four activities, two mental stress activities and two physical stress activities, which will respectively induce mental and physical stress. Vital parameter data, such as heart rate and HRV will be measured by wearable devices.
Bachelorcongres BMW Jolijn van Uden: The influence of the cold pressor test on the cerebral blood
Background: Major cardiovascular and cerebrovascular diseases are strongly linked to the de- velopment of atherosclerosis, which is preceded by endothelial dysfunction. Therefore, detection of endothelial dysfunction may contribute to the prevention of cardiovascular or cerebrovascular events. Recent work suggests that changes in cerebral blood flow in response to sympathetic ac- tivation (at the level of the carotid artery (CA), middle cerebral artery (MCA) and microvasculature) may have such predictive value. It is known that healthy subjects show an increase in blood flow in the CA and the MCA as a response to sympathetic activation and patients with cardiovascular diseases show a constriction in the carotid artery. However, little is known about the (temporal) relation between CA, MCA and microvasculature during sympathetic stimulation.
Objective: Simultaneously examine perfusion to the brain during sympathetic stimulation at the level of the CA, MCA and microvasculature in healthy subjects. Methods: 5 healthy subjects aged 18-30 years were included. The sympathetic nervous system was activated by the cold pressor test (CPT). During the experiment, the subject was in a supine resting position for 5 minutes. Subsequently, CPT was applied for 3 minutes, followed by another 5 minutes of rest. Across the entire experiment, blood cell velocity and diameter in the CA was measured with ultrasound. Simultaneously, Transcranial Doppler was used to measure the blood flow velocity in the MCA and Near Infrared Spectroscopy was used to determine changes in perfu- sion of the microvasculature of the frontal cortex.
Results: The diameter of the CA increased 3.57% on average with a maximal increase of 5.54% at 70- 80s during the CPT compared to baseline (N=3). The velocity increased 18.59% on average with a maximal increase of 34.91% at 80-90s. Blood flow increased 26.54% on average with a maximal increase of 45.02% at 60-70s. Results from other parameters are not available yet.
Astrid Verhoijsen: Health system constrains and cost-effectiveness analysis –
an integrated approach
Which assessment of the antiretroviral treatment (ART) is most cost-effective within the feasibility and affordability constraints in Ghana? Introduction: Since 2003 ART has been introduced in Ghana to give therapy to the HIV-infected people eligible for treatment (<350 CD4 cell count). Due to this therapy the mortality decrease, opportunistic infections decrease and sexual transmission reduce among HIV-infected people. In Sub Saharan Africa several studies have shown that scaling up an ART treatment is cost-effec- tive, but only few have assessed the cost-effectiveness in light of health system constraint such as affordability and feasibility. To reduce the costs of providing treatment and to get knowledge of how much funding is needed, it is relevant to know which ART intervention is most cost-effec- tive. Therefore this study examines how much more funding and human capacity is needed to reach the most cost-effective ART intervention within the available measures of costs and human resources in Ghana.
Method: The costs and cost-effectiveness are estimated based on the results from an epidemio- logical model, STDSIM (stochastic simulation model). A calculation is made for the gap of human resources that are needed. The duration of visits, work days in a month and efficient hours in a work day are taken into account in the calculation. The costs of the gap include salary costs, workshop costs and medication costs.
Bachelorcongres BMW Evy Verstraaten: Costing analysis for outreach HIV Testing & counselling for female
sex workers in brothels in Bandung, Indonesia.
Background - The HIV epidemic in Indonesia is still growing among female sex workers (FSW) and their clients. Voluntary counselling and testing (VCT) functions as an entry point for care and treatment. By the end of 2009, only 27,8% of the FSW had received a HIV test during the previous year. To reach more FSW mobile VCT can play an important role as it improves the physical accessibility. No data on costs of mobile VCT is known in Indonesia. Knowing the costs of mobile VCT is an important input for decision-making for health policy makers.
Objective - To determine the costs of mobile voluntary counselling and testing (VCT) service delivery among FSW in Bandung, Indonesia in 2015. The results of the study will be used to inform the local AIDS commission Komisi Penanggulangan AIDS (KPA). Methods Data on utilization and costs of mobile VCT among FSW was collected in a STI-clinic in Bandung for the period of January 2015-December 2015. The total amount of FSW tested that year was 407. Costing was performed using the micro-cost- ing approach. The costs are total programme costs from a societal perspective. The costs were divided in healthcare costs and non-healthcare costs.
Results - In 2015 the clinic tested 407 FSW during their mobile VCT activities. The unit costs per FSW tested by the intervention were $7.3. The total costs made in the analyzed period were $2972.87. The costs for the personnel formed the biggest cost component (83.34%) with $2359. In the 1-year period 21 new cases of HIV were founded among the FSW by the help of mobile VCT activities. The FSW were interviewed about the main effect about the mobile VCT, the results were Conclusion - The unit costs per FSW tested by mobile VCT are lower compared to the unit costs per VCT. Therefore it is important for decision-making to determine the effects of the intervention to perform a cost-effectiveness analysis. In addition, the clinic indicated that the clinic don't perform at full capacity for the mobile VCT activities. Up-scaling scenarios for the area Bandung are being calculated.
Maike Wientjes: Hospitalization costs for surgery patients in Malawi
What are the direct and indirect costs for patients who have undergone surgery at district hospitals and tertiary hospitals in Malawi and how do these costs relate to their income? INTRODUCTION African countries in particular have far too few surgeons to tackle the population burden of disease. Surgical services are often centralized in cities and only available for patients who can pay for them. A direct result of having to pay for health care can be financial catastrophe, which means that the total costs people have to pay for health care are too high in relation to income. Task-shifting of surgery for common conditions from medical officers to non-physician clinicians, like clinical officers, can be a life-saving measure in rural Africa. The clinical officers can provide basic, low-cost essential surgical interventions in district hospitals in a cost-effective way. COST-Africa is a research project that designed and implemented a scalable Clinical Officer surgical training programme in Malawi and Zambia. This programme trains clinical officers at district hospitals, what makes them able to do cases of major surgery themselves. In this study we want to assess the direct and indirect costs for patients who have undergone surgery at district hospitals and tertiary hospitals in Malawi and see how they relate to the patients' income.
METHOD Part of the COST-Africa study involved interviews with patients who have undergone pregnancy related surgery or surgery due to a hernia in 4 district hospitals and 2 central hospitals in Malawi. The interviews included i.a. questions about the hospital stay, financing the costs and the financial consequences of the surgery. Data was collected by clinical officers in the hospitals and sent periodically to the researchers. Statistical analysis were performed using SPSS Statistics 22, the Mann-Whitney- U-Test is used since the data is not normally distributed.
RESULTS 318 patients from district hospitals were included, of which 137 underwent hernia-related surgery and 181 obstetric-related surgery. 74 patients were included from central hospitals, who all underwent hernia- related surgery. Analysis is still ongoing.
Bachelorcongres BMW Kim van Bergen: The correlation between clinical measurements and evalua-
tion tests at the Gait-Realtime-Analysis-Interactive- Lab (GRAIL)
Background: Patients with mobility deficits commonly have disturbed static and dynamic balance, which impacts the ability to stand safely and the execution of ambulatory activities. Recovering this is frequently the principal intention during rehabilitation. In order to maintain balance, patients need to alter their walking speed, movement kinetics, kinematics and spatiotemporal charac- teristics. It depends on the ability of the patients to adapt to their environment if it is possible to reach functional independence and are, for example, able to cross an intersection safely. For this reason, rehabilitation is nowadays also focused on adapting to environments which patients will face in daily life. This is possible in a virtual environment, in which patients have the opportunity to be exposed to complex physical environments and experience daily life situations without physical danger. The improvement in balance and walking ability can be assessed with clinical measure- ments. For static balance the validated clinical measurement is the Berg Balance Scale (BBS) and for dynamic balance the Functional Gait Assessment (FGA). In this study, we used a virtual reality system to assess the clinical measurements, which is called the GRAIL. The main objective was to correlate the clinical measurements over-ground with balance tests on the GRAIL, because it is more convenient to perform the clinical measurements on the GRAIL when someone is in a GRAIL training program.
Methods: 20 able-bodied adults and 10 patients with a spinal cord injury, amputation or stroke participated in this study. The BBS and FGA were assessed for all patients and the GRAIL tests, which consisted of two static balance tasks on a moving platform and a two minute walking test, were performed by all subjects. The primary outcome measures were the Margin of Stability, symmetry in spatiotemporal characteristics, BBS and FGA score.
Results: This study is still active, results are expected to be presented at the end of June.
Mies van Bergen: Reduced sitting intervention to decrease total sitting time in
overweight subjects: an explorative study
Introduction: Physical activity has decreased in modern society, resulting in a sedentary life- style. A sedentary lifestyle is, independent of performing moderate-to- vigorous physical activity, associated with higher all-cause mortality and an increased risk for cardiovascular and metabolic diseases. Short-term studies using interventions to break up prolonged sitting showed a potential reduction in cardiovascular risk factors when regularly breaking up sitting. However, there are no interventions that can be used in daily life yet. Therefore, the aim of this study is to examine the feasibility of a novel, 4-week reduced sitting intervention in overweight subjects to reduce total sitting time and increase physical activity breaks.
Methods: Ten overweight (BMI>25) adults with self-reported sitting time of >6 hours per day received a 4-week reduced sitting intervention. The subjects used a wristband pedometer and a smartphone application. The wristband vibrated after every period of prolonged sitting (i.e. 30- minutes uninterrupted sitting) as a signal for the subjects to break up their sitting behaviour by light intensity walking. Physical activity was measured by an activity monitor, i.e. SenseWear Armband, for 7 days during waking hours before the intervention and during the fourth week of the intervention. Main outcomes were number of sit-to- stand transitions and total sitting time per day.
Results: Mean BMI of the subjects was 33.3 kg/m 2 (SD ±5.1). The mean wear time of the activity monitor was 14.4 (SD±0.87) hours per day for 6 (SD ±2) valid days. Prior to the intervention, we found a mean sitting time per day during baseline measurements of 12.1 hours (SD ±1.2) and a mean number of sit-to- stand transitions per day of 20 (SD ±5). Data during intervention are not Conclusion: The baseline measurements show that our subjects sit a considerably part during the day. Whether the intervention improved sitting time will be analysed during follow-up.
Bachelorcongres BMW Nadine Boers: Determination of patient acceptable symptom state by using different
patient reported outcomes in patients with knee osteoarthritis.
Background: The Patient Acceptable Symptom State (PASS) is the value beyond which patients consider themselves well. Although this is an important concept for clinical practice and trials, few studies have deter- mined PASS values for patients with osteoarthritis (OA). Objective: To determine PASS-values for pain, patient global assessment, function and stiffness in patients with knee OA undergoing a conservative treatment and to determine possible determinants for the PASS Methods: Patients completed questionnaires at baseline and 3 months including the following patient report- ed outcomes: pain on movement during the 24 hours before the visit and patient global assessment (PGA) of disease activity (assessed with the numerical rating scale with a score range of 0-10), and physical func- tion, measured on the Lequesne Algofunctional Index (LAI), the physical function subscale of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC-PF), the short version of the Knee Injury and Osteoarthritis Outcome Score (KOOS-PS) and the Lower Extremity Functional Scale (LEFS). All scores were standardized to a score range of 0-100. PASS values were defined as the 75 th percentile of the score of questionnaires for those patients who consider their state satisfactory.
Results: 161 patients completed questionnaires at both time points. 99 (62%) of patients were female, with a mean age of 59 years (sd = 9). The standardized estimates of the PASS were 60 for pain, PGA of disease activity and stiffness. PASS values for physical function varied between 47.9 and 60, depending on the questionnaire. Patients with depressive symptoms have a smaller probability of reaching a satisfactory state than non-depressed patients with odds ratios varying from 0.61 (0.30-1.23) to 0.26 (0.13-0.54).
Conclusion: PASS values found in this population are higher than found in earlier studies. Ourfindings sug- gest that PASS values are relatively stable among different questionnaires but vary among different groups of patients and cultures.
Hannah Boogert: Assessment of Valedomotion kinematic
Introduction: Motion capture systems (MCSs) are being used to objectively measure physical activities or movement. These systems can be used to measure the expected change a new therapy is supposed to accomplice in a quantifiable manner. One of the MCS that are used in the Radboud-UMC is the ValedoMotion system (Hocama), which tracks motion using inertial and magnetic measurement units (IMMU). The ValedoMotion system is an ambulatory MCS that measures the change in gait in terms of symmetry of the back and pelvis of patients after they have received an osseo-integrated prosthesis. However, the data derived from the ValedoMotion system was never validated. Because of known difficulties with the ValedoMotion system another ambulatory MCS was also examined, the Xsens MVN Biomech suit, which also uses IMMU's. The following research question was investigated: What is the gait symmetry of a healthy adult male while walking on a treadmill measured with two ambulatory motion capture systems com- pared to the gold standard? Method: The ValedoMotion system and the Xsens MVN Biomech suit were compared with an optoelectronic measurement system, the gold standard for motion tracking. The healthy subject performed five times a 2-minute walking test on a treadmill, all the three MCS systems were measuring simultaneously. Furthermore a list of MCS that are used within the hospital was made based on interviews. Bachelorcongres BMW Nathan den Broeder: Prediction of radiographic progression in patients with
knee or hip osteoarthritis: an exploratory analysis
Background: Osteoarthritis (OA) is a common rheumatic disease caused by the breakdown of car- tilage and bone that may occur in any joint, resulting in pain, stiffness and limitation of movement. The damage OA causes to a joint can be detected on radiographs in the forms of joint space narrowing (JSN) and the formation of osteophytes. A subset of patients show radiographic pro- gression over time, and it may be important for both patients and physicians to know the likelihood of progression when making treatment decisions.
Methods: This study uses data from the CONTROL-PRO cohort consisting of patients with knee or hip OA who received a conservative treatment program. To measure pain and physical func- tioning, the Western Ontario and McMaster Universities of Osteoarthritis Index (WOMAC) was used in addition to a numeric rating scale measuring patient global assessment. Measurements were performed at baseline, 3 and 24 months follow up. Anterior-posterior radiographs of knee and hip were made at baseline and at 24 months follow up. JSN and osteophytes were graded on a scale ranging from 0 to 6 and 0 to 12 respectively, according to the revised OARSI Atlas of individual radiographic features in osteoarthritis. Radiographic progression was defined as either an increase in JSN grade ≥2, an increase in osteophyte grade of ≥3, or an increase of one grade in both JSN and osteophytes. Patients who received a total joint replacement or an osteotomy during two years follow up will be regarded as having progressed. Backward logistic regression will be performed to identify factors predicting radiographic progression.
Results: 301 patients completed the 24 months follow up and were included in the study with a mean age of 54.9 years (95% CI 53.8-56.0), of whom 197 (65.5%) were female. Radiographs at baseline and 24 months were available in 262 patients, of whom 132 (50.4%) met the definition for progression. Further results will follow.
Iris Kolenbrander: Validation of a dual force plate instrumented treadmill
during the step adjustment test, using Vicon as golden standard.
Background: The step adjustment test is developed to evaluate a person's ability to adjust an ongoing step, which is a part of gait adaptability. Assessing someone's gait adaptability might be helpful to predict the risk of falling. The test detected impairments in the ability to adjust steps in stroke survivors, elderly people and patients with a lower limb amputation, compared to healthy individuals. These impairments were not detected by currently used clinical tests such as the Berg Balance Scale. Therefore, the step adjustment test could be useful as clinical test. It will be done, ideally, on a stationary treadmill instrumented with force plates, as these instrumented treadmills are increasingly applied in clinical settings. The golden standard for measuring the outcome, the foot placement error (FPE), is a 3D motion analysis system called Vicon. Currently, the use of the test is confined to laboratory settings, because Vicon is too large, expensive and specialized. It might also be possible to measure the FPE with force plates by measuring the center-of- pressure (CoP). It would be favorable to replace Vicon with the less expensive force plates.
Objective: To determine the accuracy of measuring the FPE in the anteroposterior and mediolater- al direction, during the step adjustment test in healthy adults, with a dual force plate instrumented treadmill, using the Vicon 3D motion analysis system as golden standard. We accept a variable error of 1 cm of the force plate data compared to Vicon.
Methods: Both systems measured simultaneously during the step adjustment test, which was performed barefoot on a stationary treadmill by 15 healthy adults. During the test, 20 ‘jump trials' and 30 ‘no jump trials' were randomly alternated in which the subject did or did not have to adjust an ongoing step, respectively.
Bachelorcongres BMW Minke ter Stal: Feasibility, reliability and external validity of the 2 minute walk
test on the Gait-Realtime- Analysis-Interactive-Lab (GRAIL)
Background: During gait training it is important for patients as well as their therapists to get insight in the effectiveness of their treatment. An innovative solution for gait training and evaluation are advanced instrumented treadmills in a virtual reality (VR) environment, for example the GRAIL. The self-paced mode of the GRAIL allows patients to initiate gait and walk at a self-selected speed, which makes it possible to perform an evaluation test such as the 6MWT or 2MWT. The 2MWT has a short duration, which makes it better tolerated than the 6MWT and more feasible for implementation as an GRAIL evaluation test. Recent research showed however no conclusive results about the clinic metric properties of evaluation tests performed on a treadmill. Performing a 2MWT on the GRAIL has not been described in literature yet. Therefore, the purpose of this study was to evaluate the feasibility, reliability and external validity of the 2MWT on the GRAIL in patients with gait problems and abled-bodied adults.
Methods: 20 abled-bodied adults and 8 patients with gait problems participated in this study so far. Patients were recruited out of the three largest diagnostic groups who receive GRAIL training: stroke, spinal cord injury and prosthesis. All subjects completed the 2MWT three times; twice on the GRAIL and once overground. The tests were performed on two separate days within one week. The primary outcomes were the percentage patients who successfully walked self-paced (feasibility) an the covered distance (reliability and external validity) during the 2MWTs. In addition, subjects wore motion sensors, for calculating the secondary outcome: spatiotemporal parameters. Other secondary outcomes were the influence of diagnosis and walking ability and the experience of the subject in relation to self-paced walking.
Results: This study is still active, results are expected to be presented at the end of June.
Friso Timmen: The effect of extra bodyweight on quadriceps muscle function
and aerobic capacity
Background: Weight loss is often accompanied by loss of fat-free mass (FFM), which is associ- ated with a decrease in muscle strength. However, the muscle strength per kg bodyweight stays the same, indicating that the muscles adapt to the altered bodyweight. This adaptation has been found in weight loss, but it is unknown if adaptation also occurs in weight gain. Previous studies reported improved exercise performances in athletes after wearing a weighted vest in daily life. However, there are no studies that have investigated the effect of wearing a weighted vest in daily life on muscle strength or on aerobic capacity. The aim of this study was to investigate the effect of wearing a weighted vest of 10% extra bodyweight for 2 weeks on (1) the quadriceps muscle function and (2) aerobic capacity.
Methods: 10 healthy volunteers (age >18) were included to wear a weighted vest set to 10% of their bodyweight, for 5 days per week during a 2 week period. Subjects were measured two times, once before wearing the vest (baseline) and once directly after wearing the vest for 2 weeks (effect). The quadriceps bench was used to assess the muscles function. Maximal voluntary con- traction (MVC), contractile properties and fatigability of the quadriceps were measured. VO 2 max (aerobic capacity) was measured with the Åstrand 6 minute bicycle test. Baseline and effect were compared within subjects.
Results: Baseline measurements of 6 subjects (3 female) have been performed. Their average length and weight were 1,73 m (SD ±0,05) and 73,0 kg (SD ±9,3) respectively. The mean VO 2 max was 3,5 L/min (SD ±1,0). The average MVC was 697,8 N (SD ±162,72). The average half relaxation time was 31,0 ms (SD ±9,1). The average decline in force output in the fatigue test was 28,9% (SD ±12,4).
Bachelorcongres BMW Eline Willems: Effect of Action Observation and Motor Imagery on the balance
recovery response by perturbations in multiple directions
Background - To recover from a balance perturbation, the leg angle of the first step is an important predictor for a successful balance recovery reaction. After repeated perturbations the leg angle increases, that results in a better recovery reaction. Another component that influence the recov- ery reaction is instruction that supports a good performance, which optimizes the learning curve. Furthermore action observation and motor imagery of balance perturbations in posterior direction contribute to a better execution of the first trial. In daily life balance perturbations occur with an unexpected direction and intensity, therefore the first trial reaction is interesting to investigate.
Objective - For the reason that balance perturbations occur unexpected in everyday life, it is necessary to test the balance recovery response after observing various perturbations in multiple Methods - One healthy young adult participated in every measurement as control. The control participant received 20 perturbations in 4 directions. Eleven young healthy adults observed these perturbations and later experienced 20 perturbations only in posterior direction. All participants received the same instruction to recover balance with one step. To measure the balance recovery reaction, the leg angle is used as a primary outcome.
Results - Action observation of the same direction resulted in a better first trial reaction than action observation of multiple directions, mean difference in leg angle of 7.16 degree (p=0,026). Action observation of different directions resulted in the same first trial reaction as the group that only received instruction. Conclusion - Action observation of multiple directions doesn't contribute to a better first trial reac- Bachelorcongres BMW Radboud Institute for Molecular Life Sciences René Bindels - Director "Understanding the molecu- lar basis of disease." The Radboud Institute for Molecular Life Sciences (RIMLS) is a leading multidisciplinary research institute within the domain of molecular mechanisms of disease and particularly in the fields of cell biology, molecular medicine, and translational research. The RIMLS accommodates research groups from the Radboud university medical center (Ra- doudumc) and the Faculty of Science of the Radboud University Nijmegen. Our mission is to achieve greater insights into the complexity of living cells in order to obtain compre- hensive knowledge of both normal and pathological processes. RIMLS aims to advance innovation in translational research, based on integrating diverse areas of scientific expertise within the molecular and medical sciences. In line with the Radboudumc's stra- tegic vision to "have a significant impact on healthcare", research is bundled into clinical- ly- orientated research themes from molecule-to-man (M-2-M) plus a "mechanism-based" theme focusing on chemical biology and nanomedicine. RIMLS works closely with the Radboud Institute for Health Sciences (RIHS), thereby extending many of the research themes from ‘man' to ‘population' studies. The multi-disciplinary approach to research in molecular life science is reflected in an established RIMLS Graduate School with a dedicated 2-year research honours MSc degree in Molecular Mechanisms of Disease and a follow-up 4-year PhD program. Our goals are: - To generate basic knowledge in the molecular medical science and to translate this knowledge into clinical applications, into the development of diagnostics and into the treatment of patients through translation- al research programs. - An international graduate institute integrating top research MSc and PhD programs constituting a challenging yet enriching learning environment where researchers of all levels are exposed to societal- relevant multidisciplinary research questions along the theme of understanding the molecular basis of disease. RIMLS inno- vation is advanced through a number of Technology Platforms, such as microscope and in vivo imaging, genomics, proteomics and bioinformatics. The RIMLS prides itself on being an international research school offering a stimulating environment for scientists of all levels. In addition to our Master‘s and PhD programs, the RIMLS actively participates in a post-doc platform and is committed to promoting career-track models, such as the Hypatia Tenure Track.
Bachelorcongres BMW Stijn van Beek: Glycerol-3- phosphate shuttle as a compensatory pathway to reduce high
NAD(P)H levels in mitochondrial complex I-deficient cells
Introduction: The mitochondrial oxidative phosphorylation system (OXPHOS) is essential for cellular ener- gy generation. The biggest and most convoluted multi-subunit OXPHOS protein complex is complex I (CI). Dysfunction of CI has been associated with Leigh syndrome which is an early onset, fatal neurodegenerative disorder. At the cellular level, Leigh syndrome is characterized by elevated levels of NAD(P)H and reactive oxygen species (ROS). When NAD(P)H is transferred to the cytosol, it could lead to ROS generation via NAD(P) H oxidases. A possible way to get rid of high NAD(P)H levels is via the glycerol-3- phosphate (G3P) shuttle. Cytosolic G3P dehydrogenase (cGPDH), one of the two enzymatic steps of the G3P shuttle, oxidizes NADH. In addition, glycerol-3- phosphate generated by cGPDH is used by mitochondrial G3P dehydrogenase (mGPDH) to reduce coenzyme Q. The latter can transfer its electrons to complex III and thus stimulate mitochondrial respi- ration while bypassing CI. Consequently, it can be hypothesized that the G3P shuttle is used as a compensatory pathway to lower the high NAD(P)H levels in CI-deficient cells.
Aim: To determine the activity of the G3P shuttle in wildtype and CI-deficient (Ndufs4 -/- ) mouse embryonic fibroblasts (MEFs).
Methods: mGPDH enzyme kinetics were determined in mitochondrial fractions of wildtype and Ndufs4 -/- MEFs using a spectrophotometric method. In addition, the cellular and mGPDH-driven respiration was measured, using the Oroboros Oxygraph-2k.
Results: Enzymatic activity assay data suggest that the Ndufs4 -/- MEF cells have a higher mGPDH activity than the wildtype cells. Genotype comparison of the mGPDH-driven respiration has yet to be conducted, but the method is suitable to measure GPDH-driven respiration.
Conclusion: The increased mGPDH-activity in CI-deficient cells could indicate that the G3P shuttle indeed oper- ates as a compensatory pathway in CI-deficient cells to lower high NAD(P)H levels.
Tijmen van den Berge: Fluid shear stress in ciliated renal epithelial cells regu-
lates the trafficking and activity of TRPV5
Background: The kidneys play an essential role in maintaining the systemic balance of calcium (Ca 2+) in our body. Ca 2+ reabsorption takes place in the distal convoluted and connecting tubules (DCT and CNT, respectively) of the nephron. This process includes the transcellular Ca 2+ transport, which occurs through cells in the DCT and CNT and is mediated by the apical calcium channel TRPV5. Recent studies have shown that renal cells respond to mechanical stimuli, such as flow/fluid shear stress (FSS) generated by urinary flow, to regulate the activity of ion channels. Epithelial cells in the nephron are stimulated by the passage of pro-urine in the lumen of the tu- bules. Protruding from the apical surface of these cells are slender, antenna-like structures known as primary cilia. Primary cilia mediate several downstream signaling pathways upon sensing flow. The relevance of transcellular Ca 2+ transport in DCT and CNT is demonstrated by the fact that slight disturbances in the process of Ca 2+ reabsorption lead to hypercalciuria and hypocalcemia, which can result in severe neurologic and cardiovascular impairments. To date, it remains unclear how these tubular cells can sense when Ca 2+ needs to be reabsorbed from the traversing tubular fluid and how these cells can adapt to differences in tubular flow rate and consequently electrolyte Methods: This internship will focus on elucidating the role of primary cilia in regulating Ca 2+ ho- meostasis in response to FSS. To enlighten the function and trafficking of TRPV5 via primary cilia, a new flow system (IBIDI) will be used to mimic urinary flow. A radioactive calcium (Ca45) assay will be used to elucidate the activity of TRPV5 during flow. For visualization Western blot and RT- PCR will be used in order to confirm the effects seen in the Ca45 Flow experiments. Bachelorcongres BMW Nikki van Bommel: Fusion capacity of DM1 and healthy human myocytes during coculture
with C2C12 myocytes
BACKGROUND: Myotonic dystrophy type 1 (DM1) is the most common hereditary muscular disorder with an adult onset. It is caused by expanded (CTG)n repeats in the 3' untranslated region of the dystrophia myotonica protein kinase (DMPK) gene. DM1 is a complex disorder with heterogeneous clinical symptoms, but myotonia and weakness and wasting of skeletal muscles are the most characteristic. At the moment there is no treatment for DM1. An important step in myogenesis is the fusion of myoblasts into myotubes, also called differentiation. It has been shown that human myoblasts with a CTG repeat are less capable of this fusion than myoblasts without the repeat. We wondered whether the fusion capacity of the human myocytes could be increased by introduc- ing C2C12 cells (mouse myocytes), since the latter might function as a stable fusion partner for the human OBJECTIVE: We aim to study fusion capacity of human myocytes cocultured with C2C12 myocytes by immu- nofluorescence imaging, polymerase chain reaction (PCR), quantitative PCR (qPCR) and Western blotting. This provides insight into the capacities of DM1 myocytes. MATERIALS AND METHODS: C2C12-H2B:GFP mouse myocytes (C2C12 cells with a green fluorescent tag) were cultured with human DM1 and isogenic healthy controls in different ratios to determine the optimal condi- tions to conduct these types of experiments. Fusion capacity was assessed by counting the amount of nuclei per myotube and the number of heterokaryons (myotubes with both mouse and human nuclei) in immunofluo- rescence images. Besides immunofluorescence assays, expression patterns of several differentiation markers were studied on both an RNA and a protein level by PCR, qPCR and Western blotting. Furthermore, the cocul- tures were filmed during differentiation.
RESULTS: This project will confirm whether fusion capacity is impaired in human DM1 myocytes containing a (CTG)2600 repeat and whether a stable fusion partner like C2C12 myocytes can improve this phenomenon. If so, the best ratio between human and mouse myocytes will be determined.
Steffie Bressers: Elucidating the molecular mechanisms of lithium-induced
prevention of albuminuria in aging mice
Lithium is a trace mineral that is essential for our mental and physical health. Besides that, lithium is also an important treatment for mental disorders, such as bipolar disorder. Unfortunately, people with a bipolar disorder have to use lithium on a daily base and chronically. This regularly intake of lithium is known to cause side effect such as the development of chronic kidney disease (CKD). CKD is diagnosed by a decrease in glomerular filtration rate (GFR) and/or the presence of albumin in the urine (albuminuria). Multiple mechanisms are contributing to the development of CKD. These mechanisms include aging, acute kidney injury, and medication interactions such as lithium. Accumulating observations suggest that in contrast to the development of adverse effects of lithium treatment, the administrations of low lithium amounts (<0.6 mM in blood) improves kidney function in different acute kidney injury models. Next to the advantageous effects of short term dosage of lithium on for example tubular cell proliferation there is evidence for the beneficial effects of low levels of lithium use on the long term. Under normal conditions aging can cause function loss of the kidney, which leads to decline in the GFR and protein loss via the urine in both human and mice. Non-published data demonstrated that chronic lithium treatment (1 year, <0.6 mM in blood) in 29 mouse strains showed a reduced albuminuria in most of these strains. There is not much known about this effect of low-dose lithium and the mechanisms behind it are not elucidated yet.
In this internship I tried to elucidate the mechanisms of reduced albuminuria in four strains of mice, by looking at three important albumin transporters in the proximal tubule: megalin, cubilin and CD36. We looked at the quantity by performing Western blot on kidney lysates, and at the pattern and location of those receptors via immunohistochemical staining.
Bachelorcongres BMW Christian van Dam: Evaluation of conditionally immortalized proximal tubular epithelial
cells (ciPTEC) as in vitro model for mitochondrial nephrotoxicity
INTRODUCTION Mitochondria are the main organelles in human cells responsible for the production of ATP. Damage to mitochondria can have severe effects to tissues, especially in highly active organs such as the kidney. Drugs can cause mitochondrial damage in the kidney, although prediction of renal-specific drug-induced mitochondrial toxicity is lacking sufficient reliability. Wilmer et al. 1 developed conditionally immortalized proximal tubular epithelial cells (ciPTEC) as potential model for testing drug-induced kidney injury, which is the focus of this METHOD To stimulate ATP production via mitochondrial OXPHOS in cultured cells, glucose in the culture medium was replaced by galactose 24h prior to experiment. By exposing ciPTEC and ciPTEC overexpressing organic anion transporter 1 (OAT1) to a range of specific mitochondrial toxicants (4h/24h), ATP levels were determined. As marker for mitochondrial activity, the ratio in fluorescence of JC-1 monomers (depolarised membrane) and aggregates (hyperpolarised membrane) was assessed. Reactive oxygen species (ROS) production and O 2 -consumption assays were performed as marker for respectively oxidative stress and activity of cellular OXPHOS, both upon exposure with model compounds for mitochondrial toxicity as well as potentially toxic compounds.
RESULTS Exposing cells to rotenone (0.1 µM) yielded a dose dependent decrease (78% ±4.8%, p=0.0083 in ciPTEC-OAT1) in ATP levels when cells were cultured in galactose medium, while no decrease was observed in glucose medium (p>0.05). Exposure of ciPTEC to a range of cisplatin (0-222 µM) or FCCP (0-2.5 µM) yielded a dose dependent decrease in JC-1 aggregate/monomer ratio correlating to a decreased mitochondrial membrane potential. Routine respiration yielded higher levels in cells cultured in galactose medium in comparison to cells in glucose medium (22.5 vs 14.4 pmol/s/ml in 2.5 million ciPTEC-OAT1 cells).
CONCLUSION Replacing glucose by galactose medium results in ciPTEC dependent on OXPHOS for ATP pro- duction. These culture conditions may improve predictivity for mitochondrial-associated toxicity compound testing.
Thomas van Ee: Rab27α and PI4K2α as a Google Maps of the phagosome commuting to the lyso-
Introduction: Dendritic cells provide the link between the innate and the adaptive immune system as they take up antigens
associated with pathogens or cancer via phagocytosis. After uptake, the phagosome fuses with lysosomes, resulting in the
degradation of the antigen. Peptides derived from the antigen are then presented to T cells of the adaptive immune system,
initiating an adaptive immune response. Traditionally the intracellular processing of antigen is studied with a focus on the
proteins involved. The lipids mediating this cascade remain understudied. Lipids can be expected to be very important anti-
gen processing regulators, since lipids are important and well-recognized mediators of intracellular trafficking in other phys-
iological processes such as cellular polarization and migration. Two proteins that have lipids as their suggested effector are
Rab27α and phosphatidylinositol 4-kinase 2 alpha (PI4K2α). Rab27α is a small GTPase involved in endosomal trafficking.
Rab27α is suggested to recruit the lipid kinase PI4K2α to the phagosome. PI4K2α produces the lipid phosphatidylinositol
4-phosphate (PI(4)P) which in turn initiates the fusion of the phagosome with lysosomes.
Understanding the antigen processing cascade is crucial for efficient cell-based anti-cancer vaccination, thus making this
subject one of the major research focusses of the Department of Tumor Immunology.
Aim: Goal of this project is to elucidate the role of Rab27α and PI4K2α in the phagosome and endosome routing to lyso-
Methods: Subcellular localization of potential effectors of Rab27α was assessed by Immune Fluorescence (IF)-staining.
Monocyte-derived dendritic cells from healthy volunteers were transfected with siRNA microporation to knock down Rab27α
and PI4K2α in human moDCs. The knock-down efficiency was assessed using Western Blot analysis and the effect of
these knock downs on the antigen processing cascade was determined using IF for phagosomal and lysosomal markers or
Fluorescent Activated Cell Sorting (FACS) for take-up efficiency using various time points.
Results: In our (pilot) experiments, we observed that Rab27α knock down blocked the degradation of cargo endosomes
containing the interleukin-6 receptor alfa (IL6Ra) and low density lipoprotein (LDL). LDL is a protein/lipid complex mediating
the trafficking of lipids to lysosomes. These findings confirm the role of Rab27α in phagosome routing to the lysosome.
Bachelorcongres BMW Janeri Fröberg: The synergic effect of TNFR2-agonist and CD28 super-agonist
on the ex-vivo production of stable regulatory T-cells: prospects for clinical
BACKGROUND: It has long been known that regulatory T-cells (Tregs) are essential for a healthy immune system. Tregs are crucial for immune homeostasis: they maintain self-tolerance, and prevent autoimmune disease. A lot of research has been done to see if Tregs can be used in immunotherapy of graft versus host disease in transplantations, and in autoimmune diseases like psoriasis, but the expansion of Tregs meets some difficulties. The amount of naturally occurring Tregs in the body is very small, making it difficult to get sufficient numbers for therapy. Additionally, in the past decade, evidence is found that the suppressive function of Tregs is not maintained in all cells, and Tregs are able to become effector T-cells. Two very promising stimulating agents are Tumour necrosis factor receptor 2 agonist (TNFR2-A) and CD28 super-agonist (CD28SA). Using them together could lead to a much bigger yield of Tregs, without losing the stability of the cell. It is however not clear how these two substances work together in stimulating Treg production, and what concentration-combination gives the optimal synergic effect. Is there a synergic effect of CD28SA and TNFR2-A on the formation of a stable Treg cell-line? METHOD: T-cells were isolated from peripheral blood (mononuclear cells) and stimulated with anti-CD3/CD28 beads, CD28SA, TNFR2-A, or a combination of TNFR2A and CD28SA for 7 days to differentiate the cells into Tregs. The phenotype of Tregs was analyzed with flow cytometry and IL-10, IFNy and IL-17 secretion were measured by ELISA. The different stimulation solutions were compared with each other in their ability to express a Treg-like phenotype, to produce suppressive cytokines and to inhibit the growth of effector T-cells.
RESULTS: no results yet. Cynthia Haanappel: Functional characterization and immunoregulation by in
vitro generated regulatory B cells.
Background: B cells are predominantly known for their positive regulation of inflammation by pro- ducing antibodies. Additionally they have an antigen presenting function that contributes to CD4+ T cell activation. However, since recent years there is evidence that b cell also play a crucial role in the negative regulation of immune responses. These cells are called regulatory B cells (Bregs). IL-10 is one of the most described mechanisms in which Bregs perform their function. The secre- tion of anti- inflammatory cytokine IL-10 namely inhibits Th1 and Th2 responses as well as the production of pro- inflammatory cytokines. This immunosuppressive capacity of Bregs gives them a potential to become new tools in the therapies of transplantation intolerance and patients suf- fering from autoimmune diseases. Studies have shown that especially in transplantation patients Bregs play an important role since B cells from tolerant patients produce significantly more IL-10 than patients who suffer from chronic rejection. Nevertheless, the exact working mechanisms of Bregs remain to be elucidated. Especially for in vitro generated Bregs a lot of questions remain considering their phenotype and best way of stimulation.
Objective: Development an ex vivo protocol to induce regulatory B cells and define their suppres- sive characteristics with the overall aim to support immunological tolerance by applying Breg- Methods: B cells were isolated from peripheral blood mononuclear cells and stimulated in vitro with αCD40, CpG-B and IL-21 as standard stimulators. Additionally B cells were cultured with the standard stimulators and IL-2. Phenotypic characterization was performed after 4 and 7 days us- ing flow cytometry. Production of IL-10 was measured by ELISA. The immunosuppressive capaci- ty of Bregs was determined by a mixed lymphocyte co-culture (MLC) assessed by flow cytometry.
Bachelorcongres BMW Tom van Haaren: Development and validation of a miniaturized mitochondrial com-
plex III assay
Background and purpose - Cardiovascular disease is the major disease burden worldwide. A high blood cholesterol level is a major risk factor for the development of cardiovascular disease. Consequently, cholesterol lowering statins, have proven to very effectively lower the risk on major cardiovascular events. However, up to 25% of all patients develop myopathies. Recently, inhibition of the third complex of the respiratory chain (CIII) was associated with the observed muscle pain. This may suggest that CIII could be a useful as a predictive marker for statin- induced myopathies. Ideally, the CIII activity should be measured in a non-invasive cost- effective manner, for which peripheral blood mononucleated cells (PBMCs) could be an ideal candidate. However, to investigate the predictive value in large clinical trials a miniaturized method is needed to determine mitochondrial CIII activity. Therefore, this study aims to develop and validate such a method.
Experimental approach - Mitochondrial fractions were isolated from C2C12 murine myoblasts, PBMC and muscle homogenate from statin-users and healthy controls, and from cultured primary human skin fibroblasts obtained from complex III-deficient patients and healthy controls. In these fractions, CIII ac- tivity was measured, and corrected for mitochondrial content using protein content and citrate synthase Key results - A miniaturized high-throughput CIII assay was developed in C2C12 mitochondrial frac- tions, and was able to discriminate between healthy control and CIII-deficient mitochondrial fractions when used on human skin fibroblasts (p<0.05). Although, it was possible to measure CIII activity in PBMC, there was no correlation between CIII activity in PBMC and muscle fractions.
Conclusions and implication - To conclude our assay is able to discriminate between healthy and CIII-deficient samples. Although the method needs further optimization in PBMCs, it is a first step towards a more personalized and safer statin use.
Jens jacobs: Detection of nerve hyperexcitability using surface-EMG in pa-
tients with acute oxaliplatin-induced neuropathy
Introduction: Oxaliplatin is a third generation platinum based antineoplastic drug used for treating metastasized colorectal and pancreatic cancer. A common side-effect is a sensory neuropathy, characterised by peripheral nerve hyperexcitability. The neuropathy starts as acute but can devel- op into a chronic variant. Because there is no way of diminishing the symptoms, it can be severe enough to lead to discontinuation of therapy. In the search to reduce the side effects, a way to quantify the hyperexcitability is needed. Therefore the primary objective of this study was to test whether the hyperexcitability can be measured by means of a surface-EMG (sEMG). The second- ary objective was to investigate if there was a measurable difference in hyperexcitability between the second and fourth round of treatment .
Methods: Patients of 18 years or older who were being treated with oxaliplatin at the Radboudumc were included. Exclusion criteria were: diabetes mellitus, chronic pain syndrome, alcohol abuse and pre-existing neuropathy. The tests occurred adjacent to the second and fourth round of treatment. First an electrode was attached to the m. interosseus dorsalis-1 where two minutes of sEMG was recorded. Afterwards the patients underwent a neurological examination and a series of questionnaires. One of the questionnaires was performed again the day after.
Results: A group of 10 patients was included.
Key words: Oxaliplatin, Metastasized Cancer, Neuropathy, Hyperexcitability, sEMG Bachelorcongres BMW Heleen Kanne: Review of umbilical metastasis
INTRODUCTION: Metastatic disease is the major cause of cancer-related death. Better knowl- edge of metastatic patterns for each tumor type could improve surveillance, prognosis and treat- ment of patients. Umbilical metastasis is a rare finding, with the vast majority of cases involving intra-abdominal cancer. This type of metastasis is often a sign of advanced malignant disease and this usually indicates a poor prognosis - the survival of these patients often ranges from 2 - 11 months after the initial diagnosis. However, the mechanisms leading to umbilical metastasis are still obscure.
AIM: This project aims at increasing the knowledge on this rare metastasis.
METHOD: The possible origins of umbilical metastases were investigated by performing a systematic review of the literature. Additionally, clinical data of 951 patients from PALGA were col- lected and analyzed to obtain an impression of the presentation of umbilical metastasis, including information about the histological tumor type, the primary tumor and other metastases. Further- more, a mutation analysis was performed on a set of umbilical metastases from the Radboudumc by targeted enrichment using Molecular Inversion Probes (MIPs) for 30 cancer related genes.
RESULTS: Of the 951 patients analyzed, 699 were female (73.5%). The most common histo- logical type was an adenocarcinoma, representing 92.7% of all the umbilical metastases. The ovarium was the most frequent location of the primary tumor (26.7%), followed by the intestinal tract (22.6%). Furthermore, in 20.0% of the cases the primary tumor remained unknown.
Jeroen Kuiper: Characterization of Biomarker Behaviour of Myotonic Dystrophy Type 1
Myoblasts During Differentiation
Background: Myotonic Dystrophy 1 (DM1) is a chronic and highly variable multisystem disorder. Currently no cure exists. The disease is characterized by myotonia and muscle weakness. An important step in myogenesis is the fusion of myoblasts into myotubes, also called differentiation. This process along with many other cell-pro- cesses is impaired in DM1 myoblasts. A promising treatment involves the use of antisense oligonucleotides (ASOs) that sterically block the mutated mRNA that causes DM1. The department of Cell Biology at the RIMLS is currently developing this strategy.
Objective: To contribute to the research into ASOs as a treatment for DM1 we extensively test a biomarker assay for DM1 myoblasts in control conditions and after ASO treatment. We also investigate the potential of apoptosis as a biomarker for DM1 myoblasts. Materials and methods: Patient myoblasts (DM11) and wildtype myoblasts (C25) were differentiated for 16 days under normal conditions and after treatment with ASOs . RNA and protein was harvested at six time points during this period. To find the difference in biomarker behaviour between C25 and DM11 and between control DM11 and DM11 treated with ASOs we determined mRNA expression, exon inclusion and protein expression with northern blotting, RT-PCR, PCR, qPCR, immunofluorescence assays and western blotting.
Results: Several of the tested biomarkers show a clear behavioural difference between C25 and DM11 during the 16 day differentiation period. Several potential apoptosis biomarkers show different expression and splicing patterns in DM11 and C25 cell lines. Conclusion: The results provide a more precise description of the behaviour of several DM1 biomarkers during a longer differentiation period than before. They could contribute to research aimed towards the development of a therapy for DM1 using ASOs by improving the ability to determine the health of patient cells, e.g. after Bachelorcongres BMW Jelena Meek: Targeting the TYK2-STAT pathway in lymphoid malignancies as a therapeu-
Background - Deregulation of the JAK-STAT pathway often plays a central role in the pathogenesis of lympho- ma. Tyrosine kinase 2 (TYK2) is a JAK family member, that when it gets activated via ligand binding of a cyto- kine receptor, induces phosphorylation of STAT transcription factors. Mutations and chromosomal translocations of the TYK2 gene have been linked to the pathogenesis of lymphoid malignancies. However, there are indica- tions that normal wild-type (wt) TYK2 expression is essential for lymphoid malignancies, since wtTYK2 T-cell acute lymphoblastic leukemia cell lines are known to be sensitive for inhibition with TYK2. The aim of this study is to investigate the therapeutic potential of targeting TYK2, in a broad spectrum of lymphoid malignancies.
Method - The expression of TYK2 and the presence of phosphorylated TYK2, a marker for activated TYK2, will be assessed in several B- and T-cell lymphoma cell lines, that express either wtTYK2 or an altered form of TYK2. Subsequently the expression of JAKs and STATs and their phosphorylation status will be examined. To examine the effect of TYK2 inhibition, the cell lines will be treated with TYK2 inhibitory drugs. Finally, to confirm the effect of TYK2 inhibition, TYK2 will be knocked down by both short hairpin RNA and CRISPR/Cas9-based genome editing.
Results - TYK2 is expressed in all lymphoma cell lines tested. The NPM1-TYK2 translocated cell line MyLa is the only cell line that demonstrated the presence of phosphorylated TYK2 . Generally cell lines with an activated JAK/TYK2 pathway were shown to be insensitive to a pan-JAK kinase inhibitor. However, when cells with a JAK mutation were treated a pan-JAK kinase inhibitor the cells stopped proliferating and showed inhibition of STAT Conclusion - JAK/TYK2 inhibition can effectively inhibit the phosphorylation of STATs of cells that are sensitive to pan-JAK kinase inhibitor. In those cases, were the lymphoma cell lines are insensitive to pan-JAK kinase inhibitor, but show activation of the STAT pathways, there is presumably another mechanism that maintains the viability and STAT phosphorylation.
Rob Meuwese: The effect of fludrocortisone on endothelium-mediated vasodilation of mesenteric resis-
tance arterioles from rats.
BACKGROUND: In congenital adrenal hyperplasia (CAH), adrenal synthesis of cortisol and aldosterone are blocked by a genetic enzyme deficiency, most commonly of 21-hydroxylase. This results in an increased produc- tion of ACTH and consequently an increased concentration of cortisol precursors, like 17-hydroxyprogesterone and progesterone, and their metabolites 21-deoxycortisol (21-DF), androstenedione and androgens. Patients are treated with cortisol, and often also with a mineralocorticoid, fludrocortisone. However, these patients are at risk to develop obesity, insulin resistance and hypertension, which are risk factors for the development of ath- erosclerosis. Still unknown is whether cortisol, fludrocortisone or one of the accumulated steroids have an acute effect on the endothelium, which may not only contribute to atherosclerosis directly, but also to the pathogenesis of hypertension. AIM: We studied the acute effects of steroids on endothelial vasodilator function in isolated mesenteric resis- tance arterioles from the rat. After previous studies with cortisol and 21-DF, the effect of fludrocortisone was investigated in this study.
METHODS: Second order mesenteric resistance arteries were isolated from adult male Wistar Hannover rats. The vasodilator response to acetylcholine (ACh; endothelium-dependent vasodilator) and sodium nitroprusside (SNP; endothelium-independent vasodilator) were studied in a Mulvany myograph in the presence of either 1 micromolar fludrocortisone or solvent as control. The maximal effect (EMAX), half maximal effective concentra- tion (EC50) and Hill slope were calculated using curve fitting according to the Hill equation. A paired-samples t-test was used to compare these values between the fludrocortisone exposed and control arteries.
RESULTS: Between fludrocortisone and solvent, EMAX, EC50 and HillSlope did not significantly differ for ACh (-13.99±8.85 (p=0.153), 8.29E-8±4.26E-7 (p=0.850) and 1.30±0.29 (p=0.365), respectively) and SNP (-14.62±5.85 (p=0.054), -1.96E-6±1.83E-6 (p=0.333) and 0.10±0.09 (p=0.354), respectively) (values are mean CONCLUSION: This study suggests that fludrocortisone has no direct acute effect on the endothelium-depen- dent and independent vasodilatation function of mesentric resistance arterioles from rats.
Bachelorcongres BMW Danny Noack: Interleukin-1 superfamily cytokines: training or tolerance?
BACKGROUND: It has been discovered that not only the specific adaptive immune system has the ability of memory,
but the innate immune system as well. Recently, the term ‘trained immunity' was proposed to describe the enhanced
innate host defence when a second infection occurs. In vitro restimulation of non-specific immune cells with lipopoly-
saccharide (LPS) leads to a response of pro- inflammatory cytokines; unrelated stimuli could possibly lead to an even
higher immune response. Now it is being studied if pro-inflammatory Interleukin-1 (IL-1) cytokine could be used as
stimuli to train immune cells, the question arises what the fundamental influence of IL-1 receptor antagonists (IL-1Ra,
IL-36Ra and IL-38) is on training. Future perspectives could exist of novel vaccine formulations that not only induce
pathogen-specific immunity, but also have innate immune-enhancing effects that reduce risk of unrelated infections.
AIM: To elucidate the influence of IL-1 family members IL-1α, IL-1β, IL-1Ra, IL-36Ra and IL-38 on inducing trained
immunity after restimulation with LPS.
METHOD: Adherent Percoll monocytes from buffy coat were incubated in vitro with either RPMI+(medium), β-glucan,
Bacille Calmette-Guérin (BCG) vaccine or LPS. IL-1α, IL-1β and their receptor antagonist (IL-1Ra) and IL-36γ (IL-
36Ra and IL-38) were used as stimuli to study the effect on inducing training or tolerance. The responsiveness of the
cells to secondary stimulation (RPMI+ or LPS) was assessed by TNFα and IL-6 cytokines production (ELISA).
RESULTS: IL-6 cytokine responses were compared to RPMI control (Mean±SEM; 1.00±0.00), IL-1α 100 ng/
ml (1.146±0.1726), IL-1β 100 ng/ml (0.9223±0.1077), IL-1Ra 10µg/ml (0.4884±0.1821), and IL-38 100 ng/ml
(1.195±0.2261). Changes in TNF-α responses were compared in IL-1α 100 ng/ml (2.350±0.4372), IL-1β 100 ng/ml
(2.351±0.5134), IL-1Ra 10µg/ml (0.6717±0.1304) and IL-38 100 ng/ml (1.385±0.0931).
CONCLUSIONS: IL-1α and IL-1β could possibly be contributors to inducing trained immunity. Although, IL-6 levels
are not significantly higher, TNF-α levels are. The receptor antagonists IL-1Ra, IL 36Ra and IL-38 do not significantly
change IL-6 and TNF-α cytokine responses after restimulation compared to controls, and therefore do most likely not
cause training or tolerance.
Roger Ottenheijm: Exploring the role of mitochondria in tuberculosis drugs-induced hepa-
INTRODUCTION: The disease burden of tuberculosis (TB) remains to be one of world's biggest threats. Globally, 9.6 million new TB cases arose in 2014. Nonetheless, standard treatment has remained the same for decades, consisting of rifampicin, isoniazid, pyrazinamide and ethambutol. This regimen is associated with various side-effects, of which the most important one is hepatotoxicity. To improve TB treatment, the mode of action of hepatotoxicity should be understood. It has been suggested that mitochondria play a key role in the hepatotoxicity of at least the TB drug isoniazid. Therefore this study aims to investigate the mitochondrial toxic potential of the ten most used TB drugs.
METHOD: Human hepatocellular carcinoma cell lines (HepG2) were exposed to 100 µM of a single TB drug (i.e. isoniazid, rifampicin, pyrazinamide, ethambutol, clofizamide, moxifloxacin, amikacin, ethionamide, linezolid and para-aminosalicylic acid). Subsequently, mitochondrial membrane potential (MMP), and mitochondrial morpholo- gy were determined using fluorescent microscopy in combination with the mitochondrial dye TMRM. RESULTS: A significant increase in MMP could be observed after exposure to isoniazid (19% ± 3.2, p<0.05) and ethambutol (29% ± 6.4, P<0.001). Exposure to para-aminosalicylic acid decreased the MMP significantly (22% ± 1.7, p<0.05). Rifampicin exposure resulted in smaller and less branched mitochondria. This may be indicative for fragmented mitochondria, which is often observed with mitochondrial toxicants. The mitochondrial area was significantly increased after exposure to clofizamide, rifampicin and amikacin. Together with the observed frag- mentation, this may indicate that rifampicin induces mitochondrial swelling. As clofizamide and amikacin did not alter other mitochondrial morphology parameters the observed increase in area could be due mitobiogenesis as a compensatory response to underlying mitochondrial dysfunction.
CONCLUSION: Exposure of HepG2 cells to isoniazid, ethambutol, para-aminosalicylic acid and rifampicin results in mitochondrial toxicity. The effects of clofizamide and amikacin need to be investigated in more detail.
Bachelorcongres BMW Eva van der Pasch: The role of phosphorylcholine on non-typeable Haemophilus influenzae
lipooligosaccharide IgM opsonization and complement-mediated killing
Background: Non-typeable Haemophilus influenzae (NTHi) is an opportunistic pathogen that can be found in the human nasopharynx. It is a primary cause of otitis media in children but can also lead to more severe diseases such as meningitis or sepsis. For this, NTHi needs to survive in the presence of the human complement system. A lot of variability in resistance to complement-mediated killing has been found amongst NTHi isolates. This can partly be explained by heterogeneity in the lipooligosaccharide (LOS) of the bacteria. The LOS of H. influenzae contains phosphorylcholine (Pcho). Incorporation of Pcho into the LOS seems to be an advantage for coloniza- tion in the nasopharynx. However, Pcho is also recognized by IgM and C-reactive protein (CRP), which can lead to activation of the classical pathway of complement.
Objective: To determine the effect of Pcho on complement activation and sensitivity to complement- mediated Methods: Different mutants of NTHi strain R2866 that express high and low Pcho had previously been created. Opsonization of the bacterial surface with IgG, IgM, CRP, complement factor C3, and the terminal complement complex C5b-9 in pooled human serum and cord blood plasma were measured by flow cytometry. To determine resistance to complement-mediated killing, survival of the bacteria in pooled human serum was tested.
Results: IgG was similar for all bacterial strains. However, opsonization with IgM, CRP, C3, and C5b-9 was increased in strains expressing high Pcho compared to strains expressing low Pcho. The strain expressing high Pcho showed lower survival in human serum compared to strains expressing low Pcho.
Conclusion: Presence of Pcho on the bacterial surface increases binding of IgM and CRP, which leads to complement activation as determined by C3 and C5b-9 opsonization. Increased complement activation leads to decreased survival in human serum. Therefore, Pcho may be a disadvantage for NTHi when causing invasive Iris te Paske: Tracking of Cathepsins; Fluorescent labelling of Cathepsin S and X via
genome editing with CRISPR/Cas9
INTRODUCTION Dendritic cells (DCs) are key players in the initiation of immune responses against pathogens and cancer. DCs can take up, process, and present antigens to T-cells, thereby activating the adaptive immune system. In processing of the antigen, cysteine cathepsins play an important role. These endosomal proteases are involved in cell proliferation, migration, maturation, and adhesion. Until now, 11 cathepsins (B/C/F/H/K/L/O/S/V/W/X) were discovered and all display specialized functions. Re- lated to their functions, cathepsins are associated with tumor metastasis and highly expressed in various forms cancer. Recent research uses activity based probes (ABP) to track cathepsin activity in vitro and in vivo. However, with those probes only active cathepsins can be visualized. Direct visualization of endog- enous expressed cathepsins will expand the knowledge about the unique and shared role of cathepsins in proteolytic processes. Understanding involvement of (in) active cathepsins in cellular pathways may improve diagnosis and treatment strategies for cancer patients.
AIM Develop a tool to visualize endogenous expressed cathepsins. Visualization will be accomplished by knock in of fluorescent tag to track inactive cathepsin S and X in vitro. This enables distinction between active cathepsin (via APBs) and inactive cathepsins during different cellular processes.
METHODS Use CRISPR/Cas9 system for genome editing in combination with homology directed repair (HDR). HDR templates and several gRNAs and Nickases have to be designed. After successful trans- fection, biological assays will be performed to validate integration and expression patterns in different cellular processes.
RESULTS HDR-templates, gRNAs and Nickases for CRISPR/cas9 are designed. HDR-constructs are successfully combined via restriction and ligation reactions. Transfection is performed on murine dendrit- ic cell line and murine macrophage cell line.
Bachelorcongres BMW Vera Poort: Unveiling calcineurin inhibitor-induced hypertension in kidney
Background: About 1000 kidney transplants a year are performed in the Netherlands. Over the past decades, the treatment and life expectancy of these patients have markedly improved. How- ever, the most widely used drugs: calcineurin inhibitors (CNIs), come with undesirable side effects. CNIs give rise to hypertension which is affecting the general health of the patient, but also the survival of the transplant. So far, the mechanism by which CNIs cause hypertension remains to be elucidated. Salt handling and controlling blood pressure is the main task of the kidneys. Studies have shown salt- sensitive induced hypertension in patients using CNIs. Disturbances in sodium reabsorption, due to mutations in sodium transporters, give rise to severe phenotypes. These patients suffer from low blood pressure and electrolyte imbalance. The opposite holds also true, hypertension is associated with increased abundance of the sodium transporters NKCC2, and NCC respectively. We therefore hypothesize that CNIs might increase the abundance and activity of these sodium transporters, and focus mainly on the sodium potassium chloride cotransporter METHODS: To address this hypothesis an in vitro and ex vivo approach was used. NKCC2 trans- fected HEK293 cells were treated with different concentrations of the CNIs, Cyclosporin A and Tacrolimus. The total NKCC2 and phosphorylated amount of NKCC2 were visualized with West- ern blotting. Urinary exosomes of renal transplant patients who use CNIs were used, and NKCC2 abundance and phophorylated NKCC2 was visualized. The composition of urinary exosomes gives a good prediction of the composition of the kidney cells.
RESULTS: CNIs do not influence total NKCC2 abundance or phosophorylation in vitro. CNIs do affect the abundance of NKCC2 in kidney transplant patients.
Karlijn Remmers: Is bedaquiline a potential new drug for infections by nontuberculous
BACKGROUND: Nontuberculous mycobacteria (NTM) are increasingly recognized as opportunistic pathogens of humans. Pulmonary infections are most frequent and resemble pulmonary tuberculosis. Current multi-drug treatment regimens often fail, partly due to extensive drug- resistance of NTM. New effective treatment regimens are needed. Bedaquiline is a novel antibiotic for multidrug-resistant tuberculosis, but its potential for treatment of NTM disease is unknown.
AIM: To investigate the in vitro activity of bedaquiline against the clinically most relevant NTM and its possible synergistic interactions with established antimycobacterial drugs, to design new treatment regimens.
METHOD: The minimum inhibitory concentration (MIC) of bedaquiline against reference and clinical isolates of Mycobacterium avium complex, M. abscessus, M. malmoense, M. simiae, M. kansasii, M. fortuitum was deter- mined by broth microdilution in both Mueller Hinton (MH) and Middlebrook 7H9 (M7H9) medium.
Synergy of bedaquiline with amikacin and tigecyclin against 10 M. abscessus isolates was assessed using the microdilution checkerboard method and with these results a fractional inhibitory concentration (FICI) was cal- culated to measure synergism. An interaction was seen as synergistic (FICI ≤0.5), additive or no reaction (FICI 0.5-4), or as antagonistic(FICI >4).
RESULTS: The MICs for bedaquiline ranged from 0.25-1µg/ml in M7H9 and from 0.03-0.5µg/ml in MH; the rapid growers (M. abscessus, M. fortuitum) had the highest MICs. The MICs for M. xenopi were >8 µg/ml in M7H9 and 4 µg/ml in MH; this species is known to be naturally resistant to bedaquiline.
The average FICI for bedaquiline-amikacin and bedaquiline-tigecyclin was 0.984 and 1.096.
CONCLUSION: Bedaquiline is active against NTM, in vitro. It is more potent in MH than in M7H9. It also shows an additive interaction, but no synergy, against M. abscessus with amikacin and tigecyclin. Bedaquiline warrants further evaluation as a treatment modality for NTM infections.
Bachelorcongres BMW Lisa Schiffelers: The role of the REST gene in the presence of neuroendocrine markers in
Merkel cell carcinoma
BACKGROUND Merkel cell carcinoma (MCC) is a rare and highly malignant skin cancer that often appears as an asymptomatic nodule on sun-exposed regions. In 80% of the cases, MCC is associated with the Merkel cell polyomavirus (MCPyV). The originating cells of this cancer type are still unknown. It was suggested that Merkel cells would be the origin of MCC, based on resemblances like the expression of neuroendocrine markers. Meanwhile, recently conducted research indicates the probability of early B-cells being the cellular ancestors of MCC. Therefore, the presence of neuroendocrine markers in MCC remains obscure. A negative regulator of neuronal gene expression, the RE1-silencing gene (REST), is presumed to play an important role in the expres- sion of these markers in MCC.
METHODS To investigate the role of the REST gene in MCC, primarily its expression will be examined by means of Immunohistochemistry (IHC) on protein level and RT-PCR on RNA level. Therefore RNA was isolated from the MCPyV positive MCC cell lines MKL-1, MKL-2, the MCPyV negative MCC cell lines MCC13 and MCC26 and B-ALL cell-line REH. Furthermore, the regulation of the REST expression by methylation was investigated with the demethylating agent 5-aza- 2'- deoxycytidin. By means of a bisulphite conversed PCR the methylation status of the REST gene was visualized.
RESULTS Cell lines MKL-1 and MKL-2 do not express the REST gene, whereas MKL-2 shows a weak presence of the REST RNA transcript. MCC13, MCC26 and REH turn out to be positive for REST on RNA and protein level. The demethylating experiments lead to a minimal increasing expression of the REST gene in the cell lines MKL-1 and MKL-2.
CONCLUSION The lack of expression of the REST gene in the MKL-1 and MKL-2 cell lines can explain the presence of neuroendocrine markers in MCC. Further experiments will be necessary to analyse if REST gene expression is regulated by its methylation status. Thereafter it will be possible to establish new treatment options Milou Smits: Role of cilium-mediated signalling in drug transporter expression
in renal proximal tubule cells
Background: Kidney injury caused by drugs is often only recognized in clinical studies and not during preclinical drug development. The human-derived proximal tubule epithelial cell model ciPTEC expresses a primary cilium, which propagates signalling as a result of fluid shear stress (FSS). Exposing ciPTEC to flow increases the physiological relevance of the model and may enhance preclinical drug toxicity testing via cilium-mediated regulation of drug transporters. This study aims to evaluate the effect of cilium-mediated signalling on drug transporter expression in proximal tubule epithelial cells (PTEC).
Methods: The gene expression of membrane transporters OAT1 (SLC22A6), OAT3 (SLC22A8), OCT2 (SLC22A2), OATP4C1 (SLCO4C1), Pgp (ABCB1), BCRP (ABCG2), MRP2 (ABCC2), MRP4 (ABCC4), MATE1 (SLC47A1), MATE2-k (SLC47A2), NaPi-IIc (SLC34A3) was quantified under FSS or static condition by qPCR in ciPTEC-parent which expresses a range of membrane transporters, and in ciPTEC-OAT1 and ciPTEC-OAT3 with recombinant expression of the respec- tive transporters. Results: Only in ciPTEC-parent, MATE1 was increased (5 fold ±2) by FSS. However, MATE1 expression in ciPTEC-OAT1 was increased in comparison to ciPTEC-parent, both under FSS (10- fold ±4) and static (65-fold ±40) condition. Comparing ciPTEC-OAT3 with ciPTEC-parent, MATE1 was increased (12-fold ±8) under static condition only. The expression of the other transporters were not significantly upregulated. Conclusion: The effect of FSS on the expression of MATE1 can affect the response to nephro- toxicants. This suggests that there is an effect of cilium-mediated signalling on drug transporter function in PTEC.
Bachelorcongres BMW Nikki Wanders: The Effect of Calcium Sulphate Microparticles on the Handling
Properties and in vitro Degradation of Injectable Calcium Phosphate Cement
Background: Bone substitute materials can be placed to aid in recovery of bone fractures. How- ever, the bone substitute material has to be biocompatible, have matching mechanical properties to that of bone tissue, and have a porous structure for proper diffusion of nutrients and oxygen. Furthermore, it has to be biodegradable over time to not interfere with the regeneration of bone tissue. Calcium phosphate cement (CPC) is an interesting synthetic bone substitute, as it is bio- compatible, injectable, and therefore able to fill irregular bone defects by the ability to be molded. However, the downside of CPC is its generally poor degradation. Poly(lactic-co- glycolic-acid) (PLGA) is a porogen that can create a porous structure to ensure degradation. Although, early degradation of the material is still up for improvement. Calcium sulphate (CS) is a material used as a bone substitute that shows too rapid degradation. By adding CS as a porogen, fast macro- porosity of CPC could be obtained. Since CS as a porogen has not been researched before, a material study was conducted. Methods: CPCs were created with the addition of CS in a ratio of 60:40 (CPC-CS), and with the addition of PLGA and CS in a ratio of 36:24:40 (CPC-PLGA- CS40) or 54:36:10 (CPC-PLGA- CS10). CPC with the addition of PLGA was used as a control group (CPC-PLGA; ratio 60:40). A saline solution was added to obtain the cement paste. By exposing the CPCs to phosphate-buff- ered saline (PBS) for 1, 2, 4 and 6 weeks at 37 degrees C, the degree of degradation was mea- sured in terms of weight loss of the CPCs and in terms of pH change of PBS. Micro-CT images were obtained at 0 and 6 weeks to compare morphology.
Results: CPC-PLGA- CS40 shows the most promising results in terms of weight loss and pH changes after 4 weeks of submersion in PBS.
Leonie Wolberink: A pharmacokinetic study on the concomitant use of metformin
and daclatasvir: it is safe.
Introduction: Daclatasvir is a drug used to treat hepatitis C virus (HCV) that also inhibits, among others, organic cation transporter (OCT) 1 and 2. Metformin is a drug used to treat diabetes mellitus (DM) and is an OCT 1 and OCT 2 substrate. When combined with daclatasvir, elevated levels of metformin may occur, which increases the risk on hypoglycaemic episodes. HCV is known to be associated with insulin resistance, which may develop into DM. This may cause a patients to need to use both daclatasvir and metformin. The aim of this study is to provide clinical information on a potential drug-drug interaction between daclatasvir and metformin. Method: An open-label, 2-period, randomized, cross-over, single-centre, phase-I, multiple dose trial in 20 healthy volunteers. For one period, volunteers will use metformin only and their pharmacokinetic pa- rameters will be determined by blood sampling and urine sampling. For the other period, volunteers will use both metformin and daclatasvir and their pharmacokinetic parameters will be determined by blood and urine sampling as well. Plasma and urine concentrations of metformin and plasma concentrations of daclatasvir will be measured with validated UPLC methods. The pharmacokinetics parameters C max (maximal plasma concentration), C trough (the lowest plasma concentration in steady state) and the Geometric Mean Ratios (GMR) of metformin levels and daclatasvir levels will be determined. Metformin levels with daclatasvir and metformin levels without daclatasvir will be compared, to see if there are statistically significant and clinically significant differences in the metformin levels. Results: From a noncompartmental analysis is has been found that there are no statically significant or clinically relevant differences in the C max , C trough and GMR of metformin levels while using daclat- asvir and while using it without daclatasvir. Conclusion: Daclatasvir and metformin can be safely used together in healthy volunteers. Bachelorcongres BMW Carolien Zeelen: Visualization and identification of the intravasation niche and the influ-
ence of hypoxia on the location of intravasation in murine breast cancer and melanoma
Background: Metastasis is the main factor that causes poor prognosis in cancer patients. Metastasis formation starts with invasion of tumor cells into the blood vessels (intravasation) were they can move to distant tissue, ex- travasate and form metastases. Tumors often outgrow their vascular resources, causing a hypoxic tumor core. Hypoxia-inducible factor 1α (HIF1α) accumulates in hypoxic cells, activating gene transcription that promotes angiogenesis, cell survival and therefore cause metastases. Until now, there has been no direct evidence of intratumor intravasation inside the tumor core neither using intravital imaging nor ex vivo in histological slides. Because of the fact that intravital imaging techniques cannot penetrate the tumor tissue deep enough to reach the hypoxic core, and thin histological slides (4µm) are too thin to reliable visualize intravasation, we want to use thicker slices (up to 70 µm) to characterize the intravasation niche and the blood vessel network in the tumor to determine the influence of hypoxia on these regions. Methods: Murine melanoma tumor slices of different thicknesses embedded in paraffin or frozen in optimum cut- ting temperature medium were stained for tumor cells, blood vessels (collagenIV) and hypoxia markers (HIF1α) using fluorescence immunohistochemistry. Furthermore, a hypoxia sensor (HRE-mCherry) was tested on its ability to report the hypoxia response in breast cancer cells. To investigate the role of hypoxia in intravasation, the expression of HIF1α will be co-registered with a blood vessel staining. Results: Blood vessels were stained for collagenIV in thick tumor slices and regions of tumor cell- blood vessel interactions have been identified. For the detection of hypoxia, we used a HIF1α staining and were able to distinguish between normoxic and hypoxic cells in 2D cultured melanoma and breast cancer cells.
Conclusion: We were able to detect tumor cell-blood vessel interaction in thick 3D tumor. The hypoxia marker HIF1α, the hypoxic sensor and a blood vessel staining will be combined to identify intravasation hot spots and hypoxic regions in tumors when the protocol for this staining is fully optimized. Bachelorcongres BMW Jur Koksma - Coördinator AVEO "Learning how to think" really means learning how to exercise some control over how and what you think. It means being conscious and aware enough to choose what you pay attention to and to choose how you construct meaning from experience." David Foster Wallace (from: This is Water) Academische vorming is een verplicht nummer in wetenschappelijke opleidingen. "We zijn toch geen HBO-opleiding", klinkt het soms, met enig dedain. Vacaturebeschrijvingen spreken vaak van ‘een academisch denkniveau' als vereiste voor een baan. Dus docenten aan de universiteit doen hun best om studenten te ‘leren denken'. "Maar ik kon toch al denken," hoor ik jullie denken (pun intended). David Foster Wallace, de man van het bovenstaande citaat, gaat hier op in tijdens de toespraak die hij houdt bij de diploma-uitreiking op Kenyon College, Ohio, USA. Ik raad jullie overigens van harte aan om het filmpje hiervan te beluisteren op Youtube. Want natúúrlijk kunnen studenten al denken voordat ze op de universiteit komen, zegt hij. Maar echt leren nadenken gaat over veel meer dan waar academische vorming over gaat bij de meeste wetenschappelijke opleidingen. Het gaat over het vermogen te reflecteren op je eigen ‘default modus' van denken. Wallace laat zien dat we eigenlijk allemaal een beetje lui zijn en niet geneigd de moeite te nemen ons echt te verplaatsen in een ander. Als je je eigen denken kunt beschouwen en daarna ook sturen, dan heb je wellicht pas echt leren denken. En als je daar beter in wordt, maakt het je een beter mens. En een veel betere professional. Onderzoek doen dat betekenisvol wil zijn, vraagt erom dat je eerst in gesprek gaat met anderen om te zien wat voor de ander van waarde is. Aangezien wij allemaal het centrum van het heelal zijn, is dat heel moeilijk. Op het Radboudumc proberen we dit nu te doen met wat dan heet de ‘persoonsgerichte zorg'. Luister nou eens goed naar dat verhaal van die persoon, naar wat het voor haar of hem betekent te leven met een ziekte. Vandaag luisteren we naar verhalen van collega-studenten over hun onderzoek. We denken na over onze eigen toekomst als professional. Wat vinden we interessant, waar gaat ons hart sneller van kloppen? Hoe komen we er achter wat goed voor ons is? Allemaal belangrijke vragen om te stellen. Eenieder heeft recht op zijn eigen paradijs. Maar misschien moeten we om daar echt goede antwoorden op te kunnen geven eerst ‘leren denken' op de manier zoals Wallace Bachelorcongres BMW Voorbeeldvragen AVEO 1. Hoe ben je bij deze afdeling gekomen? 2. Hoe heb je contact opgenomen met de afdeling? 3. Hoe zag een dag voor jou er uit? 4. Hoe was de werkdruk? 5. Hoe was de communicatie met je begeleider? 6. Was alles goed te plannen? 7. Hoe heb je het uiteindelijk ervaren? 8. Wat waren je verwachtingen? 9. Zou je achteraf voor een ander onderwerp gekozen hebben? 10. Wat zijn je plannen voor de toekomst? Bachelorcongres BMW Bachelorcongres BMW Bachelorcongres BMW
Osteoporos IntDOI 10.1007/s00198-012-1958-1 A framework for the development of guidelinesfor the management of glucocorticoid-induced osteoporosis S. Lekamwasam & J. D. Adachi & D. Agnusdei &J. Bilezikian & S. Boonen & F. Borgström & C. Cooper &A. Diez Perez & R. Eastell & L. C. Hofbauer & J. A. Kanis &B. L. Langdahl & O. Lesnyak & R. Lorenc &E. McCloskey & O. D. Messina & N. Napoli &B. Obermayer-Pietsch & S. H. Ralston & P. N. Sambrook &S. Silverman & M. Sosa & J. Stepan & G. Suppan &D. A. Wahl & J. E. Compston &Joint IOF-ECTS GIO Guidelines Working Group