Publications by Year: 2014

2014

Hengameh A, Reyhaneh D, Nima MM, Hamed H. Effects of two bioactive materials on survival and osteoblastic differentiation of human mesenchymal stem cells. J Conserv Dent. 2014;17(4):349–53. doi:10.4103/0972-0707.136509
OBJECTIVES: Activation of mineralization process in periradicular tissues following the injuries, is important in repair mechanisms. The objective of this study was to investigate the effects of CEM cement on survival and mineralization of human mesenchymal stem cells (hMSCs) and compare it with MTA. MATERIALS AND METHODS: hMSCs that were planted on test material extracts and culture media were the experimental and control groups, respectively. The cytotoxicity of these materials was investigated using Methyl thiazol tetrazolium assay. After 7 days, alizarin red staining, alkaline phosphatase (ALP) assays, and qRT-PCR were used to assess the mineralization, expression of ALP, and gene expression (collagen type 1 and osteocalcin), respectively. The results were evaluated by ANOVA analysis and multiple comparisons test. P 0.05 was considered as statistically significant. RESULTS: Cell viability was not significantly different. Alizarin red and alkaline phosphatase staining showed mineralization in all three groups. In qRT-PCR, the expression of collagen type 1 is not significantly different among the three groups. Osteocalcin gene expression was significantly higher in the CEM group compared to the control (P 0.05). CONCLUSION: CEM cement has acceptable toxicity and could induce mineralization process and enhance osteocalcin gene expression which is associated with mineralization in hMSCs.
Forsberg D, Lundström C, Knutsson H. Eigenspine: computing the correlation between measures describing vertebral pose for patients with adolescent idiopathic scoliosis. Comput Med Imaging Graph. 2014;38(7):549–57. doi:10.1016/j.compmedimag.2014.06.011
This paper describes the concept of eigenspine, a concept applicable for determining the correlation between pair-wise combinations of measures useful for describing the three-dimensional spinal deformities associated with adolescent idiopathic scoliosis. The proposed data analysis scheme is based upon the use of principal component analysis (PCA) and canonical correlation analysis (CCA). PCA is employed to reduce the dimensionality of the data space, thereby providing a regularization of the measurements, and CCA is employed to determine the linear dependence between pair-wise combinations of different measures. The usefulness of the eigenspine concept is demonstrated by analyzing the position and the rotation of all lumbar and thoracic vertebrae as obtained from 46 patients suffering from adolescent idiopathic scoliosis. The analysis showed that the strongest linear relationship is found between the lateral displacement and the coronal rotation of the vertebrae, and that a somewhat weaker but still strong correlation is found between the coronal rotation and the axial rotation of the vertebrae. These results are well in-line with the general understanding of idiopathic scoliosis. Noteworthy though is that the correlation between the anterior-posterior displacement and the sagittal rotation was not as strong as expected and that the obtained results further indicate the need for including the axial vertebral rotation as a measure when characterizing different types of idiopathic scoliosis. Apart from analyzing pair-wise correlations between different measures, the method is believed to be suitable for finding a maximally descriptive low-dimensional combination of measures describing spinal deformities in idiopathic scoliosis.
Hayashi K, Yoshimura R, Kakeda S, Kishi T, Abe O, Umene-Nakano W, Katsuki A, Hori H, Ikenouchi-Sugita A, Watanabe K, et al. COMT Val158Met, but not BDNF Val66Met, is associated with white matter abnormalities of the temporal lobe in patients with first-episode, treatment-na ıve major depressive disorder: a diffusion tensor imaging study. Neuropsychiatr Dis Treat. 2014;10:1183–90. doi:10.2147/NDT.S61275
We investigated the association between the Val158Met polymorphism of the catechol-O-methyltransferase (COMT) gene, the Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF) gene, and white matter changes in patients with major depressive disorder (MDD) and healthy subjects using diffusion tensor imaging (DTI). We studied 30 patients with MDD (17 males and 13 females, with mean age ± standard deviation [SD] =44±12 years) and 30 sex- and age-matched healthy controls (17 males and 13 females, aged 44±13 years). Using DTI analysis with a tract-based spatial statistics (TBSS) approach, we investigated the differences in fractional anisotropy, radial diffusivity, and axial diffusivity distribution among the three groups (patients with the COMT gene Val158Met, those with the BDNF gene Val66Met, and the healthy subjects). In a voxel-wise-based group comparison, we found significant decreases in fractional anisotropy and axial diffusivity within the temporal lobe white matter in the Met-carriers with MDD compared with the controls (P
Bernin D, Koch V, en MN, Topgaard D. Multi-scale characterization of lyotropic liquid crystals using 2H and diffusion MRI with spatial resolution in three dimensions. PLoS One. 2014;9(6):e98752. doi:10.1371/journal.pone.0098752
The ability of lyotropic liquid crystals to form intricate structures on a range of length scales can be utilized for the synthesis of structurally complex inorganic materials, as well as in devices for controlled drug delivery. Here we employ magnetic resonance imaging (MRI) for non-invasive characterization of nano-, micro-, and millimeter scale structures in liquid crystals. The structure is mirrored in the translational and rotational motion of the water, which we assess by measuring spatially resolved self-diffusion tensors and 2H spectra. Our approach differs from previous works in that the MRI parameters are mapped with spatial resolution in all three dimensions, thus allowing for detailed studies of liquid crystals with complex millimeter-scale morphologies that are stable on the measurement time-scale of 10 hours. The 2H data conveys information on the nanometer-scale structure of the liquid crystalline phase, while the combination of diffusion and 2H data permits an estimate of the orientational distribution of micrometer-scale anisotropic domains. We study lamellar phases consisting of the nonionic surfactant C10E3 in 2H2O, and follow their structural equilibration after a temperature jump and the cessation of shear. Our experimental approach may be useful for detailed characterization of liquid crystalline materials with structures on multiple length scales, as well as for studying the mechanisms of phase transitions.
Björklund S, Andersson JM, Pham QD, Nowacka A, Topgaard D, Sparr E. Stratum corneum molecular mobility in the presence of natural moisturizers. Soft Matter. 2014;10(25):4535–46. doi:10.1039/c4sm00137k
The outermost layer of the skin, the stratum corneum (SC), is a lipid-protein membrane that experiences considerable osmotic stress from a dry and cold climate. The natural moisturizing factor (NMF) comprises small and polar substances, which like osmolytes can protect living systems from osmotic stress. NMF is commonly claimed to increase the water content in the SC and thereby protect the skin from dryness. In this work we challenge this proposed mechanism, and explore the influence of NMF on the lipid and protein components in the SC. We employ natural-abundance (13)C solid-state NMR methods to investigate how the SC molecular components are influenced by urea, glycerol, pyrrolidone carboxylic acid (PCA), and urocanic acid (UCA), all of which are naturally present in the SC as NMF compounds. Experiments are performed with intact SC, isolated corneocytes and model lipids. The combination of NMR experiments provides molecularly resolved qualitative information on the dynamics of different SC lipid and protein components. We obtain completely novel molecular information on the interaction of these NMF compounds with the SC lipids and proteins. We show that urea and glycerol, which are also common ingredients in skin care products, increase the molecular mobility of both SC lipids and proteins at moderate relative humidity where the SC components are considerably more rigid in the absence of these compounds. This effect cannot be attributed to increased SC water content. PCA has no detectable effect on SC molecular mobility under the conditions investigated. It is finally shown that the more apolar compound, UCA, specifically influences the mobility of the SC lipid regions. The present results show that the NMF components act to retain the fluidity of the SC molecular components under dehydrating conditions in such a way that the SC properties remain largely unchanged as compared to more hydrated SC. These findings provide a new molecular insight into how small polar molecules in NMF and skin care products act to protect the human skin from drying.
Fitzsimmons J, Schneiderman JS, Whitford TJ, Swisher T, Niznikiewicz MA, Pelavin PE, Terry DP, Mesholam-Gately RI, Seidman LJ, Goldstein JM, et al. Cingulum bundle diffusivity and delusions of reference in first episode and chronic schizophrenia. Psychiatry Res. 2014;224(2):124–32. doi:10.1016/j.pscychresns.2014.08.002
The goal of this study was to assess integrity of the cingulum bundle in patients diagnosed with first episode schizophrenia, chronic schizophrenia, and matched controls as well as to determine the relationship between diffusion measures of cingulum bundle integrity and severity of patients’ delusions of reference. Participants, who comprised 18 first episode patients, 20 chronic patients, and two groups of matched controls (20 subjects in each), underwent 3 T MRI diffusion tensor imaging. Patients diagnosed with schizophrenia (chronic+first episode) showed decreased fractional anisotropy in the right cingulum bundle compared with controls. First episode patients exhibited higher trace bilaterally, compared with matched controls, and on the left compared with chronic patients. Axial diffusivity was increased in first episode patients, bilaterally, compared with matched controls and chronic patients. Radial diffusivity was also higher, bilaterally, in first episode patients compared with matched controls, and on the right compared with chronic patients. Trace diffusity and radial diffusivity in first episode patients were significantly correlated with increased severity of delusions of reference. Given that the abnormalities were present only in first episode patients and were not observed in chronic cases, it appears that they normalize over time. These abnormalities in first episode patients involved diffusivity measures in all directions (trace, radial and axial), suggesting a likely acute, partially reversible process in which there is an increase in brain water content, i.e., swelling, edema, or inflammation, that may reflect an early neuroinflammatory response in first episode patients.
Juenger H, Koerte IK, Muehlmann M, Mayinger M, Mall V, Krägeloh-Mann I, Shenton ME, Berweck S, Staudt M, Heinen F. Microstructure of transcallosal motor fibers reflects type of cortical (re-)organization in congenital hemiparesis. Eur J Paediatr Neurol. 2014;18(6):691–7. doi:10.1016/j.ejpn.2014.05.006
BACKGROUND: Early unilateral brain lesions can lead to different types of corticospinal (re-)organization of motor networks. In one group of patients, the contralesional hemisphere exerts motor control not only over the contralateral non-paretic hand but also over the (ipsilateral) paretic hand, as the primary motor cortex is (re-)organized in the contralesional hemisphere. Another group of patients with early unilateral lesions shows "normal" contralateral motor projections starting in the lesioned hemisphere. AIM: We investigated how these different patterns of cortical (re-)organization affect interhemispheric transcallosal connectivity in patients with congenital hemiparesis. METHOD: Eight patients with ipsilateral motor projections (group IPSI) versus 7 patients with contralateral motor projections (group CONTRA) underwent magnetic resonance diffusion tensor imaging (DTI). The corpus callosum (CC) was subdivided in 5 areas (I-V) in the mid-sagittal slice and volumetric information. The following diffusion parameters were calculated: fractional anisotropy (FA), trace, radial diffusivity (RD), and axial diffusivity (AD). RESULTS: DTI revealed significantly lower FA, increased trace and RD for group IPSI compared to group CONTRA in area III of the corpus callosum, where transcallosal motor fibers cross the CC. In the directly neighboring area IV, where transcallosal somatosensory fibers cross the CC, no differences were found for these DTI parameters between IPSI and CONTRA. Volume of callosal subsections showed significant differences for area II (connecting premotor cortices) and III, where group IPSI had lower volume. INTERPRETATION: The results of this study demonstrate that the callosal microstructure in patients with congenital hemiparesis reflects the type of cortical (re-)organization. Early lesions disrupting corticospinal motor projections to the paretic hand consecutively affect the development or maintenance of transcallosal motor fibers.
Garlapati RR, Roy A, Joldes GR, Wittek A, Mostayed A, Doyle B, Warfield SK, Kikinis R, Knuckey N, Bunt S, et al. More accurate neuronavigation data provided by biomechanical modeling instead of rigid registration. J Neurosurg. 2014;120(6):1477–83. doi:10.3171/2013.12.JNS131165
It is possible to improve neuronavigation during image-guided surgery by warping the high-quality preoperative brain images so that they correspond with the current intraoperative configuration of the brain. In this paper, the accuracy of registration results obtained using comprehensive biomechanical models is compared with the accuracy of rigid registration, the technology currently available to patients. This comparison allows investigation into whether biomechanical modeling provides good-quality image data for neuronavigation for a larger proportion of patients than rigid registration. Preoperative images for 33 neurosurgery cases were warped onto their respective intraoperative configurations using both the biomechanics-based method and rigid registration. The Hausdorff distance-based evaluation process, which measures the difference between images, was used to quantify the performance of both registration methods. A statistical test for difference in proportions was conducted to evaluate the null hypothesis that the proportion of patients for whom improved neuronavigation can be achieved is the same for rigid and biomechanics-based registration. The null hypothesis was confidently rejected (p 10(-4)). Even the modified hypothesis that fewer than 25% of patients would benefit from the use of biomechanics-based registration was rejected at a significance level of 5% (p = 0.02). The biomechanics-based method proved particularly effective in cases demonstrating large craniotomy-induced brain deformations. The outcome of this analysis suggests that nonlinear biomechanics-based methods are beneficial to a large proportion of patients and can be considered for use in the operating theater as a possible means of improving neuronavigation and surgical outcomes.
Knöös P, Wahlgren M, Topgaard D, Ulvenlund S, Piculell L. Effects of added surfactant on swelling and molecular transport in drug-loaded tablets based on hydrophobically modified poly(acrylic acid). J Phys Chem B. 2014;118(32):9757–67. doi:10.1021/jp501288u
A combination of NMR chemical shift imaging and self-diffusion experiments is shown to give a detailed molecular picture of the events that occur when tablets of hydrophobically modified poly(acrylic acid) loaded with a drug (griseofulvin) swell in water in the presence or absence of surfactant (sodium octylbenzenesulfonate). The hydrophobic substituents on the polymer bind and trap the surfactant molecules in mixed micelles, leading to a slow effective surfactant transport that occurs via a small fraction of individually dissolved surfactant molecules in the water domain. Because of the efficient binding of surfactant, the penetrating water is found to diffuse past the penetrating surfactant into the polymer matrix, pushing the surfactant front outward as the matrix swells. The added surfactant has little effect on the transport of drug because both undissolved solid drug and surfactant-solubilized drug function as reservoirs that essentially follow the polymer as it swells. However, the added surfactant nevertheless has a strong indirect effect on the release of griseofulvin, through the effect of the surfactant on the solubility and erosion of the polymer matrix. The surfactant effectively solubilizes the hydrophobically modified polymer, making it fully miscible with water, leading to a more pronounced swelling and a slower erosion of the polymer matrix.
Agzenai Y, Lindman B, Alfredsson V, Topgaard D, Renamayor CS, Pacios IE. In situ X-ray polymerization: from swollen lamellae to polymer-surfactant complexes. J Phys Chem B. 2014;118(4):1159–67. doi:10.1021/jp411894e
The influence of the monomer diallyldimethylammonium chloride (D) on the lamellar liquid crystal formed by the anionic surfactant aerosol OT (AOT) and water is investigated, determining the lamellar spacings by SAXS and the quadrupolar splittings by deuterium NMR, as a function of the D or AOT concentrations. The cationic monomer D induces a destabilization of the AOT lamellar structure such that, at a critical concentration higher than 5 wt %, macroscopic phase separation takes place. When the monomer, which is dissolved in the AOT lamellae, is polymerized in situ by X-ray initiation, a new collapsed lamellar phase appears, corresponding to the complexation of the surfactant with the resulting polymer. A theoretical model is employed to analyze the variation of the interactions between the AOT bilayers and the stability of the lamellar structure.