Mucopolysaccharidosis IVA (Morquio A syndrome) and VI (Maroteaux-Lamy syndrome): under-recognized and challenging to diagnose

OBJECTIVE: Mucopolysaccharidosis IVA (MPS IVA, or Morquio A syndrome) and VI (MPS VI, or Maroteaux-Lamy syndrome) are autosomal recessive lysosomal storage disorders. Skeletal abnormalities are common initial presenting symptoms and, when recognized early, may facilitate timely diagnosis and intervention, leading to improved patient outcomes. Patients with slowly progressing disease and nonclassic phenotypes can be particularly challenging to diagnose. The objective was to describe the radiographic features of patients with a delayed diagnosis of MPS IVA or VI. MATERIALS AND METHODS: This was a retrospective study. The records of 5 MPS IVA and 3 MPS VI patients with delayed diagnosis were reviewed. Radiographs were evaluated by a radiologist with special expertise in skeletal dysplasias. RESULTS: An important common theme in these cases was the appearance of multiple epiphyseal dysplasia (MED) with epiphyseal changes seemingly confined to the capital (proximal) femoral epiphyses. Very few patients had the skeletal features of classical dysostosis multiplex. CONCLUSIONS: Radiologists should appreciate the wide phenotypic variability of MPS IVA and VI. The cases presented here illustrate the importance of considering MPS in the differential diagnosis of certain skeletal dysplasias/disorders, including MED, some forms of spondylo-epiphyseal dysplasia (SED), and bilateral Perthes-like disease. It is important to combine radiographic findings with clinical information to facilitate early testing and accurate diagnosis

Structural, spectroscopic, photophysical, magnetic and electrochemical studies of highly conjugated bis(porphyrin) compounds

This thesis focusses on probing how strongly coupled porphyrin macrocycles influences: (i) the singlet and triplet photophysics manifest by electronically asymmetric bis(porphyrin) complexes, (ii) the ground state structure in solution and the solid state, and (iii) the nature and extent of electronic and magnetic interactions between bound central metal ions in these systems. The first single X-ray crystallographic study of a meso-to- meso ethyne-bridged bis(porphinato)zinc(II) compound is presented. This class of highly conjugated compounds adopts a coplanar geometry in the solid state. Spectroscopic studies demonstrate that the origin of the spectral heterogeneity exhibited in the solution optical spectrum of these compounds derives from the presence of two classes of structural conformers: an optimally conjugated (planar) conformational population and a second population of species which features a large dihedral angle between the two porphyrin macrocycle least squares planes. The spectroscopy and photophysics of the singlet and triplet states of meso-to-meso ethyne-bridged bis(porphyrin) systems were examined, probing the degree of electronic delocalization manifest over the ns to ms time domain and assessing how minor electronic symmetry perturbations impact the nature of the excited state. Electronic structure calculations of zinc-free base and free base-free base arrays indicate that meso-appended (porphinato)zincyl- or porphyryl-ethynyl group affect a much larger electronic perturbation to the D4h-symmetric porphyrin dianion than do the presence of the two pyrrolic protons. This prediction has been confirmed experimentally via time-resolved fluorescence anisotropy experiments which unequivocally show the reorientation of S1 excited state transition dipoles along the conjugated axis of these molecules. In marked contrast to their highly delocalized and polarized singlet excited states, the triplet excited states of these compounds are localized on one porphyrin macrocycle. The magnetic behavior of transition metal bis(porphyrin) complexes with the meso-to-meso ethyne-bridge structural motif was studied. DC magnetic susceptibility data indicate that a meso-to-meso ethyne-bridged bis(porphinato)cobalt oxygen adduct is a canted antiferromagnet at temperatures below 15 K. Powder EPR spectra demonstrate that dioxygen ligands are present in samples which exhibit non-Curie magnetic behavior, and solution EPR spectra suggest that the spin density nearly exclusively resides on the superoxide moities. Preliminary electrochemical data of a bis(porphinato)iron(III) complex is presented. Coulometry indicates that the first reduction process is one-electron in nature and EPR data suggest that this corresponds to an iron(III) to iron(II) reduction

SANDIA REPORT Diffusionless fluid transport and routing using novel microfluidic devices Diffusionless fluid transport and routing using novel microfluidic devices

ABSTRACT Microfluidic devices have been proposed for "Lab-on-a-Chip" applications for nearly a decade. Despite the unquestionable promise of these devices to allow rapid, sensitive and portable biochemical analysis, few practical devices exist. It is often difficult to adapt current laboratory techniques to the microscale because bench-top methods use discrete liquid volumes, while most current microfluidic devices employ streams of liquid confined in a branching network of micron-scale channels. The goal of this research was to use two phase liquid flows, creating discrete packets of liquid. Once divided into discrete packets, the packets can be moved controllably within the microchannels without loss of material. Each packet is equivalent to a minute test tube, holding a fraction from a separation or an aliquot to be reacted. We report on the fabrication of glass and PDMS (polydimethylsiloxane) devices that create and store packets. 4 This page intentionally has only this sentence. 5 CONTENT

Diffusionless fluid transport and routing using novel microfluidic devices.

Microfluidic devices have been proposed for 'Lab-on-a-Chip' applications for nearly a decade. Despite the unquestionable promise of these devices to allow rapid, sensitive and portable biochemical analysis, few practical devices exist. It is often difficult to adapt current laboratory techniques to the microscale because bench-top methods use discrete liquid volumes, while most current microfluidic devices employ streams of liquid confined in a branching network of micron-scale channels. The goal of this research was to use two phase liquid flows, creating discrete packets of liquid. Once divided into discrete packets, the packets can be moved controllably within the microchannels without loss of material. Each packet is equivalent to a minute test tube, holding a fraction from a separation or an aliquot to be reacted. We report on the fabrication of glass and PDMS (polydimethylsiloxane) devices that create and store packets