Maisoon Al-Jawad

Clinical overview and treatment options for non-skeletal manifestations of mucopolysaccharidosis type IVA

Mucopolysaccharidosis type IVA (MPS IVA) or Morquio syndrome is a multisystem disorder caused by galactosamine-6-sulfatase deficiency. Skeletal manifestations, including short stature, skeletal dysplasia, cervical instability, and joint destruction, are known to be associated with this condition. Due to the severity of these skeletal manifestations, the non-skeletal manifestations are frequently overlooked despite their significant contribution to disease progression and impact on quality of life. This review provides detailed information regarding the non-skeletal manifestations and suggests long-term assessment guidelines. The visual, auditory, digestive, cardiovascular, and respiratory systems are addressed and overall quality of life as measured by endurance and other functional abilities is discussed. Impairments such as corneal clouding, astigmatism, glaucoma, hearing loss, hernias, hepatomegaly, dental abnormalities, cardiac valve thickening and regurgitation, obstructive sleep apnea, tracheomalacia, restrictive and obstructive respiratory compromise, and muscular weakness are discussed. Increased awareness of these non-skeletal features is needed to improve patient care.

Distribution of enamel crystallite orientation through an entire tooth crown studied using synchrotron X‐ray diffraction

The biomineralization of human dental enamel has resulted in a highly anisotropic and heterogeneous distribution of hydroxyapatite crystallites, which in combination with its high mineral content has resulted in one of the most durable and hardest tissues in the human body. In this study, we used position-sensitive synchrotron X-ray diffraction to quantify the spatial variation in the direction and magnitude of the preferred orientation of enamel crystallites across a whole tooth crown. Two-dimensional synchrotron X-ray diffraction images were collected with 300 μm spatial resolution over a series of six sequential tooth sections obtained from a single maxillary first premolar and were analyzed using Rietveld refinement. Both the magnitude and the direction of the crystallite orientation were found to have a high spatial heterogeneity. Areas of high crystallite alignment were directed perpendicular to the biting surfaces, which is thought to meet the functional requirements of mastication. The results may assist in our understanding of the structure-function relationship and of the evolutionary development of enamel.

High temperature neutron diffraction studies of 0.9BiFeO3―0.1PbTiO3

Neutron diffraction data were collected from sintered polycrystalline 0.9BiFeO3–0.1PbTiO3 at temperatures between 293 and 793 K and the crystal and magnetic structures refined by the Rietveld method. An antiferromagnetic Neel temperature of 592 K was determined from a Brillouin fit to the refined magnetic moments with a ground state of 4.34μB, showing no loss of moment per Fe site compared to BiFeO3. Some magnetic order was observed to persist above the Neel temperature. A maximum in the spontaneous rhombohedral strain was observed close to the Neel temperature, in a significant departure from typical Landau behavior for a ferroelectric and suggesting a coupling between the magnetic and nuclear structures.

Fibronectin adsorption studied using neutron reflectometry and complementary techniques

In implantology it is known that fibronectin affects cell-substrate adhesion, consequently, the structure and composition of the initially adsorbed fibronectin layer to a large extent determines the biological response to a biomaterial implanted into the body. In this study we have used neutron reflectometry and quartz-crystal microbalance with dissipation to investigate the amount of fibronectin adsorbed, the layer density, thickness and structure of films adsorbed to polished silicon oxide surfaces. We have cultured MG63 osteoblast-like cells on surfaces coated and uncoated with fibronectin and monitored the cellular response to these surfaces. The results show that at fibronectin concentrations in the range 0.01 to 0.1mg/ml a single highly hydrated layer of fibronectin approximately 40-50Å in thickness adsorbs to a polished silicon oxide surface and is likely to correspond to one diffuse monolayer of fibronectin arranged side-on. Cells cultured on this fibronectin layer have dramatically different morphology and growth to those grown on bare surfaces. Using a model silicon oxide surface has enabled us to study the substrate/protein interface, together with the impact of a fibronectin layer on the cellular response using consistent experimental conditions across a unique set of experimental techniques.

Mapping the spatial and temporal progression of human dental enamel biomineralization using synchrotron X-ray diffraction

OBJECTIVE The complex biological, physicochemical process of human dental enamel formation begins in utero and for most teeth takes several years to complete. Lost enamel tissue cannot regenerate, therefore a better understanding of the spatial and temporal progression of mineralization of this tissue is needed in order to design improved in vivo mineral growth processes for regenerative dentistry and allow the possibility to grow a synthetic whole or partial tooth. METHOD Human dental enamel samples across a range of developmental stages available through archaeological collections have been used to explore the spatial and temporal progression of enamel biomineralization. Position sensitive synchrotron X-ray diffraction was used to quantify spatial and temporal variations in crystallite organization, lattice parameters and crystallite thickness at three different stages in enamel maturation. In addition X-ray microtomography was used to study mineral content distributions. RESULTS An inverse correlation was found between the spatial variation in mineral content and the distribution of crystallite organization and thickness as a function of time during enamel maturation. Combined X-ray microtomography and synchrotron X-ray diffraction results show that as enamel matures the mineral content increases and the mineral density distribution becomes more homogeneous. Starting concurrently but proceeding at a slower rate, the enamel crystallites become more oriented and larger; and the crystallite organization becomes spatially more complex and heterogeneous. CONCLUSION During the mineralization of human dental enamel, the rate of mineral formation and mineral organization are not identical. Whilst the processes start simultaneously, full mineral content is achieved earlier, and crystallite organization is slower and continues for longer. These findings provide detailed insights into mineral development in human dental enamel which can inform synthetic biomimetic approaches for the benefit of clinical dentistry.

Phase-specific magnetic ordering in BiFeO3−PbTiO3

The multiferroic 0.7 BiFeO3–0.3 PbTiO3 has been fabricated in both sintered ceramic and powder form using conventional mixed oxide synthesis. Rietveld’s analysis of neutron powder diffraction data has shown that the sintered ceramic and powder are predominantly R3c and P4mm phases, respectively. It is shown explicitly that magnetic ordering does not occur for the P4mm phase at room temperature.

Disruption of enamel crystal formation quantified by synchrotron microdiffraction

OBJECTIVES To understand the pathology of the ultrastructure of enamel affected by systemic disorders which disrupt enamel tissue formation in order to give insight into the precise mechanisms of matrix-mediated biomineralization in dental enamel in health and disease. METHODS Two-dimensional synchrotron X-ray diffraction has been utilized as a sophisticated and useful technique to spatially quantify preferred orientation in mineralized healthy deciduous dental enamel, and the disrupted crystallite organization in enamel affected by a systemic disease affecting bone and dental mineralization (mucopolysaccharidosis Type IVA and Type II are used as examples). The lattice spacing of the hydroxyapatite phase, the crystallite size and aspect ratio, and the quantified preferred orientation of crystallites across whole intact tooth sections, have been determined using synchrotron microdiffraction. RESULTS Significant differences in mineral crystallite orientation distribution of affected enamel have been observed compared to healthy mineralized tissue. The gradation of enamel crystal orientation seen in healthy tissue is absent in the affected enamel, indicating a continual disruption in the crystallite alignment during mineral formation. CONCLUSIONS This state of the art technique has the potential to provide a unique insight into the mechanisms leading to deranged enamel formation in a wide range of disease states. CLINICAL RELEVANCE Characterising crystal orientation patterns and geometry in health and following disruption can be a powerful tool in advancing our overall understanding of mechanisms leading to the tissue phenotypes seen clinically. Findings can be used to inform the appropriate dental management of these tissues and/or to investigate the influence of therapeutic interventions or external stressors which may impact on amelogenesis.

Physical chemical effects of zinc on in vitro enamel demineralization

OBJECTIVES Zinc salts are formulated into oral health products as antibacterial agents, yet their interaction with enamel is not clearly understood. The aim was to investigate the effect of zinc concentration [Zn(2+)] on the in vitro demineralization of enamel during exposure to caries-simulating conditions. Furthermore, the possible mechanism of zincs action for reducing demineralization was determined. METHODS Enamel blocks and synthetic hydroxyapatite (HAp) were demineralized in a range of zinc-containing acidic solutions (0-3565ppm [Zn(2+)]) at pH 4.0 and 37°C. Inductively coupled-plasma optical emission spectroscopy (ICP-OES) was used to measure ion release into solution. Enamel blocks were analysed by Attenuated Total Reflectance-Fourier Transform Infrared Spectroscopy (ATR-FTIR), and HAp by X-ray diffraction (XRD) and neutron diffraction (ND). RESULTS ICP-OES analysis of the acidic solutions showed a decrease in [Ca(2+)] and [PO4(3-)] release with increasing [Zn(2+)]. FTIR revealed a α-hopeite (α-Zn3(PO4)2.4H2O)-like phase on the enamel surfaces at >107ppm [Zn(2+)]. XRD and ND analysis confirmed a zinc-phosphate phase present alongside the HAp. CONCLUSIONS This study confirms that zinc reduces enamel demineralization. Under the conditions studied, zinc acts predominantly on enamel surfaces at PO4(3-) sites in the HAp lattice to possibly form an α-hopeite-like phase. CLINICAL SIGNIFICANCE These results have a significant implication on the understanding of the fundamental chemistry of zinc in toothpastes and demonstrate its therapeutic potential in preventing tooth mineral loss.

Recovery of crystallographic texture in remineralized dental enamel.

Dental caries is the most prevalent disease encountered by people of all ages around the world. Chemical changes occurring in the oral environment during the caries process alter the crystallography and microstructure of dental enamel resulting in loss of mechanical function. Little is known about the crystallographic effects of demineralization and remineralization. The motivation for this study was to develop understanding of the caries process at the crystallographic level in order to contribute towards a long term solution. In this study synchrotron X-ray diffraction combined with scanning electron microscopy and scanning microradiography have been used to correlate enamel crystallography, microstructure and mineral concentration respectively in enamel affected by natural caries and following artificial demineralization and remineralization regimes. In particular, the extent of destruction and re-formation of this complex structure has been measured. 2D diffraction patterns collected at the European Synchrotron Radiation Facility were used to quantify changes in the preferred orientation (crystallographic texture) and position of the (002) Bragg reflection within selected regions of interest in each tooth slice, and then correlated with the microstructure and local mineral mass. The results revealed that caries and artificial demineralization cause a large reduction in crystallographic texture which is coupled with the loss of mineral mass. Remineralization restores the texture to the original level seen in healthy enamel and restores mineral density. The results also showed that remineralization promotes ordered formation of new crystallites and growth of pre-existing crystallites which match the preferred orientation of healthy enamel. Combining microstructural and crystallographic characterization aids the understanding of caries and erosion processes and assists in the progress towards developing therapeutic treatments to allow affected enamel to regain structural integrity.

A new paradigm for fabricating bulk high-field superconductors

Superconductivity provides the enabling technology for producing high-field magnets in applications including medical body scanners and particle accelerators. The upper critical field (BC2(0)) of the superconductor ultimately limits the field that the magnet can produce. The reports about PbMo6S8 and Nb3Sn provide a new method for fabricating high-field superconductors in which superconducting materials are made in nanocrystalline form and the very fine microstructure and high density of defects present are controlled at the nanoscale to significantly increase the electron scattering and hence BC2(0). Here we show direct measurements of BC2(0) for a series of nanocrystalline niobium materials with an unprecedented maximum BC2(0) for bulk Nb of ~3 T. We provide a theoretical description of our results, using the well-established fundamental properties of Nb, that explains why the peak in BC2(0) occurs and can predict optimal BC2(0) for other materials in this new class of nanocrystalline high-field superconductors.