Controlled crystallisation of calcium phosphate and calcium carbonate via bio-inspired approaches: additives and confinement

This thesis describes the investigation of the two bio-inspired approaches, confinement and additives, to manipulate the crystallization of calcium carbonate and calcium phosphate. The first experimental chapter deals with the investigation of calcium phosphate rods grown in confined environments in the absence and presence of polyaspartic acid. Although similar results were obtained in the absence and presence of the additive, growing calcium phosphate in confinement allowed formation of polycrystalline rods with an orientation comparable to bone. This demonstrated that confinement may play a more significant role in bone formation than previously anticipated. The second chapter deals with the effect of positively charged additives on the crystallisation of CaCO3. Although neglected before in literature, this chapter demonstrates that positively charged additives have a profound effect on the crystallisation of CaCO3 changing the morphology to films and fibers. This morphology change was linked to a phase separation process, forming hydrated amorphous droplets of calcium carbonate by a carbonate-polymer interaction, which had the tendency to coalesce and form films. Fiber formation was attributed to oriented attachment of anisotropic particles due to unequal distribution of charge. In the third chapter, based on bone, the mineralisation of collagen by CaCO3 was investigated. By formation of a highly hydrated liquid-like amorphous phase of CaCO3, it was possible to infiltrate the nanoscale gaps of collagen. After crystallisation, nanocrystals of calcite and vaterite were formed, 5 nm thick, but randomly oriented, demonstrating collagen templates the shape but not the orientation of the crystals. In a final chapter hollow rods of CaCO3 were formed by templating them inside membrane pores. The influence of time, pore size, additives and surface chemistry was investigated. Most hollow rods were formed at early timescales which filled up at later times. By changing the surface chemistry, the amount of hollow rods increased significantly in the 200 nm pore

Volunteer policy in palliative care in Flanders : a content analysis of policy documents

Background: Volunteers are considered a third resource of palliative care (PC), next to family and professional caregivers, and can potentially increase the quality of patient care. Yet, conflicting expectations exist regarding volunteer roles, which may lead to role strain and attrition. Moreover, it is unclear how policy pertaining to volunteering within PC services addresses these issues. Therefore, volunteering policies of PC services in Flanders (Belgium) were analyzed, in terms of measures to combat role strain and how these vary across services. Methods: A full-population sample of services providing dedicated – PC units, day-care centers and home-care teams – or generalist PC – sitting services, community home-care, medical oncology departments and a random sample of nursing homes – were asked for their volunteer policy documents in 2016. Qualitative content analysis was performed using a coding frame comprising four main measures to combat role strain: leadership behavior, co-worker support, formalization and empowerment. Results: 264 (N=334; 79%) organizations responded to the survey. 67% claim to have and 45% sent in policy documents. Policy varies considerably, with measures mainly focused on formal aspects: role description, supervision, intervision, governance. Supportive measures such as training, recognition, autonomy, teamwork and emotional support are less accentuated. Dedicated PC services describe leadership behavior, co-worker support and empowerment more extensively and more often than generalist PC services. Conclusion: Given that best practices to tackle volunteer role strain are not widely integrated in organizational policy, their importance may not be acknowledged and their implementation in practice limited. Dedicated PC services appear to employ more role strain-reducing measures than generalist PC services. Further research is warranted to determine the exact impact of these policy measures on volunteer role strain and attrition. This study was funded by IWT SBO nr 140009

Perceptions of physicians, medical and nursing students concerning shared decision-making : a cross-sectional study

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Antibody-independent functions of B cells during viral infections

The humoral immune response and antibody-mediated functions of B cells during viral infections are well described. However, we have limited understanding of antibody-independent B cell functions, such as cytokine production and antigen presentation, in acute and chronic viral infections and their role in protection and/or immunopathogenesis. Here, we summarize the current literature on these antibody-independent B cell functions and identify remaining knowledge gaps. B cell subsets produce anti- and pro-inflammatory cytokines, which can have both beneficial and detrimental effects during viral clearance. As professional antigen presenting cells, B cells also play an important role in immune regulation/shaping of the developing adaptive immune responses. Since B cells primarily express TLR7 and TLR9, we specifically discuss the role of Toll-like receptor (TLR)-mediated B cell responses to viral infections and their role in augmenting adaptive immunity through enhanced cytokine production and antigen presentation. However, viruses have evolved strategies to subvert TLR signaling and additional stimulation via B cell receptor (BCR) may be required to overcome the defective TLR response in B cells. To conclude, antibody-independent B cell functions seem to have an important role in regulating both acute and chronic viral infections and may form the basis for novel therapeutic approaches in treatment of viral infections in the future

Formation and structure of calcium carbonate thin films and nanofibers precipitated in the presence of poly(allylamine hydrochloride) and magnesium ions

That the cationic polyelectrolyte poly(allylamine hydrochloride) (PAH) exerts a significant influence on CaCO₃ precipitation challenges the idea that only anionic additives have this effect. Here, we show that in common with anionic polyelectrolytes such as poly(aspartic acid), PAH supports the growth of calcite thin films and abundant nanofibers. While investigating the formation of these structures, we also perform the first detailed structural analysis of the nanofibers by transmission electron microscopy (TEM) and selected area electron diffraction. The nanofibers are shown to be principally single crystal, with isolated domains of polycrystallinity, and the single crystal structure is even preserved in regions where the nanofibers dramatically change direction. The formation mechanism of the fibers, which are often hundreds of micrometers long, has been the subject of intense speculation. Our results suggest that they form by aggregation of amorphous particles, which are incorporated into the fibers uniquely at their tips, before crystallizing. Extrusion of polymer during crystallization may inhibit particle addition at the fiber walls and result in local variations in the fiber nanostructure. Finally, we investigate the influence of Mg²+ on CaCO₃ precipitation in the presence of PAH, which gives thinner and smoother films, together with fibers with more polycrystalline, granular structures

Direct Infection of B Cells by Dengue Virus Modulates B Cell Responses in a Cambodian Pediatric Cohort

Dengue is an acute viral disease caused by dengue virus (DENV), which is transmitted by Aedes mosquitoes. Symptoms of DENV infection range from inapparent to severe and can be life-threatening. DENV replicates in primary immune cells such as dendritic cells and macrophages, which contribute to the dissemination of the virus. Susceptibility of other immune cells such as B cells to direct infection by DENV and their subsequent response to infection is not well defined. In a cohort of 60 Cambodian children, we showed that B cells are susceptible to DENV infection. Moreover, we show that B cells can support viral replication of laboratory adapted and patient-derived DENV strains. B cells were permissive to DENV infection albeit low titers of infectious virions were released in cell supernatants CD300a, a phosphatidylserine receptor, was identified as a potential attachment factor or receptor for entry of DENV into B cells. In spite of expressing Fcγ-receptors, antibody-mediated enhancement of DENV infection was not observed in B cells in an in vitro model. Direct infection by DENV induced proliferation of B cells in dengue patients in vivo and plasmablast/plasma cell formation in vitro. To summarize, our results show that B cells are susceptible to direct infection by DENV via CD300a and the subsequent B cell responses could contribute to dengue pathogenesis

Diagnostic value of anti-human citrullinated fibrinogen ELISA and comparison with four other anti-citrullinated protein assays

We studied the diagnostic performance of the anti-human citrullinated fibrinogen antibody (AhFibA) ELISA for rheumatoid arthritis (RA) in a consecutive cohort (population 1) and evaluated the agreement between the AhFibA ELISA and four other assays for anti-citrullinated protein/peptide antibodies (ACPAs) as well as rheumatoid factor in patients with longstanding RA (population 2). Population 1 consisted of 1024 patients with rheumatic symptoms; serum samples from these patients were sent to our laboratory for ACPA testing within the context of a diagnostic investigation for RA. Ninety-two of these patients were classified as having RA according to the American College of Rheumatology criteria and 463 were classified as non-RA patients. Population 2 consisted of 180 patients with longstanding RA and was used to assess agreement and correlations between five ACPA assays: anti-cyclic citrullinated peptide (CCP)1 and anti-CCP2 antibodies were detected using a commercially available ELISA, AhFibA using ELISA, and anti-PepA and anti-PepB antibodies using line immunoassay. Applying previously proposed cut-offs for AhFibA, we obtained a sensitivity of 60.9% and a specificity of 98.7% in population 1. Receiver operating characteristic curve analysis could not detect a significant difference in diagnostic performance between the AhFibA ELISA and anti-CCP2 assay. Performing a hierarchical nearest neighborhood cluster analysis of the five different ACPA assays in population 2, we identified two clusters: a cluster of anti-pepA, anti-pepB and anti-CCP1, and a cluster of AhFibA and anti-CCP2. In conclusion, we found that AhFibA and anti-CCP2 antibodies had similar diagnostic performance. However, disagreement between ACPA tests may occur

Autoimmune Responses in the Rheumatoid Synovium

Rene Toes and Tom Huizinga discuss a new study indicating that lymphoneogenesis in the inflamed synovial tissue of patients with rheumatoid arthritis is fostering potentially pathogenic immune responses