Depression and Risk of Cardiovascular Disease in older General Practice patients

Hart- en vaatziekten (HVZ) veroorzaken een enorme ziektelast in Nederland, vooral bij ouderen. Deze aandoeningen vormen al jaren de meest voorkomende doodsoorzaak. Depressie, een psychische stoornis die veel voor komt, lijkt de kans op het krijgen van HVZ of op voortijdig overlijden aanzienlijk te verhogen. Hoewel in de literatuur de vraag:Beekman, A.T.F. [Promotor]Haan, M. de [Promotor]Hout, H.P.J. van [Copromotor]Marwijk, H.W.J. van [Copromotor

De zin van het economische opnieuw beschouwd

In 1950 heb ik het hoogleraarschap in de economie aan de juridische faculteit der Vrije Universiteit te Amsterdam aanvaard m et een rede over de zin van het economische. Sinds- dien heeft dit centiaal m elhodologisch vraagstuk van de we- tenschap der economie mij ook verder bezig gehouden. Het is voor een economist een m oeilijk vraagstuk, om dat het tevens een wijsgerig vraagstuk is. Over het algemeen vindt de econo­ m ist daarover weinig in de filosofische liLeratuur. Dit is zeer begrijpelijk, w ant wijsgeren kunnen op zijn best m aar heel sum m ier kennis nem en van wat er in de vakw etenschappen omgaat, terw ijl zij, voor zover mij bekend, in den regel slechts weinig belangstelling voor de economie aan den dag leggen. Omgekeerd zijn econom islen m eestal niet bijzonder filosofisch aangelegd, en hebben zij de handen vol om de storm achtige ontwikkeling van liun eigen literatuur enigzins bij te houden afgezien nog van het l'eit dat zij in den regel vele praktischc beslom m eringen hebben, ten gevolge waarvan zij zich niet ongestoord aan de studie kunnen wijden. Van een behoorlijk sam enspel tussen filosolen en economislen komt over het ge- heel ook niet veel terecht. Wat de wijsgerige kant van m ijn overpeizingen betreft, ben ik dus door de nood gedwongen slechts am ateur. Ik kom daar gaarne voor uit, en ik ben steeds bereid te zwichten voor het beter oordeel der wijsgeren, m its ik dat kan vatten, en in m ijn eigen w erk daar iets mee uit kan richten. Men behoeft nog geen door de wol geverfd prag­ m atist of operationalist te zijn om te weten dat ieder werk zijn eigen eisen stelt

Isolation of Retinal Stem Cells from the Mouse Eye

The adult mouse retinal stem cell (RSC) is a rare quiescent cell found within the ciliary epithelium (CE) of the mammalian eye1,2,3. The CE is made up of non-pigmented inner and pigmented outer cell layers, and the clonal RSC colonies that arise from a single pigmented cell from the CE are made up of both pigmented and non-pigmented cells which can be differentiated to form all the cell types of the neural retina and the RPE. There is some controversy about whether all the cells within the spheres all contain at least some pigment4; however the cells are still capable of forming the different cell types found within the neural retina1-3. In some species, such as amphibians and fish, their eyes are capable of regeneration after injury5, however; the mammalian eye shows no such regenerative properties. We seek to identify the stem cell in vivo and to understand the mechanisms that keep the mammalian retinal stem cells quiescent6-8, even after injury as well as using them as a potential source of cells to help repair physical or genetic models of eye injury through transplantation9-12. Here we describe how to isolate the ciliary epithelial cells from the mouse eye and grow them in culture in order to form the clonal retinal stem cell spheres. Since there are no known markers of the stem cell in vivo, these spheres are the only known way to prospectively identify the stem cell population within the ciliary epithelium of the eye

Critical Evaluation of Imprinted Gene Expression by RNA–Seq: A New Perspective

In contrast to existing estimates of approximately 200 murine imprinted genes, recent work based on transcriptome sequencing uncovered parent-of-origin allelic effects at more than 1,300 loci in the developing brain and two adult brain regions, including hundreds present in only males or females. Our independent replication of the embryonic brain stage, where the majority of novel imprinted genes were discovered and the majority of previously known imprinted genes confirmed, resulted in only 12.9% concordance among the novel imprinted loci. Further analysis and pyrosequencing-based validation revealed that the vast majority of the novel reported imprinted loci are false-positives explained by technical and biological variation of the experimental approach. We show that allele-specific expression (ASE) measured with RNA–Seq is not accurately modeled with statistical methods that assume random independent sampling and that systematic error must be accounted for to enable accurate identification of imprinted expression. Application of a robust approach that accounts for these effects revealed 50 candidate genes where allelic bias was predicted to be parent-of-origin–dependent. However, 11 independent validation attempts through a range of allelic expression biases confirmed only 6 of these novel cases. The results emphasize the importance of independent validation and suggest that the number of imprinted genes is much closer to the initial estimates

Changes in body composition and fat distribution in response to weight loss and weight regain

This thesis describes the effects of weight loss and subsequent weight regain on body composition, fat distribution and resting energy expenditure in moderately obese men and moderately obese premenopausal women. Participants were subjected to a controlled 4.2 MJ/day energy deficit diet for 13 weeks, and re-examined more than one year after weight loss intervention. Five techniques to assess the changes in body composition after weight loss (on average 12.2 ± 3.7 kg (mean ± SD)) were compared. The results from densitometry (hydrostatic weighing) and the deuterium oxide dilution technique were similar, whereas, bioelectrical impedance and two anthropometric methods (skinfold thicknesses and body mass index) showed larger reductions in fat-free mass (FFM) than estimated by densitometry and the dilution technique. These findings were similar in both sexes. Magnetic resonance imaging (MRI) was used to assess the reductions after weight loss in the visceral and subcutaneous abdominal fat depots and the subcutaneous fat depot at trochanter level. The proportional reduction of fat was largest in the visceral depot (men 40%, women 33%) and less fat was lost subcutaneously, especially at trochanter level (men 29%, women 26%). The reductions in visceral fat as measured by MRI were compared with changes in anthropometric measurements. The change in waist-to-hip ratio (WHR) was not related to the change in visceral fat, and the change in sagittal-to-transverse abdominal diameter ratio was only moderately associated with visceral fat loss in both sexes. During the follow-up of 67 weeks after weight loss, 80% of the weight lost was regained on average. In men but not in women, the reduction in resting metabolic rate (RMR) after weight loss was larger than expected from the losses of FFM and fat mass. The RMR returned to baseline level in both sexes after weight regain. The reduction in RMR was not related to later weight regain. Percentage body fat and amount of visceral fat also nearly returned to the level similar to that before weight loss.It is concluded that bioelectrical impedance and anthropometric measurements are not as good as densitometry or the deuterium-oxide dilution method for the evaluation of changes in body composition. Only approximate estimates of visceral fat can be achieved by anthropometry. As a consequence, the assessment of changes in visceral fat by anthropometry is limited. Finally, one weight cycle as observed in this study does not lead to a permanently reduced RMR, nor to a greater body fatness nor to an increase in visceral fat compared with initial levels

The medicinal and chemical aspects of naphthoquinones isolated from Euclea natalensis A. DC. on Mycobacterium tuberculosis

The isolation and antimycobacterial activity of several naphthoquinones from Euclea natalensis were previously reported and initiated this study into the occurrence, chemistry and biological activity of this class of compounds. The structure activity relationship of the isolated naphthoquinones, and commercially available derivatives were also studied. Several plant species were investigated to establish a possible link between their traditional use for chest related symptoms (including tuberculosis infection) and the occurrence of 7-methyljuglone in these plants. The plants were extracted and tested qualitatively with the use of three analytical tools for the presence of 7-methyljuglone or related naphthoquinones. Due to its commercial unavailability, the chemical synthesis of two of these naphthoquinones, 7-methyljuglone and diospyrin, was attempted with varying degrees of success. The Friedel-Crafts acylation method was used to synthesise 7-methyljuglone from m-cresol and maleic anhydride as starting material. The optimisation of the synthesis was also investigated. Through a two-step pathway of epoxidation and steam distillation, diospyrin was successfully synthesised albeit in small quantities. During the attempts to synthesise diospyrin, two other related compounds were also synthesised. These compounds, neodiospyrin and mamegakinone, are structural isomers of diospyrin. The stability of some of the naphthoquinones was tested in various carriers in an attempt to explain the influence this will have on the obtained antituberculosis and toxicity data. The BACTEC vial solution, which is widely used to determine potency against Mycobacterium tuberculosis, was analysed with HPLC to determine the stability of these compounds in it. In addition the stability in organic solvents especially DMSO, was also tested as this is the solvent of choice for hydrophobic compounds in almost all bioassays. The antituberculosis activity and/or toxicity of 7-methyljuglone was investigated with three bioassays, to broaden our knowledge on the mechanism of action of naphthoquinones. Vero cells were employed to determine the inhibitory concentration (IC50) of most of the naphthoquinones. Mice experiments were carried out to determine the toxicity of 7-methyljuglone and diospyrin in vivo. In addition the lead compound, 7-methyljuglone, was tested on Musca domestica (house fly) to establish its toxicity on this organism. In order to find the pharmacophore of this class of compounds, a preliminary structure-activity relationship was conducted. During this study the active site in the compounds which confers potency and toxicity was partly established. The mode of action of some of the naphthoquinones was investigated and it was established that the compounds might interfere with the mycobacterial electron transport chain. A fluorinated 7-methyljuglone stops the production of menaquinone which transports electrons from the NADH dehydrogenase complex to the cytochrome bc complex and effectively kills the mycobacterium.Thesis (PhD (Botany))--University of Pretoria, 2007.Plant Scienceunrestricte

Differential susceptibility to an early literacy intervention

Letters in Beweging is een interventieprogramma voor kleuters met een achterstand in alfabetische kennis. Op 15 scholen is dit programma uitgetest onder vijfjarigen (n = 135) met de laagste scores (30% laagst) op alfabetische kennis. Het programma waarmee een deel 15 weken lang telkens een kwartier zelfstandig oefende, liet niet alleen direct na afloop van het programma effecten zien. Gedurende de volgende twee leerjaren bleven effecten zichtbaar in de leesprestaties. De groep die het programma kreeg, was in groep 3 en 4 niet meer te onderscheiden van de klasgenoten (n = 269) die als kleuter geen achterstand hadden in alfabetische kennis. De controle groep raakte in groep 3 en 4 steeds verder achter. Het meest verrassende resultaat is dat een risicogroep met lichte perinatale afwijkingen in het bijzonder profiteerde van de interventie. Vanaf 2000 worden zwangerschap- en geboortegegevens van alle Nederlandse kinderen in het perinatale register opgeslagen dat met toestemming van de moeder toegankelijk is voor onderzoekers. In de groep met lichte perinatale problemen (ruim 20%) scoorde de interventiegroep meer dan een standaarddeviatie hoger dan de controlegroep zowel direct na de interventie als een jaar later. In de groep zonder perinatale problemen werden geen effecten van het programma aangetoond. Dit resultaat is niet alleen een verdere onderbouwing van de theorie van differenti_le gevoeligheid, i.e., sommige kinderen zijn gevoeliger voor zowel een positieve als negatieve omgeving, maar impliceert ook uitbreiding van de theorie naar het cognitieve domein.UBL - phd migration 201

Dutch Perinatal System: performance and innovative strategies

The organization of the Dutch perinatal care system is unique since, in contrast to most other high-income countries, certified community midwives play an independent role in the care for pregnant women. Community midwives care for pregnant women with an assumed or estimated low-risk for medical complications starting from the early prenatal until the postpartum period. If during pregnancy no risks are detected, women have the option of delivering at home, at a birthing centre or in a hospital, in all cases under the supervision of their community midwife. Should complications (threaten to) occur, community midwives refer women under their supervision to secondary care by obstetricians in a hospital setting. If necessary, secondary caregivers then refer women who are severely ill and/or have threatened pregnancies to tertiary perinatal care, which is located in academic hospitals and in non-academic hospitals with obstetric high care and neonatal intensive care units. Approximately one out five women directly starts antenatal care at a secondary or tertiary hospital due to their initial high-risk status. The functioning of this unique system depends on the mutual cooperation of the health care professionals involved, the availability of (different) facilities, the absence of financial barriers, and adequate information to the patients

Vascular endothelial growth factor directly inhibits primitive neural stem cell survival but promotes definitive neural stem cell survival

There are two types of neural stem cells (NSCs). Primitive NSCs [leukemia inhibitory factor (LIF) dependent but exogenous fibroblast growth factor (FGF) 2 independent] can be derived from mouse embryonic stem (ES) cells in vitro and from embryonic day 5.5 (E5.5) to E7.5 epiblast and E7.5-E8.5 neuroectoderm in vivo. Definitive NSCs (LIF independent but FGF2 dependent) first appear in the E8.5 neural plate and persist throughout life. Primitive NSCs give rise to definitive NSCs. Loss and gain of functions were used to study the role of vascular endothelial growth factor (VEGF)-A and its receptor, Flk1, in NSCs. The numbers of Flk1 knock-out mice embryo-derived and ES cell-derived primitive NSCs were increased because of the enhanced survival of primitive NSCs. In contrast, neural precursor-specific, Flk1 conditional knock-out mice-derived, definitive NSCs numbers were decreased because of the enhanced cell death of definitive NSCs. These effects were not observed in cells lacking Flt1, another VEGF receptor. In addition, the cell death stimulated by VEGF-A of primitive NSC and the cell survival stimulated by VEGF-A of definitive NSC were blocked by Flk1/Fc-soluble receptors and VEGF-A function-blocking antibodies. These VEGF-A phenotypes also were blocked by inhibition of the downstream effector nuclear factor kappa B (NF-kappa B). Thus, both the cell death of primitive NSC and the cell survival of definitive NSC induced by VEGF-A stimulation are mediated by bifunctional NF-kappa B effects. In conclusion, VEGF-A function through Flk1 mediates survival (and not proliferative or fate change) effects on NSCs, specifically