Hereditary dementia, a clinical genetic perspective

Meijers-Heijboer, E.J. [Promotor]Swieten, J.C. van [Promotor]Pijnenburg, Y.A.L. [Copromotor

A phosphorylcholine-containing glycolipid-like antigen present on the surface of infective stage larvae of Ascaris spp. is a major antibody target in infected pigs and humans

BACKGROUND: The pig parasite Ascaris suum plays and important role in veterinary medicine and represents a suitable model for A. lumbricoides, which infects over 800 million people. In pigs, continued exposure to Ascaris induces immunity at the level of the gut, protecting the host against migrating larvae. The objective of this study was to identify and characterize parasite antigens targeted by this local immune response that may be crucial for parasite invasion and establishment and to evaluate their protective and diagnostic potential. METHODOLOGY/PRINCIPAL FINDINGS: Pigs were immunized by trickle infection for 30 weeks, challenged with 2,000 eggs at week 32 and euthanized two weeks after challenge. At necropsy, there was a 100% reduction in worms recovered from the intestine and a 97.2% reduction in liver white spots in comparison with challenged non-immune control animals. Antibodies purified from the intestinal mucus or from the supernatant of cultured antibody secreting cells from mesenteric lymph nodes of immune pigs were used to probe L3 extracts to identify antibody targets. This resulted in the recognition of a 12kDa antigen (As12) that is actively shed from infective Ascaris L3. As12 was characterized as a phosphorylcholine-containing glycolipid-like antigen that is highly resistant to different enzymatic and chemical treatments. Vaccinating pigs with an As12 fraction did not induce protective immunity to challenge infection. However, serological analysis using sera or plasma from experimentally infected pigs or naturally infected humans demonstrated that the As12 ELISA was able to detect long-term exposure to Ascaris with a high diagnostic sensitivity (98.4% and 92%, respectively) and specificity (95.5% and 90.0%) in pigs and humans, respectively. CONCLUSIONS/SIGNIFICANCE: These findings show the presence of a highly stage specific, glycolipid-like component (As12) that is actively secreted by infectious Ascaris larvae and which acts as a major antibody target in infected humans and pigs

Verbindende suikerverbindingen

Oratie uitgesproken door Prof.dr. C.H. Hokke bij de aanvaarding van het ambt van hoogleraar op het gebied van Glycobiologie van Gastheer-pathogeen Interactie aan de Universiteit Leiden op maandag 16 oktober 2017Oratie uitgesproken door Prof.dr. C.H. Hokke bij de aanvaarding van het ambt van hoogleraar op het gebied van Glycobiologie van Gastheer-pathogeen Interactie aan de Universiteit Leiden op maandag 16 oktober 2017LUMC / Geneeskunde Repositoriu

Adhesion of electrolessly deposited Ni(P) layers on alumina ceramic II. Interface characterization

The interface microstructure and interface chem. of electrolessly deposited Ni(P) on alumina ceramics is studied to obtain insight into the influence of mol. interactions upon the adhesion. Detailed static secondary-ion-mass spectrometry, XPS, Auger electron spectroscopy, and transmission electron microscopy (TEM) analyses have been carried out with samples with various roughness, of which the mech. analyses are described in a companion article. TEM cross-section micrographs showed a close contact between the two phases on a nanometer scale for all sample types. In addn., a 1-2-nm-thick interfacial layer was obsd. This layer consists of nucleation material and compds. from the metalization soln. Fracture surface analyses showed that fracture takes place through this layer, which is therefore considered to be the weak boundary layer in this system. The presence of this weak boundary layer explains the importance of substrate surface roughness and mech. interlocking for the fracture energy. [on SciFinder (R)

Rethinking Schistosomiasis Vaccine Development:Synthetic Vesicles

There is currently no vaccine against schistosomiasis. With few Schistosoma vaccine candidates in clinical trials, unexplored antigens from the vulnerable schistosomulum should be considered as possible vaccine candidates. In addition, we suggest developing synthetic vesicles as a new delivery vehicle and adjuvant for immunoprophylactic schistosomula vaccine candidates

Healing the past by nurturing the future: Aboriginal parents’ views of what helps support recovery from complex trauma

We aimed to understand support needs for Aboriginal and Torres Strait Islander parents experiencing complex trauma.Becoming a parent is an exciting yet challenging transition, particularly for parents who have experienced past hurt in their own childhood which can have long lasting effects, including complex trauma. Complex trauma-related distress can make it harder to care for a baby, but the parenting transition offers unique opportunities for recovery. This formative research is part of a community-based participatory action research project which aims to co-design perinatal awareness, recognition, assessment and support strategies for Aboriginal and Torres Strait Islander parents experiencing complex trauma. We used an Indigenist approach and grounded theory methods. Aboriginal and Torres Strait Islander parents who were pregnant and/or have children up to two years old were recruited through perinatal care services and community networks in three Australian sites (Alice Springs, Adelaide and Melbourne). Parents were offered a group discussion or individual interview, facilitated by Aboriginal researchers. Third-person scenarios and visual tools were used to facilitate reflections about the impact of past experiences, what keeps parents strong, hopes and dreams, and what is needed to achieve those dreams. Parents were also shown themes from a previous systematic review of parents’ experiences as a prompt to identify any additional key issues. Seventeen Aboriginal and Torres Strait Islander parents participated in August to September 2019. Most were mothers (n = 15). The study’s grounded theory methods provided the foundation of a theoretical supposition that positions the transformation of the compounding cycle of trauma, to a reinforcing cycle of nurturing at the intersection of: 1) parents’ connectedness; 2) social and emotional wellbeing; and 3) the transition to parenting. Unique opportunities and challenges situated at the interface are bound to the compounding or reinforcing nature of the intersecting factors. Findings reveal complexity, differing experiences by gender and age, as well as within and between communities

Community rates of IgG4 antibodies to Ascaris haemoglobin reflect changes in community egg loads following mass drug administration

BACKGROUND:Conventional diagnostic methods for human ascariasis are based on the detection of Ascaris lumbricoides eggs in stool samples. However, studies of ascariasis in pigs have shown that the prevalence and the number of eggs detected in the stool do not correlate well with exposure of the herd to the parasite. On the other hand, an ELISA test measuring antibodies to Ascaris suum haemoglobin (AsHb) has been shown to be useful for estimating transmission intensity on pig farms. In this study, we further characterized the AsHb antigen and screened samples from a population-based study conducted in an area that is endemic for Ascaris lumbricoides in Indonesia to assess changes in AsHb antibody rates and levels in humans following mass drug administration (MDA). METHODOLOGY/PRINCIPAL FINDINGS:We developed and evaluated an ELISA to detect human IgG4 antibodies to AsHb. We tested 1066 plasma samples collected at different times from 599 subjects who lived in a village in rural Indonesia that was highly endemic for ascariasis. The community received 6 rounds of MDA for lymphatic filariasis with albendazole plus diethylcarbamazine between 2002 and 2007. While the AsHb antibody assay was not sensitive for detecting all individuals with Ascaris eggs in their stools, the percentage of seropositive individuals decreased rapidly following MDA. Reductions in antibody rates reflected decreased mean egg output per person both at the community level and in different age groups. Two years after the last round of MDA the community egg output and antibody prevalence rate were reduced by 81.6% and 78.9% respectively compared to baseline levels. CONCLUSION/SIGNIFICANCE:IgG4 antibody levels to AsHb appear to reflect recent exposure to Ascaris. The antibody prevalence rate may be a useful indicator for Ascaris transmission intensity in communities that can be used to assess the impact of control measures on the force of transmission

PILOTSTUDIE NAAR DE INZET VAN EEN COMPASSIETRAINING VOOR MENSEN MET EEN VISUELE, LICHAMELIJKE EN LICHTE TOT MATIGE VERSTANDELIJKE BEPERKING

Mensen met een visuele en verstandelijke beperking zijn kwetsbaar voor het ervaren van psychologische lijdensdruk, waarbij een hoge mate van schaamte en zelfkritiek een belangrijke rol kunnen spelen. Op compassie gebaseerde interventies richten zich op het vergroten van het welbevinden door het ontwikkelen van (zelf)compassie. Deze pilotstudie beschrijft de inzet en het effect van een van Mindfulness Based Compassionate Living afgeleide compassietraining bij vier mensen met een visuele en verstandelijke beperking. Op basis van de resultaten lijkt een compassietraining een haalbare en toepasbare interventie te zijn met potentieel positieve uitkomsten (meer zelfcompassie en zelfwaardering), mits goed aangepast aan de voorkeuren en mogelijkheden van deelnemers

Haemodynamical stress in mouse aortic arch with atherosclerotic plaques: Preliminary study of plaque progression

Atherosclerotic plaques develop at particular sites in the arterial tree, and this regional localisation depends largely on haemodynamic parameters (such as wall shear stress; WSS) as described in the literature. Plaque rupture can result in heart attack or stroke and hence understanding the development and vulnerability of atherosclerotic plaques is critically important. The purpose of this study is to characterise the haemodynamics of blood flow in the mouse aortic arch using numerical modelling. The geometries are digitalised from synchrotron imaging and realistic pulsatile blood flow is considered under rigid wall assumptions. Two cases are considered; arteries with and without plaque. Mice that are fed under fat diet present plaques in the aortic arch whose size is dependent on the number of weeks under the diet. The plaque distribution in the region is however relatively constant through the different samples. This result underlines the influence of the geometry and consequently of the wall shear stresses for plaque formation with plaques growing in region of relative low shear stresses. A discussion of the flow field in real geometry in the presence and absence of plaques is conducted. The presence of plaques was shown to alter the blood flow and hence WSS distribution, with regions of localised high WSS, mainly on the wall of the brachiocephalic artery where luminal narrowing is most pronounced. In addition, arch plaques are shown to induce recirculation in the blood flow, a phenomenon with potential influence on the progression of the plaques. The oscillatory shear index and the relative residence time have been calculated on the geometry with plaques to show the presence of this recirculation in the arch, an approach that may be useful for future studies on plaque progression