Plastering mortar with antibacterial and antifungal properties studied by 1H NMR relaxometry

NASA Astrophysics Data System (ADS)

Jumate, E.; Aciu, C.; Manea, D. L.; Moldovan, D.; Chelcea, R.; Fechete, R.

2017-12-01

The Plastering mortars, with good antibacterial (in particular Escherichia coli, Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa) and antifungal (Aspergillus niger and Penicillium chrysogenum) properties, were studied by 1D NMR relaxometry and internal humidity measurements. Three recipes based on plastering mortar with variable content (0, 5 and 10 %) of Ag/ZnO nanopowders and with adequate physical characteristics regarding the mechanical strengths (CS IV), good adhesion to the substrate and low water absorption by capillarity (W2) were considered. The distributions of transverse relaxation times T2 were measured at 2 h after preparation (for mortar pasta) and then for the same samples at 2, 7, and 28 days during the hydration of mineralogical components. The T2 distributions are characterized by four components associated with hydration water and water in three types of pores of different dimension. The dimension of pores formed during hydration process are strongly dependent on the Ag/ZnO nanopowders content but finally at 28 days the pores distributions, as resulted from the T2 distributions, looks similar. Finally, the transverse relaxation ratio was linearly correlated to the compressive strength and the hydration behaviour during 132 days measured with a dedicated humidity sensor embedded inside sampled was discussed.

Characterization of wet aggregate stability of soils by ¹H-NMR relaxometry.

PubMed

Buchmann, C; Meyer, M; Schaumann, G E

2015-09-01

For the assessment of soil structural stability against hydraulic stress, wet sieving or constant head permeability tests are typically used but rather limited in their intrinsic information value. The multiple applications of several tests is the only possibility to assess important processes and mechanisms during soil aggregate breakdown, e.g. the influences of soil fragment release or differential swelling on the porous systems of soils or soil aggregate columns. Consequently, the development of new techniques for a faster and more detailed wet aggregate stability assessment is required. (1)H nuclear magnetic resonance relaxometry ((1)H-NMR relaxometry) might provide these requirements because it has already been successfully applied on soils. We evaluated the potential of (1)H-NMR relaxometry for the assessment of wet aggregate stability of soils, with more detailed information on occurring mechanisms at the same time. Therefore, we conducted single wet sieving and constant head permeability tests on untreated and 1% polyacrylic acid-treated soil aggregates of different textures and organic matter contents, subsequently measured by (1)H-NMR relaxometry after percolation. The stability of the soil aggregates were mainly depending on their organic matter contents and the type of aggregate stabilization, whereby additional effects of clay swelling on the measured wet aggregate stability were identified by the transverse relaxation time (T2) distributions. Regression analyses showed that only the percentage of water stable aggregates could be determined accurately from percolated soil aggregate columns by (1)H-NMR relaxometry measurements. (1)H-NMR relaxometry seems a promising technique for wet aggregate stability measurements but should be further developed for nonpercolated aggregate columns and real soil samples. Copyright © 2014 John Wiley & Sons, Ltd.

Characterization of the Embryogenic Tissue of the Norway Spruce Including a Transition Layer between the Tissue and the Culture Medium by Magnetic Resonance Imaging

NASA Astrophysics Data System (ADS)

Kořínek, R.; Mikulka, J.; Hřib, J.; Hudec, J.; Havel, L.; Bartušek, K.

2017-02-01

The paper describes the visualization of the cells (ESEs) and mucilage (ECMSN) in an embryogenic tissue via magnetic resonance imaging (MRI) relaxometry measurement combined with the subsequent multi-parametric segmentation. The computed relaxometry maps T1 and T2 show a thin layer (transition layer) between the culture medium and the embryogenic tissue. The ESEs, mucilage, and transition layer differ in their relaxation times T1 and T2; thus, these times can be used to characterize the individual parts within the embryogenic tissue. The observed mean values of the relaxation times T1 and T2 of the ESEs, mucilage, and transition layer are as follows: 1469 ± 324 and 53 ± 10 ms, 1784 ± 124 and 74 ± 8 ms, 929 ± 164 and 32 ± 4.7 ms, respectively. The multi-parametric segmentation exploiting the T1 and T2 relaxation times as a classifier shows the distribution of the ESEs and mucilage within the embryogenic tissue. The discussed T1 and T2 indicators can be utilized to characterize both the growth-related changes in an embryogenic tissue and the effect of biotic/abiotic stresses, thus potentially becoming a distinctive indicator of the state of any examined embryogenic tissue.

Quantitative T2 mapping of white matter: applications for ageing and cognitive decline

NASA Astrophysics Data System (ADS)

Knight, Michael J.; McCann, Bryony; Tsivos, Demitra; Dillon, Serena; Coulthard, Elizabeth; Kauppinen, Risto A.

2016-08-01

In MRI, the coherence lifetime T2 is sensitive to the magnetic environment imposed by tissue microstructure and biochemistry in vivo. Here we explore the possibility that the use of T2 relaxometry may provide information complementary to that provided by diffusion tensor imaging (DTI) in ageing of healthy controls (HC), Alzheimer’s disease (AD) and mild cognitive impairment (MCI). T2 and diffusion MRI metrics were quantified in HC and patients with MCI and mild AD using multi-echo MRI and DTI. We used tract-based spatial statistics (TBSS) to evaluate quantitative MRI parameters in white matter (WM). A prolonged T2 in WM was associated with AD, and able to distinguish AD from MCI, and AD from HC. Shorter WM T2 was associated with better cognition and younger age in general. In no case was a reduction in T2 associated with poorer cognition. We also applied principal component analysis, showing that WM volume changes independently of  T2, MRI diffusion indices and cognitive performance indices. Our data add to the evidence that age-related and AD-related decline in cognition is in part attributable to WM tissue state, and much less to WM quantity. These observations suggest that WM is involved in AD pathology, and that T2 relaxometry is a potential imaging modality for detecting and characterising WM in cognitive decline and dementia.

Use of 2D U-Net Convolutional Neural Networks for Automated Cartilage and Meniscus Segmentation of Knee MR Imaging Data to Determine Relaxometry and Morphometry.

PubMed

Norman, Berk; Pedoia, Valentina; Majumdar, Sharmila

2018-03-27

Purpose To analyze how automatic segmentation translates in accuracy and precision to morphology and relaxometry compared with manual segmentation and increases the speed and accuracy of the work flow that uses quantitative magnetic resonance (MR) imaging to study knee degenerative diseases such as osteoarthritis (OA). Materials and Methods This retrospective study involved the analysis of 638 MR imaging volumes from two data cohorts acquired at 3.0 T: (a) spoiled gradient-recalled acquisition in the steady state T1 ρ -weighted images and (b) three-dimensional (3D) double-echo steady-state (DESS) images. A deep learning model based on the U-Net convolutional network architecture was developed to perform automatic segmentation. Cartilage and meniscus compartments were manually segmented by skilled technicians and radiologists for comparison. Performance of the automatic segmentation was evaluated on Dice coefficient overlap with the manual segmentation, as well as by the automatic segmentations' ability to quantify, in a longitudinally repeatable way, relaxometry and morphology. Results The models produced strong Dice coefficients, particularly for 3D-DESS images, ranging between 0.770 and 0.878 in the cartilage compartments to 0.809 and 0.753 for the lateral meniscus and medial meniscus, respectively. The models averaged 5 seconds to generate the automatic segmentations. Average correlations between manual and automatic quantification of T1 ρ and T2 values were 0.8233 and 0.8603, respectively, and 0.9349 and 0.9384 for volume and thickness, respectively. Longitudinal precision of the automatic method was comparable with that of the manual one. Conclusion U-Net demonstrates efficacy and precision in quickly generating accurate segmentations that can be used to extract relaxation times and morphologic characterization and values that can be used in the monitoring and diagnosis of OA. © RSNA, 2018 Online supplemental material is available for this article.

Experimental NMR spin-lattice relaxometry study in the liquid crystalline nematic phase of propylcyano-phenylcyclohexane.

PubMed

Acosta, R H; Pusiol, D J

2001-01-01

The NMR spin-lattice proton relaxation dispersion T1(nu(L)) of the liquid crystal propylcyano-phenylcyclohexane is studied over several decades of Larmor frequencies and at different temperatures in the nematic mesophase. The results show that the order fluctuation of the local nematic director contribution to T1(nu(L)) undergoes a transition between two power regimes: from T1(nu(L)) protional to nu(1/2)L to nu(alpha)L (alpha approximately 1/3) on going from low to high Larmor frequencies.

Combined Diffusion Tensor Imaging and Transverse Relaxometry in Early-Onset Bipolar Disorder

ERIC Educational Resources Information Center

Gonenc, Atilla; Frazier, Jean A.; Crowley, David J.; Moore, Constance M.

2010-01-01

Objective: Transverse relaxation time (T2) imaging provides the opportunity to examine membrane fluidity, which can affect a number of cellular functions. The objective of the present work was to examine T2 abnormalities in children with unmodified DSM-IV-TR bipolar disorder (BD) in bilateral cingulate-paracingulate (CPC) white matter. Method: A…

Development and Validation of Noninvasive Magnetic Resonance Relaxometry for the In Vivo Assessment of Tissue-Engineered Graft Oxygenation

PubMed Central

Einstein, Samuel A.; Weegman, Bradley P.; Firpo, Meri T.; Papas, Klearchos K.

2016-01-01

Techniques to monitor the oxygen partial pressure (pO2) within implanted tissue-engineered grafts (TEGs) are critically necessary for TEG development, but current methods are invasive and inaccurate. In this study, we developed an accurate and noninvasive technique to monitor TEG pO2 utilizing proton (1H) or fluorine (19F) magnetic resonance spectroscopy (MRS) relaxometry. The value of the spin-lattice relaxation rate constant (R1) of some biocompatible compounds is sensitive to dissolved oxygen (and temperature), while insensitive to other external factors. Through this physical mechanism, MRS can measure the pO2 of implanted TEGs. We evaluated six potential MRS pO2 probes and measured their oxygen and temperature sensitivities and their intrinsic R1 values at 16.4 T. Acellular TEGs were constructed by emulsifying porcine plasma with perfluoro-15-crown-5-ether, injecting the emulsion into a macroencapsulation device, and cross-linking the plasma with a thrombin solution. A multiparametric calibration equation containing R1, pO2, and temperature was empirically generated from MRS data and validated with fiber optic (FO) probes in vitro. TEGs were then implanted in a dorsal subcutaneous pocket in a murine model and evaluated with MRS up to 29 days postimplantation. R1 measurements from the TEGs were converted to pO2 values using the established calibration equation and these in vivo pO2 measurements were simultaneously validated with FO probes. Additionally, MRS was used to detect increased pO2 within implanted TEGs that received supplemental oxygen delivery. Finally, based on a comparison of our MRS data with previously reported data, ultra-high-field (16.4 T) is shown to have an advantage for measuring hypoxia with 19F MRS. Results from this study show MRS relaxometry to be a precise, accurate, and noninvasive technique to monitor TEG pO2 in vitro and in vivo. PMID:27758135

Development and Validation of Noninvasive Magnetic Resonance Relaxometry for the In Vivo Assessment of Tissue-Engineered Graft Oxygenation.

PubMed

Einstein, Samuel A; Weegman, Bradley P; Firpo, Meri T; Papas, Klearchos K; Garwood, Michael

2016-11-01

Techniques to monitor the oxygen partial pressure (pO 2 ) within implanted tissue-engineered grafts (TEGs) are critically necessary for TEG development, but current methods are invasive and inaccurate. In this study, we developed an accurate and noninvasive technique to monitor TEG pO 2 utilizing proton ( 1 H) or fluorine ( 19 F) magnetic resonance spectroscopy (MRS) relaxometry. The value of the spin-lattice relaxation rate constant (R 1 ) of some biocompatible compounds is sensitive to dissolved oxygen (and temperature), while insensitive to other external factors. Through this physical mechanism, MRS can measure the pO 2 of implanted TEGs. We evaluated six potential MRS pO 2 probes and measured their oxygen and temperature sensitivities and their intrinsic R 1 values at 16.4 T. Acellular TEGs were constructed by emulsifying porcine plasma with perfluoro-15-crown-5-ether, injecting the emulsion into a macroencapsulation device, and cross-linking the plasma with a thrombin solution. A multiparametric calibration equation containing R 1 , pO 2 , and temperature was empirically generated from MRS data and validated with fiber optic (FO) probes in vitro. TEGs were then implanted in a dorsal subcutaneous pocket in a murine model and evaluated with MRS up to 29 days postimplantation. R 1 measurements from the TEGs were converted to pO 2 values using the established calibration equation and these in vivo pO 2 measurements were simultaneously validated with FO probes. Additionally, MRS was used to detect increased pO 2 within implanted TEGs that received supplemental oxygen delivery. Finally, based on a comparison of our MRS data with previously reported data, ultra-high-field (16.4 T) is shown to have an advantage for measuring hypoxia with 19 F MRS. Results from this study show MRS relaxometry to be a precise, accurate, and noninvasive technique to monitor TEG pO 2 in vitro and in vivo.

Plaster mortars with polymer fibers and additives investigated by 1H NMR relaxometry

NASA Astrophysics Data System (ADS)

Mustea, Andrei; Manea, Daniela L.; Jumate, Elena; Orbán, Yvette A.; Fechete, Radu

2017-12-01

Plaster mortars with polypropylene (pp) fibers and/or additives were investigated by 1H NMR relaxometry. Two recipes are proposed and are based on a commercially available mortar or are self-prepared and have different content of polypropylene fibers, which play the role of reinforcement agent, and/or Sika additive which is a waterproofing agent. The distributions of transverse relaxation times, T2 were obtained at 1, 3, 7 and 28 days after preparation. For the majority of T2-distributions four peaks are observed and, are associated with the hydration water (to the mineralogical components) and water in small, medium and large pores. The evolution in time, from 1 to 28 days, of the T2-distributions indicates the effects of pp fibers and Sika additive in the formation of pore microstructure. The degree of homogeneity of prepared receipts was evaluated from the relative peak-width and compared with mechanical measurements. Finally, we shown that the inverse of the transverse relaxation time values, T2-1, characteristic to the hydration water depends linearly on the resistance at compression measured for the 1÷28 days period, proving the important role of hydrations to the mechanical properties of the final product.

Evidence of solvent-gelator interaction in sugar-based organogel studied by field-cycling NMR relaxometry.

PubMed

Bielejewski, Michal; Tritt-Goc, Jadwiga

2010-11-16

The dynamics of bulk toluene and toluene confined in the 1,2-O-(1-ethylpropylidene)-α-D-glucofuranose gel was studied using (1)H field-cycling nuclear magnetic resonance relaxometry. The proton spin-lattice relaxation time T(1) was measured as a function of the magnetic field strength and temperature. The observed dispersion in the frequency range 10(4)-10(6) Hz for the relaxation rate of toluene in the gel system give evidence of the interaction between the toluene and the gelator aggregates. The data were interpreted in terms of the two-fraction fast-exchange model. Additionally it was also shown that a cooling rate during gel preparation process influences the gel microstructure and leads to different gelator-solvent interactions as reflected in a different behavior of the proton spin-lattice relaxation rate of toluene within the gel observed at the low frequency range.

R2*-relaxometry of the pancreas in patients with human hemochromatosis protein associated hereditary hemochromatosis.

PubMed

Henninger, B; Rauch, S; Zoller, H; Plaikner, M; Jaschke, W; Kremser, C

2017-04-01

To evaluate pancreatic iron in patients with human hemochromatosis protein associated hereditary hemochromatosis (HHC) using R2* relaxometry. 81 patients (58 male, 23 female; median age 49.5, range 10-81 years) with HHC were retrospectively studied. All underwent 1.5T magnetic resonance imaging (MRI) of the abdomen. A fat-saturated multi-gradient echo sequence with 12 echoes (TR=200ms; TE-initial 0.99ms; Delta-TE 1.41ms; 12 echoes; flip-angle: 20°) was used for the R2* quantification of the liver and the pancreas. Parameter maps were analyzed using regions of interest (3 in the liver and 2 in the pancreas) and R2* values were correlated. 59/81 patients had a liver R2*≥70 1/s of which 10/59 patients had a pancreas R2*≥50 1/s. No patient presented with a liver R2*<70 1/s and pancreas R2*≥50 1/s. All patients with pancreas R2* values≥50 1/s had liver R2* values≥70 1/s. ROC analysis resulted in a threshold of 209.4 1/s for liver R2* values to identify HFE positive patients with pancreas R2* values≥50 1/s with a median specificity of 78.87% and a median sensitivity of 90%. In patients with HHC R2* relaxometry of the pancreas should be performed when liver iron overload is present and can be omitted in cases with no sign of hepatic iron. Copyright © 2017 Elsevier B.V. All rights reserved.

Untangle soil-water-mucilage interactions: 1H NMR Relaxometry is lifting the veil

NASA Astrophysics Data System (ADS)

Brax, Mathilde; Buchmann, Christian; Schaumann, Gabriele Ellen

2017-04-01

Mucilage is mainly produced at the root tips and has a high water holding capacity derived from highly hydrophilic gel-forming substances. The objective of the MUCILAGE project is to understand the mechanistic role of mucilage for the regulation of water supply for plants. Our subproject investigates the chemical and physical properties of mucilage as pure gel and mixed with soil. 1H-NMR Relaxometry and PFG NMR represent non-intrusive powerful methods for soil scientific research by allowing quantification of the water distribution as well as monitoring of the water mobility in soil pores and gel phases.Relaxation of gel water differs from the one of pure water due to additional interactions with the gel matrix. Mucilage in soil leads to a hierarchical pore structure, consisting of the polymeric biohydrogel network surrounded by the surface of soil particles. The two types of relaxation rates 1/T1 and 1/T2 measured with 1H-NMR relaxometry refer to different relaxation mechanisms of water, while PFG-NMR measures the water self-diffusion coefficient. The objective of our study is to distinguish in situ water in gel from pore water in a simplified soil system, and to determine how the "gel effect" affects both relaxation rates and the water self-diffusion coefficient in porous systems. We demonstrate how the mucilage concentration and the soil solution alter the properties of water in the respective gel phases and pore systems in model soils. To distinguish gel-inherent processes from classical processes, we investigated the variations of the water mobility in pure chia mucilage under different conditions by using 1H-NMR relaxometry and PFG NMR. Using model soils, the signals coming from pore water and gel water were differentiated. We combined the equations describing 1H-NMR relaxation in porous systems and our experimental results, to explain how the presence of gel in soil affects 1H-NMR relaxation. Out of this knowledge we propose a method, which determines in situ the presence of mucilage in soil and characterizes several gel-specific parameters of the mucilage. Based on these findings, we discussed the potential and limitations of 1H-NMR relaxometry for following natural swelling and shrinking processes of a natural biopolymer in soil.

NMR Relaxometry to Characterize the Drug Structural Phase in a Porous Construct.

PubMed

Thrane, Linn W; Berglund, Emily A; Wilking, James N; Vodak, David; Seymour, Joseph D

2018-06-14

Nuclear magnetic resonance (NMR) frequency spectra and T 2 relaxation time measurements, using a high-power radio frequency probe, are shown to characterize the presence of an amorphous drug in a porous silica construct. The results indicate the ability of non-solid-state NMR methods to characterize crystalline and amorphous solid structural phases in drugs. Two-dimensional T 1 - T 2 magnetic relaxation time correlation experiments are shown to monitor the impact of relative humidity on the drug in a porous silica tablet.

Bone marrow fat content in 70 adolescent girls with anorexia nervosa: Magnetic resonance imaging and magnetic resonance spectroscopy assessment.

PubMed

Ecklund, Kirsten; Vajapeyam, Sridhar; Mulkern, Robert V; Feldman, Henry A; O'Donnell, Jennifer M; DiVasta, Amy D; Gordon, Catherine M

2017-07-01

Adolescents and women with anorexia nervosa have increased bone marrow fat and decreased bone formation, at least in part due to hormonal changes leading to preferential stem cell differentiation to adipocytes over osteoblasts. The purpose of this study was to evaluate marrow fat content and correlate with age and disease severity using knee MRI with T1 relaxometry (T1-R) and MR spectroscopy (MRS) in 70 adolescents with anorexia nervosa. We enrolled 70 girls with anorexia nervosa who underwent 3-T knee MRI with coronal T1-W images, T1-R and single-voxel proton MRS at 30 and 60 ms TE. Metaphyses were scored visually on the T1-W images for red marrow. Visual T1 score, T1 relaxometry values, MRS lipid indices and fat fractions were analyzed by regression on age, body mass index (BMI) and bone mineral density (BMD) as disease severity markers. MRS measures included unsaturated fat index, T2 water, unsaturated and saturated fat fractions. All red marrow measures declined significantly with age. T1-R values were associated negatively with BMI and BMD for girls ≤16 years (P=0.03 and P=0.002, respectively) and positively for those≥17 years (P=0.05 and P=0.003, respectively). MRS identified a strong inverse association between T2 water and saturated fat fraction from 60 ms TE data (r=-0.85, P<0.0001). There was no association between unsaturated fat index and BMI or BMD. The association between T1 and BMI and BMD among older girls suggests more marrow fat in those with severe anorexia nervosa. In contrast, the physiological association between marrow fat content and age remained dominant in younger patients. The strong association between T2 water and saturated fat may relate to the restricted mobility of water with increasing marrow fat.

Low-field nuclear magnetic resonance characterization of organic content in shales

USGS Publications Warehouse

Washburn, Kathryn E.; Birdwell, Justin E.; Seymour, Joseph D.; Kirkland, Catherine; Vogt, Sarah J.

2013-01-01

Low-field nuclear magnetic resonance (LF-NMR) relaxometry is a non-invasive technique commonly used to assess hydrogen-bearing fluids in petroleum reservoir rocks. Longitudinal T1 and transverse T2 relaxation time measurements made using LF-NMR on conventional reservoir systems provides information on rock porosity, pore size distributions, and fluid types and saturations in some cases. Recent improvements in LF-SNMR instrument electronics have made it possible to apply these methods to assess highly viscous and even solid organic phases within reservoir rocks. T1 and T2 relaxation responses behave very differently in solids and liquids, therefore the relationship between these two modes of relaxation can be used to differentiate organic phases in rock samples or to characterize extracted organic materials. Using T1-T2 correlation data, organic components present in shales, such as kerogen and bitumen, can be examined in laboratory relaxometry measurements. In addition, implementation of a solid-echo pulse sequence to refocus some types of T2 relaxation during correlation measurements allows for improved resolution of solid phase photons. LF-NMR measurements of T1 and T2 relaxation time correlations were carried out on raw oil shale samples from resources around the world. These shales vary widely in mineralogy, total organic carbon (TOC) content and kerogen type. NMR results were correlcated with Leco TOC and geochemical data obtained from Rock-Eval. There is excellent correlation between NMR data and programmed pyrolysis parameters, particularly TOC and S2, and predictive capability is also good. To better understand the NMR response, the 2D NMR spectra were compared to similar NMR measurements made using high-field (HF) NMR equipment.

Combining 7Li NMR field-cycling relaxometry and stimulated-echo experiments: a powerful approach to lithium ion dynamics in solid-state electrolytes.

PubMed

Graf, Magnus; Kresse, Benjamin; Privalov, Alexei F; Vogel, Michael

2013-01-01

We use (7)Li NMR to study lithium ion dynamics in a (Li2S)-(P2S5) glass. In particular, it is shown that a combination of (7)Li field-cycling relaxometry and (7)Li stimulated-echo experiments allows us to cover a time window extending over 10 orders of magnitude without any gaps. While the (7)Li stimulated-echo method proved suitable to measure correlation functions F2(t) of lithium ion dynamics in solids in recent years, we establish the (7)Li field-cycling technique as a versatile tool to ascertain the spectral density J2(ω) of the lithium ionic motion in this contribution. It is found that the dynamic range of (7)Li field-cycling relaxometry is 10(-9)-10(-5)s and, hence, it complements in an ideal way that of (7)Li stimulated-echo experiments, which amounts to 10(-5)-10(1)s. Transformations between time and frequency domains reveal that the field-cycling and stimulated-echo approaches yield results for the translational motion of the lithium ions that are consistent both with each other and with findings for the motional narrowing of (7)Li NMR spectra of the studied (Li2S)-(P2S5) glass. In the (7)Li field-cycling studies of the (Li2S)-(P2S5) glass, we observe the translational ionic motion at higher temperatures and the nearly constant loss at lower temperatures. For the former motion, the frequency dependence of the measured spectral density is well described by a Cole-Davidson function. For the latter phenomenon, which was considered as an universal phenomenon of disordered solids in the literature, we find an exponential temperature dependence. Copyright © 2013 Elsevier Inc. All rights reserved.

Calibration standard of body tissue with magnetic nanocomposites for MRI and X-ray imaging

NASA Astrophysics Data System (ADS)

Rahn, Helene; Woodward, Robert; House, Michael; Engineer, Diana; Feindel, Kirk; Dutz, Silvio; Odenbach, Stefan; StPierre, Tim

2016-05-01

We present a first study of a long-term phantom for Magnetic Resonance Imaging (MRI) and X-ray imaging of biological tissues with magnetic nanocomposites (MNC) suitable for 3-dimensional and quantitative imaging of tissues after, e.g. magnetically assisted cancer treatments. We performed a cross-calibration of X-ray microcomputed tomography (XμCT) and MRI with a joint calibration standard for both imaging techniques. For this, we have designed a phantom for MRI and X-ray computed tomography which represents biological tissue enriched with MNC. The developed phantoms consist of an elastomer with different concentrations of multi-core MNC. The matrix material is a synthetic thermoplastic gel, PermaGel (PG). The developed phantoms have been analyzed with Nuclear Magnetic Resonance (NMR) Relaxometry (Bruker minispec mq 60) at 1.4 T to obtain R2 transverse relaxation rates, with SQUID (Superconducting QUantum Interference Device) magnetometry and Inductively Coupled Plasma Mass Spectrometry (ICP-MS) to verify the magnetite concentration, and with XμCT and 9.4 T MRI to visualize the phantoms 3-dimensionally and also to obtain T2 relaxation times. A specification of a sensitivity range is determined for standard imaging techniques X-ray computed tomography (XCT) and MRI as well as with NMR. These novel phantoms show a long-term stability over several months up to years. It was possible to suspend a particular MNC within the PG reaching a concentration range from 0 mg/ml to 6.914 mg/ml. The R2 relaxation rates from 1.4 T NMR-relaxometry show a clear connection (R2=0.994) with MNC concentrations between 0 mg/ml and 4.5 mg/ml. The MRI experiments have shown a linear correlation of R2 relaxation and MNC concentrations as well but in a range between MNC concentrations of 0 mg/ml and 1.435 mg/ml. It could be shown that XμCT displays best moderate and high MNC concentrations. The sensitivity range for this particular XμCT apparatus yields from 0.569 mg/ml to 6.914 mg/ml. The cross-calibration has defined a shared sensitivity range of XμCT, 1.4 T NMR relaxometer minispec, and 9.4 T MRI. The shared sensitivity range for the measuring method (NMR relaxometry) and the imaging modalities (XμCT and MRI) is from 0.569 mg/ml, limited by XμCT, and 1.435 mg/ml, limited by MRI. The presented phantoms have been found to be suitable to act as a body tissue substitute for XCT imaging as well as an acceptable T2 phantom of biological tissue enriched with magnetic nanoparticles for MRI.

Stabilization of the Inverse Laplace Transform of Multiexponential Decay through Introduction of a Second Dimension

PubMed Central

Celik, Hasan; Bouhrara, Mustapha; Reiter, David A.; Fishbein, Kenneth W.; Spencer, Richard G.

2013-01-01

We propose a new approach to stabilizing the inverse Laplace transform of a multiexponential decay signal, a classically ill-posed problem, in the context of nuclear magnetic resonance relaxometry. The method is based on extension to a second, indirectly detected, dimension, that is, use of the established framework of two-dimensional relaxometry, followed by projection onto the desired axis. Numerical results for signals comprised of discrete T1 and T2 relaxation components and experiments performed on agarose gel phantoms are presented. We find markedly improved accuracy, and stability with respect to noise, as well as insensitivity to regularization in quantifying underlying relaxation components through use of the two-dimensional as compared to the one-dimensional inverse Laplace transform. This improvement is demonstrated separately for two different inversion algorithms, nonnegative least squares and non-linear least squares, to indicate the generalizability of this approach. These results may have wide applicability in approaches to the Fredholm integral equation of the first kind. PMID:24035004

Dexamethasone exacerbates cerebral edema and brain injury following lithium-pilocarpine induced status epilepticus☆

PubMed Central

Duffy, B.A.; Chun, K.P.; Ma, D.; Lythgoe, M.F.; Scott, R.C.

2014-01-01

Anti-inflammatory therapies are the current most plausible drug candidates for anti-epileptogenesis and neuroprotection following prolonged seizures. Given that vasogenic edema is widely considered to be detrimental for outcome following status epilepticus, the anti-inflammatory agent dexamethasone is sometimes used in clinic for alleviating cerebral edema. In this study we perform longitudinal magnetic resonance imaging in order to assess the contribution of dexamethasone on cerebral edema and subsequent neuroprotection following status epilepticus. Lithium-pilocarpine was used to induce status epilepticus in rats. Following status epilepticus, rats were either post-treated with saline or with dexamethasone sodium phosphate (10 mg/kg or 2 mg/kg). Brain edema was assessed by means of magnetic resonance imaging (T2 relaxometry) and hippocampal volumetry was used as a marker of neuronal injury. T2 relaxometry was performed prior to, 48 h and 96 h following status epilepticus. Volume measurements were performed between 18 and 21 days after status epilepticus. Unexpectedly, cerebral edema was worse in rats that were treated with dexamethasone compared to controls. Furthermore, dexamethasone treated rats had lower hippocampal volumes compared to controls 3 weeks after the initial insult. The T2 measurements at 2 days and 4 days in the hippocampus correlated with hippocampal volumes at 3 weeks. Finally, the mortality rate in the first week following status epilepticus increased from 14% in untreated rats to 33% and 46% in rats treated with 2 mg/kg and 10 mg/kg dexamethasone respectively. These findings suggest that dexamethasone can exacerbate the acute cerebral edema and brain injury associated with status epilepticus. PMID:24333865

MRI for Iron Overload in Thalassemia.

PubMed

Fernandes, Juliano Lara

2018-04-01

MRI is a key tool in the current management of patients with thalassemia. Given its capability of assessing iron overload in different organs noninvasively and without contrast, it has significant advantages over other metrics, including serum ferritin. Liver iron concentration can be measured either with relaxometry methods T2*/T2 or signal intensity ratio techniques. Myocardial iron can be assessed in the same examination through T2* imaging. In this review, we focus on showing how MRI evaluates iron in both organs and the clinical applications as well as practical approaches to using this tool by clinicians taking care of patients with thalassemia. Copyright © 2017 Elsevier Inc. All rights reserved.

Simultaneous Gaussian and exponential inversion for improved analysis of shales by NMR relaxometry

USGS Publications Warehouse

Washburn, Kathryn E.; Anderssen, Endre; Vogt, Sarah J.; Seymour, Joseph D.; Birdwell, Justin E.; Kirkland, Catherine M.; Codd, Sarah L.

2014-01-01

Nuclear magnetic resonance (NMR) relaxometry is commonly used to provide lithology-independent porosity and pore-size estimates for petroleum resource evaluation based on fluid-phase signals. However in shales, substantial hydrogen content is associated with solid and fluid signals and both may be detected. Depending on the motional regime, the signal from the solids may be best described using either exponential or Gaussian decay functions. When the inverse Laplace transform, the standard method for analysis of NMR relaxometry results, is applied to data containing Gaussian decays, this can lead to physically unrealistic responses such as signal or porosity overcall and relaxation times that are too short to be determined using the applied instrument settings. We apply a new simultaneous Gaussian-Exponential (SGE) inversion method to simulated data and measured results obtained on a variety of oil shale samples. The SGE inversion produces more physically realistic results than the inverse Laplace transform and displays more consistent relaxation behavior at high magnetic field strengths. Residuals for the SGE inversion are consistently lower than for the inverse Laplace method and signal overcall at short T2 times is mitigated. Beyond geological samples, the method can also be applied in other fields where the sample relaxation consists of both Gaussian and exponential decays, for example in material, medical and food sciences.

A New Approach for Deep Gray Matter Analysis Using Partial-Volume Estimation.

PubMed

Bonnier, Guillaume; Kober, Tobias; Schluep, Myriam; Du Pasquier, Renaud; Krueger, Gunnar; Meuli, Reto; Granziera, Cristina; Roche, Alexis

2016-01-01

The existence of partial volume effects in brain MR images makes it challenging to understand physio-pathological alterations underlying signal changes due to pathology across groups of healthy subjects and patients. In this study, we implement a new approach to disentangle gray and white matter alterations in the thalamus and the basal ganglia. The proposed method was applied to a cohort of early multiple sclerosis (MS) patients and healthy subjects to evaluate tissue-specific alterations related to diffuse inflammatory or neurodegenerative processes. Forty-three relapsing-remitting MS patients and nineteen healthy controls underwent 3T MRI including: (i) fluid-attenuated inversion recovery, double inversion recovery, magnetization-prepared gradient echo for lesion count, and (ii) T1 relaxometry. We applied a partial volume estimation algorithm to T1 relaxometry maps to gray and white matter local concentrations as well as T1 values characteristic of gray and white matter in the thalamus and the basal ganglia. Statistical tests were performed to compare groups in terms of both global T1 values, tissue characteristic T1 values, and tissue concentrations. Significant increases in global T1 values were observed in the thalamus (p = 0.038) and the putamen (p = 0.026) in RRMS patients compared to HC. In the Thalamus, the T1 increase was associated with a significant increase in gray matter characteristic T1 (p = 0.0016) with no significant effect in white matter. The presented methodology provides additional information to standard MR signal averaging approaches that holds promise to identify the presence and nature of diffuse pathology in neuro-inflammatory and neurodegenerative diseases.

Gelation of Na-alginate aqueous solution: A study of sodium ion dynamics via NMR relaxometry.

PubMed

Zhao, Congxian; Zhang, Chao; Kang, Hongliang; Xia, Yanzhi; Sui, Kunyan; Liu, Ruigang

2017-08-01

Sodium alginate (SA) hydrogels have a wide range of applications including tissue engineering, drug delivery and formulations for preventing gastric reflux. The dynamics of sodium ions during the gelation process of SA solution is critical for clarification of the gelation procedure. In this work, nuclear magnetic resonance (NMR) relaxometry and pulsed-field-gradient (PFG) NMR diffusometry were used to investigate the dynamics of the sodium ions during the gelation of SA alginate. We find that sodium ions are in two different states with the addition of divalent calcium ions, corresponding to Ca 2+ crosslinked and un-crosslinked regions in the hydrogels. The sodium ions within the un-crosslinked regions are those released from the alginate chains without Ca 2+ crosslinking. The relative content of sodium ions within the Ca 2+ crosslinked regions decreased with the increase in the content of calcium ions in the system. The relaxation time T 2 of sodium ions within the Ca 2+ crosslinked and un-crosslinked regions shift to shorter and longer relaxation time with the increase in concentration of calcium ion, which indicates the closer package of SA chains and the larger space for the diffusion of free sodium ions. This work clarifies the dynamics of 23 Na + in a calcium alginate gel at the equilibrium state. Copyright © 2017 Elsevier Ltd. All rights reserved.

Magnetic resonance microscopy for assessment of morphological changes in hydrating hydroxypropylmethyl cellulose matrix tablets in situ.

PubMed

Kulinowski, Piotr; Młynarczyk, Anna; Dorożyński, Przemysław; Jasiński, Krzysztof; Gruwel, Marco L H; Tomanek, Bogusław; Węglarz, Władysław P

2012-12-01

To resolve contradictions found in morphology of hydrating hydroxypropylmethyl cellulose (HPMC) matrix as studied using Magnetic Resonance Imaging (MRI) techniques. Until now, two approaches were used in the literature: either two or three regions that differ in physicochemical properties were identified. Multiparametric, spatially and temporally resolved T(2) MR relaxometry in situ was applied to study the hydration progress in HPMC matrix tablets using a 11.7 T MRI system. Two spin-echo based pulse sequences-one of them designed to specifically study short T(2) signals-were used. Two components in the T(2) decay envelope were estimated and spatial distributions of their parameters, i.e. amplitudes and T(2) values, were obtained. Based on the data, five different regions and their temporal evolution were identified: dry glassy, hydrated solid like, two interface layers and gel layer. The regions were found to be separated by four evolving fronts identified as penetration, full hydration, total gelification and apparent erosion. The MRI results showed morphological details of the hydrating HPMC matrices matching compound theoretical models. The proposed method will allow for adequate evaluation of controlled release polymeric matrix systems loaded with drug substances of different solubility.

Rotatable Small Permanent Magnet Array for Ultra-Low Field Nuclear Magnetic Resonance Instrumentation: A Concept Study.

PubMed

Vogel, Michael W; Giorni, Andrea; Vegh, Viktor; Pellicer-Guridi, Ruben; Reutens, David C

2016-01-01

We studied the feasibility of generating the variable magnetic fields required for ultra-low field nuclear magnetic resonance relaxometry with dynamically adjustable permanent magnets. Our motivation was to substitute traditional electromagnets by distributed permanent magnets, increasing system portability. The finite element method (COMSOL®) was employed for the numerical study of a small permanent magnet array to calculate achievable magnetic field strength, homogeneity, switching time and magnetic forces. A manually operated prototype was simulated and constructed to validate the numerical approach and to verify the generated magnetic field. A concentric small permanent magnet array can be used to generate strong sample pre-polarisation and variable measurement fields for ultra-low field relaxometry via simple prescribed magnet rotations. Using the array, it is possible to achieve a pre-polarisation field strength above 100 mT and variable measurement fields ranging from 20-50 μT with 200 ppm absolute field homogeneity within a field-of-view of 5 x 5 x 5 cubic centimetres. A dynamic small permanent magnet array can generate multiple highly homogeneous magnetic fields required in ultra-low field nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) instruments. This design can significantly reduce the volume and energy requirements of traditional systems based on electromagnets, improving portability considerably.

NMR relaxometry study of cement hydration in the presence of different oxidic fine fraction materials.

PubMed

Nestle, Nikolaus

2004-01-01

NMR relaxometry has been applied to study hydrating cements for about 25 years now. The most important advantage over other experimental approaches is the possibility to conduct non-destructive measurements with a time resolution of minutes. NMR relaxometry data thus can help to identify details in the time course of cement hydration that possibly would be overlooked in other experiments with lower temporal resolution. Time-resolved information on cement hydration kinetics can provide interesting insights into the impact of oxidic additive materials on cement hydration. For PbO, a very strong delay was observed which then was systematically studied. An explanation for this delay is suggested.

Hypothesis-driven classification of materials using nuclear magnetic resonance relaxometry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Espy, Michelle A.; Matlashov, Andrei N.; Schultz, Larry J.

Technologies related to identification of a substance in an optimized manner are provided. A reference group of known materials is identified. Each known material has known values for several classification parameters. The classification parameters comprise at least one of T.sub.1, T.sub.2, T.sub.1.rho., a relative nuclear susceptibility (RNS) of the substance, and an x-ray linear attenuation coefficient (LAC) of the substance. A measurement sequence is optimized based on at least one of a measurement cost of each of the classification parameters and an initial probability of each of the known materials in the reference group.

Time-Domain Nuclear Magnetic Resonance Investigation of Water Dynamics in Different Ginger Cultivars.

PubMed

Huang, Chongyang; Zhou, Qi; Gao, Shan; Bao, Qingjia; Chen, Fang; Liu, Chaoyang

2016-01-20

Different ginger cultivars may contain different nutritional and medicinal values. In this study, a time-domain nuclear magnetic resonance method was employed to study water dynamics in different ginger cultivars. Significant differences in transverse relaxation time T2 values assigned to the distribution of water in different parts of the plant were observed between Henan ginger and four other ginger cultivars. Ion concentration and metabolic analysis showed similar differences in Mn ion concentrations and organic solutes among the different ginger cultivars, respectively. On the basis of Pearson's correlation analysis, many organic solutes and 6-gingerol, the main active substance of ginger, exhibited significant correlations with water distribution as determined by NMR T2 relaxation, suggesting that the organic solute differences may impact water distribution. Our work demonstrates that low-field NMR relaxometry provides useful information about water dynamics in different ginger cultivars as affected by the presence of different organic solutes.

NMR relaxometry study of plaster mortar with polymer additives

NASA Astrophysics Data System (ADS)

Jumate, E.; Moldovan, D.; Fechete, R.; Manea, D.

2013-11-01

The cement mixed with water forms a plastic paste or slurry which stiffness in time and finally hardens into a resistant stone. The addition of sand aggregates, polymers (Walocel) and/or calcium carbonate will modify dramatically the final mortar mechanic and thermal properties. The hydration processes can be observed using the 1D NMR measurements of transverse T2 relaxation times distributions analysed by a Laplace inversion algorithm. These distributions were obtained for mortar pasta measured at 2 hours after preparation then at 3, 7 and 28 days after preparation. Multiple components are identified in the T2 distributions. These can be associated with the proton bounded chemical or physical to the mortar minerals characterized by a short T2 relaxation time and to water protons in pores with three different pore sizes as observed from SEM images. The evaporation process is faster in the first hours after preparation, while the mortar hydration (bonding of water molecules to mortar minerals) can be still observed after days or months from preparation. Finally, the mechanic resistance was correlated with the transverse T2 relaxation rates corresponding to the bound water.

Automated two-point dixon screening for the evaluation of hepatic steatosis and siderosis: comparison with R2-relaxometry and chemical shift-based sequences.

PubMed

Henninger, B; Zoller, H; Rauch, S; Schocke, M; Kannengiesser, S; Zhong, X; Reiter, G; Jaschke, W; Kremser, C

2015-05-01

To evaluate the automated two-point Dixon screening sequence for the detection and estimated quantification of hepatic iron and fat compared with standard sequences as a reference. One hundred and two patients with suspected diffuse liver disease were included in this prospective study. The following MRI protocol was used: 3D-T1-weighted opposed- and in-phase gradient echo with two-point Dixon reconstruction and dual-ratio signal discrimination algorithm ("screening" sequence); fat-saturated, multi-gradient-echo sequence with 12 echoes; gradient-echo T1 FLASH opposed- and in-phase. Bland-Altman plots were generated and correlation coefficients were calculated to compare the sequences. The screening sequence diagnosed fat in 33, iron in 35 and a combination of both in 4 patients. Correlation between R2* values of the screening sequence and the standard relaxometry was excellent (r = 0.988). A slightly lower correlation (r = 0.978) was found between the fat fraction of the screening sequence and the standard sequence. Bland-Altman revealed systematically lower R2* values obtained from the screening sequence and higher fat fraction values obtained with the standard sequence with a rather high variability in agreement. The screening sequence is a promising method with fast diagnosis of the predominant liver disease. It is capable of estimating the amount of hepatic fat and iron comparable to standard methods. • MRI plays a major role in the clarification of diffuse liver disease. • The screening sequence was introduced for the assessment of diffuse liver disease. • It is a fast and automated algorithm for the evaluation of hepatic iron and fat. • It is capable of estimating the amount of hepatic fat and iron.

Rotatable Small Permanent Magnet Array for Ultra-Low Field Nuclear Magnetic Resonance Instrumentation: A Concept Study

PubMed Central

Vegh, Viktor; Reutens, David C.

2016-01-01

Object We studied the feasibility of generating the variable magnetic fields required for ultra-low field nuclear magnetic resonance relaxometry with dynamically adjustable permanent magnets. Our motivation was to substitute traditional electromagnets by distributed permanent magnets, increasing system portability. Materials and Methods The finite element method (COMSOL®) was employed for the numerical study of a small permanent magnet array to calculate achievable magnetic field strength, homogeneity, switching time and magnetic forces. A manually operated prototype was simulated and constructed to validate the numerical approach and to verify the generated magnetic field. Results A concentric small permanent magnet array can be used to generate strong sample pre-polarisation and variable measurement fields for ultra-low field relaxometry via simple prescribed magnet rotations. Using the array, it is possible to achieve a pre-polarisation field strength above 100 mT and variable measurement fields ranging from 20–50 μT with 200 ppm absolute field homogeneity within a field-of-view of 5 x 5 x 5 cubic centimetres. Conclusions A dynamic small permanent magnet array can generate multiple highly homogeneous magnetic fields required in ultra-low field nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) instruments. This design can significantly reduce the volume and energy requirements of traditional systems based on electromagnets, improving portability considerably. PMID:27271886

Water dynamics in different biochar fractions.

PubMed

Conte, Pellegrino; Nestle, Nikolaus

2015-09-01

Biochar is a carbonaceous porous material deliberately applied to soil to improve its fertility. The mechanisms through which biochar acts on fertility are still poorly understood. The effect of biochar texture size on water dynamics was investigated here in order to provide information to address future research on nutrient mobility towards plant roots as biochar is applied as soil amendment. A poplar biochar has been stainless steel fractionated in three different textured fractions (1.0-2.0 mm, 0.3-1.0 mm and <0.3 mm, respectively). Water-saturated fractions were analyzed by fast field cycling (FFC) NMR relaxometry. Results proved that 3D exchange between bound and bulk water predominantly occurred in the coarsest fraction. However, as porosity decreased, water motion was mainly associated to a restricted 2D diffusion among the surface-site pores and the bulk-site ones. The X-ray μ-CT imaging analyses on the dry fractions revealed the lowest surface/volume ratio for the coarsest fraction, thereby corroborating the 3D water exchange mechanism hypothesized by FFC NMR relaxometry. However, multi-micrometer porosity was evidenced in all the samples. The latter finding suggested that the 3D exchange mechanism cannot even be neglected in the finest fraction as previously excluded only on the basis of NMR relaxometry results. X-ray μ-CT imaging showed heterogeneous distribution of inorganic materials inside all the fractions. The mineral components may contribute to the water relaxation mechanisms by FFC NMR relaxometry. Further studies are needed to understand the role of the inorganic particles on water dynamics. Copyright © 2015 John Wiley & Sons, Ltd.

Observation of exchange of micropore water in cement pastes by two-dimensional T(2)-T(2) nuclear magnetic resonance relaxometry.

PubMed

Monteilhet, L; Korb, J-P; Mitchell, J; McDonald, P J

2006-12-01

The first detailed analysis of the two-dimensional (2D) NMR T(2)-T(2) exchange experiment with a period of magnetization storage between the two T(2) relaxation encoding periods (T(2)-store-T(2)) is presented. It is shown that this experiment has certain advantages over the T(1)-T(2) variant for the quantization of chemical exchange. New T(2)-store-T(2) 2D 1H NMR spectra of the pore water within white cement paste are presented. Based on these spectra, the exchange rate of water between the two smallest porosity reservoirs is estimated for the first time. It is found to be of the order of 5 ms{-1}. Further, a careful estimate of the pore sizes of these reservoirs is made. They are found to be of the order of 1.4 nm and 10-30 nm , respectively. A discussion of the results is developed in terms of possible calcium silicate hydrate products. A water diffusion coefficient inferred from the exchange rate and the cement particle size is found to compare favorably with the results of molecular-dynamics simulations to be found in the literature.

Non-destructive Analysis of Oil-Contaminated Soil Core Samples by X-ray Computed Tomography and Low-Field Nuclear Magnetic Resonance Relaxometry: a Case Study

PubMed Central

Mitsuhata, Yuji; Nishiwaki, Junko; Kawabe, Yoshishige; Utsuzawa, Shin; Jinguuji, Motoharu

2010-01-01

Non-destructive measurements of contaminated soil core samples are desirable prior to destructive measurements because they allow obtaining gross information from the core samples without touching harmful chemical species. Medical X-ray computed tomography (CT) and time-domain low-field nuclear magnetic resonance (NMR) relaxometry were applied to non-destructive measurements of sandy soil core samples from a real site contaminated with heavy oil. The medical CT visualized the spatial distribution of the bulk density averaged over the voxel of 0.31 × 0.31 × 2 mm3. The obtained CT images clearly showed an increase in the bulk density with increasing depth. Coupled analysis with in situ time-domain reflectometry logging suggests that this increase is derived from an increase in the water volume fraction of soils with depth (i.e., unsaturated to saturated transition). This was confirmed by supplementary analysis using high-resolution micro-focus X-ray CT at a resolution of ∼10 μm, which directly imaged the increase in pore water with depth. NMR transverse relaxation waveforms of protons were acquired non-destructively at 2.7 MHz by the Carr–Purcell–Meiboom–Gill (CPMG) pulse sequence. The nature of viscous petroleum molecules having short transverse relaxation times (T2) compared to water molecules enabled us to distinguish the water-saturated portion from the oil-contaminated portion in the core sample using an M0–T2 plot, where M0 is the initial amplitude of the CPMG signal. The present study demonstrates that non-destructive core measurements by medical X-ray CT and low-field NMR provide information on the groundwater saturation level and oil-contaminated intervals, which is useful for constructing an adequate plan for subsequent destructive laboratory measurements of cores. PMID:21258437

Extended phase graph formalism for systems with magnetization transfer and exchange

PubMed Central

Teixeira, Rui Pedro A.G.; Hajnal, Joseph V.

2017-01-01

Purpose An extended phase graph framework (EPG‐X) for modeling systems with exchange or magnetization transfer (MT) is proposed. Theory EPG‐X models coupled two‐compartment systems by describing each compartment with separate phase graphs that exchange during evolution periods. There are two variants: EPG‐X(BM) for systems governed by the Bloch‐McConnell equations, and EPG‐X(MT) for the pulsed MT formalism. For the MT case, the “bound” protons have no transverse components, so their phase graph consists of only longitudinal states. Methods The EPG‐X model was validated against steady‐state solutions and isochromat‐based simulation of gradient‐echo sequences. Three additional test cases were investigated: (i) MT effects in multislice turbo spin‐echo; (ii) variable flip angle gradient‐echo imaging of the type used for MR fingerprinting; and (iii) water exchange in multi‐echo spin‐echo T2 relaxometry. Results EPG‐X was validated successfully against isochromat based transient simulations and known steady‐state solutions. EPG‐X(MT) simulations matched in‐vivo measurements of signal attenuation in white matter in multislice turbo spin‐echo images. Magnetic resonance fingerprinting–style experiments with a bovine serum albumin (MT) phantom showed that the data were not consistent with a single‐pool model, but EPG‐X(MT) could be used to fit the data well. The EPG‐X(BM) simulations of multi‐echo spin‐echo T2 relaxometry suggest that exchange could lead to an underestimation of the myelin‐water fraction. Conclusions The EPG‐X framework can be used for modeling both steady‐state and transient signal response of systems exhibiting exchange or MT. This may be particularly beneficial for relaxometry approaches that rely on characterizing transient rather than steady‐state sequences. Magn Reson Med 80:767–779, 2018. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. PMID:29243295

Effects of total saponins from Trillium tschonoskii rhizome on grey and white matter injury evaluated by quantitative multiparametric MRI in a rat model of ischemic stroke.

PubMed

Li, Manzhong; Ouyang, Junyao; Zhang, Yi; Cheng, Brian Chi Yan; Zhan, Yu; Yang, Le; Zou, Haiyan; Zhao, Hui

2018-04-06

Trillium tschonoskii rhizome (TTR), a medicinal herb, has been traditionally used to treat traumatic brain injury and headache in China. Although the potential neuroprotective efficacy of TTR has gained increasing interest, the pharmacological mechanism remains unclear. Steroid saponins are the main bioactive components of the herb. To investigate the protective and repair-promoting effects of the total saponins from TTR (TSTT) on grey and white matter damages in a rat model of middle cerebral artery occlusion (MCAO) using magnetic resonance imaging (MRI) assay. Ischemic stroke was induced by MCAO. TSTT and Ginaton (positive control) were administered orally to rats 6h after stroke and daily thereafter. After 15 days of treatment, the survival rate of each group was calculated. We then conducted neurological deficit scores and beam walking test to access the neurological function after ischemic stroke. Subsequently, T2-weighted imaging (T2WI) and T2 relaxometry mapping were performed to measure infarct volume and grey and white matter integrity, respectively. Moreover, diffusion tensor imaging (DTI) was carried out to evaluate the grey and white matter microstructural damage. Additionally, arterial spin labelling (ASL) - cerebral blood flow (CBF) and magnetic resonance angiography (MRA) images provided dynamic information about vascular hemodynamic dysfunction after ischemic stroke. Finally, haematoxylin and eosin (HE) staining was carried out to evaluate the stroke-induced pathological changes in the brain. The survival rate and neurological behavioural outcomes (Bederson scores and beam walking tests) were markedly ameliorated by TSTT (65mg/kg) treatment within 15 days after ischemic stroke. Moreover, T2WI and T2 relaxometry mapping showed that TSTT (65mg/kg) significantly reduced infarct volume and attenuated grey and white matter injury, respectively, which was confirmed by histopathological evaluation of brain tissue. The results obtained from DTI showed that TSTT (65mg/kg) not only significantly alleviated axonal damage and demyelination, but also promoted axonal remodelling and re-myelination. In addition, TSTT treatment also enhanced vascular signal density and increased CBF in rats after MCAO. Our results suggested the potential protective and repair-promoting effects of TSTT on grey and white matter from damage induced by ischemia. This study provides a modern pharmacological basis for the application of TSTT in managing ischemic stroke. Copyright © 2018 Elsevier B.V. All rights reserved.

Homing and Tracking of Iron Oxide Labelled Mesenchymal Stem Cells After Infusion in Traumatic Brain Injury Mice: a Longitudinal In Vivo MRI Study.

PubMed

Mishra, Sushanta Kumar; Khushu, Subash; Singh, Ajay K; Gangenahalli, Gurudutta

2018-06-17

Stem cells transplantation has emerged as a promising alternative therapeutic due to its potency at injury site. The need to monitor and non-invasively track the infused stem cells is a significant challenge in the development of regenerative medicine. Thus, in vivo tracking to monitor infused stem cells is especially vital. In this manuscript, we have described an effective in vitro labelling method of MSCs, a serial in vivo tracking of implanted stem cells at traumatic brain injury (TBI) site through 7 T magnetic resonance imaging (MRI). Proper homing of infused MSCs was carried out at different time points using histological analysis and Prussian blue staining. Longitudinal in vivo tracking of infused MSCs were performed up to 21 days in different groups through MRI using relaxometry technique. Results demonstrated that MSCs incubated with iron oxide-poly-L-lysine complex (IO-PLL) at a ratio of 50:1.5 μg/ml and a time period of 6 h was optimised to increase labelling efficiency. T2*-weighted images and relaxation study demonstrated a significant signal loss and effective decrease in transverse relaxation time on day-3 at injury site after systemic transplantation, revealed maximum number of stem cells homing to the lesion area. MRI results further correlate with histological and Prussian blue staining in different time periods. Decrease in negative signal and increase in relaxation times were observed after day-14, may indicate damage tissue replacement with healthy tissue. MSCs tracking with synthesized negative contrast agent represent a great advantage during both in vitro and in vivo analysis. The proposed absolute bias correction based relaxometry analysis could be extrapolated for stem cell tracking and therapies in various neurodegenerative diseases.

NMR relaxometry study of plaster mortar with polymer additives

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jumate, E.; Manea, D.; Moldovan, D.

2013-11-13

The cement mixed with water forms a plastic paste or slurry which stiffness in time and finally hardens into a resistant stone. The addition of sand aggregates, polymers (Walocel) and/or calcium carbonate will modify dramatically the final mortar mechanic and thermal properties. The hydration processes can be observed using the 1D NMR measurements of transverse T{sub 2} relaxation times distributions analysed by a Laplace inversion algorithm. These distributions were obtained for mortar pasta measured at 2 hours after preparation then at 3, 7 and 28 days after preparation. Multiple components are identified in the T{sub 2} distributions. These can bemore » associated with the proton bounded chemical or physical to the mortar minerals characterized by a short T{sub 2} relaxation time and to water protons in pores with three different pore sizes as observed from SEM images. The evaporation process is faster in the first hours after preparation, while the mortar hydration (bonding of water molecules to mortar minerals) can be still observed after days or months from preparation. Finally, the mechanic resistance was correlated with the transverse T{sub 2} relaxation rates corresponding to the bound water.« less

Quantitative rotating frame relaxometry methods in MRI.

PubMed

Gilani, Irtiza Ali; Sepponen, Raimo

2016-06-01

Macromolecular degeneration and biochemical changes in tissue can be quantified using rotating frame relaxometry in MRI. It has been shown in several studies that the rotating frame longitudinal relaxation rate constant (R1ρ ) and the rotating frame transverse relaxation rate constant (R2ρ ) are sensitive biomarkers of phenomena at the cellular level. In this comprehensive review, existing MRI methods for probing the biophysical mechanisms that affect the rotating frame relaxation rates of the tissue (i.e. R1ρ and R2ρ ) are presented. Long acquisition times and high radiofrequency (RF) energy deposition into tissue during the process of spin-locking in rotating frame relaxometry are the major barriers to the establishment of these relaxation contrasts at high magnetic fields. Therefore, clinical applications of R1ρ and R2ρ MRI using on- or off-resonance RF excitation methods remain challenging. Accordingly, this review describes the theoretical and experimental approaches to the design of hard RF pulse cluster- and adiabatic RF pulse-based excitation schemes for accurate and precise measurements of R1ρ and R2ρ . The merits and drawbacks of different MRI acquisition strategies for quantitative relaxation rate measurement in the rotating frame regime are reviewed. In addition, this review summarizes current clinical applications of rotating frame MRI sequences. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Magnetic resonance evaluation of cardiac thrombi and masses by T1 and T2 mapping: an observational study.

PubMed

Caspar, Thibault; El Ghannudi, Soraya; Ohana, Mickaël; Labani, Aïssam; Lawson, Aubrietia; Ohlmann, Patrick; Morel, Olivier; De Mathelin, Michel; Roy, Catherine; Gangi, Afshin; Germain, Philippe

2017-04-01

The purpose of this work was to evaluate CMR T1 and T2 mapping sequences in patients with intracardiac thrombi and masses in order to assess T1 and T2 relaxometry usefulness and to allow better etiological diagnosis. This observational study of patients scheduled for routine CMR was performed from September 2014 to August 2015. All patients referred to our department for a 1.5 T CMR were screened to participate. T1 mapping were acquired before and after Gadolinium injection; T2 mapping images were obtained before injection. 41 patients were included. 22 presented with cardiac thrombi and 19 with cardiac masses. The native T1 of thrombi was 1037 ± 152 ms (vs 1032 ± 39 ms for myocardium, p = 0.88; vs 1565 ± 88 ms for blood pool, p < 0.0001). T2 were 74 ± 13 ms (vs 51 ± 3 ms for myocardium, p < 0.0001; vs 170 ± 32 ms for blood pool, p < 0.0001). Recent thrombi had a native T1 shorter than old thrombi (911 ± 177 vs 1169 ± 107 ms, p = 0.01). The masses having a shorter T1 than the myocardium were lipomas (278 ± 29 ms), calcifications (621 ± 218 ms), and melanoma (736 ms). All other masses showed T1 values higher than myocardial T1, with T2 consistently >70 ms. T1 and T2 mapping CMR sequences can be useful and represent a new approach for the evaluation of cardiac thrombi and masses.

Noninvasive monitoring of moisture uptake in Ca(NO3)2 -polluted calcareous stones by 1H-NMR relaxometry.

PubMed

Casieri, Cinzia; Terenzi, Camilla; De Luca, Francesco

2015-01-01

NMR transverse relaxation time (T(2)) distribution of (1)H nuclei of water has been used to monitor the moisture condensation kinetics in Ca(NO(3))(2)  · (4)H(2)O-polluted Lecce stone, a calcareous stone with highly regular porous structure often utilized as basic material in Baroque buildings. Polluted samples have been exposed to water vapor adsorption at controlled relative humidity to mimic environmental conditions. In presence of pollutants, the T(2) distributions of water in stone exhibit a range of relaxation time values and amplitudes not observed in the unpolluted case. These characteristics could be exploited for in situ noninvasive detection of salt pollution in Lecce stone or as damage precursors in architectural buildings of cultural heritage interest. Copyright © 2014 John Wiley & Sons, Ltd.

Liquid-phase characterization of molecular interactions in polyunsaturated and n-fatty acid methyl esters by (1)H low-field nuclear magnetic resonance.

PubMed

Meiri, Nitzan; Berman, Paula; Colnago, Luiz Alberto; Moraes, Tiago Bueno; Linder, Charles; Wiesman, Zeev

2015-01-01

To identify and develop the best renewable and low carbon footprint biodiesel substitutes for petroleum diesel, the properties of different biodiesel candidates should be studied and characterized with respect to molecular structures versus biodiesel liquid property relationships. In our previous paper, (1)H low-field nuclear magnetic resonance (LF-NMR) relaxometry was investigated as a tool for studying the liquid-phase molecular packing interactions and morphology of fatty acid methyl esters (FAMEs). The technological potential was demonstrated with oleic acid and methyl oleate standards having similar alkyl chains but different head groups. In the present work, molecular organization versus segmental and translational movements of FAMEs in their pure liquid phase, with different alkyl chain lengths (10-20 carbons) and degrees of unsaturation (0-3 double bonds), were studied with (1)H LF-NMR relaxometry and X-ray, (1)H LF-NMR diffusiometry, and (13)C high-field NMR. Based on density values and X-ray measurements, it was proposed that FAMEs possess a liquid crystal-like order above their melting point, consisting of random liquid crystal aggregates with void spaces between them, whose morphological properties depend on chain length and degree of unsaturation. FAMEs were also found to exhibit different degrees of rotational and translational motions, which were rationalized by chain organization within the clusters, and the degree and type of molecular interactions and temperature effects. At equivalent fixed temperature differences from melting point, saturated FAME molecules were found to have similar translational motion regardless of chain length, expressed by viscosity, self-diffusion coefficients, and spin-spin (T 2) (1)H LF-NMR. T 2 distributions suggest increased alkyl chain rigidity, and reduced temperature response of the peaks' relative contribution with increasing unsaturation is a direct result of the alkyl chain's morphological packing and molecular interactions. Both the peaks' assignments for T 2 distributions of FAMEs and the model for their liquid crystal-like morphology in the liquid phase were confirmed. The study of morphological structures within liquids and their response to temperature changes by (1)H LF-NMR has a high value in the field of biodiesel and other research and applied disciplines in numerous physicochemical- and organizational-based properties, processes, and mechanisms of alkyl chains, molecular interactions, and morphologies.

Sex- and Age-Dependence of Region- and Layer-Specific Knee Cartilage Composition (Spin-Spin-Relaxation Time) in Healthy Reference Subjects

PubMed Central

Wirth, Wolfgang; Maschek, Susanne; Eckstein, Felix

2016-01-01

SUMMARY Compositional measures of articular cartilage are accessible in vivo by magnetic resonance imaging (MRI) based relaxometry and cartilage spin-spin transverse relaxation time (T2) has been related to tissue hydration, collagen content and orientation, and mechanical (functional) properties of articular cartilage. The objective of the current study was therefore to evaluate subregional variation, and sex- and age-differences, in laminar (deep and superficial) femorotibial cartilage T2 relaxation time in healthy adults. To this end, we studied the right knees of 92 healthy subjects from the Osteoarthritis Initiative reference cohort (55 women, 37 men; age range 45–78 years; BMI 24.4±3.1) without knee pain, radiographic signs, or risk factors of knee osteoarthritis in either knee. T2 of the deep and superficial femorotibial cartilages was determined in 16 femorotibial subregions, using a multi-echo spin-echo (MESE) MRI sequence. Significant subregional variation in femorotibial cartilage T2 was observed for the superficial and for the deep (both p<0.001) cartilage layer (Friedman test). Yet, layer- and region-specific femorotibial T2 did not differ between men and women, or between healthy adults below and above the median age (54y). In conclusion, this first study to report subregional (layer-specific) compositional variation of femorotibial cartilage T2 in healthy adults identifies significant differences in both superficial and deep cartilage T2 between femorotibial subregions. However, no relevant sex- or age-dependence of cartilage T2 was observed between age 45–78y. The findings suggest that a common, non-sex-specific set of layer-and region-specific T2 reference values can be used to identify compositional pathology in joint disease for this age group. PMID:27836800

Brain tissues atrophy is not always the best structural biomarker of physiological aging: A multimodal cross-sectional study.

PubMed

Cherubini, Andrea; Caligiuri, Maria Eugenia; Péran, Patrice; Sabatini, Umberto; Cosentino, Carlo; Amato, Francesco

2015-01-01

This study presents a voxel-based multiple regression analysis of different magnetic resonance image modalities, including anatomical T1-weighted, T2* relaxometry, and diffusion tensor imaging. Quantitative parameters sensitive to complementary brain tissue alterations, including morphometric atrophy, mineralization, microstructural damage, and anisotropy loss, were compared in a linear physiological aging model in 140 healthy subjects (range 20-74 years). The performance of different predictors and the identification of the best biomarker of age-induced structural variation were compared without a priori anatomical knowledge. The best quantitative predictors in several brain regions were iron deposition and microstructural damage, rather than macroscopic tissue atrophy. Age variations were best resolved with a combination of markers, suggesting that multiple predictors better capture age-induced tissue alterations. These findings highlight the importance of a combined evaluation of multimodal biomarkers for the study of aging and point to a number of novel applications for the method described.

Magnetic resonance imaging and relaxometry to study water transport mechanisms in a commercially available gastrointestinal therapeutic system (GITS) tablet.

PubMed

Broadbent, Amber L; Fell, Rob J; Codd, Sarah L; Lightley, Kim A; Konagurthu, Sanjay; Koehler-King, Dory G; Seymour, Joseph D

2010-09-15

The hydration of 4 mg Cardura XL (Pfizer), a commercially available gastrointestinal therapeutic system (GITS) tablet, was investigated using magnetic resonance imaging (MRI). A short echo time (T(e)=2.81 ms) technique for MRI of the hydration of a GITS tablet was implemented. From the MR images, signal intensity profiles were generated and interpreted in the context of diffusive and osmotic transport mechanisms. A distinct transition from diffusive to osmotic transport was measured at a timescale relevant to the measured drug release time. Diffusion and osmotic rate coefficients for water in the drug and polymer sweller layers of the tablet were quantified. Spin-lattice T(1) and spin-spin T(2) relaxation times of the water signal from within the tablet were measured as a function of hydration time in order to incorporate the effects of relaxation into interpretation of signal intensity and provide unique information on the distribution of water in different physical and chemical environments within the tablet. Copyright 2010 Elsevier B.V. All rights reserved.

NMR relaxation in natural soils: Fast Field Cycling and T1-T2 Determination by IR-MEMS

NASA Astrophysics Data System (ADS)

Haber-Pohlmeier, S.; Pohlmeier, A.; Stapf, S.; van Dusschoten, D.

2009-04-01

Soils are natural porous media of highest importance for food production and sustainment of water resources. For these functions, prominent properties are their ability of water retainment and transport, which are mainly controlled by pore size distribution. The latter is related to NMR relaxation times of water molecules, of which the longitudinal relaxation time can be determined non-invasively by fast-field cycling relaxometry (FFC) and both are obtainable by inversion recovery - multi-echo- imaging (IR-MEMS) methods. The advantage of the FFC method is the determination of the field dependent dispersion of the spin-lattice relaxation rate, whereas MRI at high field is capable of yielding spatially resolved T1 and T2 times. Here we present results of T1- relaxation time distributions of water in three natural soils, obtained by the analysis of FFC data by means of the inverse Laplace transformation (CONTIN)1. Kaldenkirchen soil shows relatively broad bimodal distribution functions D(T1) which shift to higher relaxation rates with increasing relaxation field. These data are compared to spatially resolved T1- and T2 distributions, obtained by IR-MEMS. The distribution of T1 corresponds well to that obtained by FFC.

Harsh Corporal Punishment Is Associated With Increased T2 Relaxation Time in Dopamine-Rich Regions

PubMed Central

Sheu, Yi-Shin; Polcari, Ann; Anderson, Carl M.; Teicher, Martin H.

2010-01-01

Harsh corporal punishment (HCP) was defined as frequent parental administration of corporal punishment (CP) for discipline, with occasional use of objects such as straps, or paddles. CP is linked to increased risk for depression and substance abuse. We examine whether long-term exposure to HCP acts as sub-traumatic stressor that contributes to brain alterations, particularly in dopaminergic pathways, which may mediate their increased vulnerability to drug and alcohol abuse. Nineteen young adults who experienced early HCP but no other forms of maltreatment and twenty-three comparable controls were studied. T2 relaxation time (T2-RT) measurements were performed with an echo planar imaging TE stepping technique and T2 maps were calculated and analyzed voxel-by-voxel to locate regional T2-RT differences between groups. Previous studies indicated that T2-RT provides an indirect index of resting cerebral blood volume. Region of interest (ROI) analyses were also conducted in caudate, putamen, nucleus accumbens, anterior cingulate cortex, dorsolateral prefrontal cortex, thalamus, globus pallidus and cerebellar hemispheres. Voxel-based relaxometry showed that HCP was associated with increased T2-RT in right caudate and putamen. ROI analyses also revealed increased T2-RT in dorsolateral prefrontal cortex, substantia nigra, thalamus and accumbens but not globus pallidus or cerebellum. There were significant associations between T2-RT measures in dopamine target regions and use of drugs and alcohol, and memory performance. Alteration in the paramagnetic or hemodynamic properties of dopaminergic cell body and projection regions were observed in subjects with HCP, and these findings may relate to their increased risk for drug and alcohol abuse. PMID:20600981

Harsh corporal punishment is associated with increased T2 relaxation time in dopamine-rich regions.

PubMed

Sheu, Yi-Shin; Polcari, Ann; Anderson, Carl M; Teicher, Martin H

2010-11-01

Harsh corporal punishment (HCP) was defined as frequent parental administration of corporal punishment (CP) for discipline, with occasional use of objects such as straps, or paddles. CP is linked to increased risk for depression and substance abuse. We examine whether long-term exposure to HCP acts as sub-traumatic stressor that contributes to brain alterations, particularly in dopaminergic pathways, which may mediate their increased vulnerability to drug and alcohol abuse. Nineteen young adults who experienced early HCP but no other forms of maltreatment and twenty-three comparable controls were studied. T2 relaxation time (T2-RT) measurements were performed with an echo planar imaging TE stepping technique and T2 maps were calculated and analyzed voxel-by-voxel to locate regional T2-RT differences between groups. Previous studies indicated that T2-RT provides an indirect index of resting cerebral blood volume. Region of interest (ROI) analyses were also conducted in caudate, putamen, nucleus accumbens, anterior cingulate cortex, dorsolateral prefrontal cortex, thalamus, globus pallidus and cerebellar hemispheres. Voxel-based relaxometry showed that HCP was associated with increased T2-RT in right caudate and putamen. ROI analyses also revealed increased T2-RT in dorsolateral prefrontal cortex, substantia nigra, thalamus and accumbens but not globus pallidus or cerebellum. There were significant associations between T2-RT measures in dopamine target regions and use of drugs and alcohol, and memory performance. Alteration in the paramagnetic or hemodynamic properties of dopaminergic cell body and projection regions were observed in subjects with HCP, and these findings may relate to their increased risk for drug and alcohol abuse. Copyright 2010 Elsevier Inc. All rights reserved.

Neuronavigation-guided focused ultrasound-induced blood-brain barrier opening: A preliminary study in swine

NASA Astrophysics Data System (ADS)

Liu, Hao-Li; Tsai, Hong-Chieh; Lu, Yu-Jen; Wei, Kuo-Chen

2012-11-01

FUS-induced BBB opening is a promising technique for noninvasive and local delivery of drugs into the brain. Here we propose the novel use of a neuronavigation system to guide the FUS-induced BBB opening procedure, and investigate its feasibility in vivo in large animals. We developed an interface between the neuronavigator and FUS to allow guidance of the focal energy produced by the FUS transducer. The system was tested in 29 pigs by more than 40 sonication procedures and evaluated by MRI. Gd-DTPA concentration was quantitated in vivo by MRI R1 relaxometry and compared by ICP-OES assay. Brain histology after FUS exposure was investigated by HE and TUNEL staining. Neuronavigation could successfully guide the focal beam with comparable precision to neurosurgical stereotactic procedures (2.3 ± 0.9 mm). FUS pressure of 0.43 MPa resulted in consistent BBB-opening. Neuronavigation-guided BBB-opening increased Gd-DTPA deposition by up to 1.83 mM (140% increase). MR relaxometry demonstrated high correlation to ICP-OES measurements (r2 = 0.822), suggesting that Gd-DTPA deposition can be directly measured by imaging. Neuronavigation could provide sufficient precision for guiding FUS to temporally and locally open the BBB. Gd-DTPA deposition in the brain could be quantified by MR relaxometry, providing a potential tool for the in vivo quantification of therapeutic agents in CNS disease treatment.

Investigation of Dynamics in BMIM TFSA Ionic Liquid through Variable Temperature and Pressure NMR Relaxometry and Diffusometry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pilar, Kartik; Rua, Armando; Suarez, Sophia N.

A comprehensive variable temperature, pressure and frequency multinuclear ( 1H, 2H, and 19F) magnetic resonance study was undertaken on selectively deuterated 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)amide (BMIM TFSA) ionic liquid isotopologues. This study builds on our earlier investigation of the effects of increasing alkyl chain length on diffusion and dynamics in imidazolium-based TFSA ionic liquids. Fast field cycling 1H T 1 data revealed multiple modes of motion. Through calculation of diffusion coefficient (D) values and activation energies, the low- and high-field regimes were assigned to the translational and reorientation dynamics respectively. Variable-pressure 2H T 1 measurements reveal site-dependent interactions in the cation withmore » strengths in the order MD 3 > CD 3 > CD 2, indicating dissimilarities in the electric field gradients along the alkyl chain, with the CD 2 sites having the largest gradient. Additionally, the α saturation effect in T 1 vs. P was observed for all three sites, suggesting significant reduction of the short-range rapid reorientational dynamics. This reduction was also deduced from the variable pressure 1H T 1 data, which showed an approach to saturation for both the methyl and butyl group terminal methyl sites. Pressure-dependent D measurements show independent motions for both cations and anions, with the cations having greater D values over the entire pressure range.« less

Investigation of Dynamics in BMIM TFSA Ionic Liquid through Variable Temperature and Pressure NMR Relaxometry and Diffusometry

DOE PAGES

Pilar, Kartik; Rua, Armando; Suarez, Sophia N.; ...

2017-05-11

A comprehensive variable temperature, pressure and frequency multinuclear ( 1H, 2H, and 19F) magnetic resonance study was undertaken on selectively deuterated 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)amide (BMIM TFSA) ionic liquid isotopologues. This study builds on our earlier investigation of the effects of increasing alkyl chain length on diffusion and dynamics in imidazolium-based TFSA ionic liquids. Fast field cycling 1H T 1 data revealed multiple modes of motion. Through calculation of diffusion coefficient (D) values and activation energies, the low- and high-field regimes were assigned to the translational and reorientation dynamics respectively. Variable-pressure 2H T 1 measurements reveal site-dependent interactions in the cation withmore » strengths in the order MD 3 > CD 3 > CD 2, indicating dissimilarities in the electric field gradients along the alkyl chain, with the CD 2 sites having the largest gradient. Additionally, the α saturation effect in T 1 vs. P was observed for all three sites, suggesting significant reduction of the short-range rapid reorientational dynamics. This reduction was also deduced from the variable pressure 1H T 1 data, which showed an approach to saturation for both the methyl and butyl group terminal methyl sites. Pressure-dependent D measurements show independent motions for both cations and anions, with the cations having greater D values over the entire pressure range.« less

SU-E-T-145: MRI Gel Dosimetry Applied to Dose Profile Determination for 50kV X-Ray Tube.

PubMed

Schwarcke, M; Marques, T; Nicolucci, P; Filho, O Baffa

2012-06-01

The aim of this study was to use MRI gel dosimetry to determine the dose profile of 50kV MAGNUM® X-ray tube, MOXTEK Inc., in order to calibrate small solid dosimeters of alanine, tooth enamel and LiF-TLDs, commonly used in clinical quality assurance and datation dosimetry. MAGIC-f polymer gel was kept in two plastic containers of 100mL, avoiding attenuation of the primary beam trough the wall. Beam aberture of 3mm and dose rate of 16.5Gy/min were set, reproducing irradiation conditions of interest. The dose rate was assumed based on data of the vendor information of the tube and dose of 30Gy was delivered at the surface of the gel. MAGIC-f gel was irradiated at source-surface distances(SSD) of 0.1cm and 1.0cm. After 24hours of irradiation, gel was scanned in an Achieva® 3T Philips® MRI tomography using relaxometry sequence with 32 Echos, Time-to-Echo(TE) of 15.0ms, Time-to-Repetition(TR) of 6000ms and Field-of-View(FOV) of 0.5×0.5×2.0mm. Dose map at the central plain of irradiation was calculated from T2 relaxometry map. The gel dosimetry results evidenced a build-up depth of 0.13cm for SSD=0.1cm and no build-up was detected for SSD=1.0cm. However, the dose profile evidenced high gradient of dose in SSD=0.1, decreasing the dose from 100% to 30% in 1.4cm depth inside the gel; In turn, the dose distribution is homogeneous after 0.4cm deth for SSD=1.0cm. MRI gel dosimetry using MAGIC-f presented as feasible technique to determine dose profiles for kilovoltage x-rays tubes. The results evidenced that the calibration of small solid dosimeters can be performed using SSD of 1.0cm in the 50kV MAGNUM® X-ray tube using 0.4cm/g/cm 3 filter. This work was funded supported by CNPQ, CAPES and FAPESP. © 2012 American Association of Physicists in Medicine.

Uptake of divalent ions (Mn+2 and Ca+2) by heat-set whey protein gels.

PubMed

Oztop, Mecit H; McCarthy, Kathryn L; McCarthy, Michael J; Rosenberg, Moshe

2012-02-01

Divalent salts are used commonly for gelation of polymer molecules. Calcium, Ca(+2), is one of the most common divalent ions that is used in whey protein gels. Manganese, Mn(+2), is also divalent, but paramagnetic, enhancing relaxation decay rates in magnetic resonance imaging (MRI) and can be used as a probe to understand the behavior of Ca(+2) in whey protein gels. The objective of this study was to investigate the diffusion of Ca(+2) and Mn(+2) ions in heat-set whey protein gels by using MRI and nuclear magnetic resonance (NMR) relaxometry. Whey protein gels were immersed in solutions containing MnCl(2) and CaCl(2) at neutral pH. Images obtained with gels immersed in MnCl(2) solution revealed a relaxation sink region in the gel's surface and the thickness of the region increased with time. These "no signal" regions in the MR images were attributed to uptake of Mn(+2) by the gel. Results obtained with CaCl(2) solution indicated that since Ca(+2) did not have the paramagnetic effect, the regions where Ca(+2) diffused into the gel exhibited a slight decrease in signal intensity. The relaxation spectrums exhibited 3 populations of protons, for gels immersed in MnCl(2) solution, and 2 populations for gels in CaCl(2) solution. No significant change in T(2) distributions was observed for the gels immersed in CaCl(2) solution. The results demonstrated that MRI and NMR relaxometry can be used to understand the diffusion of ions into the whey protein gel, which is useful for designing gels of different physical properties for controlled release applications. Design of food systems for delivery of bioactive compounds requires knowledge of diffusion rates and structure. Utilizing magnetic resonance imaging the diffusion rates of ions can be measured. Relaxation spectra could yield information concerning molecular interactions. © 2012 Institute of Food Technologists®

In-vitro Gd-DTPA Relaxometry Studies in Oxygenated Venous Human Blood and Aqueous Solution at 3 and 7T

PubMed Central

Kalavagunta, Chaitanya; Michaeli, Shalom; Metzger, Gregory J.

2014-01-01

In-vitro T1 and T2* relaxivities (r1 and r2*) of Gd-DTPA (GaD) in oxygenated human venous blood (OVB) and aqueous solution (AS) at 3T and 7T were calculated. GaD concentrations ([GaD]) in OVB and AS were prepared in the range 0–5 mM. All measurements were acquired at 37±2 °C. At both 3T and 7T, a linear relationship was observed between [GaD] and R1 in both AS and OVB. At 7T, r1 in AS decreased by 7.5% (p = 0.045) while there was a negligible change in OVB. With respect to R2*, a linear relationship with [GaD] was only observed in AS, while a more complex relationship was observed in OVB; quadratic below and linear above 2 mM at both field strengths. There was a significant increase of over four-fold in r2* with GaD in OVB at 7T (for [GaD] above 2mM, p ≪0.01) as compared to 3T. Furthermore, in comparison to r1, r2* in AS was less than two-fold higher at both field strengths while in OVB it was ~twenty-fold and ~ninety-fold higher at 3T and 7T, respectively. This observation emphasizes the importance of r2* knowledge at high magnetic fields, ≥3T. The comparison between r1 and r2* presented in this work is crucial in the design and optimization of high field MRI studies making use of paramagnetic contrast agents. This is especially true in multiple compartment systems such as blood where r2* dramatically increases while r1 remains relatively constant with increasing magnetic field strength. PMID:24523062

Preparation, spectroscopic and high field NMR relaxometry studies of gadolinium(III) complexes with the asymmetric tetraamine 1,4,7,11-tetraazaundecane

NASA Astrophysics Data System (ADS)

Hatzipanayioti, Despina; Veneris, Antonis

2009-10-01

The reaction of Gd(III) with asymmetric tetramine 1,4,7,11-tetraazaundecane (2,2,3-tet, L1) ligand has been studied via NMR spectroscopy. The ligand proton longitudinal relaxation rates ( R1) have been used to estimate the distances of these protons from the Gd(III) center, in Gd(III)- L1 reaction solutions, in H 2O/D 2O 5/1 mixtures. Two Gd(III) complexes [Gd(III)( L1)(NH 3)(H 2O) 4](CH 3COO) 3·2H 2O ( 1) and [Gd(III)( L1)(NH 3)(H 2O) 2]Cl 3·EtOH ( 2) have been isolated and characterized by elemental analyses, TGA, IR, NMR and relaxometry measurements. The NMR relaxation measurements of 2 in aqueous solutions have been performed, under various temperature or concentration conditions, and compared with those of the commercial contrast agents Gd(III)-DTPA and Gd(III)-DTPA-BMA. It has also been studied the influence of (i) the Gd(III) inner-sphere water molecule number ( q) alteration and (ii) the steric constraint enhancement on the metal site, over the relaxation rate values of the parent aqueous solution of Gd(III)-2,2,3-tet, and of the aqueous solutions of 2.

Multiparametric or practical quantitative liver MRI: towards millisecond, fat fraction, kilopascal and function era.

PubMed

Unal, Emre; Idilman, Ilkay Sedakat; Karçaaltıncaba, Muşturay

2017-02-01

New advances in liver magnetic resonance imaging (MRI) may enable diagnosis of unseen pathologies by conventional techniques. Normal T1 (550-620 ms for 1.5 T and 700-850 ms for 3 T), T2, T2* (>20 ms), T1rho (40-50 ms) mapping, proton density fat fraction (PDFF) (≤5%) and stiffness (2-3kPa) values can enable differentiation of a normal liver from chronic liver and diffuse diseases. Gd-EOB-DTPA can enable assessment of liver function by using postcontrast hepatobiliary phase or T1 reduction rate (normally above 60%). T1 mapping can be important for the assessment of fibrosis, amyloidosis and copper overload. T1rho mapping is promising for the assessment of liver collagen deposition. PDFF can allow objective treatment assessment in NAFLD and NASH patients. T2 and T2* are used for iron overload determination. MR fingerprinting may enable single slice acquisition and easy implementation of multiparametric MRI and follow-up of patients. Areas covered: T1, T2, T2*, PDFF and stiffness, diffusion weighted imaging, intravoxel incoherent motion imaging (ADC, D, D* and f values) and function analysis are reviewed. Expert commentary: Multiparametric MRI can enable biopsyless diagnosis and more objective staging of diffuse liver disease, cirrhosis and predisposing diseases. A comprehensive approach is needed to understand and overcome the effects of iron, fat, fibrosis, edema, inflammation and copper on MR relaxometry values in diffuse liver disease.

Numerical study of ultra-low field nuclear magnetic resonance relaxometry utilizing a single axis magnetometer for signal detection.

PubMed

Vogel, Michael W; Vegh, Viktor; Reutens, David C

2013-05-01

This paper investigates optimal placement of a localized single-axis magnetometer for ultralow field (ULF) relaxometry in view of various sample shapes and sizes. The authors used finite element method for the numerical analysis to determine the sample magnetic field environment and evaluate the optimal location of the single-axis magnetometer. Given the different samples, the authors analysed the magnetic field distribution around the sample and determined the optimal orientation and possible positions of the sensor to maximize signal strength, that is, the power of the free induction decay. The authors demonstrate that a glass vial with flat bottom and 10 ml volume is the best structure to achieve the highest signal out of samples studied. This paper demonstrates the importance of taking into account the combined effects of sensor configuration and sample parameters for signal generation prior to designing and constructing ULF systems with a single-axis magnetometer. Through numerical simulations the authors were able to optimize structural parameters, such as sample shape and size, sensor orientation and location, to maximize the measured signal in ultralow field relaxometry.

Importance of Multimodal MRI in Characterizing Brain Tissue and Its Potential Application for Individual Age Prediction.

PubMed

Cherubini, Andrea; Caligiuri, Maria Eugenia; Peran, Patrice; Sabatini, Umberto; Cosentino, Carlo; Amato, Francesco

2016-09-01

This study presents a voxel-based multiple regression analysis of different magnetic resonance image modalities, including anatomical T1-weighted, T2(*) relaxometry, and diffusion tensor imaging. Quantitative parameters sensitive to complementary brain tissue alterations, including morphometric atrophy, mineralization, microstructural damage, and anisotropy loss, were compared in a linear physiological aging model in 140 healthy subjects (range 20-74 years). The performance of different predictors and the identification of the best biomarker of age-induced structural variation were compared without a priori anatomical knowledge. The best quantitative predictors in several brain regions were iron deposition and microstructural damage, rather than macroscopic tissue atrophy. Age variations were best resolved with a combination of markers, suggesting that multiple predictors better capture age-induced tissue alterations. The results of the linear model were used to predict apparent age in different regions of individual brain. This approach pointed to a number of novel applications that could potentially help highlighting areas particularly vulnerable to disease.

Magnetic resonance microscopy for assessment of morphological changes in hydrating hydroxypropylmethylcellulose matrix tablets in situ-is it possible to detect phenomena related to drug dissolution within the hydrated matrices?

PubMed

Kulinowski, Piotr; Młynarczyk, Anna; Jasiński, Krzysztof; Talik, Przemysław; Gruwel, Marco L H; Tomanek, Bogusław; Węglarz, Władysław P; Dorożyński, Przemysław

2014-09-01

So far, the hydrated part of the HPMC matrix has commonly been denoted as a "gel" or "pseudogel" layer. No MRI-based results have been published regarding observation of internal phenomena related to drug dissolution inside swelling polymeric matrices during hydration. The purpose of the study was to detect such phenomena. Multiparametric, spatially and temporally resolved T2 MR relaxometry, in situ, was applied to study formation of the hydration progress in HPMC matrix tablets loaded with L-dopa and ketoprofen using a 11.7 T MRI system. Two spin-echo based pulse sequences were used, one of them specifically designed to study short T2 signals. Two components in the T2 decay envelope were estimated and spatial distributions of their parameters, i.e. amplitudes and T2 values, were obtained. Based on the data, different region formation patterns (i.e. multilayer structure) were registered depending on drug presence and solubility. Inside the matrix with incorporated sparingly soluble drug a specific layer formation due to drug dissolution was detected, whereas a matrix with very slightly soluble drug does not form distinct external "gel-like" layer. We have introduced a new paradigm in the characterization of hydrating matrices using (1)H MRI methods. It reflects molecular mobility and concentration of water inside the hydrated matrix. For the first time, drug dissolution related phenomena, i.e. particular front and region formation, were observed by MRI methods.

Measurement and Visualization of Tight Rock Exposed to CO2 Using NMR Relaxometry and MRI

PubMed Central

Wang, Haitao; Lun, Zengmin; Lv, Chengyuan; Lang, Dongjiang; Ji, Bingyu; Luo, Ming; Pan, Weiyi; Wang, Rui; Gong, Kai

2017-01-01

Understanding mechanisms of oil mobilization of tight matrix during CO2 injection is crucial for CO2 enhanced oil recovery (EOR) and sequestration engineering design. In this study exposure behavior between CO2 and tight rock of the Ordos Basin has been studied experimentally by using nuclear magnetic resonance transverse relaxation time (NMR T2) spectrum and magnetic resonance imaging (MRI) under the reservoir pressure and temperature. Quantitative analysis of recovery at the pore scale and visualization of oil mobilization are achieved. Effects of CO2 injection, exposure times and pressure on recovery performance have been investigated. The experimental results indicate that oil in all pores can be gradually mobilized to the surface of rock by CO2 injection. Oil mobilization in tight rock is time-consuming while oil on the surface of tight rock can be mobilized easily. CO2 injection can effectively mobilize oil in all pores of tight rock, especially big size pores. This understanding of process of matrix exposed to CO2 could support the CO2 EOR in tight reservoirs. PMID:28281697

Interactions between cations and peat organic matter monitored with NMR wideline, static and FFC NMR relaxometry

NASA Astrophysics Data System (ADS)

Schaumann, Gabriele E.; Conte, Pellegrino; Jäger, Alexander; Alonzo, Giuseppe; Bertmer, Marko

2010-05-01

The molecular size of humic substances is still under debate and is believed to range up to several hundred thousands Dalton, although a number of recent studies suggest much lower molecular weights. Nowadays an increasing number of authors suggest a model of molecular aggregates. One explanation why results on the molecular mass of humic materials are contradictory, may be that individual OM molecules are linked via intermolecular interactions, by bridges of water molecules or by cations bridging cation exchange sites (Schaumann, 2006a, b). Properties of such cross-linked systems can be similar to macromolecular systems revealing covalent cross-links. In this context, multivalent cations play an important ecological role, serving as reversible cross-linking agent. Formation and disruption of such cation bridges may close or open sorption sites in soil organic matter. Although cross-linking by multivalent cations has been proposed in many studies, the cross-linking effect has not yet been demonstrated on the molecular scale. The objective of this study was to investigate the interactions between cations and peat organic matter using NMR wideline techniques as well as static and fast field cycling (FFC) NMR relaxometry. Peat treated with solutions containing either Na+, Ca2+ or Al3+ was investigated in air-dried state for longitudinal relaxation times (T1) and NMR wideline characteristics. T1 distributions were separated into two Gaussian functions which were interpreted to represent two proton populations belonging to two environments of differing mobility. The relaxation rates (R1 = T1-1) in the cation treated samples spread over a range of 87-123 s-1 (R1a: fast component) and 32-42 s-1 (R1b: slow component). The rates in all treatments are significantly different from each other. and decrease in the order conditioned sample > desalinated sample > Na-treated sample. The treatment with multivalent cations affects R1a and R1b in different ways and needs more detailed explanation. Wideline proton NMR spectra can be used to quantify proton containing material, mainly water, based on their mobility. Spectra were decomposed into a Gaussian and Lorentzian line and changes to mobility after heat treatment indicate the water binding strength. In this study, differences in the various NMR parameters on the cation treatments will be presented and discussed with respect to the crosslinking hypothesis.

Thalamotemporal impairment in temporal lobe epilepsy: a combined MRI analysis of structure, integrity, and connectivity.

PubMed

Keller, Simon S; O'Muircheartaigh, Jonathan; Traynor, Catherine; Towgood, Karren; Barker, Gareth J; Richardson, Mark P

2014-02-01

Thalamic abnormality in temporal lobe epilepsy (TLE) is well known from imaging studies, but evidence is lacking regarding connectivity profiles of the thalamus and their involvement in the disease process. We used a novel multisequence magnetic resonance imaging (MRI) protocol to elucidate the relationship between mesial temporal and thalamic pathology in TLE. For 23 patients with TLE and 23 healthy controls, we performed T1 -weighted (for analysis of tissue structure), diffusion tensor imaging (tissue connectivity), and T1 and T2 relaxation (tissue integrity) MRI across the whole brain. We used connectivity-based segmentation to determine connectivity patterns of thalamus to ipsilateral cortical regions (occipital, parietal, prefrontal, postcentral, precentral, and temporal). We subsequently determined volumes, mean tractography streamlines, and mean T1 and T2 relaxometry values for each thalamic segment preferentially connecting to a given cortical region, and of the hippocampus and entorhinal cortex. As expected, patients had significant volume reduction and increased T2 relaxation time in ipsilateral hippocampus and entorhinal cortex. There was bilateral volume loss, mean streamline reduction, and T2 increase of the thalamic segment preferentially connected to temporal lobe, corresponding to anterior, dorsomedial, and pulvinar thalamic regions, with no evidence of significant change in any other thalamic segments. Left and right thalamotemporal segment volume and T2 were significantly correlated with volume and T2 of ipsilateral (epileptogenic), but not contralateral (nonepileptogenic), mesial temporal structures. These convergent and robust data indicate that thalamic abnormality in TLE is restricted to the area of the thalamus that is preferentially connected to the epileptogenic temporal lobe. The degree of thalamic pathology is related to the extent of mesial temporal lobe damage in TLE. © 2014 The Authors. Epilepsia published by Wiley Periodicals, Inc. on behalf of International League Against Epilepsy.

Magnetic Resonance Fingerprinting of Adult Brain Tumors: Initial Experience

PubMed Central

Badve, Chaitra; Yu, Alice; Dastmalchian, Sara; Rogers, Matthew; Ma, Dan; Jiang, Yun; Margevicius, Seunghee; Pahwa, Shivani; Lu, Ziang; Schluchter, Mark; Sunshine, Jeffrey; Griswold, Mark; Sloan, Andrew; Gulani, Vikas

2016-01-01

Background Magnetic resonance fingerprinting (MRF) allows rapid simultaneous quantification of T1 and T2 relaxation times. This study assesses the utility of MRF in differentiating between common types of adult intra-axial brain tumors. Methods MRF acquisition was performed in 31 patients with untreated intra-axial brain tumors: 17 glioblastomas, 6 WHO grade II lower-grade gliomas and 8 metastases. T1, T2 of the solid tumor (ST), immediate peritumoral white matter (PW), and contralateral white matter (CW) were summarized within each region of interest. Statistical comparisons on mean, standard deviation, skewness and kurtosis were performed using univariate Wilcoxon rank sum test across various tumor types. Bonferroni correction was used to correct for multiple comparisons testing. Multivariable logistic regression analysis was performed for discrimination between glioblastomas and metastases and area under the receiver operator curve (AUC) was calculated. Results Mean T2 values could differentiate solid tumor regions of lower-grade gliomas from metastases (mean±sd: 172±53ms and 105±27ms respectively, p =0.004, significant after Bonferroni correction). Mean T1 of PW surrounding lower-grade gliomas differed from PW around glioblastomas (mean±sd: 1066±218ms and 1578±331ms respectively, p=0.004, significant after Bonferroni correction). Logistic regression analysis revealed that mean T2 of ST offered best separation between glioblastomas and metastases with AUC of 0.86 (95% CI 0.69–1.00, p<0.0001). Conclusion MRF allows rapid simultaneous T1, T2 measurement in brain tumors and surrounding tissues. MRF based relaxometry can identify quantitative differences between solid-tumor regions of lower grade gliomas and metastases and between peritumoral regions of glioblastomas and lower grade gliomas. PMID:28034994

MR Fingerprinting of Adult Brain Tumors: Initial Experience.

PubMed

Badve, C; Yu, A; Dastmalchian, S; Rogers, M; Ma, D; Jiang, Y; Margevicius, S; Pahwa, S; Lu, Z; Schluchter, M; Sunshine, J; Griswold, M; Sloan, A; Gulani, V

2017-03-01

MR fingerprinting allows rapid simultaneous quantification of T1 and T2 relaxation times. This study assessed the utility of MR fingerprinting in differentiating common types of adult intra-axial brain tumors. MR fingerprinting acquisition was performed in 31 patients with untreated intra-axial brain tumors: 17 glioblastomas, 6 World Health Organization grade II lower grade gliomas, and 8 metastases. T1, T2 of the solid tumor, immediate peritumoral white matter, and contralateral white matter were summarized within each ROI. Statistical comparisons on mean, SD, skewness, and kurtosis were performed by using the univariate Wilcoxon rank sum test across various tumor types. Bonferroni correction was used to correct for multiple-comparison testing. Multivariable logistic regression analysis was performed for discrimination between glioblastomas and metastases, and area under the receiver operator curve was calculated. Mean T2 values could differentiate solid tumor regions of lower grade gliomas from metastases (mean, 172 ± 53 ms, and 105 ± 27 ms, respectively; P = .004, significant after Bonferroni correction). The mean T1 of peritumoral white matter surrounding lower grade gliomas differed from peritumoral white matter around glioblastomas (mean, 1066 ± 218 ms, and 1578 ± 331 ms, respectively; P = .004, significant after Bonferroni correction). Logistic regression analysis revealed that the mean T2 of solid tumor offered the best separation between glioblastomas and metastases with an area under the curve of 0.86 (95% CI, 0.69-1.00; P < .0001). MR fingerprinting allows rapid simultaneous T1 and T2 measurement in brain tumors and surrounding tissues. MR fingerprinting-based relaxometry can identify quantitative differences between solid tumor regions of lower grade gliomas and metastases and between peritumoral regions of glioblastomas and lower grade gliomas. © 2017 by American Journal of Neuroradiology.

Dynamic contrast-enhanced magnetic resonance imaging of the sarcopenic muscle

PubMed Central

Nicolato, Elena; Farace, Paolo; Asperio, Roberto M; Marzola, Pasquina; Lunati, Ernesto; Sbarbati, Andrea; Osculati, Francesco

2002-01-01

Background Studies about capillarity of the aged muscle provided conflicting results and no data are currently available about the magnetic resonance imaging (MRI) in vivo characteristics of the microvascular bed in aged rats. We have studied age-related modifications of the skeletal muscle by in vivo T2-relaxometry and dynamic contrast-enhanced magnetic resonance imaging (CE-MRI) at high field intensity (4.7 T). The aim of the work was to test the hypothesis that the ageing process involves microvessels in skeletal muscle. Methods The study was performed in 4-month-old (n = 6) and 20-month-old (n = 6) rats. Results At MRI examination, the relaxation time T2 of the gastrocnemius muscle showed no significant difference between these two groups. The kinetic of contrast penetration in the tissue showed that in 4-month-old rats the enhancement values of the signal intensity at different time-points were significantly higher than those found in senescent rats. Conclusion The reported finding suggests that there is a modification of the microcirculatory function in skeletal muscle of aged rats. This work also demonstrates that CE-MRI allows for an in vivo quantification of the multiple biological processes involving the skeletal muscle during aging. Therefore, CE-MRI could represent a further tool for the follow up of tissue modification and therapeutic intervention both in patients with sarcopenia and in experimental models of this pathology. PMID:12049675

Lithium ion dynamics in Li2S+GeS2+GeO2 glasses studied using (7)Li NMR field-cycling relaxometry and line-shape analysis.

PubMed

Gabriel, Jan; Petrov, Oleg V; Kim, Youngsik; Martin, Steve W; Vogel, Michael

2015-09-01

We use (7)Li NMR to study the ionic jump motion in ternary 0.5Li2S+0.5[(1-x)GeS2+xGeO2] glassy lithium ion conductors. Exploring the "mixed glass former effect" in this system led to the assumption of a homogeneous and random variation of diffusion barriers in this system. We exploit that combining traditional line-shape analysis with novel field-cycling relaxometry, it is possible to measure the spectral density of the ionic jump motion in broad frequency and temperature ranges and, thus, to determine the distribution of activation energies. Two models are employed to parameterize the (7)Li NMR data, namely, the multi-exponential autocorrelation function model and the power-law waiting times model. Careful evaluation of both of these models indicates a broadly inhomogeneous energy landscape for both the single (x=0.0) and the mixed (x=0.1) network former glasses. The multi-exponential autocorrelation function model can be well described by a Gaussian distribution of activation barriers. Applicability of the methods used and their sensitivity to microscopic details of ionic motion are discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

In vivo mapping of tumor oxygen consumption using (19)F MRI relaxometry.

PubMed

Diepart, Caroline; Magat, Julie; Jordan, Bénédicte F; Gallez, Bernard

2011-06-01

Recently, we have developed a new electron paramagnetic resonance (EPR) protocol in order to estimate tissue oxygen consumption in vivo. Because it is crucial to probe the heterogeneity of response in tumors, the aim of this study was to apply our protocol, together with (19)F MRI relaxometry, to the mapping of the oxygen consumption in tumors. The protocol includes the continuous measurement of tumor po(2) during the following respiratory challenge: (i) basal values during air breathing; (ii) increasing po(2) values during carbogen breathing until saturation of tissue with oxygen; (iii) switching back to air breathing. We have demonstrated previously using EPR oximetry that the kinetics of return to the basal value after oxygen saturation are mainly governed by tissue oxygen consumption. This challenge was applied in hyperthyroid mice (generated by chronic treatment with L-thyroxine) and control mice, as hyperthyroidism is known to dramatically affect the oxygen consumption rate of tumor cells. Our recently developed snapshot inversion recovery MRI fluorocarbon oximetry technique allowed the po(2) return kinetics to be measured with a high temporal resolution. The kinetic constants (i.e. oxygen consumption rates) were higher for tumors from hyperthyroid mice than from control mice, data that are consistent with our previous EPR study. The corresponding histograms of the (19)F MRI data showed that the kinetic constants displayed a shift to the right for the hyperthyroid group, indicating a higher oxygen consumption in these tumors. The color maps showed a large heterogeneity in terms of oxygen consumption rate within a tumor. In conclusion, (19)F MRI relaxometry allows the noninvasive mapping of the oxygen consumption in tumors. The ability to assess the heterogeneity of tumor response is critical in order to identify potential tumor regions that might be resistant to treatment and therefore produce a poor response to therapy. Copyright © 2010 John Wiley & Sons, Ltd.

T1 correlates age: A short-TE MR relaxometry study in vivo on human cortical bone free water at 1.5T.

PubMed

Akbari, Atena; Abbasi-Rad, Shahrokh; Rad, Hamidreza Saligheh

2016-02-01

Large pores of human cortical bone (>30μm) are filled with fluids, essentially consisting of water, suggesting that cortical bone free water can be considered as a reliable surrogate measure of cortical bone porosity and hence quality. Signal from such pores can be reliably captured using Short Echo Time (STE) pulse sequence with echo-time in the range of 1-1.5msec (which should be judiciously selected correspond to T2(⁎) value of free water molecules). Furthermore, it is well-known that cortical bone T1-relaxivity is a function of its geometry, suggesting that cortical bone free water increases with age. In this work, we quantified cortical bone free water longitudinal relaxation time (T1) by a Dual-TR technique using STE pulse sequence. In the sequel, we investigated relationship between STE-derived cortical bone free water T1-values and age in a group of healthy volunteers (thirty subjects covering the age range of 20-70years) at 1.5T. Preliminary results showed that cortical bone free water T1 highly correlates with age (r(2)=0.73, p<0.0001), representing cortical bone free water T1 as a reliable indicator of cortical bone porosity and age-related deterioration. It can be concluded that STE-MRI can be utilized as proper alternative in quantifying cortical bone porosity parameters in-vivo, with the advantages of widespread clinical availability and being cost-effective. Copyright © 2015 Elsevier Inc. All rights reserved.

Ultralow field NMR spectrometer with an atomic magnetometer near room temperature

NASA Astrophysics Data System (ADS)

Liu, Guobin; Li, Xiaofeng; Sun, Xianping; Feng, Jiwen; Ye, Chaohui; Zhou, Xin

2013-12-01

We present a Cs atomic magnetometer with a sensitivity of 150 fT/Hz1/2 operating near room temperature. The nuclear magnetic resonance (NMR) signal of 125 μL tap water was detected at an ultralow magnetic field down to 47 nT, with the signal-to-noise ratio (SNR) of the NMR signal approaching 50 after eight averages. Relaxivity experiments with a Gd(DTPA) contrast agent in zero field were performed, in order to show the magnetometer's ability to measure spin-lattice relaxation time with high accuracy. This demonstrates the feasibility of an ultralow field NMR spectrometer based on a Cs atomic magnetometer, which has a low working temperature, short data acquisition time and high sensitivity. This kind of NMR spectrometer has great potential in applications such as chemical analysis and magnetic relaxometry detection in ultralow or zero fields.

Open Science CBS Neuroimaging Repository: Sharing ultra-high-field MR images of the brain.

PubMed

Tardif, Christine Lucas; Schäfer, Andreas; Trampel, Robert; Villringer, Arno; Turner, Robert; Bazin, Pierre-Louis

2016-01-01

Magnetic resonance imaging at ultra high field opens the door to quantitative brain imaging at sub-millimeter isotropic resolutions. However, novel image processing tools to analyze these new rich datasets are lacking. In this article, we introduce the Open Science CBS Neuroimaging Repository: a unique repository of high-resolution and quantitative images acquired at 7 T. The motivation for this project is to increase interest for high-resolution and quantitative imaging and stimulate the development of image processing tools developed specifically for high-field data. Our growing repository currently includes datasets from MP2RAGE and multi-echo FLASH sequences from 28 and 20 healthy subjects respectively. These datasets represent the current state-of-the-art in in-vivo relaxometry at 7 T, and are now fully available to the entire neuroimaging community. Copyright © 2015 Elsevier Inc. All rights reserved.

New insight into the contrast in diffusional kurtosis images: does it depend on magnetic susceptibility?

PubMed

Palombo, Marco; Gentili, Silvia; Bozzali, Marco; Macaluso, Emiliano; Capuani, Silvia

2015-05-01

In this MRI study, diffusional kurtosis imaging (DKI) and T2 * multiecho relaxometry were measured from the white matter (WM) of human brains and correlated with each other, with the aim of investigating the influence of magnetic-susceptibility (Δχ (H2O-TISSUE) ) on the contrast. We focused our in vivo analysis on assessing the dependence of mean, axial, and radial kurtosis (MK, K‖ , K⊥ ), as well as DTI indices on Δχ (H2O-TISSUE) (quantified by T2 *) between extracellular water and WM tissue molecules. Moreover, Monte Carlo (MC) simulations were used to elucidate experimental data. A significant positive correlation was observed between K⊥ , MK and R2 * = 1/T2 *, suggesting that Δχ (H2O-TISSUE) could be a source of DKI contrast. In this view, K⊥ and MK-map contrasts in human WM would not just be due to different restricted diffusion processes of compartmentalized water but also to local Δχ (H2O-TISSUE) . However, MC simulations show a strong dependence on microstructure rearrangement and a feeble dependence on Δχ (H2O-TISSUE) of DKI signal. Our results suggests a concomitant and complementary existence of multi-compartmentalized diffusion process and Δχ (H2O-TISSUE) in DKI contrast that might explain why kurtosis contrast is more sensitive than DTI in discriminating between different tissues. However, more realistic numerical simulations are needed to confirm this statement. © 2014 Wiley Periodicals, Inc.

Non-invasive evaluation of blood oxygen saturation and hematocrit from T1 and T2 relaxation times: In-vitro validation in fetal blood.

PubMed

Portnoy, Sharon; Seed, Mike; Sled, John G; Macgowan, Christopher K

2017-12-01

We propose an analytical method for calculating blood hematocrit (Hct) and oxygen saturation (sO 2 ) from measurements of its T 1 and T 2 relaxation times. Through algebraic substitution, established two-compartment relationships describing R1=T1-1 and R2=T2-1 as a function of hematocrit and oxygen saturation were rearranged to solve for Hct and sO 2 in terms of R 1 and R 2 . Resulting solutions for Hct and sO 2 are the roots of cubic polynomials. Feasibility of the method was established by comparison of Hct and sO 2 estimates obtained from relaxometry measurements (at 1.5 Tesla) in cord blood specimens to ground-truth values obtained by blood gas analysis. Monte Carlo simulations were also conducted to assess the effect of T 1 , T 2 measurement uncertainty on precision of Hct and sO 2 estimates. Good agreement was observed between estimated and ground-truth blood properties (bias = 0.01; 95% limits of agreement = ±0.13 for Hct and sO 2 ). Considering the combined effects of biological variability and random measurement noise, we estimate a typical uncertainty of ±0.1 for Hct, sO 2 estimates. Results demonstrate accurate quantification of Hct and sO 2 from T 1 and T 2 . This method is applicable to noninvasive fetal vessel oximetry-an application where existing oximetry devices are unusable or require risky blood-sampling procedures. Magn Reson Med 78:2352-2359, 2017. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

Effect of freezing on microstructure and degree of syneresis in differently formulated fruit fillings.

PubMed

Cropotova, Janna; Tylewicz, Urszula; Dellarosa, Nicolò; Laghi, Luca; Romani, Santina; Dalla Rosa, Marco

2016-03-15

This study describes the syneresis and its effect on microstructure in fruit fillings within a wide range of the total soluble solids content and with or without hydrocolloids upon freezing. Linear models showed the relevance of the addition of pectin and gellan gum to fillings to prevent syneresis, increasing the water-holding capacity especially after freezing. Microstructural experiments by means of NMR spin-spin relaxometry combined with fluorescence microscopy allowed to observe that the continuous hydrocolloid gel, containing the dispersed solution of native fruit parts with the addition of inulin and sugars, changed its structure/distribution according to the amount of each ingredient and due to the freezing process. Relaxometry results confirmed that hydrocolloids strength was correlated (R(2)>0.92) with water-holding capacity, due to a relationship between the signal given by the water chemically exchanging with biopolymers, and the changes in the degree of syneresis. Copyright © 2015 Elsevier Ltd. All rights reserved.

A simulation based method to assess inversion algorithms for transverse relaxation data

NASA Astrophysics Data System (ADS)

Ghosh, Supriyo; Keener, Kevin M.; Pan, Yong

2008-04-01

NMR relaxometry is a very useful tool for understanding various chemical and physical phenomena in complex multiphase systems. A Carr-Purcell-Meiboom-Gill (CPMG) [P.T. Callaghan, Principles of Nuclear Magnetic Resonance Microscopy, Clarendon Press, Oxford, 1991] experiment is an easy and quick way to obtain transverse relaxation constant (T2) in low field. Most of the samples usually have a distribution of T2 values. Extraction of this distribution of T2s from the noisy decay data is essentially an ill-posed inverse problem. Various inversion approaches have been used to solve this problem, to date. A major issue in using an inversion algorithm is determining how accurate the computed distribution is. A systematic analysis of an inversion algorithm, UPEN [G.C. Borgia, R.J.S. Brown, P. Fantazzini, Uniform-penalty inversion of multiexponential decay data, Journal of Magnetic Resonance 132 (1998) 65-77; G.C. Borgia, R.J.S. Brown, P. Fantazzini, Uniform-penalty inversion of multiexponential decay data II. Data spacing, T2 data, systematic data errors, and diagnostics, Journal of Magnetic Resonance 147 (2000) 273-285] was performed by means of simulated CPMG data generation. Through our simulation technique and statistical analyses, the effects of various experimental parameters on the computed distribution were evaluated. We converged to the true distribution by matching up the inversion results from a series of true decay data and a noisy simulated data. In addition to simulation studies, the same approach was also applied on real experimental data to support the simulation results.

High-Field MRI Reveals a Drastic Increase of Hypoxia-Induced Microhemorrhages upon Tissue Reoxygenation in the Mouse Brain with Strong Predominance in the Olfactory Bulb.

PubMed

Hoffmann, Angelika; Kunze, Reiner; Helluy, Xavier; Milford, David; Heiland, Sabine; Bendszus, Martin; Pham, Mirko; Marti, Hugo H

2016-01-01

Human pathophysiology of high altitude hypoxic brain injury is not well understood and research on the underlying mechanisms is hampered by the lack of well-characterized animal models. In this study, we explored the evolution of brain injury by magnetic resonance imaging (MRI) and histological methods in mice exposed to normobaric hypoxia at 8% oxygen for 48 hours followed by rapid reoxygenation and incubation for further 24 h under normoxic conditions. T2*-, diffusion-weighted and T2-relaxometry MRI was performed before exposure, immediately after 48 hours of hypoxia and 24 hours after reoxygenation. Cerebral microhemorrhages, previously described in humans suffering from severe high altitude cerebral edema, were also detected in mice upon hypoxia-reoxygenation with a strong region-specific clustering in the olfactory bulb, and to a lesser extent, in the basal ganglia and cerebral white matter. The number of microhemorrhages determined immediately after hypoxia was low, but strongly increased 24 hours upon onset of reoxygenation. Histologically verified microhemorrhages were exclusively located around cerebral microvessels with disrupted interendothelial tight junction protein ZO-1. In contrast, quantitative T2 and apparent-diffusion-coefficient values immediately after hypoxia and after 24 hours of reoxygenation did not show any region-specific alteration, consistent with subtle multifocal but not with regional or global brain edema.

Quantitative Proton Magnetic Resonance Techniques for Measuring Fat

PubMed Central

Harry, Houchun; Kan, Hermien E.

2014-01-01

Accurate, precise, and reliable techniques for quantifying body and organ fat distributions are important tools in physiology research. They are critically needed in studies of obesity and diseases involving excess fat accumulation. Proton magnetic resonance methods address this need by providing an array of relaxometry-based (T1, T2) and chemical-shift-based approaches. These techniques can generate informative visualizations of regional and whole-body fat distributions, yield measurements of fat volumes within specific body depots, and quantify fat accumulation in abdominal organs and muscles. MR methods are commonly used to investigate the role of fat in nutrition and metabolism, to measure the efficacy of short and long-term dietary and exercise interventions, to study the implications of fat in organ steatosis and muscular dystrophies, and to elucidate pathophysiological mechanisms in the context of obesity and its comorbidities. The purpose of this review is to provide a summary of mainstream MR strategies for fat quantification. The article will succinctly describe the principles that differentiate water and fat proton signals, summarize advantages and limitations of various techniques, and offer a few illustrative examples. The article will also highlight recent efforts in MR of brown adipose tissue and conclude by briefly discussing some future research directions. PMID:24123229

Relaxivity of Ferumoxytol at 1.5 T and 3.0 T.

PubMed

Knobloch, Gesine; Colgan, Timothy; Wiens, Curtis N; Wang, Xiaoke; Schubert, Tilman; Hernando, Diego; Sharma, Samir D; Reeder, Scott B

2018-05-01

The aim of this study was to determine the relaxation properties of ferumoxytol, an off-label alternative to gadolinium-based contrast agents, under physiological conditions at 1.5 T and 3.0 T. Ferumoxytol was diluted in gradually increasing concentrations (0.26-4.2 mM) in saline, human plasma, and human whole blood. Magnetic resonance relaxometry was performed at 37°C at 1.5 T and 3.0 T. Longitudinal and transverse relaxation rate constants (R1, R2, R2*) were measured as a function of ferumoxytol concentration, and relaxivities (r1, r2, r2*) were calculated. A linear dependence of R1, R2, and R2* on ferumoxytol concentration was found in saline and plasma with lower R1 values at 3.0 T and similar R2 and R2* values at 1.5 T and 3.0 T (1.5 T: r1saline = 19.9 ± 2.3 smM; r1plasma = 19.0 ± 1.7 smM; r2saline = 60.8 ± 3.8 smM; r2plasma = 64.9 ± 1.8 smM; r2*saline = 60.4 ± 4.7 smM; r2*plasma = 64.4 ± 2.5 smM; 3.0 T: r1saline = 10.0 ± 0.3 smM; r1plasma = 9.5 ± 0.2 smM; r2saline = 62.3 ± 3.7 smM; r2plasma = 65.2 ± 1.8 smM; r2*saline = 57.0 ± 4.7 smM; r2*plasma = 55.7 ± 4.4 smM). The dependence of relaxation rates on concentration in blood was nonlinear. Formulas from second-order polynomial fittings of the relaxation rates were calculated to characterize the relationship between R1blood and R2 blood with ferumoxytol. Ferumoxytol demonstrates strong longitudinal and transverse relaxivities. Awareness of the nonlinear relaxation behavior of ferumoxytol in blood is important for ferumoxytol-enhanced magnetic resonance imaging applications and for protocol optimization.

Neuroimaging in epilepsy.

PubMed

Sidhu, Meneka Kaur; Duncan, John S; Sander, Josemir W

2018-05-17

Epilepsy neuroimaging is important for detecting the seizure onset zone, predicting and preventing deficits from surgery and illuminating mechanisms of epileptogenesis. An aspiration is to integrate imaging and genetic biomarkers to enable personalized epilepsy treatments. The ability to detect lesions, particularly focal cortical dysplasia and hippocampal sclerosis, is increased using ultra high-field imaging and postprocessing techniques such as automated volumetry, T2 relaxometry, voxel-based morphometry and surface-based techniques. Statistical analysis of PET and single photon emission computer tomography (STATISCOM) are superior to qualitative analysis alone in identifying focal abnormalities in MRI-negative patients. These methods have also been used to study mechanisms of epileptogenesis and pharmacoresistance.Recent language fMRI studies aim to localize, and also lateralize language functions. Memory fMRI has been recommended to lateralize mnemonic function and predict outcome after surgery in temporal lobe epilepsy. Combinations of structural, functional and post-processing methods have been used in multimodal and machine learning models to improve the identification of the seizure onset zone and increase understanding of mechanisms underlying structural and functional aberrations in epilepsy.

Amygdala Volumetry in Patients with Temporal Lobe Epilepsy and Normal Magnetic Resonance Imaging

PubMed Central

Singh, Paramdeep; Kaur, Rupinderjeet; Saggar, Kavita; Singh, Gagandeep; Aggarwal, Simmi

2016-01-01

Summary Background It has been suggested that the pathophysiology of temporal lobe epilepsy may relate to abnormalities in various brain structures, including the amygdala. Patients with mesial temporal lobe epilepsy (MTLE) without MRI abnormalities (MTLE-NMRI) represent a challenge for diagnosis of the underlying abnormality and for presurgical evaluation. To date, however, only few studies have used quantitative structural Magnetic Resonance Imaging-based techniques to examine amygdalar pathology in these patients. Material/Methods Based on clinical examination, 24-hour video EEG recordings and MRI findings, 50 patients with EEG lateralized TLE and normal structural Magnetic Resonance Imaging results were included in this study. Volumetric magnetic resonance imaging (MRI) studies of the amygdalas and hippocampi were conducted in 50 non-epileptic controls (age 7–79 years) and 50 patients with MTLE with normal MRI on a 1.5-Tesla scanner. Visual assessment and amygdalar volumetry were performed on oblique coronal T2W and T1W MP-RAGE images respectively. The T2 relaxation times were measured using the 16-echo Carr-Purcell-Meiboom-Gill sequence (TE, 22–352). Volumetric data were normalized for variation in head size between individuals. Results were assessed by SSPS statistic program. Results Individual manual volumetric analysis confirmed statistically significant amygdala enlargement (AE) in eight (16%) patients. Overall, among all patients with AE and a defined epileptic focus, 7 had predominant increased volume ipsilateral to the epileptic focus. The T2 relaxometry demonstrated no hyperintense signal of the amygdala in any patient with significant AE. Conclusions This paper presented AE in a few patients with TLE and normal MRI. These findings support the hypothesis that there might be a subgroup of patients with MTLE-NMRI in which the enlarged amygdala could be related to the epileptogenic process. PMID:27231493

Water T2 as an early, global and practical biomarker for metabolic syndrome: an observational cross-sectional study.

PubMed

Robinson, Michelle D; Mishra, Ina; Deodhar, Sneha; Patel, Vipulkumar; Gordon, Katrina V; Vintimilla, Raul; Brown, Kim; Johnson, Leigh; O'Bryant, Sid; Cistola, David P

2017-12-19

Metabolic syndrome (MetS) is a highly prevalent condition that identifies individuals at risk for type 2 diabetes mellitus and atherosclerotic cardiovascular disease. Prevention of these diseases relies on early detection and intervention in order to preserve pancreatic β-cells and arterial wall integrity. Yet, the clinical criteria for MetS are insensitive to the early-stage insulin resistance, inflammation, cholesterol and clotting factor abnormalities that characterize the progression toward type 2 diabetes and atherosclerosis. Here we report the discovery and initial characterization of an atypical new biomarker that detects these early conditions with just one measurement. Water T 2 , measured in a few minutes using benchtop nuclear magnetic resonance relaxometry, is exquisitely sensitive to metabolic shifts in the blood proteome. In an observational cross-sectional study of 72 non-diabetic human subjects, the association of plasma and serum water T 2 values with over 130 blood biomarkers was analyzed using bivariate, multivariate and logistic regression. Plasma and serum water T 2 exhibited strong bivariate correlations with markers of insulin, lipids, inflammation, coagulation and electrolyte balance. After correcting for confounders, low water T 2 values were independently and additively associated with fasting hyperinsulinemia, dyslipidemia and subclinical inflammation. Plasma water T 2 exhibited 100% sensitivity and 87% specificity for detecting early insulin resistance in normoglycemic subjects, as defined by the McAuley Index. Sixteen normoglycemic subjects with early metabolic abnormalities (22% of the study population) were identified by low water T 2 values. Thirteen of the 16 did not meet the harmonized clinical criteria for metabolic syndrome and would have been missed by conventional screening for diabetes risk. Low water T 2 values were associated with increases in the mean concentrations of 6 of the 16 most abundant acute phase proteins and lipoproteins in plasma. Water T 2 detects a constellation of early abnormalities associated with metabolic syndrome, providing a global view of an individual's metabolic health. It circumvents the pitfalls associated with fasting glucose and hemoglobin A1c and the limitations of the current clinical criteria for metabolic syndrome. Water T 2 shows promise as an early, global and practical screening tool for the identification of individuals at risk for diabetes and atherosclerosis.

LiBi{sub 3}S{sub 5}—A lithium bismuth sulfide with strong cation disorder

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nakhal, Suliman; Wiedemann, Dennis, E-mail: dennis.wiedemann@chem.tu-berlin.de; Stanje, Bernhard

Among chalcogenide semiconductors for thermoelectric applications, alkali-metal bismuth compounds occur in many complex compositions favorable for high performance. Although LiBi{sub 3}S{sub 5} had been announced in 1977, the potential 1D lithium-ion conductor has hitherto eluded selective synthesis and structure determination. In this study, we present a solid-state route to phase-pure LiBi{sub 3}S{sub 5} powder starting from LiBiS{sub 2} and Bi{sub 2}S{sub 3}. Neutron diffractograms and lithium NMR spectra reveal its crystal structure to be a cation-disordered variety of the AgBi{sub 3}S{sub 5} type (synthetic pavonite; monoclinic, C2/m). Topological analyses and lithium NMR relaxometry suggest that correlated lithium-ion diffusion with activationmore » energies up to 0.66(2) eV occurs along the channels in b direction including tetrahedral voids. Because of cation disorder, immobile bismuth(III) ions clog these pathways, making LiBi{sub 3}S{sub 5} a moderate to poor ionic conductor. The synthesis route reported is nonetheless promising for new lithium bismuth sulfides with, possibly ordered, structure types of the pavonite homologous series. - Graphical abstract: Phase-pure LiBi{sub 3}S{sub 5} has been synthesized and shown to crystallize in cation-disordered variety of the AgBi{sub 3}S{sub 5} type (synthetic pavonite, C2/m) using neutron diffractometry. Topological analyses and NMR relaxometry suggest that immobile Bi{sup 3+} ions clog migration channels along b, making the material a poor lithium conductor. Display Omitted - Highlights: • Phase-pure LiBi{sub 3}S{sub 5} has been synthesized using a promising solid-state route. • LiBi{sub 3}S{sub 5} crystallizes in a cation-disordered variant of the AgBi{sub 3}S{sub 5} type. • Topological analyses suggest lithium diffusion in channels along b. • NMR relaxometry finds activation energies of diffusion as high as 0.66(2) eV. • Because of disorder, LiBi{sub 3}S{sub 5} is a moderate to poor lithium-ion conductor.« less

Field-cycling NMR with high-resolution detection under magic-angle spinning: determination of field-window for nuclear hyperpolarization in a photosynthetic reaction center.

PubMed

Gräsing, Daniel; Bielytskyi, Pavlo; Céspedes-Camacho, Isaac F; Alia, A; Marquardsen, Thorsten; Engelke, Frank; Matysik, Jörg

2017-09-21

Several parameters in NMR depend on the magnetic field strength. Field-cycling NMR is an elegant way to explore the field dependence of these properties. The technique is well developed for solution state and in relaxometry. Here, a shuttle system with magic-angle spinning (MAS) detection is presented to allow for field-dependent studies on solids. The function of this system is demonstrated by exploring the magnetic field dependence of the solid-state photochemically induced nuclear polarization (photo-CIDNP) effect. The effect allows for strong nuclear spin-hyperpolarization in light-induced spin-correlated radical pairs (SCRPs) under solid-state conditions. To this end, 13 C MAS NMR is applied to a photosynthetic reaction center (RC) of the purple bacterium Rhodobacter (R.) sphaeroides wildtype (WT). For induction of the effect in the stray field of the magnet and its subsequent observation at 9.4 T under MAS NMR conditions, the sample is shuttled by the use of an aerodynamically driven sample transfer technique. In the RC, we observe the effect down to 0.25 T allowing to determine the window for the occurrence of the effect to be between about 0.2 and 20 T.

Etiology of hippocampal sclerosis

PubMed Central

Tsai, Meng-Han; Pardoe, Heath R.; Perchyonok, Yuliya; Fitt, Gregory J.; Scheffer, Ingrid E.; Berkovic, Samuel F.

2013-01-01

Objective: We sought evidence of a hereditary component for hippocampal sclerosis (HS) by determining whether close relatives of probands with temporal lobe epilepsy (TLE) with HS also had asymptomatic HS or subtle variation in hippocampal morphology. Methods: First-degree relatives from 15 families in which probands had TLE with HS and 32 age- and sex-matched controls were included in the study. Left and right hippocampal volumes and T2 relaxometry were measured using 3-tesla MRI. Results: Thirty-two asymptomatic first-degree relatives and 3 relatives with a history of seizures or epilepsy were studied. None of the first-degree relatives had HS on visual analysis and T2 relaxation times were normal, excluding the presence of HS. Mean hippocampal volume was smaller (6.4%) in asymptomatic relatives (2.94 ± 0.27 cm3, 95% confidence interval = 2.87–3.01) than in controls (3.14 ± 0.22 cm3, 95% confidence interval = 3.09–3.19, p < 0.005); the effect was greater in relatives of probands with a positive family history of epilepsy. The relatives also had more asymmetric hippocampi (asymmetric index 0.92 ± 0.05) than controls (0.96 ± 0.03, p = 0.001). Conclusions: Small asymmetric hippocampi in healthy relatives are likely to represent a familial developmental variant that may predispose to the formation of TLE with HS. The underlying histopathology of these small hippocampi is unknown. This observation may provide an imaging marker for future studies seeking susceptibility genes for HS. PMID:23749796

17O Relaxation Times in the Rat Brain at 16.4T

PubMed Central

Wiesner, Hannes M.; Balla, Dávid Z.; Shajan, G.; Scheffler, Klaus; Uğurbil, Kâmil; Chen, Wei; Uludağ, Kâmil; Pohmann, Rolf

2015-01-01

Purpose Measurement of the cerebral metabolic rate of oxygen (CMRO2) via direct imaging of the 17O signal can be a valuable tool in neuroscientific research. However, knowledge of the longitudinal and transverse relaxation times of different brain tissue types is required, which is difficult to obtain because of the low sensitivity of natural abundance H217O measurements. Methods Using the improved sensitivity at a field strength of 16.4 T, relaxation time measurements in the rat brain were performed in vivo and postmortem with relatively high spatial resolutions, using a chemical shift imaging sequence. Results In vivo relaxation times of rat brain were found to be T1 = 6.84 ± 0.67 ms and T2* = 1.77 ± 0.04 ms. Postmortem H217O relaxometry at enriched concentrations after inhalation of 17O2 showed similar T2* values for gray (1.87 ± 0.04 ms) and white matter, significantly longer than muscle (1.27 ± 0.05 ms) and shorter than CSF (2.30 ± 0.16 ms). Conclusion Relaxation times of brain H217O were measured for the first time in vivo in different types of tissues with high spatial resolution. Since the relaxation times of H217O are expected to be independent of field strength, our results should help in optimizing the acquisition parameters for experiments also at other MRI field strengths. PMID:26098931

Diagnosis and quantification of the iron overload through Magnetic resonance.

PubMed

Alústiza Echeverría, J M; Barrera Portillo, M C; Guisasola Iñiguiz, A; Ugarte Muño, A

There are different magnetic resonance techniques and models to quantify liver iron concentration. T2 relaxometry methods evaluate the iron concentration in the myocardium, and they are able to discriminate all the levels of iron overload in the liver. Signal intensity ratio methods saturate with high levels of liver overload and can not assess iron concentration in the myocardium but they are more accessible and are very standardized. This article reviews, in different clinical scenarios, when Magnetic Resonance must be used to assess iron overload in the liver and myocardium and analyzes the current challenges to optimize the aplication of the technique and to be it included in the clinical guidelines. Copyright © 2017 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

Probing numerical Laplace inversion methods for two and three-site molecular exchange between interconnected pore structures.

PubMed

Silletta, Emilia V; Franzoni, María B; Monti, Gustavo A; Acosta, Rodolfo H

2018-01-01

Two-dimension (2D) Nuclear Magnetic Resonance relaxometry experiments are a powerful tool extensively used to probe the interaction among different pore structures, mostly in inorganic systems. The analysis of the collected experimental data generally consists of a 2D numerical inversion of time-domain data where T 2 -T 2 maps are generated. Through the years, different algorithms for the numerical inversion have been proposed. In this paper, two different algorithms for numerical inversion are tested and compared under different conditions of exchange dynamics; the method based on Butler-Reeds-Dawson (BRD) algorithm and the fast-iterative shrinkage-thresholding algorithm (FISTA) method. By constructing a theoretical model, the algorithms were tested for a two- and three-site porous media, varying the exchange rates parameters, the pore sizes and the signal to noise ratio. In order to test the methods under realistic experimental conditions, a challenging organic system was chosen. The molecular exchange rates of water confined in hierarchical porous polymeric networks were obtained, for a two- and three-site porous media. Data processed with the BRD method was found to be accurate only under certain conditions of the exchange parameters, while data processed with the FISTA method is precise for all the studied parameters, except when SNR conditions are extreme. Copyright © 2017 Elsevier Inc. All rights reserved.

Magnetic relaxometry as applied to sensitive cancer detection and localization

DOE PAGES

De Haro, Leyma P.; Karaulanov, Todor; Vreeland, Erika C.; ...

2015-06-02

Abstract Here we describe superparamagnetic relaxometry (SPMR), a technology that utilizes highly sensitive magnetic sensors and superparamagnetic nanoparticles for cancer detection. Using SPMR, we sensitively and specifically detect nanoparticles conjugated to biomarkers for various types of cancer. SPMR offers high contrast In SPMR measurements, a brief magnetizing pulse is used to align superparamagnetic nanoparticles of a discrete size. Following the pulse, an array of superconducting quantum interference detectors (SQUID) sensors detect the decaying magnetization field. NP size is chosen so that, when bound, the induced field decays in seconds. They are functionalized with specific biomarkers and incubated with cancer cellsmore » As a result, superparamagnetic NPs developed here have small size dispersion. Cell incubation studies measure specificity for different cell lines and antibodies with very high contrast.« less

The "long tail" of the protein tumbling correlation function: observation by (1)H NMR relaxometry in a wide frequency and concentration range.

PubMed

Roos, Matthias; Hofmann, Marius; Link, Susanne; Ott, Maria; Balbach, Jochen; Rössler, Ernst; Saalwächter, Kay; Krushelnitsky, Alexey

2015-12-01

Inter-protein interactions in solution affect the auto-correlation function of Brownian tumbling not only in terms of a simple increase of the correlation time, they also lead to the appearance of a weak slow component ("long tail") of the correlation function due to a slowly changing local anisotropy of the microenvironment. The conventional protocol of correlation time estimation from the relaxation rate ratio R1/R2 assumes a single-component tumbling correlation function, and thus can provide incorrect results as soon as the "long tail" is of relevance. This effect, however, has been underestimated in many instances. In this work we present a detailed systematic study of the tumbling correlation function of two proteins, lysozyme and bovine serum albumin, at different concentrations and temperatures using proton field-cycling relaxometry combined with R1ρ and R2 measurements. Unlike high-field NMR relaxation methods, these techniques enable a detailed study of dynamics on a time scale longer than the normal protein tumbling correlation time and, thus, a reliable estimate of the parameters of the "long tail". In this work we analyze the concentration dependence of the intensity and correlation time of the slow component and perform simulations of high-field (15)N NMR relaxation data demonstrating the importance of taking the "long tail" in the analysis into account.

Novel pulsed switched power supply for a fast field cycling NMR spectrometer.

PubMed

Sousa, D M; Fernandes, P A L; Marques, G D; Ribeiro, A C; Sebastião, P J

2004-01-01

In this paper, we outline the operating principles of a pulsed switched power supply for a fast field-cycling nuclear magnetic resonance spectrometer. The power supply uses a variant of a four-quadrant chopper with a duty cycle that defines the average output current. With this topology only two semiconductors are necessary to drive hundreds of amperes with an output power of several kilowatts. The output current ripple has a well-defined shape that can be reduced to acceptable values by a careful design of the semiconductors' controlling circuits and drivers. A power supply prototype was tested with a home build air-core magnet operating with fields between 0 and 0.21 T. The system is computer controlled using pulse generator and data acquisition PC cards, and specific user-friendly home-developed software. A comparative proton relaxometry study in two well-known liquid crystal compounds 5CB and MBBA was performed to check the reproducibility of the T1 measurements.

Slow molecular dynamics of water in a lyotropic complex fluid studied by deuterium conventional and spin-lattice relaxometry NMR.

PubMed

Rodríguez, C R; Pusiol, D J; Figueiredo Neto, A M; Seitter, R-O

2002-03-01

A nuclear magnetic resonance study of protons and deuterons in the mesomorphic phases of the micellar lyotropic mixture potassium laurate/1-decanol/heavy water is reported. The slow dynamical behavior of water molecules has been investigated with deuterons spin-lattice relaxation dispersion in the Larmor frequency range 10(3)

Cluster analysis of quantitative MRI T2 and T1ρ relaxation times of cartilage identifies differences between healthy and ACL-injured individuals at 3T.

PubMed

Monu, U D; Jordan, C D; Samuelson, B L; Hargreaves, B A; Gold, G E; McWalter, E J

2017-04-01

To identify focal lesions of elevated MRI T 2 and T 1ρ relaxation times in articular cartilage of an ACL-injured group using a novel cluster analysis technique. Eighteen ACL-injured patients underwent 3T MRI T 2 and T 1ρ relaxometry at baseline, 6 months and 1 year and six healthy volunteers at baseline, 1 day and 1 year. Clusters of contiguous pixels above or below T 2 and T 1ρ intensity and area thresholds were identified on a projection map of the 3D femoral cartilage surface. The total area of femoral cartilage plate covered by clusters (%CA) was split into areas above (%CA+) and below (%CA-) the thresholds and the differences in %CA(+ or -) over time in the ACL-injured group were determined using the Wilcoxon signed rank test. %CA+ was greater in the ACL-injured patients than the healthy volunteers at 6 months and 1 year with average %CA+ of 5.2 ± 4.0% (p = 0.0054) and 6.6 ± 3.7% (p = 0.0041) for T 2 and 6.2 ± 7.1% (p = 0.063) and 8.2 ± 6.9% (p = 0.042) for T 1ρ , respectively. %CA- at 6 months and 1 year was 3.0 ± 1.8% (p > 0.1) and 5.9 ± 5.0% (p > 0.1) for T 2 and 4.4 ± 4.9% (p > 0.1) and 4.5 ± 4.6% (p > 0.1) for T 1ρ , respectively. With the proposed cluster analysis technique, we have quantified cartilage lesion coverage and demonstrated that the ACL-injured group had greater areas of elevated T 2 and T 1ρ relaxation times as compared to healthy volunteers. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

The Combined Quantification and Interpretation of Multiple Quantitative Magnetic Resonance Imaging Metrics Enlightens Longitudinal Changes Compatible with Brain Repair in Relapsing-Remitting Multiple Sclerosis Patients.

PubMed

Bonnier, Guillaume; Maréchal, Benedicte; Fartaria, Mário João; Falkowskiy, Pavel; Marques, José P; Simioni, Samanta; Schluep, Myriam; Du Pasquier, Renaud; Thiran, Jean-Philippe; Krueger, Gunnar; Granziera, Cristina

2017-01-01

Quantitative and semi-quantitative MRI (qMRI) metrics provide complementary specificity and differential sensitivity to pathological brain changes compatible with brain inflammation, degeneration, and repair. Moreover, advanced magnetic resonance imaging (MRI) metrics with overlapping elements amplify the true tissue-related information and limit measurement noise. In this work, we combined multiple advanced MRI parameters to assess focal and diffuse brain changes over 2 years in a group of early-stage relapsing-remitting MS patients. Thirty relapsing-remitting MS patients with less than 5 years disease duration and nine healthy subjects underwent 3T MRI at baseline and after 2 years including T1, T2, T2* relaxometry, and magnetization transfer imaging. To assess longitudinal changes in normal-appearing (NA) tissue and lesions, we used analyses of variance and Bonferroni correction for multiple comparisons. Multivariate linear regression was used to assess the correlation between clinical outcome and multiparametric MRI changes in lesions and NA tissue. In patients, we measured a significant longitudinal decrease of mean T2 relaxation times in NA white matter ( p  = 0.005) and a decrease of T1 relaxation times in the pallidum ( p  < 0.05), which are compatible with edema reabsorption and/or iron deposition. No longitudinal changes in qMRI metrics were observed in controls. In MS lesions, we measured a decrease in T1 relaxation time ( p -value < 2.2e-16) and a significant increase in MTR ( p -value < 1e-6), suggesting repair mechanisms, such as remyelination, increased axonal density, and/or a gliosis. Last, the evolution of advanced MRI metrics-and not changes in lesions or brain volume-were correlated to motor and cognitive tests scores evolution (Adj- R 2  > 0.4, p  < 0.05). In summary, the combination of multiple advanced MRI provided evidence of changes compatible with focal and diffuse brain repair at early MS stages as suggested by histopathological studies.

Polymer dynamics under nanoscopic constraints: the "corset effect" as revealed by NMR relaxometry and diffusometry.

PubMed

Fatkullin, Nail; Fischer, Elmar; Mattea, Carlos; Beginn, Uwe; Kimmich, Rainer

2004-06-21

A spinodal demixing technique was employed for the preparation of linear poly(ethylene oxide) (PEO) confined in nanoscopic strands, which in turn are embedded in a quasi-solid methacrylate matrix impenetrable to PEO. Both the molecular weight of the PEO and the mean diameter of the strands are variable to a certain degree. Chain dynamics of the PEO in the molten state were examined with the aid of field-gradient NMR diffusometry and field-cycling NMR relaxometry. The dominating mechanism for translational displacements in the nanoscopic strands is shown to be reptation. A formalism for the evaluation of NMR diffusometry is presented, which permits the estimation of the mean PEO strand diameter. Samples of different composition revealed diameters in the range 9-58 nm, in reasonable agreement with electron micrographs. The time scale of the diffusion measurements was 10-300 ms. On the much shorter time scale of field-cycling NMR relaxometry, 10(-9)-10(-4)s, a frequency dispersion of the spin-lattice relaxation time characteristic for reptation clearly showed up in all samples. An effective tube diameter of only 0.6 nm was found even when the strand diameter was larger than the radius of gyration of the PEO chain random coils. The finding that the tube diameter effective on the short time scale of field-cycling NMR relaxometry is much smaller than the diameter of the confining structure is termed the "corset effect", and is traced back to the lack of local free-volume fluctuation capacity under nanoscale confinements. The order of magnitude of the 'pore' diameter, at which the cross-over from confined to bulk chain dynamics is expected, is estimated.

Capillary trapping quantification in sandstones using NMR relaxometry

NASA Astrophysics Data System (ADS)

Connolly, Paul R. J.; Vogt, Sarah J.; Iglauer, Stefan; May, Eric F.; Johns, Michael L.

2017-09-01

Capillary trapping of a non-wetting phase arising from two-phase immiscible flow in sedimentary rocks is critical to many geoscience scenarios, including oil and gas recovery, aquifer recharge and, with increasing interest, carbon sequestration. Here we demonstrate the successful use of low field 1H Nuclear Magnetic Resonance [NMR] to quantify capillary trapping; specifically we use transverse relaxation time [T2] time measurements to measure both residual water [wetting phase] content and the surface-to-volume ratio distribution (which is proportional to pore size] of the void space occupied by this residual water. Critically we systematically confirm this relationship between T2 and pore size by quantifying inter-pore magnetic field gradients due to magnetic susceptibility contrast, and demonstrate that our measurements at all water saturations are unaffected. Diffusion in such field gradients can potentially severely distort the T2-pore size relationship, rendering it unusable. Measurements are performed for nitrogen injection into a range of water-saturated sandstone plugs at reservoir conditions. Consistent with a water-wet system, water was preferentially displaced from larger pores while relatively little change was observed in the water occupying smaller pore spaces. The impact of cyclic wetting/non-wetting fluid injection was explored and indicated that such a regime increased non-wetting trapping efficiency by the sequential occupation of the most available larger pores by nitrogen. Finally the replacement of nitrogen by CO2 was considered; this revealed that dissolution of paramagnetic minerals from the sandstone caused by its exposure to carbonic acid reduced the in situ bulk fluid T2 relaxation time on a timescale comparable to our core flooding experiments. The implications of this for the T2-pore size relationship are discussed.

Effects of Peach Cultivar on Enzymatic Browning Following Cell Damage from High-Pressure Processing.

PubMed

Techakanon, Chukwan; Gradziel, Thomas M; Barrett, Diane M

2016-10-12

Peach cultivars contribute to unique product characteristics and may affect the degree of browning after high-pressure processing (HPP). Nine peach cultivars were subjected to HPP at 0, 100, and 400 MPa for 10 min. Proton nuclear magnetic resonance ( 1 H NMR) relaxometry, light microscopy, color, polyphenol oxidase (PPO) activity, and total phenols were evaluated. The development of enzymatic browning during refrigerated storage occurred because of damage during HPP that triggered loss of cell integrity, allowing substrates to interact with enzymes. Increasing pressure levels resulted in greater damage, as determined by shifts in transverse relaxation time (T 2 ) and by light micrographs. Discoloration was triggered by membrane decompartmentalization but limited by PPO activity, which was found to correlate to cultivar harvest time (early, mid, and late season). Outcomes from the microstructure, 1 H NMR ,and PPO activity evaluation were an effective means of determining membrane decompartmentalization and allowed for prediction of browning scenarios.

Magnetic susceptibility characterisation of superparamagnetic microspheres

NASA Astrophysics Data System (ADS)

Grob, David Tim; Wise, Naomi; Oduwole, Olayinka; Sheard, Steve

2018-04-01

The separation of magnetic materials in microsystems using magnetophoresis has increased in popularity. The wide variety and availability of magnetic beads has fuelled this drive. It is important to know the magnetic characteristics of the microspheres in order to accurately use them in separation processes integrated on a lab-on-a-chip device. To investigate the magnetic susceptibility of magnetic microspheres, the magnetic responsiveness of three types of Dynabeads microspheres were tested using two different approaches. The magnetophoretic mobility of individual microspheres is studied using a particle tracking system and the magnetization of each type of Dynabeads microsphere is measured using SQUID relaxometry. The magnetic beads' susceptibility is obtained at four different applied magnetic fields in the range of 38-70 mT for both the mobility and SQUID measurements. The susceptibility values in both approaches show a consistent magnetic field dependence.

Radiofrequency Ablation, MR Thermometry, and High-Spatial-Resolution MR Parametric Imaging with a Single, Minimally Invasive Device.

PubMed

Ertürk, M Arcan; Sathyanarayana Hegde, Shashank; Bottomley, Paul A

2016-12-01

Purpose To develop and demonstrate in vitro and in vivo a single interventional magnetic resonance (MR)-active device that integrates the functions of precise identification of a tissue site with the delivery of radiofrequency (RF) energy for ablation, high-spatial-resolution thermal mapping to monitor thermal dose, and quantitative MR imaging relaxometry to document ablation-induced tissue changes for characterizing ablated tissue. Materials and Methods All animal studies were approved by the institutional animal care and use committee. A loopless MR imaging antenna composed of a tuned microcable either 0.8 or 2.2 mm in diameter with an extended central conductor was switched between a 3-T MR imaging unit and an RF power source to monitor and perform RF ablation in bovine muscle and human artery samples in vitro and in rabbits in vivo. High-spatial-resolution (250-300-μm) proton resonance frequency shift MR thermometry was interleaved with ablations. Quantitative spin-lattice (T1) and spin-spin (T2) relaxation time MR imaging mapping was performed before and after ablation. These maps were compared with findings from gross tissue examination of the region of ablated tissue after MR imaging. Results High-spatial-resolution MR imaging afforded temperature mapping in less than 8 seconds for monitoring ablation temperatures in excess of 85°C delivered by the same device. This produced irreversible thermal injury and necrosis. Quantitative MR imaging relaxation time maps demonstrated up to a twofold variation in mean regional T1 and T2 after ablation versus before ablation. Conclusion A simple, integrated, minimally invasive interventional probe that provides image-guided therapy delivery, thermal mapping of dose, and detection of ablation-associated MR imaging parametric changes was developed and demonstrated. With this single-device approach, coupling-related safety concerns associated with multiple conductor approaches were avoided. © RSNA, 2016 Online supplemental material is available for this article.

Benchtop-NMR and MRI--a new analytical tool in drug delivery research.

PubMed

Metz, Hendrik; Mäder, Karsten

2008-12-08

During the last years, NMR spectroscopy and NMR imaging (magnetic resonance imaging, MRI) have been increasingly used to monitor drug delivery systems in vitro and in vivo. However, high installation and running costs of the commonly used superconducting magnet technology limits the application range and prevents the further spread of this non-invasive technology. Benchtop-NMR (BT-NMR) relaxometry uses permanent magnets and is much less cost intensive. BT-NMR relaxometry is commonly used in the food and chemical industry, but so far scarcely used in the pharmaceutical field. The paper shows on several examples that the application field of BT-NMR relaxometry can be extended into the field of drug delivery, including the characterisation of emulsions and lipid ingredients (e.g. the amount and physicochemical state of the lipid) and the monitoring of adsorption characteristics (e.g. oil binding of porous ingredients). The most exciting possibilities of BT-NMR technology are linked with the new development of BT-instruments with imaging capability. BT-MRI examples on the monitoring of hydration and swelling of HPMC-based monolayer and double-layer tablets are shown. BT-MRI opens new MRI opportunities for the non-invasive monitoring of drug delivery processes.

Mechanistic understanding of cellular level of water in plant-based food material

NASA Astrophysics Data System (ADS)

Khan, Md. Imran H.; Kumar, C.; Karim, M. A.

2017-06-01

Understanding of water distribution in plant-based food material is crucial for developing an accurate heat and mass transfer drying model. Generally, in plant-based food tissue, water is distributed in three different spaces namely, intercellular water, intracellular water, and cell wall water. For hygroscopic material, these three types of water transport should be considered for actual understanding of heat and mass transfer during drying. However, there is limited study dedicated to the investigation of the moisture distribution in a different cellular environment in the plant-based food material. Therefore, the aim of the present study was to investigate the proportion of intercellular water, intracellular water, and cell wall water inside the plant-based food material. During this study, experiments were performed for two different plant-based food tissues namely, eggplant and potato tissue using 1H-NMR-T2 relaxometry. Various types of water component were calculated by using multicomponent fits of the T2 relaxation curves. The experimental result showed that in potato tissue 80-82% water exist in intracellular space; 10-13% water in intercellular space and only 4-6% water exist in the cell wall space. In eggplant tissue, 90-93% water in intracellular space, 4-6% water exists in intercellular space and the remaining percentage of water is recognized as cell wall water. The investigated results quantify different types of water in plant-based food tissue. The highest proportion of water exists in intracellular spaces. Therefore, it is necessary to include different transport mechanism for intracellular, intercellular and cell wall water during modelling of heat and mass transfer during drying.

R1 dispersion contrast at high field with fast field-cycling MRI

NASA Astrophysics Data System (ADS)

Bödenler, Markus; Basini, Martina; Casula, Maria Francesca; Umut, Evrim; Gösweiner, Christian; Petrovic, Andreas; Kruk, Danuta; Scharfetter, Hermann

2018-05-01

Contrast agents with a strong R1 dispersion have been shown to be effective in generating target-specific contrast in MRI. The utilization of this R1 field dependence requires the adaptation of an MRI scanner for fast field-cycling (FFC). Here, we present the first implementation and validation of FFC-MRI at a clinical field strength of 3 T. A field-cycling range of ±100 mT around the nominal B0 field was realized by inserting an additional insert coil into an otherwise conventional MRI system. System validation was successfully performed with selected iron oxide magnetic nanoparticles and comparison to FFC-NMR relaxometry measurements. Furthermore, we show proof-of-principle R1 dispersion imaging and demonstrate the capability of generating R1 dispersion contrast at high field with suppressed background signal. With the presented ready-to-use hardware setup it is possible to investigate MRI contrast agents with a strong R1 dispersion at a field strength of 3 T.

Dynamical behavior of a single polymer chain under nanometric confinement

NASA Astrophysics Data System (ADS)

Lagrené, K.; Zanotti, J.-M.; Daoud, M.; Farago, B.; Judeinstein, P.

2010-10-01

We address the dynamical behavior of a single polymer chain under nanometric confinement. We consider a polymer melt made of a mixture of hydrogenated and deuterated high molecular mass Poly(Ethylene Oxide) (PEO). The confining material is a membrane of Anodic Aluminum Oxide (AAO), a macroscopically highly ordered confining system made of parallel cylindrical channels. We use Neutron Spin-Echo (NSE) under the Zero Average Contrast (ZAC) condition to, all at once, i) match the intense porous AAO detrimental elastic SANS (Small Angle Neutron Scattering) contribution to the total intermediate scattering function I(Q,t) and ii) measure the Q dependence of the dynamical modes of a single chain under confinement. The polymer dynamics is probed on an extremely broad spacial ([2.2 10-2 Å-1, 0.2 Å-1]) and temporal ([0.1 ns, 600 ns]) ranges. We do not detect any influence of confinement on the polymer dynamics. This result is discussed in the framework of the debate on the existence of a "corset effect" recently suggested by NMR relaxometry data.

3D single point imaging with compressed sensing provides high temporal resolution R 2* mapping for in vivo preclinical applications.

PubMed

Rioux, James A; Beyea, Steven D; Bowen, Chris V

2017-02-01

Purely phase-encoded techniques such as single point imaging (SPI) are generally unsuitable for in vivo imaging due to lengthy acquisition times. Reconstruction of highly undersampled data using compressed sensing allows SPI data to be quickly obtained from animal models, enabling applications in preclinical cellular and molecular imaging. TurboSPI is a multi-echo single point technique that acquires hundreds of images with microsecond spacing, enabling high temporal resolution relaxometry of large-R 2 * systems such as iron-loaded cells. TurboSPI acquisitions can be pseudo-randomly undersampled in all three dimensions to increase artifact incoherence, and can provide prior information to improve reconstruction. We evaluated the performance of CS-TurboSPI in phantoms, a rat ex vivo, and a mouse in vivo. An algorithm for iterative reconstruction of TurboSPI relaxometry time courses does not affect image quality or R 2 * mapping in vitro at acceleration factors up to 10. Imaging ex vivo is possible at similar acceleration factors, and in vivo imaging is demonstrated at an acceleration factor of 8, such that acquisition time is under 1 h. Accelerated TurboSPI enables preclinical R 2 * mapping without loss of data quality, and may show increased specificity to iron oxide compared to other sequences.

1H NMR relaxometry and quadrupole relaxation enhancement as a sensitive probe of dynamical properties of solids—[C(NH2)3]3Bi2I9 as an example

NASA Astrophysics Data System (ADS)

Florek-Wojciechowska, M.; Wojciechowski, M.; Jakubas, R.; Brym, Sz.; Kruk, D.

2016-02-01

1H nuclear magnetic resonance relaxometry has been applied to reveal information on dynamics and structure of Gu3Bi2I9 ([Gu = C(NH2)3] denotes guanidinium cation). The data have been analyzed in terms of a theory of quadrupole relaxation enhancement, which has been extended here by including effects associated with quadrupole (14N) spin relaxation caused by a fast fluctuating component of the electric field gradient tensor. Two motional processes have been identified: a slow one occurring on a timescale of about 8 × 10-6 s which has turned out to be (almost) temperature independent, and a fast process in the range of 10-9 s. From the 1H-14N relaxation contribution (that shows "quadrupole peaks") the quadrupole parameters, which are a fingerprint of the arrangement of the anionic network, have been determined. It has been demonstrated that the magnitude of the quadrupole coupling considerably changes with temperature and the changes are not caused by phase transitions. At the same time, it has been shown that there is no evidence of abrupt changes in the cationic dynamics and the anionic substructure upon the phase transitions.

Correlation of porous and functional properties of food materials by NMR relaxometry and multivariate analysis.

PubMed

Haiduc, Adrian Marius; van Duynhoven, John

2005-02-01

The porous properties of food materials are known to determine important macroscopic parameters such as water-holding capacity and texture. In conventional approaches, understanding is built from a long process of establishing macrostructure-property relations in a rational manner. Only recently, multivariate approaches were introduced for the same purpose. The model systems used here are oil-in-water emulsions, stabilised by protein, and form complex structures, consisting of fat droplets dispersed in a porous protein phase. NMR time-domain decay curves were recorded for emulsions with varied levels of fat, protein and water. Hardness, dry matter content and water drainage were determined by classical means and analysed for correlation with the NMR data with multivariate techniques. Partial least squares can calibrate and predict these properties directly from the continuous NMR exponential decays and yields regression coefficients higher than 82%. However, the calibration coefficients themselves belong to the continuous exponential domain and do little to explain the connection between NMR data and emulsion properties. Transformation of the NMR decays into a discreet domain with non-negative least squares permits the use of multilinear regression (MLR) on the resulting amplitudes as predictors and hardness or water drainage as responses. The MLR coefficients show that hardness is highly correlated with the components that have T2 distributions of about 20 and 200 ms whereas water drainage is correlated with components that have T2 distributions around 400 and 1800 ms. These T2 distributions very likely correlate with water populations present in pores with different sizes and/or wall mobility. The results for the emulsions studied demonstrate that NMR time-domain decays can be employed to predict properties and to provide insight in the underlying microstructural features.

A diffusion model-free framework with echo time dependence for free-water elimination and brain tissue microstructure characterization.

PubMed

Molina-Romero, Miguel; Gómez, Pedro A; Sperl, Jonathan I; Czisch, Michael; Sämann, Philipp G; Jones, Derek K; Menzel, Marion I; Menze, Bjoern H

2018-03-23

The compartmental nature of brain tissue microstructure is typically studied by diffusion MRI, MR relaxometry or their correlation. Diffusion MRI relies on signal representations or biophysical models, while MR relaxometry and correlation studies are based on regularized inverse Laplace transforms (ILTs). Here we introduce a general framework for characterizing microstructure that does not depend on diffusion modeling and replaces ill-posed ILTs with blind source separation (BSS). This framework yields proton density, relaxation times, volume fractions, and signal disentanglement, allowing for separation of the free-water component. Diffusion experiments repeated for several different echo times, contain entangled diffusion and relaxation compartmental information. These can be disentangled by BSS using a physically constrained nonnegative matrix factorization. Computer simulations, phantom studies, together with repeatability and reproducibility experiments demonstrated that BSS is capable of estimating proton density, compartmental volume fractions and transversal relaxations. In vivo results proved its potential to correct for free-water contamination and to estimate tissue parameters. Formulation of the diffusion-relaxation dependence as a BSS problem introduces a new framework for studying microstructure compartmentalization, and a novel tool for free-water elimination. © 2018 International Society for Magnetic Resonance in Medicine.

Size, charge and concentration dependent uptake of iron oxide particles by non-phagocytic cells.

PubMed

Thorek, Daniel L J; Tsourkas, Andrew

2008-09-01

A promising new direction for contrast-enhanced magnetic resonance (MR) imaging involves tracking the migration and biodistribution of superparamagnetic iron oxide (SPIO)-labeled cells in vivo. Despite the large number of cell labeling studies that have been performed with SPIO particles of differing size and surface charge, it remains unclear which SPIO configuration provides optimal contrast in non-phagocytic cells. This is largely because contradictory findings have stemmed from the variability and imprecise control over surface charge, the general need and complexity of transfection and/or targeting agents, and the limited number of particle configurations examined in any given study. In the present study, we systematically evaluated the cellular uptake of SPIO in non-phagocytic T cells over a continuum of particle sizes ranging from 33nm to nearly 1.5microm, with precisely controlled surface properties, and without the need for transfection agents. SPIO labeling of T cells was analyzed by flow cytometry and contrast enhancement was determined by relaxometry. SPIO uptake was dose-dependent and exhibited sigmoidal charge dependence, which was shown to saturate at different levels of functionalization. Efficient labeling of cells was observed for particles up to 300nm, however, micron-sized particle uptake was limited. Our results show that an unconventional highly cationic particle configuration at 107nm maximized MR contrast of T cells, outperforming the widely utilized USPIO (<50nm).

Size, Charge and Concentration Dependent Uptake of Iron Oxide Particles by Non-Phagocytic Cells

PubMed Central

Thorek, Daniel L.J.; Tsourkas, Andrew

2008-01-01

A promising new direction for contrast-enhanced magnetic resonance (MR) imaging involves tracking the migration and biodistribution of superparamagnetic iron oxide (SPIO)-labeled cells in vivo. Despite the large number of cell labeling studies that have been performed with SPIO particles of differing size and surface charge, it remains unclear which SPIO configuration provides optimal contrast in non-phagocytic cells. This is largely because contradictory findings have stemmed from the variability and imprecise control over surface charge, the general need and complexity of transfection and/or targeting agents, and the limited number of particle configurations examined in any given study. In the present study, we systematically evaluated the cellular uptake of SPIO in non-phagocytic T cells over a continuum of particle sizes ranging from 33 nm to nearly 1.5 μm, with precisely controlled surface properties, and without the need for transfection agents. SPIO labeling of T cells was analyzed by flow cytometry and contrast enhancement was determined by relaxometry. SPIO uptake was dose dependent and exhibited sigmoidal charge dependence, which was shown to saturate at different levels of functionalization. Efficient labeling of cells was observed for particles up to 300nm, however micron-sized particle uptake was limited. Our results show that an unconventional highly cationic particle configuration at 107 nm maximized MR contrast of T cells, outperforming the widely utilized USPIO (<50 nm). PMID:18533252

In vivo measurements of proton relaxation times in human brain, liver, and skeletal muscle: a multicenter MRI study.

PubMed

de Certaines, J D; Henriksen, O; Spisni, A; Cortsen, M; Ring, P B

1993-01-01

Quantitative magnetic resonance imaging may offer unique potential for tissue characterization in vivo. In this connection texture analysis of quantitative MR images may be of special importance. Because evaluation of texture analysis needs large data material, multicenter approaches become mandatory. Within the frame of BME Concerted Action on Tissue Characterization by MRI and MRS, a pilot multicenter study was launched in order to evaluate the technical problems including comparability of relaxation time measurements carried out in the individual sites. Human brain, skeletal muscle, and liver were used as models. A total of 218 healthy volunteers were studied. Fifteen MRI scanners with field strength ranging from 0.08 T to 1.5 T were induced. Measurement accuracy was tested on the Eurospin relaxation time test object (TO5) and the obtained calibration curve was used for correction of the in vivo data. The results established that, by following a standardized procedure, comparable quantitative measurements can be obtained in vivo from a number of MR sites. The overall variation coefficient in vivo was in the same order of magnitude as ex vivo relaxometry. Thus, it is possible to carry out international multicenter studies on quantitative imaging, provided that quality control with respect to measurement accuracy and calibration of the MR equipments are performed.

Brain abnormalities in cognition, anxiety, and depression regulatory regions in adolescents with single ventricle heart disease.

PubMed

Pike, Nancy A; Roy, Bhaswati; Gupta, Ritika; Singh, Sadhana; Woo, Mary A; Halnon, Nancy J; Lewis, Alan B; Kumar, Rajesh

2018-06-01

Single ventricle heart disease (SVHD) adolescents show cognitive impairments and anxiety and depressive symptoms, indicating the possibility of brain injury in regions that control these functions. However, brain tissue integrity in cognition, anxiety, and depression regulatory sites in SVHD remains unclear. We examined brain tissue changes in SVHD compared to controls using T2-relaxometry procedures, which measure free water content and show tissue injury. Proton-density and T2-weighted images, using a 3.0-Tesla MRI, as well as anxiety (Beck anxiety inventory [BAI]), depressive symptoms (patient health questionnaire-9 [PHQ-9]), and cognition (wide range assessment of memory and learning 2 [WRAML2] and Montreal cognitive assessment [MoCA]) data were collected from 20 SVHD (age: 15.8 ± 1.1 years, male/female: 11/9) and 36 controls (age: 16.0 ± 1.1 years, male/female: 19/17). Whole-brain T2-relaxation maps were calculated, normalized to a common space, smoothed, and compared between groups and sexes (analysis of covariance; covariates: age, sex; p < 0.001). SVHD subjects showed significantly increased BAI and PHQ-9 and reduced MoCA and WRAML2 scores over controls. Several brain regions in SVHD showed increased T2-relaxation values (chronic injury), including the cingulate, and insula, hippocampus/para-hippocampal gyrus, thalamus, hypothalamus, amygdala, frontal white matter, corpus callosum, brainstem, and cerebellar areas. Decreased T2-relaxation values (acute injury) emerged in a few regions, including the prefrontal and cerebellar cortices in SVHD over controls. In addition, male SVHD showed more brain changes over female SVHD. Adolescents with SVHD showed significant brain injury with variable male-female differences in areas that control cognition, anxiety, and depression, which may contribute to functional deficits found in the condition. © 2018 Wiley Periodicals, Inc.

Effect of sodium bicarbonate and varying concentrations of sodium chloride in brine on the liquid retention of fish (Pollachius virens L.) muscle.

PubMed

Åsli, Magnus; Ofstad, Ragni; Böcker, Ulrike; Jessen, Flemming; Einen, Olai; Mørkøre, Turid

2016-03-15

Negative health effects associated with excessive sodium (Na) intake have increased the demand for tasty low-Na products (<2% NaCl) rather than traditional heavily salted fish products (∼20% NaCl). This study investigates the causes of improved yield and liquid retention of fish muscle brined with a combination of salt (NaCl) and sodium bicarbonate (NaHCO3 ). Water characteristics and microstructure of saithe (Pollachius virens L.) muscle brined in solutions of NaCl and NaHCO3 or NaCl alone were compared using low-field nuclear magnetic resonance (LF-NMR) T2 relaxometry, microscopy, salt content, liquid retention and colorimetric measurements. Saithe muscle was brined for 92 h in 0, 30, 60, 120 or 240 g kg(-1) NaCl or the respective solutions with added 7.5 g kg(-1) NaHCO3 . NaHCO3 inclusion improved the yield in solutions ranging from 0 to 120 g kg(-1) NaCl, with the most pronounced effect being observed at 30 g kg(-1) NaCl. The changes in yield were reflected in water mobility, with significantly shorter T2 relaxation times in all corresponding brine concentrations. Salt-dependent microstructural changes were revealed by light microscopy, where NaHCO3 supplementation resulted in greater intracellular space at 30 and 60 g kg(-1) NaCl. Sodium bicarbonate addition to low-salt solutions can improve yield and flesh quality of fish muscle owing to altered water mobility and wider space between the muscle cells. © 2015 Society of Chemical Industry.

In situ nuclear magnetic resonance microimaging of live biofilms in a microchannel

DOE Office of Scientific and Technical Information (OSTI.GOV)

Renslow, R. S.; Marshall, M. J.; Tucker, A. E.

Nuclear magnetic resonance (NMR) microimaging and spectroscopy was used to interrogate fluids of biological importance (e.g., water, buffer, medium solution) and live biofilms in a microchannel compatible for analyses at ambient pressure and under vacuum. Studies using buffer, growth medium, and actively growing Shewanella oneidensis biofilms were used to demonstrate in situ NMR microimaging measurement capabilities including velocity mapping, diffusion coefficient mapping, relaxometry, localized spectroscopy, and 2D and 3D imaging within a microchannel suitable for different analytical platforms. This technique is promising for diverse applications of correlative imaging using a portable microfluidic platform.

{sup 1}H NMR relaxometry and quadrupole relaxation enhancement as a sensitive probe of dynamical properties of solids—[C(NH{sub 2}){sub 3}]{sub 3}Bi{sub 2}I{sub 9} as an example

DOE Office of Scientific and Technical Information (OSTI.GOV)

Florek-Wojciechowska, M.; Wojciechowski, M.; Brym, Sz.

{sup 1}H nuclear magnetic resonance relaxometry has been applied to reveal information on dynamics and structure of Gu{sub 3}Bi{sub 2}I{sub 9} ([Gu = C(NH{sub 2}){sub 3}] denotes guanidinium cation). The data have been analyzed in terms of a theory of quadrupole relaxation enhancement, which has been extended here by including effects associated with quadrupole ({sup 14}N) spin relaxation caused by a fast fluctuating component of the electric field gradient tensor. Two motional processes have been identified: a slow one occurring on a timescale of about 8 × 10{sup −6} s which has turned out to be (almost) temperature independent, andmore » a fast process in the range of 10{sup −9} s. From the {sup 1}H-{sup 14}N relaxation contribution (that shows “quadrupole peaks”) the quadrupole parameters, which are a fingerprint of the arrangement of the anionic network, have been determined. It has been demonstrated that the magnitude of the quadrupole coupling considerably changes with temperature and the changes are not caused by phase transitions. At the same time, it has been shown that there is no evidence of abrupt changes in the cationic dynamics and the anionic substructure upon the phase transitions.« less

Continuously manufactured magnetic polymersomes - a versatile tool (not only) for targeted cancer therapy

NASA Astrophysics Data System (ADS)

Bleul, Regina; Thiermann, Raphael; Marten, Gernot U.; House, Michael J.; Pierre, Timothy G. St.; Häfeli, Urs O.; Maskos, Michael

2013-11-01

Micromixer technology was used to prepare polymeric vesicles (Pluronic® L-121) dual loaded with the anti-cancer drug camptothecin and magnetic nanoparticles. Successful incorporation of the magnetic nanoparticles was confirmed by transmission electron microscopy. Dynamic light scattering measurements showed a relatively narrow size distribution of the hybrid polymersomes. Camptothecin polymersomes reduced the cell viability of prostate cancer cells (PC-3) measured after 72 h significantly, while drug-free polymersomes showed no cytotoxic effects. Covalent attachment of a cancer targeting peptide (bombesin) as well as a fluorescent label (Alexa Fluor® 647) to the hybrid polymersomes was performed and specific cell binding and internalization were shown by flow cytometry and confocal microscopy. Relaxometry measurements clearly demonstrated the capacity of magnetic polymersomes to generate significant T2-weighted MRI contrast and potentially allow for direct monitoring of the biodistribution of the polymersomes. Micromixer technology as an easy, fast and efficient way to manufacture hybrid polymersomes as theranostic drug delivery devices is a further step from basic research to personalized medicine.

Monitoring early tumor response to drug therapy with diffuse optical tomography

NASA Astrophysics Data System (ADS)

Flexman, Molly L.; Vlachos, Fotios; Kim, Hyun Keol; Sirsi, Shashank R.; Huang, Jianzhong; Hernandez, Sonia L.; Johung, Tessa B.; Gander, Jeffrey W.; Reichstein, Ari R.; Lampl, Brooke S.; Wang, Antai; Borden, Mark A.; Yamashiro, Darrell J.; Kandel, Jessica J.; Hielscher, Andreas H.

2012-01-01

Although anti-angiogenic agents have shown promise as cancer therapeutics, their efficacy varies between tumor types and individual patients. Providing patient-specific metrics through rapid noninvasive imaging can help tailor drug treatment by optimizing dosages, timing of drug cycles, and duration of therapy--thereby reducing toxicity and cost and improving patient outcome. Diffuse optical tomography (DOT) is a noninvasive three-dimensional imaging modality that has been shown to capture physiologic changes in tumors through visualization of oxygenated, deoxygenated, and total hemoglobin concentrations, using non-ionizing radiation with near-infrared light. We employed a small animal model to ascertain if tumor response to bevacizumab (BV), an anti-angiogenic agent that targets vascular endothelial growth factor (VEGF), could be detected at early time points using DOT. We detected a significant decrease in total hemoglobin levels as soon as one day after BV treatment in responder xenograft tumors (SK-NEP-1), but not in SK-NEP-1 control tumors or in non-responder control or BV-treated NGP tumors. These results are confirmed by magnetic resonance imaging T2 relaxometry and lectin perfusion studies. Noninvasive DOT imaging may allow for earlier and more effective control of anti-angiogenic therapy.

In vivo field-cycling relaxometry using an insert coil for magnetic field offset.

PubMed

Pine, Kerrin J; Goldie, Fred; Lurie, David J

2014-11-01

The T(1) of tissue has a strong dependence on the measurement magnetic field strength. T(1) -dispersion could be a useful contrast parameter, but is unavailable to clinical MR systems which operate at fixed magnetic field strength. The purpose of this work was to implement a removable insert magnet coil for field-cycling T(1) -dispersion measurements on a vertical-field MRI scanner, by offsetting the static field over a volume of interest. An insert magnet coil was constructed for use with a whole-body sized 59 milli-Tesla (mT) vertical-field, permanent-magnet based imager. The coil has diameter 38 cm and thickness 6.1 cm and a homogeneous region (± 5%) of 5 cm DSV, offset by 5 cm from the coil surface. Surface radiofrequency (RF) coils were also constructed. The insert coil was used in conjunction with a surface RF coil and a volume-localized inversion-recovery pulse sequence to plot T(1) -dispersion in a human volunteer's forearm over a range of field strengths from 1 mT to 70 mT. T(1) -dispersion measurements were demonstrated on a fixed-field MRI scanner, using an insert coil. This demonstrates the feasibility of relaxation dispersion measurements on an otherwise conventional MR imager, facilitating the exploitation of T(1) -dispersion contrast for enhanced diagnosis. Copyright © 2013 Wiley Periodicals, Inc.

R1 dispersion contrast at high field with fast field-cycling MRI.

PubMed

Bödenler, Markus; Basini, Martina; Casula, Maria Francesca; Umut, Evrim; Gösweiner, Christian; Petrovic, Andreas; Kruk, Danuta; Scharfetter, Hermann

2018-05-01

Contrast agents with a strong R 1 dispersion have been shown to be effective in generating target-specific contrast in MRI. The utilization of this R 1 field dependence requires the adaptation of an MRI scanner for fast field-cycling (FFC). Here, we present the first implementation and validation of FFC-MRI at a clinical field strength of 3 T. A field-cycling range of ±100 mT around the nominal B 0 field was realized by inserting an additional insert coil into an otherwise conventional MRI system. System validation was successfully performed with selected iron oxide magnetic nanoparticles and comparison to FFC-NMR relaxometry measurements. Furthermore, we show proof-of-principle R 1 dispersion imaging and demonstrate the capability of generating R 1 dispersion contrast at high field with suppressed background signal. With the presented ready-to-use hardware setup it is possible to investigate MRI contrast agents with a strong R 1 dispersion at a field strength of 3 T. Copyright © 2018 Elsevier Inc. All rights reserved.

Biodegradable Magnetic Particles for Cellular MRI

NASA Astrophysics Data System (ADS)

Nkansah, Michael Kwasi

Cell transplantation has the potential to treat numerous diseases and injuries. While magnetic particle-enabled, MRI-based cell tracking has proven useful for visualizing the location of cell transplants in vivo, current formulations of particles are either too weak to enable single cell detection or have non-degradable polymer matrices that preclude clinical translation. Furthermore, the off-label use of commercial agents like Feridex®, Bangs beads and ferumoxytol for cell tracking significantly stunts progress in the field, rendering it needlessly susceptible to market externalities. The recent phasing out of Feridex from the market, for example, heightens the need for a dedicated agent specifically designed for MRI-based cell tracking. To this end, we engineered clinically viable, biodegradable particles of iron oxide made using poly(lactide-co-glycolide) (PLGA) and demonstrated their utility in two MRI-based cell tracking paradigms in vivo. Both micro- and nanoparticles (2.1±1.1 μm and 105±37 nm in size) were highly magnetic (56.7-83.7 wt% magnetite), and possessed excellent relaxometry (r2* relaxivities as high as 614.1 s-1mM-1 and 659.1 s -1mM-1 at 4.7 T respectively). Magnetic PLGA micropartides enabled the in vivo monitoring of neural progenitor cell migration to the olfactory bulb in rat brains over 2 weeks at 11.7 T with ˜2-fold greater contrast-to-noise ratio and ˜4-fold better sensitivity at detecting migrated cells in the olfactory bulb than Bangs beads. Highly magnetic PLGA nanoparticles enabled MRI detection (at 11.7 T) of up to 10 rat mesenchymal cells transplanted into rat brain at 100-μm resolution. Highly magnetic PLGA particles were also shown to degrade by 80% in mice liver over 12 weeks in vivo. Moreover, no adverse effects were observed on cellular viability and function in vitro after labeling a wide range of cells. Magnetically labeled rat mesenchymal and neural stem cells retained their ability to differentiate into multiple lineages. Particle-labeled bone marrow-derived mouse macrophages exhibited little to no immune response to particles and were still capable of normal TNF-α and IL-6 release upon stimulation by lipopolysaccharide. Minimal generation of reactive oxygen species was observed in mouse macrophages and embryonic fibroblasts labeled with particles. In addition, magnetic particles of cellulose and chitin (69.6 wt% and 52 wt% magnetite) were fabricated as more bioresponsive agents that could potentially relay richer information on cellular fate in vivo and enable sophisticated immunocellular investigations via MRI. Magnetic cellulose particles showed a 63% increase in r2 relaxivity and 15% increase in r2* relaxivity upon degradation by cellulase in vitro, consistent with theoretical predictions of relaxometry in the static dephasing regime for a particle of reduced size. Magnetofluorescent chitin nanoparticles efficiently labeled rat peripheral blood monocytes in vitro (72% labeling efficiency) with little adverse effect on viability (92% viability). This thesis describes the first clinically translatable agent specifically designed for MRI-based cell tracking with immediate implications for preclinical investigations in (stem) cell therapy.

Laplace Inversion of Low-Resolution NMR Relaxometry Data Using Sparse Representation Methods

PubMed Central

Berman, Paula; Levi, Ofer; Parmet, Yisrael; Saunders, Michael; Wiesman, Zeev

2013-01-01

Low-resolution nuclear magnetic resonance (LR-NMR) relaxometry is a powerful tool that can be harnessed for characterizing constituents in complex materials. Conversion of the relaxation signal into a continuous distribution of relaxation components is an ill-posed inverse Laplace transform problem. The most common numerical method implemented today for dealing with this kind of problem is based on L2-norm regularization. However, sparse representation methods via L1 regularization and convex optimization are a relatively new approach for effective analysis and processing of digital images and signals. In this article, a numerical optimization method for analyzing LR-NMR data by including non-negativity constraints and L1 regularization and by applying a convex optimization solver PDCO, a primal-dual interior method for convex objectives, that allows general linear constraints to be treated as linear operators is presented. The integrated approach includes validation of analyses by simulations, testing repeatability of experiments, and validation of the model and its statistical assumptions. The proposed method provides better resolved and more accurate solutions when compared with those suggested by existing tools. © 2013 Wiley Periodicals, Inc. Concepts Magn Reson Part A 42A: 72–88, 2013. PMID:23847452

Laplace Inversion of Low-Resolution NMR Relaxometry Data Using Sparse Representation Methods.

PubMed

Berman, Paula; Levi, Ofer; Parmet, Yisrael; Saunders, Michael; Wiesman, Zeev

2013-05-01

Low-resolution nuclear magnetic resonance (LR-NMR) relaxometry is a powerful tool that can be harnessed for characterizing constituents in complex materials. Conversion of the relaxation signal into a continuous distribution of relaxation components is an ill-posed inverse Laplace transform problem. The most common numerical method implemented today for dealing with this kind of problem is based on L 2 -norm regularization. However, sparse representation methods via L 1 regularization and convex optimization are a relatively new approach for effective analysis and processing of digital images and signals. In this article, a numerical optimization method for analyzing LR-NMR data by including non-negativity constraints and L 1 regularization and by applying a convex optimization solver PDCO, a primal-dual interior method for convex objectives, that allows general linear constraints to be treated as linear operators is presented. The integrated approach includes validation of analyses by simulations, testing repeatability of experiments, and validation of the model and its statistical assumptions. The proposed method provides better resolved and more accurate solutions when compared with those suggested by existing tools. © 2013 Wiley Periodicals, Inc. Concepts Magn Reson Part A 42A: 72-88, 2013.

Targeting experimental orthotopic glioblastoma with chitosan-based superparamagnetic iron oxide nanoparticles (CS-DX-SPIONs).

PubMed

Shevtsov, Maxim; Nikolaev, Boris; Marchenko, Yaroslav; Yakovleva, Ludmila; Skvortsov, Nikita; Mazur, Anton; Tolstoy, Peter; Ryzhov, Vyacheslav; Multhoff, Gabriele

2018-01-01

Glioblastoma is the most devastating primary brain tumor of the central nervous system in adults. Magnetic nanocarriers may help not only for a targeted delivery of chemotherapeutic agents into the tumor site but also provide contrast enhancing properties for diagnostics using magnetic resonance imaging (MRI). Synthesized hybrid chitosan-dextran superparamagnetic nanoparticles (CS-DX-SPIONs) were characterized using transmission electron microscopy (TEM) and relaxometry studies. Nonlinear magnetic response measurements were employed for confirming the superparamagnetic state of particles. Following in vitro analysis of nanoparticles cellular uptake tumor targeting was assessed in the model of the orthotopic glioma in rodents. CS-DX-SPIONs nanoparticles showed a uniform diameter of 55 nm under TEM and superparamagentic characteristics as determined by T 1 (spin-lattice relaxation time) and T 2 (spin-spin relaxation time) proton relaxation times. Application of the chitosan increased the charge from +8.9 to +19.3 mV of the dextran-based SPIONs. The nonlinear magnetic response at second harmonic of CS-DX-SPIONs following the slow change of stationary magnetic fields with very low hysteresis evidenced superparamagnetic state of particles at ambient temperatures. Confocal microscopy and flow cytometry studies showed an enhanced internalization of the chitosan-based nanoparticles in U87, C6 glioma and HeLa cells as compared to dextran-coated particles. Cytotoxicity assay demonstrated acceptable toxicity profile of the synthesized nanoparticles up to a concentration of 10 μg/ml. Intravenously administered CS-DX-SPIONs in orthotopic C6 gliomas in rats accumulated in the tumor site as shown by high-resolution MRI (11.0 T). Retention of nanoparticles resulted in a significant contrast enhancement of the tumor image that was accompanied with a dramatic drop in T 2 values ( P <0.001). Subsequent histological studies proved the accumulation of the nanoparticles inside glioblastoma cells. Hybrid chitosan-dextran magnetic particles demonstrated high MR contrast enhancing properties for the delineation of the brain tumor. Due to a significant retention of the particles in the tumor an application of the CS-DX-SPIONs could not only improve the tumor imaging but also could allow a targeted delivery of chemotherapeutic agents.

Relation of short-range and long-range lithium ion dynamics in glass-ceramics: Insights from 7Li NMR field-cycling and field-gradient studies

NASA Astrophysics Data System (ADS)

Haaks, Michael; Martin, Steve W.; Vogel, Michael

2017-09-01

We use various 7Li NMR methods to investigate lithium ion dynamics in 70Li 2S-30 P 2S5 glass and glass-ceramic obtained from this glass after heat treatment. We employ 7Li spin-lattice relaxometry, including field-cycling measurements, and line-shape analysis to investigate short-range ion jumps as well as 7Li field-gradient approaches to characterize long-range ion diffusion. The results show that ceramization substantially enhances the lithium ion mobility on all length scales. For the 70Li 2S-30 P 2S5 glass-ceramic, no evidence is found that bimodal dynamics result from different ion mobilities in glassy and crystalline regions of this sample. Rather, 7Li field-cycling relaxometry shows that dynamic susceptibilities in broad frequency and temperature ranges can be described by thermally activated jumps governed by a Gaussian distribution of activation energies g (Ea) with temperature-independent mean value Em=0.43 eV and standard deviation σ =0.07 eV . Moreover, use of this distribution allows us to rationalize 7Li line-shape results for the local ion jumps. In addition, this information about short-range ion dynamics further explains 7Li field-gradient results for long-range ion diffusion. In particular, we quantitatively show that, consistent with our experimental results, the temperature dependence of the self-diffusion coefficient D is not described by the mean activation energy Em of the local ion jumps, but by a significantly smaller apparent value whenever the distribution of correlation times G (logτ ) of the jump motion derives from an invariant distribution of activation energies and, hence, continuously broadens upon cooling. This effect occurs because the harmonic mean, which determines the results of diffusivity or also conductivity studies, continuously separates from the peak position of G (logτ ) when the width of this distribution increases.

Magnetic colloidal superparticles of Co, Mn and Ni ferrite featured with comb-type and/or linear amphiphilic polyelectrolytes; NMR and MRI relaxometry.

PubMed

Menelaou, Melita; Iatridi, Zacharoula; Tsougos, Ioannis; Vasiou, Katerina; Dendrinou-Samara, Catherine; Bokias, Georgios

2015-06-28

The ability to encapsulate hydrophobic ferrites in colloidal superparticle structures of an a-telechelic hexadecyl-functionalized poly(methacrylic acid) (C16H33-PMAA) polymer with a linear architecture was investigated and compared with that of two amphiphilic comb-type water-soluble copolymers, namely, P(ANa-co-DAAm) and P(MANa-co-DMA), which are comprised of a poly(sodium acrylate) or poly(sodium methacrylate) backbone and pendent dodecyl acrylamide or dodecyl methacrylate chains, respectively. In the case of C16H33-PMAA, the pH-sensitive self-assembly behavior, which was studied through Nile Red probing and TEM, was related to its encapsulation properties. Hydrophobic MFe2O4 nanoparticles coated with oleylamine (MFe2O4@OAm MNPs, where M = Co, Mn, Ni) with a similar shape and size (∼9 nm) and magnetization values of 87.4, 63.1 and 55.0 emu g(-1) for CoFe2O4@OAm, MnFe2O4@OAm and NiFe2O4@OAm, respectively, were successfully encapsulated into the hydrophobic cores of spherical micellar structures formed by the copolymers in an aqueous solution through a solvent mixing procedure. The synthesized magnetic colloidal superparticles fell in the static dephasing regime (SDR). NMR relaxivity measurements of MFe2O4@P(ANa-co-DAAm), MFe2O4@P(MANa-co-DMA) and MFe2O4@C16H33-PMAA at pH = 4.5 and pH = 7 (where M = Co, Mn, Ni) at 11.7 T were recorded and the transverse relaxivity (r2) (mM(-1) s(-1)) was determined. Among all, the CoFe2O4@polymers demonstrated the highest r2 relaxivity values, ranging from 61.6 for CoFe2O4@C16H33-PMAA (pH = 7) to 316.0 mM(-1) s(-1) for CoFe2O4@P(ANa-co-DAAm). The relaxation efficiency (r1 and r2) of CoFe2O4@P(ANa-co-DAAm) was investigated further by magnetic resonance imaging (MRI) at 1.5 T and 3 T and the r2/r1 ratios were found to be 16.5 and 18.2, respectively, indicating its potential use as a T2 contrast agent.

Amplified Sensitivity of Nitrogen-Vacancy Spins in Nanodiamonds Using All-Optical Charge Readout.

PubMed

Hopper, David A; Grote, Richard R; Parks, Samuel M; Bassett, Lee C

2018-04-23

Nanodiamonds containing nitrogen-vacancy (NV) centers offer a versatile platform for sensing applications spanning from nanomagnetism to in vivo monitoring of cellular processes. In many cases, however, weak optical signals and poor contrast demand long acquisition times that prevent the measurement of environmental dynamics. Here, we demonstrate the ability to perform fast, high-contrast optical measurements of charge distributions in ensembles of NV centers in nanodiamonds and use the technique to improve the spin-readout signal-to-noise ratio through spin-to-charge conversion. A study of 38 nanodiamonds with sizes ranging between 20 and 70 nm, each hosting a small ensemble of NV centers, uncovers complex, multiple time scale dynamics due to radiative and nonradiative ionization and recombination processes. Nonetheless, the NV-containing nanodiamonds universally exhibit charge-dependent photoluminescence contrasts and the potential for enhanced spin readout using spin-to-charge conversion. We use the technique to speed up a T 1 relaxometry measurement by a factor of 5.

Lanthanide chelates of (bis)-hydroxymethyl-substituted DTTA with potential application as contrast agents in magnetic resonance imaging.

PubMed

Silvério, Sara; Torres, Susana; Martins, André F; Martins, José A; André, João P; Helm, Lothar; Prata, M Isabel M; Santos, Ana C; Geraldes, Carlos F G C

2009-06-28

A novel bis-hydroxymethyl-substituted DTTA chelator N'-Bz-C(4,4')-(CH(2)OH)(2)-DTTA () and its DTPA analogue C(4,4')-(CH(2)OH)(2)-DTPA () were synthesized and characterized. A variable-temperature (1)H NMR spectroscopy study of the solution dynamics of their diamagnetic (La) and paramagnetic (Sm, Eu) Ln(3+) complexes showed them to be rigid when compared with analogous Ln(3+)-DTTA and Ln(3+)-DTPA complexes, as a result of their C(4,4')-(CH(2)OH)(2) ligand backbone substitution. The parameters that govern the water (1)H relaxivity of the [Gd()(H(2)O)(2)](-) and [Gd()(H(2)O)](2-) complexes were obtained by (17)O and (1)H NMR relaxometry. While the relaxometric behaviour of the [Gd()(H(2)O)](2-) complex is very similar to the parent [Gd(DTPA)(H(2)O)](2-) system, the [Gd()(H(2)O)(2)](-) complex displays higher relaxivity, due to the presence of two inner sphere water molecules and an accelerated, near optimal water exchange rate. The [Gd()(H(2)O)(2)](-) complex interacts weakly with human serum albumin (HSA), and its fully bound relaxivity is limited by slow water exchange, as monitored by (1)H NMR relaxometry. This complex interacts weakly with phosphate, but does not form ternary complexes with bidentate bicarbonate and l-lactate anions, indicating that the two inner-sphere water molecules of the [Gd()(H(2)O)(2)](-) complex are not located in adjacent positions in the coordination sphere of the Gd(3+) ion. The transmetallation reaction rate of [Gd()(H(2)O)(2)](-) with Zn(2+) in phosphate buffer solution (pH 7.0) was measured to be similar to that of the backbone unsubstituted [Gd(DTTA-Me)(H(2)O)(2)](-), but twice faster than for [Gd(DTPA-BMA)(H(2)O)]. The in vivo biodistribution studies of the (153)Sm(3+)-labelled ligand () in Wistar rats reveal slow blood elimination and short term fixation in various organs, indicating some dissociation. The bis-hydroxymethyl-substituted DTTA skeleton can be seen as a new lead for the synthesis of high relaxivity contrast agents, although its low thermodynamic and kinetic stability will limit its use to in vitro and animal studies.

Determinants of iron accumulation in the normal aging brain.

PubMed

Pirpamer, Lukas; Hofer, Edith; Gesierich, Benno; De Guio, François; Freudenberger, Paul; Seiler, Stephan; Duering, Marco; Jouvent, Eric; Duchesnay, Edouard; Dichgans, Martin; Ropele, Stefan; Schmidt, Reinhold

2016-07-01

In a recent postmortem study, R2* relaxometry in gray matter (GM) of the brain has been validated as a noninvasive measure for iron content in brain tissue. Iron accumulation in the normal aging brain is a common finding and relates to brain maturation and degeneration. The goal of this study was to assess the determinants of iron accumulation during brain aging. The study cohort consisted of 314 healthy community-dwelling participants of the Austrian Stroke Prevention Study. Their age ranged from 38-82 years. Quantitative magnetic resonance imaging was performed on 3T and included R2* mapping, based on a 3D multi-echo gradient echo sequence. The median of R2* values was measured in all GM regions, which were segmented automatically using FreeSurfer. We investigated 25 possible determinants for cerebral iron deposition. These included demographics, brain volume, lifestyle factors, cerebrovascular risk factors, serum levels of iron, and single nucleotide polymorphisms related to iron regulating genes (rs1800562, rs3811647, rs1799945, and rs1049296). The body mass index (BMI) was significantly related to R2* in 15/32 analyzed brain regions with the strongest correlations found in the amygdala (p = 0.0091), medial temporal lobe (p = 0.0002), and hippocampus (p ≤ 0.0001). Further associations to R2* values were found in deep GM for age and smoking. No significant associations were found for gender, GM volume, serum levels of iron, or iron-associated genetic polymorphisms. In conclusion, besides age, the BMI and smoking are the only significant determinants of brain iron accumulation in normally aging subjects. Smoking relates to iron deposition in the basal ganglia, whereas higher BMI is associated with iron content in the neocortex following an Alzheimer-like distribution. Copyright © 2016 Elsevier Inc. All rights reserved.

Gd2O3 nanoparticles stabilized by hydrothermally modified dextrose for positive contrast magnetic resonance imaging

NASA Astrophysics Data System (ADS)

Babić-Stojić, Branka; Jokanović, Vukoman; Milivojević, Dušan; Požek, Miroslav; Jagličić, Zvonko; Makovec, Darko; Arsikin, Katarina; Paunović, Verica

2016-04-01

Gd2O3 nanoparticles of a few nm in size and their agglomerates dispersed in dextrose derived polymer template were synthesized by hydrothermal treatment. The produced nanosized material was investigated by TEM, FTIR spectroscopy, SQUID measurements and NMR relaxometry. Biological evaluation of this material was done by crystal violet and MTT assays to determine the cell viability. Longitudinal and transverse NMR relaxivities of water diluted Gd2O3 nanoparticle dispersions measured at the magnetic field of 1.5 T, estimated to be r1(Gd2O3)=9.6 s-1 mM-1 in the Gd concentration range 0.1-30 mM and r2(Gd2O3)=17.7 s-1 mM-1 in the lower concentration range 0.1-0.8 mM, are significantly higher than the corresponding relaxivities measured for the standard contrast agent r1(Gd-DTPA)=4.1 s-1 mM-1 and r2(Gd-DTPA)=5.1 s-1 mM-1. The ratio of the two relaxivities for Gd2O3 nanoparticles r2/r1=1.8 is suitable for T1-weighted imaging. Good MRI signal intensities of the water diluted Gd2O3 nanoparticle dispersions were recorded at lower Gd concentrations 0.2-0.8 mM. The Gd2O3 samples did not exert any significant cytotoxic effects at Gd concentrations of 0.2 mM and below. These properties of the produced Gd2O3 nanoparticles in hydrothermally modified dextrose make them promising for potential application in MRI for the design of a positive MRI contrast agent.

Correlations of low-field NMR and variable-field NMR parameters with osteoarthritis in human articular cartilage under load.

PubMed

Rössler, Erik; Mattea, Carlos; Saarakkala, Simo; Lehenkari, Petri; Finnilä, Mikko; Rieppo, Lassi; Karhula, Sakari; Nieminen, Miika T; Stapf, Siegfried

2017-08-01

NMR experiments carried out at magnetic fields below 1 T provide new relaxation parameters unavailable with conventional clinical scanners. Contrast of T 1 generally becomes larger towards low fields, as slow molecular reorientation processes dominate relaxation at the corresponding Larmor frequencies. This advantage has to be considered in the context of lower sensitivity and frequently reduced spatial resolution. The layered structure of cartilage is one example where a particularly strong variation of T 1 across the tissue occurs, being affected by degenerative diseases such as osteoarthritis (OA). Furthermore, the presence of 1 H- 14  N cross-relaxation, leading to so-called quadrupolar dips in the 1 H relaxation time dispersion, provide insight into the concentration and mobility of proteoglycans and collagen in cartilage, both being affected by OA. In this study, low-field imaging and variable-field NMR relaxometry were combined for the first time for tissue samples, employing unidirectional load to probe the mechanical properties. 20 human knee cartilage samples were placed in a compression cell, and studied by determining relaxation profiles without and with applied pressure (0.6 MPa) at 50 μm in-plane resolution, and comparing with volume-averaged T 1 dispersion. Samples were subsequently stored in formalin, prepared for histology and graded according to the Mankin score system. Quadrupolar dips and thickness change under load showed the strongest correlation with Mankin grade. Average T 1 and change of maximum T 1 under load, as well as its position, correlate with thickness and thickness change. Furthermore, T 1 (ω) above 25 mT was found to correlate with thickness change. While volume-averaged T 1 is not a suitable indicator for OA, its change due to mechanical load and its extreme values are suggested as biomarkers available in low-field MRI systems. The shape of the dispersion T 1 (ω) represents a promising access to understanding and quantifying molecular dynamics in tissue, pointing toward future in vivo tissue studies. Copyright © 2017 John Wiley & Sons, Ltd.

Dynamics of water solutions of natural polysaccharides by fast field cycling nmr relaxometry

NASA Astrophysics Data System (ADS)

Prusova, Alena; Conte, Pellegrino; Kucerik, Jiri; de Pasquale, Claudio; Alonzo, Giuseppe

2010-05-01

Cryobiology studies the effect of low temperatures on living systems such as microorganisms and plants. In particular, plants growing in cold or frozen environments can survive such extreme conditions due to the cold hardening process. Hardening is a three step process during which, first, translocation of polysaccharides to the plant roots affects water structure in the cell-soil surface. For this reason, increase of cell-membrane permeability and resistance to temperatures from -5°C to -10°C is achieved. In a second step, chemical alteration of cell membrane arises and resistance to temperatures up to -20°C is obtained. The last hardening step consists in the vitrification of the plant tissues which allow plants to survive at temperatures as low as -50°C. Since polysaccharides play a very important role in the initial part of the cold hardening process, it is of paramount importance to study the effect of such natural biopolymers on water structure. Here, we present preliminary data obtained by fast field cycling NMR relaxometry on the effect of hyaluronan (an anionic, non-sulfated glycosaminoglycan) on water structure at different concentrations of the polysaccharide. Although hyaluronan is a polysaccharide found exceptionally in animal, human or bacterial bodies, in the present work it was used as a model "pilot" compound. In fact, it has an unique ability to hold water and it contains both polysaccharide and protein-like acetamido functionalities. For this reason, hyaluronan promotes the future research on other plant biopolymers such as, for instance, starch and other very specific proteins. Results revealed that different water-structure systems surround the molecule of hyaluronan in diluted and semidiluted systems. Namely, at the lowest hyaluronan concentration, three hydration shells can be recognized. The first hydration shell is made by bound water (BW) which is strongly fixed to the hyaluronan surface mainly through electrostatic interactions. A second hydration shell contains water molecules, also recognized as partly-bound (PBW), which are not directly interacting with the hyaluronan chains but with BW. Finally, water molecules, which dynamics is resembling that of the pure and undisturbed water, are indicated either as a bulk water or free water (FW). As hyaluronan concentration is increased the third FW hydration shell is lost and all water molecules are affected by the presence of hyaluronan molecules. This work showed the great potential of FFC-NMR relaxometry in revealing water nature in polysaccharide solutions and the possibility for future applications on complex biological systems. Acknowledgements A.P. gratefully acknowledges a bilateral Erasmus project between Brno University of Technology and University of Palermo which provided grant sustainment for working in Italy. Ministry of Education of the Czech Republic, project MSM 0021630501 is also acknwledged. This work was partially funded by Ce.R.T.A. s.c.r.l. (Centri Regionali per le Tecnologie Alimentari; Italy). Authors kindly acknowledge Dr. Vladimír Velebný (CPN company, Dolní Dobrouč, Czech Republic) for providing of hyaluronan sample.

Non-cooperative immobilization of residual water bound in lyophilized photosynthetic lamellae.

PubMed

Harańczyk, Hubert; Baran, Ewelina; Nowak, Piotr; Florek-Wojciechowska, Małgorzata; Leja, Anna; Zalitacz, Dorota; Strzałka, Kazimierz

2015-12-01

This study applied 1H-NMR in time and in frequency domain measurements to monitor the changes that occur in bound water dynamics at decreased temperature and with increased hydration level in lyophilizates of native wheat photosynthetic lamellae and in photosynthetic lamellae reconstituted from lyophilizate. Proton relaxometry (measured as free induction decay = FID) distinguishes a Gaussian component S within the NMR signal (o). This comes from protons of the solid matrix of the lamellae and consists of (i) an exponentially decaying contribution L1 from mobile membrane protons, presumably from lipids, and from water that is tightly bound to the membrane surface and thus restricted in mobility; and (ii) an exponentially decaying component L2 from more mobile, loosely bound water pool. Both proton relaxometry data and proton spectroscopy show that dry lyophilizate incubated in dry air, i.e., at a relative humidity (p/p0) of 0% reveals a relatively high hydration level. The observed liquid signal most likely originates from mobile membrane protons and a tightly bound water fraction that is sealed in pores of dry lyophilizate and thus restricted in mobility. The estimations suggest that the amount of sealed water does not exceed the value characteristic for the main hydration shell of a phospholipid. Proton spectra collected for dry lyophilizate of photosynthetic lamellae show a continuous decrease in the liquid signal component without a distinct freezing transition when it is cooled down to -60ºC, which is significantly lower than the homogeneous ice nucleation temperature [Bronshteyn, V.L. et al. Biophys. J. 65 (1993) 1853].

Abnormal white matter properties in adolescent girls with anorexia nervosa

PubMed Central

Travis, Katherine E.; Golden, Neville H.; Feldman, Heidi M.; Solomon, Murray; Nguyen, Jenny; Mezer, Aviv; Yeatman, Jason D.; Dougherty, Robert F.

2015-01-01

Anorexia nervosa (AN) is a serious eating disorder that typically emerges during adolescence and occurs most frequently in females. To date, very few studies have investigated the possible impact of AN on white matter tissue properties during adolescence, when white matter is still developing. The present study evaluated white matter tissue properties in adolescent girls with AN using diffusion MRI with tractography and T1 relaxometry to measure R1 (1/T1), an index of myelin content. Fifteen adolescent girls with AN (mean age = 16.6 years ± 1.4) were compared to fifteen age-matched girls with normal weight and eating behaviors (mean age = 17.1 years ± 1.3). We identified and segmented 9 bilateral cerebral tracts (18) and 8 callosal fiber tracts in each participant's brain (26 total). Tract profiles were generated by computing measures for fractional anisotropy (FA) and R1 along the trajectory of each tract. Compared to controls, FA in the AN group was significantly decreased in 4 of 26 white matter tracts and significantly increased in 2 of 26 white matter tracts. R1 was significantly decreased in the AN group compared to controls in 11 of 26 white matter tracts. Reduced FA in combination with reduced R1 suggests that the observed white matter differences in AN are likely due to reductions in myelin content. For the majority of tracts, group differences in FA and R1 did not occur within the same tract. The present findings have important implications for understanding the neurobiological factors underlying white matter changes associated with AN and invite further investigations examining associations between white matter properties and specific physiological, cognitive, social, or emotional functions affected in AN. PMID:26740918

Application of Solid-State NMR Relaxometry for Characterization and Formulation Optimization of Grinding-Induced Drug Nanoparticle.

PubMed

Ueda, Keisuke; Higashi, Kenjirou; Moribe, Kunikazu

2016-03-07

The formation mechanism of drug nanoparticles was investigated using solid-state nuclear magnetic resonance (NMR) techniques for the efficient discovery of an optimized nanoparticle formulation. The cogrinding of nifedipine (NIF) with polymers, including hydroxypropyl methylcellulose (HPMC) and polyvinylpyrrolidone (PVP), and sodium dodecyl sulfate (SDS) was performed to prepare the NIF nanoparticle formulations. Then, solid-state NMR relaxometry was used for the nanometer-order characterization of NIF in the polymer matrix. Solid-state NMR measurements revealed that the crystal size of NIF was reduced to several tens of nanometers with amorphization of NIF by cogrinding with HPMC and SDS for 100 min. Similarly, the size of the NIF crystal was reduced to less than 90 nm in the 40 min ground mixture of NIF/PVP/SDS. Furthermore, 100 min grinding of NIF/PVP/SDS induced amorphization of almost all the NIF crystals followed by nanosizing. The hydrogen bond between NIF and PVP led to the efficient amorphization of NIF in the NIF/PVP/SDS system compared with NIF/HPMC/SDS system. The efficient nanosizing of the NIF crystal in the solid state, revealed by the solid-state NMR relaxation time measurements, enabled the formation of large amounts of NIF nanoparticles in water followed by the polymer dissolution. In contrast, excess amorphization of the NIF crystals failed to efficiently prepare the NIF nanoparticles. The solid-state characterization of the crystalline NIF revealed good correlation with the NIF nanoparticles formation during aqueous dispersion. Furthermore, the solid-state NMR measurements including relaxometry successfully elucidated the nanometer-order dispersion state of NIF in polymer matrix, leading to the discovery of optimized conditions for the preparation of suitable drug nanoparticles.

Isotropic morphometry and multicomponent T1 ρ mapping of human knee articular cartilage in vivo at 3T.

PubMed

Baboli, Rahman; Sharafi, Azadeh; Chang, Gregory; Regatte, Ravinder R

2018-05-02

The progressive loss of hyaline articular cartilage due to osteoarthritis (OA) changes the functional and biochemical properties of cartilage. Measuring the T 1 ρ along with the morphological assessment can potentially be used as noninvasive biomarkers in detecting early-stage OA. To correlate the biochemical and morphological data, submillimeter isotropic resolution for both studies is required. To implement a high spatial resolution 3D-isotropic-MRI sequence for simultaneous assessment of morphological and biexponential T 1 ρ relaxometry of human knee cartilage in vivo. Prospective. Ten healthy volunteers with no known inflammation, trauma, or pain in the knee. Standard FLASH sequence and customized Turbo-FLASH sequence to acquire 3D-isotropic-T 1 ρ-weighted images on a 3T MRI scanner. The mean volume and thickness along with mono- and biexponential T 1 ρ relaxations were assessed in the articular cartilage of 10 healthy volunteers. Nonparametric rank-sum tests. Bland-Altman analysis and coefficient of variation. The mean monoexponential T 1 ρ relaxation was 40.7 ± 4.8 msec, while the long and short components were 58.2 ± 3.9 msec and 6.5 ± 0.6 msec, respectively. The mean fractions of long and short T 1 ρ relaxation components were 63.7 ± 5.9% and 36.3 ± 5.9%, respectively. Statistically significant (P ≤ 0.03) differences were observed in the monoexponential and long components between some of the regions of interest (ROIs). No gender differences between biexponential components were observed (P > 0.05). Mean cartilage volume and thickness were 25.9 ± 6.4 cm 3 and 2.2 ± 0.7 mm, respectively. Cartilage volume (P = 0.01) and thickness (P = 0.03) were significantly higher in male than female participants across all ROIs. Bland-Altman analysis showed agreement between two morphological methods with limits of agreement between -1000 mm 3 and +1100 mm 3 for volume, and -0.78 mm and +0.46 mm for thickness, respectively. Simultaneous assessment of morphological and multicomponent T 1 ρ relaxation of knee joint with 0.7 × 0.7 × 0.7 mm isotropic spatial resolution is demonstrated in vivo. Comparison with a standard method showed that the proposed technique is suitable for assessing the volume and thickness of articular cartilage. 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;00:000-000. © 2018 International Society for Magnetic Resonance in Medicine.

Characterization of Cerebral White Matter Properties Using Quantitative Magnetic Resonance Imaging Stains

PubMed Central

Hurley, Samuel A.; Samsonov, Alexey A.; Adluru, Nagesh; Hosseinbor, Ameer Pasha; Mossahebi, Pouria; Tromp, Do P.M.; Zakszewski, Elizabeth; Field, Aaron S.

2011-01-01

Abstract The image contrast in magnetic resonance imaging (MRI) is highly sensitive to several mechanisms that are modulated by the properties of the tissue environment. The degree and type of contrast weighting may be viewed as image filters that accentuate specific tissue properties. Maps of quantitative measures of these mechanisms, akin to microstructural/environmental-specific tissue stains, may be generated to characterize the MRI and physiological properties of biological tissues. In this article, three quantitative MRI (qMRI) methods for characterizing white matter (WM) microstructural properties are reviewed. All of these measures measure complementary aspects of how water interacts with the tissue environment. Diffusion MRI, including diffusion tensor imaging, characterizes the diffusion of water in the tissues and is sensitive to the microstructural density, spacing, and orientational organization of tissue membranes, including myelin. Magnetization transfer imaging characterizes the amount and degree of magnetization exchange between free water and macromolecules like proteins found in the myelin bilayers. Relaxometry measures the MRI relaxation constants T1 and T2, which in WM have a component associated with the water trapped in the myelin bilayers. The conduction of signals between distant brain regions occurs primarily through myelinated WM tracts; thus, these methods are potential indicators of pathology and structural connectivity in the brain. This article provides an overview of the qMRI stain mechanisms, acquisition and analysis strategies, and applications for these qMRI stains. PMID:22432902

Determination of mean droplet sizes of water-in-oil emulsions using an Earth's field NMR instrument.

PubMed

Fridjonsson, Einar O; Flux, Louise S; Johns, Michael L

2012-08-01

The use of the Earth's magnetic field (EF) to conduct nuclear magnetic resonance (NMR) experiments has a long history with a growing list of applications (e.g. ground water detection, diffusion measurements of Antarctic sea ice). In this paper we explore whether EFNMR can be used to accurately and practically measure the mean droplet size () of water-in-oil emulsions (paraffin and crude oil). We use both pulsed field gradient (PFG) measurements of restricted self-diffusion and T₂ relaxometry, as appropriate. T₂ relaxometry allows the extension of droplet sizing ability below the limits set by the available magnetic field gradient strength of the EFNMR apparatus. A commercially available bench-top NMR spectrometer is used to verify the results obtained using the EFNMR instrument, with good agreement within experimental error, seen between the two instruments. These results open the potential for further investigation of the application of EFNMR for emulsion droplet sizing. Copyright © 2012 Elsevier Inc. All rights reserved.

Using 3D spatial correlations to improve the noise robustness of multi component analysis of 3D multi echo quantitative T2 relaxometry data.

PubMed

Kumar, Dushyant; Hariharan, Hari; Faizy, Tobias D; Borchert, Patrick; Siemonsen, Susanne; Fiehler, Jens; Reddy, Ravinder; Sedlacik, Jan

2018-05-12

We present a computationally feasible and iterative multi-voxel spatially regularized algorithm for myelin water fraction (MWF) reconstruction. This method utilizes 3D spatial correlations present in anatomical/pathological tissues and underlying B1 + -inhomogeneity or flip angle inhomogeneity to enhance the noise robustness of the reconstruction while intrinsically accounting for stimulated echo contributions using T2-distribution data alone. Simulated data and in vivo data acquired using 3D non-selective multi-echo spin echo (3DNS-MESE) were used to compare the reconstruction quality of the proposed approach against those of the popular algorithm (the method by Prasloski et al.) and our previously proposed 2D multi-slice spatial regularization spatial regularization approach. We also investigated whether the inter-sequence correlations and agreements improved as a result of the proposed approach. MWF-quantifications from two sequences, 3DNS-MESE vs 3DNS-gradient and spin echo (3DNS-GRASE), were compared for both reconstruction approaches to assess correlations and agreements between inter-sequence MWF-value pairs. MWF values from whole-brain data of six volunteers and two multiple sclerosis patients are being reported as well. In comparison with competing approaches such as Prasloski's method or our previously proposed 2D multi-slice spatial regularization method, the proposed method showed better agreements with simulated truths using regression analyses and Bland-Altman analyses. For 3DNS-MESE data, MWF-maps reconstructed using the proposed algorithm provided better depictions of white matter structures in subcortical areas adjoining gray matter which agreed more closely with corresponding contrasts on T2-weighted images than MWF-maps reconstructed with the method by Prasloski et al. We also achieved a higher level of correlations and agreements between inter-sequence (3DNS-MESE vs 3DNS-GRASE) MWF-value pairs. The proposed algorithm provides more noise-robust fits to T2-decay data and improves MWF-quantifications in white matter structures especially in the sub-cortical white matter and major white matter tract regions. Copyright © 2018 Elsevier Inc. All rights reserved.

Prediction of beef color using time-domain nuclear magnetic resonance (TD-NMR) relaxometry data and multivariate analyses.

PubMed

Moreira, Luiz Felipe Pompeu Prado; Ferrari, Adriana Cristina; Moraes, Tiago Bueno; Reis, Ricardo Andrade; Colnago, Luiz Alberto; Pereira, Fabíola Manhas Verbi

2016-05-19

Time-domain nuclear magnetic resonance and chemometrics were used to predict color parameters, such as lightness (L*), redness (a*), and yellowness (b*) of beef (Longissimus dorsi muscle) samples. Analyzing the relaxation decays with multivariate models performed with partial least-squares regression, color quality parameters were predicted. The partial least-squares models showed low errors independent of the sample size, indicating the potentiality of the method. Minced procedure and weighing were not necessary to improve the predictive performance of the models. The reduction of transverse relaxation time (T 2 ) measured by Carr-Purcell-Meiboom-Gill pulse sequence in darker beef in comparison with lighter ones can be explained by the lower relaxivity Fe 2+ present in deoxymyoglobin and oxymyoglobin (red beef) to the higher relaxivity of Fe 3+ present in metmyoglobin (brown beef). These results point that time-domain nuclear magnetic resonance spectroscopy can become a useful tool for quality assessment of beef cattle on bulk of the sample and through-packages, because this technique is also widely applied to measure sensorial parameters, such as flavor, juiciness and tenderness, and physicochemical parameters, cooking loss, fat and moisture content, and instrumental tenderness using Warner Bratzler shear force. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Structural Changes in Senescing Oilseed Rape Leaves at Tissue and Subcellular Levels Monitored by Nuclear Magnetic Resonance Relaxometry through Water Status

PubMed Central

Musse, Maja; De Franceschi, Loriane; Cambert, Mireille; Sorin, Clément; Le Caherec, Françoise; Burel, Agnès; Bouchereau, Alain; Mariette, François; Leport, Laurent

2013-01-01

Nitrogen use efficiency is relatively low in oilseed rape (Brassica napus) due to weak nitrogen remobilization during leaf senescence. Monitoring the kinetics of water distribution associated with the reorganization of cell structures, therefore, would be valuable to improve the characterization of nutrient recycling in leaf tissues and the associated senescence processes. In this study, nuclear magnetic resonance (NMR) relaxometry was used to describe water distribution and status at the cellular level in different leaf ranks of well-watered plants. It was shown to be able to detect slight variations in the evolution of senescence. The NMR results were linked to physiological characterization of the leaves and to light and electron micrographs. A relationship between cell hydration and leaf senescence was revealed and associated with changes in the NMR signal. The relative intensities and the transverse relaxation times of the NMR signal components associated with vacuole water were positively correlated with senescence, describing water uptake and vacuole and cell enlargement. Moreover, the relative intensity of the NMR signal that we assigned to the chloroplast water decreased during the senescence process, in agreement with the decrease in relative chloroplast volume estimated from micrographs. The results are discussed on the basis of water flux occurring at the cellular level during senescence. One of the main applications of this study would be for plant phenotyping, especially for plants under environmental stress such as nitrogen starvation. PMID:23903438

Superoxygenated Water as an Experimental Sample for NMR Relaxometry

ERIC Educational Resources Information Center

Nestle, Nikolaus; Dakkouri, Marwan; Rauscher, Hubert

2004-01-01

The increase in NMR relaxation rates as a result of dissolved paramagnetic species on the sample of superoxygenated drinking water is demonstrated. It is concluded that oxygen content in NMR samples is an important issue and can give rise to various problems in the interpretation of both spectroscopic and NMR imaging or relaxation experiments.

The Impact of Post-Pretreatment Conditioning on Enzyme Accessibility and Water Interactions in Alkali Pretreated Rice Straw

NASA Astrophysics Data System (ADS)

Karuna, Nardrapee

Rice straw, a high-abundance lignocellulosic residue from rice production has tremendous potential as a feedstock for biofuel production in California. In this study, the impact of post-alkali pretreatment conditioning schemes on enzyme saccharification efficiency was examined, particularly focusing on understanding resulting biomass compositional impacts on water interactions with the biomass and enzyme accessibility to the cellulose fraction. Rice straw was pretreated with sodium hydroxide and subsequently washed by two different conditions: 1) by extensive washing with distilled water to reduce the pH to the optimum for cellulases which is pH 5--6, and 2) immediate pH adjustment to pH 5--6 with hydrochloric acid before extensive washing with distilled water. The two post-pretreatment conditions gave significant differences in ash, acid-insoluble lignin, glucan and xylan compositions. Alkali pretreatment improved cellulase digestibility of rice straw, and water washing improved enzymatic digestibility more than neutralization. Hydrolysis reactions with a purified Trichoderma reesei Cel7A, a reducing-end specific cellulase, demonstrated that the differences in saccharification are likely due to differences in the accessibility of the cellulose fraction to the cellulolytic enzymes. Further analyses were conducted to study the mobility of the water associated with the rice straw samples by measuring T2 relaxation times of the water protons by 1H-Nuclear Magnetic Resonance (NMR) relaxometry. Results showed significant changes in water association with the rice straw due to the pretreatment and due to the two different post-pretreatment conditions. Pretreatment increased the amount of water at the surface of the rice straw samples as indicated by increased amplitude of the shortest T2 time peaks in the relaxation spectra. Moreover, the amount of water in the first T2 pool in the water washed sample was significantly greater than in the neutralized sample. These results suggest that the specific surface area of rice straw accessible to water protons was increased by the alkali pretreatment, likely due to solubilization of alkali-soluble components of the cell walls. Post-pretreatment processes resulted in differences in the specific surface area likely due to re-precipitation of alkali solubilized components during neutralization. The T2 relaxation times of the surface water pool in washed and raw rice straw were not significantly different, at 4.4 and 4.5 ms, respectively, but both T2 times were significantly shorter than that of the neutralized and then washed sample, at 5.5 ms. The expectation was that the T2 times of the surface water peaks would reflect differences in surface composition of the rice straw samples. Further analysis of surface composition is necessary to further interpret the shortest T2 times observed in the samples. The T2 spectra of the rice straw samples contained longer T2 time peaks that were interpreted as differences in porosity of the rice straw due to the treatments. Pretreatment caused physical changes to rice straw that impacted water organization (3 peaks to 4 peaks), but the amount of water in the peaks were greater in the washed rice straw than the neutralized rice straw suggesting that water-washed rice straw had more of the larger pores than the neutralized and then washed rice straw. One possible explanation is that the neutralization caused precipitation of alkali solubilized components that filled the volumes of the pores.

The magnetic, relaxometric, and optical properties of gadolinium-catalyzed single walled carbon nanotubes

NASA Astrophysics Data System (ADS)

Sitharaman, Balaji; Jacobson, Barry D.; Wadghiri, Youssef Z.; Bryant, Henry; Frank, Joseph

2013-04-01

We report the magnetic behavior, relaxometry, phantom magnetic resonance imaging (MRI), and near-infrared (NIR) photoluminescence spectroscopy of gadolinium (Gd) catalyzed single-walled carbon nanotubes (Gd-SWCNTs). Gd-SWCNTs are paramagnetic with an effective magnetic moment of 7.29 μB. Gd-SWCNT solutions show high r1 and r2 relaxivities at very low (0.01 MHz) to clinically relevant (61 MHz) magnetic fields (r1 ≥ 130 mM-1 s-1, r2 ≥ 160 mM-1 s-1). Analysis of nuclear magnetic resonance dispersion profiles using Solomon, Bloembergen, and Morgan equations suggests that multiple structural and dynamic parameters such as rotational correlation time τR, rate of water exchange τM, and the number of fast-exchanging water molecules within the inner sphere q may be responsible for the increase in r1 and r2 relaxivity. The T1 weighted MRI signal intensity (gradient echo sequence; repetition time (TR) = 66 ms, echo time (TE) = 3 ms, flop angle = 108°) of Gd-SWCNT phantom solution is 14 times greater than the Gd-based clinical MRI contrast agent Magnevist. Additionally, these nanotubes exhibit near infrared fluorescence with distinct E11 transitions of several semiconducting SWCNTs. Taken together, these results demonstrate that Gd-SWCNTs have potential as a novel, highly efficacious, multimodal MRI-NIR optical imaging contrast agent.

Designing Tripodal and Triangular Gadolinium Oxide Nanoplates and Self-Assembled Nanofibrils as Potential Multimodal Bioimaging Probes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Paik, T; Gordon, TR; Prantner, AM

2013-03-01

Here, we report the shape-controlled synthesis of tripodal and triangular gadolinium oxide (Gd2O3) nanoplates. In the presence of lithium ions, the shape of the nanocrystals is readily controlled by tailoring reaction parameters such as temperature and time. We observe that the morphology transforms from an initial tripodal shape to a triangular shape with increasing reaction time or elevated temperatures. Highly uniform Gd2O3 nanoplates are self-assembled into nanofibril-like liquid-crystalline superlattices with long-range orientational and positional order. In addition, shape-directed self-assemblies are investigated by tailoring the aspect ratio of the arms of the Gd2O3 nanoplates. Due to a strong paramagnetic response, Gd2O3more » nanocrystals are excellent candidates for MRI contrast agents and also can be doped with rare-earth ions to form nanophosphors, pointing to their potential in multimodal imaging. In this work, we investigate the MR relaxometry at high magnetic fields (9,4 and 14.1 T) and the optical properties including near-IR to visible upconversion luminescence and X-ray excited optical luminescence of doped Gd2O3 nanoplates. The complex shape of Gd2O3 nanoplates, coupled with their magnetic properties and their ability to phosphoresce under NIR or X-ray excitation which penetrate deep into tissue, makes these nanoplates a promising platform for multimodal imaging in biomedical applications.« less

Role of liver magnetic resonance imaging in hyperferritinaemia and the diagnosis of iron overload.

PubMed

Ruefer, Axel; Bapst, Christine; Benz, Rudolf; Bremerich, Jens; Cantoni, Nathan; Infanti, Laura; Samii, Kaveh; Schmid, Mathias; Vallée, Jean-Paul

2017-11-09

Hyperferritinaemia is a frequent clinical problem. Elevated serum ferritin levels can be detected in different genetic and acquired diseases and can occur with or without anaemia. It is therefore important to determine whether hyperferritinaemia is due to iron overload or due to a secondary cause. The main causes of iron overload are intestinal iron hyperabsorption disorders and transfusion-dependent disorders. Iron homeostasis and iron overload are quantified by different diagnostic approaches. The evaluation of serum ferritin and transferrin saturation is the first diagnostic step to identify the cause of hyperferritinaemia. The assessment of liver iron concentration by liver biopsy or magnetic resonance imaging (MRI) may guide the further diagnostic and therapeutic workup. Liver biopsy is invasive and poorly accepted by patients and should only be carried out in selected patients with hereditary haemochromatosis. As a non-invasive approach, MRI is considered the standard method to diagnose and to monitor both hepatic iron overload and the effectiveness of iron chelation therapy in many clinical conditions such as thalassaemia and myelodysplastic syndromes. Accurate evaluation and monitoring of iron overload has major implications regarding adherence, quality of life and prognosis. There are different technical MRI approaches to measuring the liver iron content. Of these, T2 and T2* relaxometry are considered the standard of care. MRI with cardiac T2* mapping is also suitable for the assessment of cardiac iron. Currently there is no consensus which technique should be preferred. The choice depends on local availability and patient population. However, it is important to use the same MRI technique in subsequent visits in the same patient to get comparable results. Signal intensity ratio may be a good adjunct to R2 and R2* methods as it allows easy visual estimation of the liver iron concentration. In this review a group of Swiss haematologists and radiologists give an overview of different conditions leading to primary or secondary iron overload and on diagnostic methods to assess hyperferritinaemia with a focus on the role of liver MRI. They summarise the standard practice in Switzerland on the use of liver iron concentration MRI as well as disease-specific guideline recommendations.

Enhancing malaria diagnosis through microfluidic cell enrichment and magnetic resonance relaxometry detection

NASA Astrophysics Data System (ADS)

Fook Kong, Tian; Ye, Weijian; Peng, Weng Kung; Wei Hou, Han; Marcos; Preiser, Peter Rainer; Nguyen, Nam-Trung; Han, Jongyoon

2015-06-01

Despite significant advancements over the years, there remains an urgent need for low cost diagnostic approaches that allow for rapid, reliable and sensitive detection of malaria parasites in clinical samples. Our previous work has shown that magnetic resonance relaxometry (MRR) is a potentially highly sensitive tool for malaria diagnosis. A key challenge for making MRR based malaria diagnostics suitable for clinical testing is the fact that MRR baseline fluctuation exists between individuals, making it difficult to detect low level parasitemia. To overcome this problem, it is important to establish the MRR baseline of each individual while having the ability to reliably determine any changes that are caused by the infection of malaria parasite. Here we show that an approach that combines the use of microfluidic cell enrichment with a saponin lysis before MRR detection can overcome these challenges and provide the basis for a highly sensitive and reliable diagnostic approach of malaria parasites. Importantly, as little as 0.0005% of ring stage parasites can be detected reliably, making this ideally suited for the detection of malaria parasites in peripheral blood obtained from patients. The approaches used here are envisaged to provide a new malaria diagnosis solution in the near future.

Dissociation kinetics of Mn2+ complexes of NOTA and DOTA.

PubMed

Drahoš, Bohuslav; Kubíček, Vojtěch; Bonnet, Célia S; Hermann, Petr; Lukeš, Ivan; Tóth, Éva

2011-03-07

The kinetics of transmetallation of [Mn(nota)](-) and [Mn(dota)](2-) was investigated in the presence of Zn(2+) (5-50-fold excess) at variable pH (3.5-5.6) by (1)H relaxometry. The dissociation is much faster for [Mn(nota)](-) than for [Mn(dota)](2-) under both experimental and physiologically relevant conditions (t(½) = 74 h and 1037 h for [Mn(nota)](-) and [Mn(dota)](2-), respectively, at pH 7.4, c(Zn(2+)) = 10(-5) M, 25 °C). The dissociation of the complexes proceeds mainly via spontaneous ([Mn(nota)](-)k(0) = (2.6 ± 0.5) × 10(-6) s(-1); [Mn(dota)](2-)k(0) = (1.8 ± 0.6) × 10(-7) s(-1)) and proton-assisted pathways ([Mn(nota)](-)k(1) = (7.8 ± 0.1) × 10(-1) M(-1) s(-1); [Mn(dota)](2-)k(1) = (4.0 ± 0.6) × 10(-2) M(-1) s(-1), k(2) = (1.6 ± 0.1) × 10(3) M(-2) s(-1)). The observed suppression of the reaction rates with increasing Zn(2+) concentration is explained by the formation of a dinuclear Mn(2+)-L-Zn(2+) complex which is about 20-times more stable for [Mn(dota)](2-) than for [Mn(nota)](-) (K(MnLZn) = 68 and 3.6, respectively), and which dissociates very slowly (k(3)∼10(-5) M(-1) s(-1)). These data provide the first experimental proof that not all Mn(2+) complexes are kinetically labile. The absence of coordinated water makes both [Mn(nota)](-) and [Mn(dota)](2-) complexes inefficient for MRI applications. Nevertheless, the higher kinetic inertness of [Mn(dota)](2-) indicates a promising direction in designing ligands for Mn(2+) complexation.

Development of Advanced Signal Processing and Source Imaging Methods for Superparamagnetic Relaxometry

PubMed Central

Huang, Ming-Xiong; Anderson, Bill; Huang, Charles W.; Kunde, Gerd J.; Vreeland, Erika C.; Huang, Jeffrey W.; Matlashov, Andrei N.; Karaulanov, Todor; Nettles, Christopher P.; Gomez, Andrew; Minser, Kayla; Weldon, Caroline; Paciotti, Giulio; Harsh, Michael; Lee, Roland R.; Flynn, Edward R.

2017-01-01

Superparamagnetic Relaxometry (SPMR) is a highly sensitive technique for the in vivo detection of tumor cells and may improve early stage detection of cancers. SPMR employs superparamagnetic iron oxide nanoparticles (SPION). After a brief magnetizing pulse is used to align the SPION, SPMR measures the time decay of SPION using Super-conducting Quantum Interference Device (SQUID) sensors. Substantial research has been carried out in developing the SQUID hardware and in improving the properties of the SPION. However, little research has been done in the pre-processing of sensor signals and post-processing source modeling in SPMR. In the present study, we illustrate new pre-processing tools that were developed to: 1) remove trials contaminated with artifacts, 2) evaluate and ensure that a single decay process associated with bounded SPION exists in the data, 3) automatically detect and correct flux jumps, and 4) accurately fit the sensor signals with different decay models. Furthermore, we developed an automated approach based on multi-start dipole imaging technique to obtain the locations and magnitudes of multiple magnetic sources, without initial guesses from the users. A regularization process was implemented to solve the ambiguity issue related to the SPMR source variables. A procedure based on reduced chi-square cost-function was introduced to objectively obtain the adequate number of dipoles that describe the data. The new pre-processing tools and multi-start source imaging approach have been successfully evaluated using phantom data. In conclusion, these tools and multi-start source modeling approach substantially enhance the accuracy and sensitivity in detecting and localizing sources from the SPMR signals. Furthermore, multi-start approach with regularization provided robust and accurate solutions for a poor SNR condition similar to the SPMR detection sensitivity in the order of 1000 cells. We believe such algorithms will help establishing the industrial standards for SPMR when applying the technique in pre-clinical and clinical settings. PMID:28072579

Eddy current-shielded x-space relaxometer for sensitive magnetic nanoparticle characterization

PubMed Central

Bauer, L. M.; Hensley, D. W.; Zheng, B.; Tay, Z. W.; Goodwill, P. W.; Griswold, M. A.; Conolly, S. M.

2016-01-01

The development of magnetic particle imaging (MPI) has created a need for optimized magnetic nanoparticles. Magnetic particle relaxometry is an excellent tool for characterizing potential tracers for MPI. In this paper, we describe the design and construction of a high-throughput tabletop relaxometer that is able to make sensitive measurements of MPI tracers without the need for a dedicated shield room. PMID:27250472

Eddy current-shielded x-space relaxometer for sensitive magnetic nanoparticle characterization.

PubMed

Bauer, L M; Hensley, D W; Zheng, B; Tay, Z W; Goodwill, P W; Griswold, M A; Conolly, S M

2016-05-01

The development of magnetic particle imaging (MPI) has created a need for optimized magnetic nanoparticles. Magnetic particle relaxometry is an excellent tool for characterizing potential tracers for MPI. In this paper, we describe the design and construction of a high-throughput tabletop relaxometer that is able to make sensitive measurements of MPI tracers without the need for a dedicated shield room.

Determination of residual monomers resulting from the chemical polymerization process of dental materials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boboia, S.; Moldovan, M.; Ardelean, I.

The residual monomer present in post-polymerized dental materials encourages premature degradation of the reconstructed tooth. That is why the residual monomer should be quantified in a simple, fast, accurate and reproducible manner. In our work we propose such an approach for accurate determination of the residual monomer in dental materials which is based on low-field nuclear magnetic resonance (NMR) relaxometry. The results of the NMR approach are compared with those of the high performance liquid chromatography (HPLC) technique. The samples under study contain the main monomers (2,2-bis[4-(2-hydroxy-3-methacryloyloxypropoxy)phenyl]propane and triethylene glycol dimethacrylate) constituting the liquid phase of most dental materials andmore » an initiator. Two samples were analyzed with different ratios of chemical initiation systems: N,N-dimethyl-p-toluide: benzoyl peroxide (1:2 and 0.7:1.2). The results obtained by both techniques highlight that by reducing the initiator the polymerization process slows down and the amount of residual monomer reduces. This prevents the premature degradation of the dental fillings and consequently the reduction of the biomaterial resistance.« less

Self-diffusion studies by intra- and inter-molecular spin-lattice relaxometry using field-cycling: Liquids, plastic crystals, porous media, and polymer segments.

PubMed

Kimmich, Rainer; Fatkullin, Nail

2017-08-01

Field-cycling NMR relaxometry is a well-established technique for probing molecular dynamics in a frequency range from typically a few kHz up to several tens of MHz. For the interpretation of relaxometry data, it is quite often assumed that the spin-lattice relaxation process is of an intra-molecular nature so that rotational fluctuations dominate. However, dipolar interactions as the main type of couplings between protons and other dipolar species without quadrupole moments can imply appreciable inter-molecular contributions. These fluctuate due to translational displacements and to a lesser degree also by rotational reorientations in the short-range limit. The analysis of the inter-molecular proton spin-lattice relaxation rate thus permits one to evaluate self-diffusion variables such as the diffusion coefficient or the mean square displacement on a time scale from nanoseconds to several hundreds of microseconds. Numerous applications to solvents, plastic crystals and polymers will be reviewed. The technique is of particular interest for polymer dynamics since inter-molecular spin-lattice relaxation diffusometry bridges the time scales of quasi-elastic neutron scattering and field-gradient NMR diffusometry. This is just the range where model-specific intra-coil mechanisms are assumed to occur. They are expected to reveal themselves by characteristic power laws for the time-dependence of the mean-square segment displacement. These can be favorably tested on this basis. Results reported in the literature will be compared with theoretical predictions. On the other hand, there is a second way for translational diffusion phenomena to affect the spin-lattice relaxation dispersion. If rotational diffusion of molecules is restricted, translational diffusion properties can be deduced even from molecular reorientation dynamics detected by intra-molecular spin-lattice relaxation. This sort of scenario will be relevant for adsorbates on surfaces or polymer segments under entanglement and chain connectivity constraints. Under such conditions, reorientations will be correlated with translational displacements leading to the so-called RMTD relaxation process (reorientation mediated by translational displacements). Applications to porous glasses, protein solutions, lipid bilayers, and clays will be discussed. Finally, we will address the intriguing fact that the various time limits of the segment mean-square displacement of polymers in some cases perfectly reproduce predictions of the tube/reptation model whereas the reorientation dynamics suggests strongly deviating power laws. Copyright © 2017 Elsevier B.V. All rights reserved.

Improved Determination of the Myelin Water Fraction in Human Brain using Magnetic Resonance Imaging through Bayesian Analysis of mcDESPOT

PubMed Central

Bouhrara, Mustapha; Spencer, Richard G.

2015-01-01

Myelin water fraction (MWF) mapping with magnetic resonance imaging has led to the ability to directly observe myelination and demyelination in both the developing brain and in disease. Multicomponent driven equilibrium single pulse observation of T1 and T2 (mcDESPOT) has been proposed as a rapid approach for multicomponent relaxometry and has been applied to map MWF in human brain. However, even for the simplest two-pool signal model consisting of MWF and non-myelin-associated water, the dimensionality of the parameter space for obtaining MWF estimates remains high. This renders parameter estimation difficult, especially at low-to-moderate signal-to-noise ratios (SNR), due to the presence of local minima and the flatness of the fit residual energy surface used for parameter determination using conventional nonlinear least squares (NLLS)-based algorithms. In this study, we introduce three Bayesian approaches for analysis of the mcDESPOT signal model to determine MWF. Given the high dimensional nature of mcDESPOT signal model, and, thereby, the high dimensional marginalizations over nuisance parameters needed to derive the posterior probability distribution of MWF parameter, the introduced Bayesian analyses use different approaches to reduce the dimensionality of the parameter space. The first approach uses normalization by average signal amplitude, and assumes that noise can be accurately estimated from signal-free regions of the image. The second approach likewise uses average amplitude normalization, but incorporates a full treatment of noise as an unknown variable through marginalization. The third approach does not use amplitude normalization and incorporates marginalization over both noise and signal amplitude. Through extensive Monte Carlo numerical simulations and analysis of in-vivo human brain datasets exhibiting a range of SNR and spatial resolution, we demonstrated the markedly improved accuracy and precision in the estimation of MWF using these Bayesian methods as compared to the stochastic region contraction (SRC) implementation of NLLS. PMID:26499810

Comparative imaging study in ultrasound, MRI, CT, and DSA using a multimodality renal artery phantom

DOE Office of Scientific and Technical Information (OSTI.GOV)

King, Deirdre M.; Fagan, Andrew J.; Moran, Carmel M.

2011-02-15

Purpose: A range of anatomically realistic multimodality renal artery phantoms consisting of vessels with varying degrees of stenosis was developed and evaluated using four imaging techniques currently used to detect renal artery stenosis (RAS). The spatial resolution required to visualize vascular geometry and the velocity detection performance required to adequately characterize blood flow in patients suffering from RAS are currently ill-defined, with the result that no one imaging modality has emerged as a gold standard technique for screening for this disease. Methods: The phantoms, which contained a range of stenosis values (0%, 30%, 50%, 70%, and 85%), were designed formore » use with ultrasound, magnetic resonance imaging, x-ray computed tomography, and x-ray digital subtraction angiography. The construction materials used were optimized with respect to their ultrasonic speed of sound and attenuation coefficient, MR relaxometry (T{sub 1},T{sub 2}) properties, and Hounsfield number/x-ray attenuation coefficient, with a design capable of tolerating high-pressure pulsatile flow. Fiducial targets, incorporated into the phantoms to allow for registration of images among modalities, were chosen to minimize geometric distortions. Results: High quality distortion-free images of the phantoms with good contrast between vessel lumen, fiducial markers, and background tissue to visualize all stenoses were obtained with each modality. Quantitative assessments of the grade of stenosis revealed significant discrepancies between modalities, with each underestimating the stenosis severity for the higher-stenosed phantoms (70% and 85%) by up to 14%, with the greatest discrepancy attributable to DSA. Conclusions: The design and construction of a range of anatomically realistic renal artery phantoms containing varying degrees of stenosis is described. Images obtained using the main four diagnostic techniques used to detect RAS were free from artifacts and exhibited adequate contrast to allow for quantitative measurements of the degree of stenosis in each phantom. Such multimodality phantoms may prove useful in evaluating current and emerging US, MRI, CT, and DSA technology.« less

Magnetic Resonance Relaxometry at Low and Ultra low Fields.

PubMed

Volegov, P; Flynn, M; Kraus, R; Magnelind, P; Matlashov, A; Nath, P; Owens, T; Sandin, H; Savukov, I; Schultz, L; Urbaitis, A; Zotev, V; Espy, M

2010-01-01

Nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) are ubiquitous tools in science and medicine. NMR provides powerful probes of local and macromolecular chemical structure and dynamics. Recently it has become possible and practical to perform MR at very low fields (from 1 μT to 1 mT), the so-called ultra-low field (ULF) regime. Pulsed pre-polarizing fields greatly enhance the signal strength and allow flexibility in signal acquisition sequences. Improvements in SQUID sensor technology allow ultra-sensitive detection in a pulsed field environment.In this regime the proton Larmor frequencies (1 Hz - 100 kHz) of ULF MR overlap (on a time scale of 10 μs to 100 ms) with "slow" molecular dynamic processes such as diffusion, intra-molecular motion, chemical reactions, and biological processes such as protein folding, catalysis and ligand binding. The frequency dependence of relaxation at ultra-low fields may provide a probe for biomolecular dynamics on the millisecond timescale (protein folding and aggregation, conformational motions of enzymes, binding and structural fluctuations of coupled domains in allosteric mechanisms) relevant to host-pathogen interactions, biofuels, and biomediation. Also this resonance-enhanced coupling at ULF can greatly enhance contrast in medical applications of ULF-MRI resulting in better diagnostic techniques.We have developed a number of instruments and techniques to study relaxation vs. frequency at the ULF regime. Details of the techniques and results are presented.Ultra-low field methods are already being applied at LANL in brain imaging, and detection of liquid explosives at airports. However, the potential power of ultra-low field MR remains to be fully exploited.

Microwave-assisted green synthesis of superparamagnetic nanoparticles using fruit peel extracts: surface engineering, T 2 relaxometry, and photodynamic treatment potential.

PubMed

Bano, Shazia; Nazir, Samina; Nazir, Alia; Munir, Saeeda; Mahmood, Tariq; Afzal, Muhammad; Ansari, Farzana Latif; Mazhar, Kehkashan

2016-01-01

Superparamagnetic iron oxide nanoparticles (SPIONs) have the potential to be used as multimodal imaging and cancer therapy agents due to their excellent magnetism and ability to generate reactive oxygen species when exposed to light. We report the synthesis of highly biocompatible SPIONs through a facile green approach using fruit peel extracts as the biogenic reductant. This green synthesis protocol involves the stabilization of SPIONs through coordination of different phytochemicals. The SPIONs were functionalized with polyethylene glycol (PEG)-6000 and succinic acid and were extensively characterized by X-ray diffraction analysis, field emission scanning electron microscopy, energy-dispersive X-ray spectroscopy, atomic force microscopy, Rutherford backscattering spectrometry, diffused reflectance spectroscopy, fluorescence emission, Fourier-transform infrared spectroscopy, ultraviolet-visible spectroscopy, and magnetization analysis. The developed SPIONs were found to be stable, almost spherical with a size range of 17-25 nm. They exhibited excellent water dispersibility, colloidal stability, and relatively high R 2 relaxivity (225 mM(-1) s(-1)). Cell viability assay data revealed that PEGylation or carboxylation appears to significantly shield the surface of the particles but does not lead to improved cytocompatibility. A highly significant increase of reactive oxygen species in light-exposed samples was found to play an important role in the photokilling of human cervical epithelial malignant carcinoma (HeLa) cells. The bio-SPIONs developed are highly favorable for various biomedical applications without risking interference from potentially toxic reagents.

Microwave-assisted green synthesis of superparamagnetic nanoparticles using fruit peel extracts: surface engineering, T2 relaxometry, and photodynamic treatment potential

PubMed Central

Bano, Shazia; Nazir, Samina; Nazir, Alia; Munir, Saeeda; Mahmood, Tariq; Afzal, Muhammad; Ansari, Farzana Latif; Mazhar, Kehkashan

2016-01-01

Superparamagnetic iron oxide nanoparticles (SPIONs) have the potential to be used as multimodal imaging and cancer therapy agents due to their excellent magnetism and ability to generate reactive oxygen species when exposed to light. We report the synthesis of highly biocompatible SPIONs through a facile green approach using fruit peel extracts as the biogenic reductant. This green synthesis protocol involves the stabilization of SPIONs through coordination of different phytochemicals. The SPIONs were functionalized with polyethylene glycol (PEG)-6000 and succinic acid and were extensively characterized by X-ray diffraction analysis, field emission scanning electron microscopy, energy-dispersive X-ray spectroscopy, atomic force microscopy, Rutherford backscattering spectrometry, diffused reflectance spectroscopy, fluorescence emission, Fourier-transform infrared spectroscopy, ultraviolet-visible spectroscopy, and magnetization analysis. The developed SPIONs were found to be stable, almost spherical with a size range of 17–25 nm. They exhibited excellent water dispersibility, colloidal stability, and relatively high R2 relaxivity (225 mM−1 s−1). Cell viability assay data revealed that PEGylation or carboxylation appears to significantly shield the surface of the particles but does not lead to improved cytocompatibility. A highly significant increase of reactive oxygen species in light-exposed samples was found to play an important role in the photokilling of human cervical epithelial malignant carcinoma (HeLa) cells. The bio-SPIONs developed are highly favorable for various biomedical applications without risking interference from potentially toxic reagents. PMID:27570452

Regularized Reconstruction of Dynamic Contrast-Enhanced MR Images for Evaluation of Breast Lesions

DTIC Science & Technology

2011-01-01

Magnetic resonance imaging contrast-enhanced relaxometry of breast tumors: an MRI multicenter investigation concerning 100 patients,” Mag. Res. Im., vol...The overall goal of this project was to develop, implement, and evaluate methods for im- proving image quality in dynamic magnetic resonance imaging ...Olafsson, H. R. Shi, and D. C. Noll, “Toeplitz-based iterative image reconstruction for MRI with correction for magnetic field inhomogeneity,” IEEE

Quantification of Liver Iron with MRI: State of the Art and Remaining Challenges

PubMed Central

Hernando, Diego; Levin, Yakir S; Sirlin, Claude B; Reeder, Scott B

2015-01-01

Liver iron overload is the histological hallmark of hereditary hemochromatosis and transfusional hemosiderosis, and can also occur in chronic hepatopathies. Iron overload can result in liver damage, with the eventual development of cirrhosis, liver failure and hepatocellular carcinoma. Assessment of liver iron levels is necessary for detection and quantitative staging of iron overload, and monitoring of iron-reducing treatments. This article discusses the need for non-invasive assessment of liver iron, and reviews qualitative and quantitative methods with a particular emphasis on MRI. Specific MRI methods for liver iron quantification include signal intensity ratio as well as R2 and R2* relaxometry techniques. Methods that are in clinical use, as well as their limitations, are described. Remaining challenges, unsolved problems, and emerging techniques to provide improved characterization of liver iron deposition are discussed. PMID:24585403

Physicochemical characterization, and relaxometry studies of micro-graphite oxide, graphene nanoplatelets, and nanoribbons.

PubMed

Paratala, Bhavna S; Jacobson, Barry D; Kanakia, Shruti; Francis, Leonard Deepak; Sitharaman, Balaji

2012-01-01

The chemistry of high-performance magnetic resonance imaging contrast agents remains an active area of research. In this work, we demonstrate that the potassium permanganate-based oxidative chemical procedures used to synthesize graphite oxide or graphene nanoparticles leads to the confinement (intercalation) of trace amounts of Mn(2+) ions between the graphene sheets, and that these manganese intercalated graphitic and graphene structures show disparate structural, chemical and magnetic properties, and high relaxivity (up to 2 order) and distinctly different nuclear magnetic resonance dispersion profiles compared to paramagnetic chelate compounds. The results taken together with other published reports on confinement of paramagnetic metal ions within single-walled carbon nanotubes (a rolled up graphene sheet) show that confinement (encapsulation or intercalation) of paramagnetic metal ions within graphene sheets, and not the size, shape or architecture of the graphitic carbon particles is the key determinant for increasing relaxivity, and thus, identifies nano confinement of paramagnetic ions as novel general strategy to develop paramagnetic metal-ion graphitic-carbon complexes as high relaxivity MRI contrast agents.

Physicochemical Characterization, and Relaxometry Studies of Micro-Graphite Oxide, Graphene Nanoplatelets, and Nanoribbons

PubMed Central

Paratala, Bhavna S.; Jacobson, Barry D.; Kanakia, Shruti; Francis, Leonard Deepak; Sitharaman, Balaji

2012-01-01

The chemistry of high-performance magnetic resonance imaging contrast agents remains an active area of research. In this work, we demonstrate that the potassium permanganate-based oxidative chemical procedures used to synthesize graphite oxide or graphene nanoparticles leads to the confinement (intercalation) of trace amounts of Mn2+ ions between the graphene sheets, and that these manganese intercalated graphitic and graphene structures show disparate structural, chemical and magnetic properties, and high relaxivity (up to 2 order) and distinctly different nuclear magnetic resonance dispersion profiles compared to paramagnetic chelate compounds. The results taken together with other published reports on confinement of paramagnetic metal ions within single-walled carbon nanotubes (a rolled up graphene sheet) show that confinement (encapsulation or intercalation) of paramagnetic metal ions within graphene sheets, and not the size, shape or architecture of the graphitic carbon particles is the key determinant for increasing relaxivity, and thus, identifies nano confinement of paramagnetic ions as novel general strategy to develop paramagnetic metal-ion graphitic-carbon complexes as high relaxivity MRI contrast agents. PMID:22685555

Engineering an effective Mn-binding MRI reporter protein by subcellular targeting

PubMed Central

Bartelle, Benjamin B.; Mana, Miyeko D.; Suero-Abreu, Giselle A.; Rodriguez, Joe J.; Turnbull, Daniel H.

2014-01-01

Purpose Manganese (Mn) is an effective contrast agent and biologically active metal, which has been widely utilized for Mn-enhanced MRI (MEMRI). The purpose of this study was to develop and test a Mn binding protein for use as an genetic reporter for MEMRI. Methods The bacterial Mn-binding protein, MntR was identified as a candidate reporter protein. MntR was engineered for expression in mammalian cells, and targeted to different subcellular organelles, including the Golgi Apparatus where cellular Mn is enriched. Transfected HEK293 cells and B16 melanoma cells were tested in vitro and in vivo, using immunocytochemistry and MR imaging and relaxometry. Results Subcellular targeting of MntR to the cytosol, endoplasmic reticulum and Golgi apparatus was verified with immunocytochemistry. After targeting to the Golgi, MntR expression produced robust R1 changes and T1 contrast in cells, in vitro and in vivo. Co-expression with the divalent metal transporter DMT1, a previously described Mn-based reporter, further enhanced contrast in B16 cells in culture, but in the in vivo B16 tumor model tested was not significantly better than MntR alone. Conclusion This second-generation reporter system both expands the capabilities of genetically-encoded reporters for imaging with MEMRI and provides important insights into the mechanisms of Mn biology which create endogenous MEMRI contrast. PMID:25522343

Protein corona affects the relaxivity and MRI contrast efficiency of magnetic nanoparticles

NASA Astrophysics Data System (ADS)

Amiri, Houshang; Bordonali, Lorenzo; Lascialfari, Alessandro; Wan, Sha; Monopoli, Marco P.; Lynch, Iseult; Laurent, Sophie; Mahmoudi, Morteza

2013-08-01

Magnetic nanoparticles (NPs) are increasingly being considered for use in biomedical applications such as biosensors, imaging contrast agents and drug delivery vehicles. In a biological fluid, proteins associate in a preferential manner with NPs. The small sizes and high curvature angles of NPs influence the types and amounts of proteins present on their surfaces. This differential display of proteins bound to the surface of NPs can influence the tissue distribution, cellular uptake and biological effects of NPs. To date, the effects of adsorption of a protein corona (PC) on the magnetic properties of NPs have not been considered, despite the fact that some of their potential applications require their use in human blood. Here, to investigate the effects of a PC (using fetal bovine serum) on the MRI contrast efficiency of superparamagnetic iron oxide NPs (SPIONs), we have synthesized two series of SPIONs with variation in the thickness and functional groups (i.e. surface charges) of the dextran surface coating. We have observed that different physico-chemical characteristics of the dextran coatings on the SPIONs lead to the formation of PCs of different compositions. 1H relaxometry was used to obtain the longitudinal, r1, and transverse, r2, relaxivities of the SPIONs without and with a PC, as a function of the Larmor frequency. The transverse relaxivity, which determines the efficiency of negative contrast agents (CAs), is very much dependent on the functional group and the surface charge of the SPIONs' coating. The presence of the PC did not alter the relaxivity of plain SPIONs, while it slightly increased the relaxivity of the negatively charged SPIONs and dramatically decreased the relaxivity of the positively charged ones, which was coupled with particle agglomeration in the presence of the proteins. To confirm the effect of the PC on the MRI contrast efficiency, in vitro MRI experiments at ν = 8.5 MHz were performed using a low-field MRI scanner. The MRI contrasts, produced by different samples, were fully in agreement with the relaxometry findings.Magnetic nanoparticles (NPs) are increasingly being considered for use in biomedical applications such as biosensors, imaging contrast agents and drug delivery vehicles. In a biological fluid, proteins associate in a preferential manner with NPs. The small sizes and high curvature angles of NPs influence the types and amounts of proteins present on their surfaces. This differential display of proteins bound to the surface of NPs can influence the tissue distribution, cellular uptake and biological effects of NPs. To date, the effects of adsorption of a protein corona (PC) on the magnetic properties of NPs have not been considered, despite the fact that some of their potential applications require their use in human blood. Here, to investigate the effects of a PC (using fetal bovine serum) on the MRI contrast efficiency of superparamagnetic iron oxide NPs (SPIONs), we have synthesized two series of SPIONs with variation in the thickness and functional groups (i.e. surface charges) of the dextran surface coating. We have observed that different physico-chemical characteristics of the dextran coatings on the SPIONs lead to the formation of PCs of different compositions. 1H relaxometry was used to obtain the longitudinal, r1, and transverse, r2, relaxivities of the SPIONs without and with a PC, as a function of the Larmor frequency. The transverse relaxivity, which determines the efficiency of negative contrast agents (CAs), is very much dependent on the functional group and the surface charge of the SPIONs' coating. The presence of the PC did not alter the relaxivity of plain SPIONs, while it slightly increased the relaxivity of the negatively charged SPIONs and dramatically decreased the relaxivity of the positively charged ones, which was coupled with particle agglomeration in the presence of the proteins. To confirm the effect of the PC on the MRI contrast efficiency, in vitro MRI experiments at ν = 8.5 MHz were performed using a low-field MRI scanner. The MRI contrasts, produced by different samples, were fully in agreement with the relaxometry findings. Electronic supplementary information (ESI) available. See DOI: 10.1039/c3nr00345k

An ultra-low cost NMR device with arbitrary pulse programming

NASA Astrophysics Data System (ADS)

Chen, Hsueh-Ying; Kim, Yaewon; Nath, Pulak; Hilty, Christian

2015-06-01

Ultra-low cost, general purpose electronics boards featuring microprocessors or field programmable gate arrays (FPGA) are reaching capabilities sufficient for direct implementation of NMR spectrometers. We demonstrate a spectrometer based on such a board, implemented with a minimal need for the addition of custom electronics and external components. This feature allows such a spectrometer to be readily implemented using typical knowledge present in an NMR laboratory. With FPGA technology, digital tasks are performed with precise timing, without the limitation of predetermined hardware function. In this case, the FPGA is used for programming of arbitrarily timed pulse sequence events, and to digitally generate required frequencies. Data acquired from a 0.53 T permanent magnet serves as a demonstration of the flexibility of pulse programming for diverse experiments. Pulse sequences applied include a spin-lattice relaxation measurement using a pulse train with small-flip angle pulses, and a Carr-Purcell-Meiboom-Gill experiment with phase cycle. Mixing of NMR signals with a digitally generated, 4-step phase-cycled reference frequency is further implemented to achieve sequential quadrature detection. The flexibility in hardware implementation permits tailoring this type of spectrometer for applications such as relaxometry, polarimetry, diffusometry or NMR based magnetometry.

Microstructural imaging of the human brain with a 'super-scanner': 10 key advantages of ultra-strong gradients for diffusion MRI.

PubMed

Jones, D K; Alexander, D C; Bowtell, R; Cercignani, M; Dell'Acqua, F; McHugh, D J; Miller, K L; Palombo, M; Parker, G J M; Rudrapatna, U S; Tax, C M W

2018-05-22

The key component of a microstructural diffusion MRI 'super-scanner' is a dedicated high-strength gradient system that enables stronger diffusion weightings per unit time compared to conventional gradient designs. This can, in turn, drastically shorten the time needed for diffusion encoding, increase the signal-to-noise ratio, and facilitate measurements at shorter diffusion times. This review, written from the perspective of the UK National Facility for In Vivo MR Imaging of Human Tissue Microstructure, an initiative to establish a shared 300 mT/m-gradient facility amongst the microstructural imaging community, describes ten advantages of ultra-strong gradients for microstructural imaging. Specifically, we will discuss how the increase of the accessible measurement space compared to a lower-gradient systems (in terms of Δ, b-value, and TE) can accelerate developments in the areas of 1) axon diameter distribution mapping; 2) microstructural parameter estimation; 3) mapping micro-vs macroscopic anisotropy features with gradient waveforms beyond a single pair of pulsed-gradients; 4) multi-contrast experiments, e.g. diffusion-relaxometry; 5) tractography and high-resolution imaging in vivo and 6) post mortem; 7) diffusion-weighted spectroscopy of metabolites other than water; 8) tumour characterisation; 9) functional diffusion MRI; and 10) quality enhancement of images acquired on lower-gradient systems. We finally discuss practical barriers in the use of ultra-strong gradients, and provide an outlook on the next generation of 'super-scanners'. Copyright © 2018. Published by Elsevier Inc.

Polymer chain dynamics under nanoscopic confinements.

PubMed

Kimmich, Rainer; Fatkullin, Nail; Mattea, Carlos; Fischer, Elmar

2005-02-01

It is shown that the confinement of polymer melts in nanopores leads to chain dynamics dramatically different from bulk behavior. This so-called corset effect occurs both above and below the critical molecular mass and induces the dynamic features predicted for reptation. A spinodal demixing technique was employed for the preparation of linear poly(ethylene oxide) (PEO) confined to nanoscopic strands that are in turn embedded in a quasi-solid and impenetrable methacrylate matrix. Both the molecular weight of the PEO and the mean diameter of the strands were varied to a certain degree. The chain dynamics of the PEO in the molten state was examined with the aid of field-gradient NMR diffusometry (time scale, 10(-2)-10(0) s) and field-cycling NMR relaxometry (time scale, 10(-9)-10(-4) s). The dominating mechanism for translational displacements probed in the nanoscopic strands by either technique is shown to be reptation. On the time scale of spin-lattice relaxation time measurements, the frequency dependence signature of reptation (i.e., T1 approximately nu(3/4)) showed up in all samples. A "tube" diameter of only 0.6 nm was concluded to be effective on this time scale even when the strand diameter was larger than the radius of gyration of the PEO random coils. This corset effect is traced back to the lack of the local fluctuation capacity of the free volume in nanoscopic confinements. The confinement dimension is estimated at which the crossover from confined to bulk chain dynamics is expected.

Dynamic signatures of the transition from stacking disordered to hexagonal ice: Dielectric and nuclear magnetic resonance studies

NASA Astrophysics Data System (ADS)

Gainaru, C.; Vynokur, E.; Köster, K. W.; Fuentes-Landete, V.; Spettel, N.; Zollner, J.; Loerting, T.; Böhmer, R.

2018-04-01

Using various temperature-cycling protocols, the dynamics of ice I were studied via dielectric spectroscopy and nuclear magnetic resonance relaxometry on protonated and deuterated samples obtained by heating high-density amorphous ices as well as crystalline ice XII. Previous structural studies of ice I established that at temperatures of about 230 K, the stacking disorder of the cubic/hexagonal oxygen lattice vanishes. The present dielectric and nuclear magnetic resonance investigations of spectral changes disclose that the memory of the existence of a precursor phase is preserved in the hydrogen matrix up to 270 K. This finding of hydrogen mobility lower than that of the undoped hexagonal ice near the melting point highlights the importance of dynamical investigations of the transitions between various ice phases and sheds new light on the dynamics in ice I in general.

On the use of superparamagnetic hydroxyapatite nanoparticles as an agent for magnetic and nuclear in vivo imaging.

PubMed

Adamiano, Alessio; Iafisco, Michele; Sandri, Monica; Basini, Martina; Arosio, Paolo; Canu, Tamara; Sitia, Giovanni; Esposito, Antonio; Iannotti, Vincenzo; Ausanio, Giovanni; Fragogeorgi, Eirini; Rouchota, Maritina; Loudos, George; Lascialfari, Alessandro; Tampieri, Anna

2018-06-01

The identification of alternative biocompatible magnetic NPs for advanced clinical application is becoming an important need due to raising concerns about iron accumulation in soft issues associated to the administration of superparamagnetic iron oxide nanoparticles (NPs). Here, we report on the performance of previously synthetized iron-doped hydroxyapatite (FeHA) NPs as contrast agent for magnetic resonance imaging (MRI). The MRI contrast abilities of FeHA and Endorem® (dextran coated iron oxide NPs) were assessed by 1 H nuclear magnetic resonance relaxometry and their performance in healthy mice was monitored by a 7 Tesla scanner. FeHA applied a higher contrast enhancement, and had a longer endurance in the liver with respect to Endorem® at iron equality. Additionally, a proof of concept of FeHA use as scintigraphy imaging agent for positron emission tomography (PET) and single photon emission computed tomography (SPECT) was given labeling FeHA with 99m Tc-MDP by a straightforward surface functionalization process. Scintigraphy/x-ray fused imaging and ex vivo studies confirmed its dominant accumulation in the liver, and secondarily in other organs of the mononuclear phagocyte system. FeHA efficiency as MRI-T 2 and PET-SPECT imaging agent combined to its already reported intrinsic biocompatibility qualifies it as a promising material for innovative nanomedical applications. The ability of iron-doped hydroxyapatite nanoaprticles (FeHA) to work in vivo as imaging agents for magnetic resonance (MR) and nuclear imaging is demonstrated. FeHA applied an higher MR contrast in the liver, spleen and kidneys of mice with respect to Endorem®. The successful radiolabeling of FeHA allowed for scintigraphy/X-ray and ex vivo biodistribution studies, confirming MR results and envisioning FeHA application for dual-imaging. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

A magnetically drivable nanovehicle for curcumin with antioxidant capacity and MRI relaxation properties.

PubMed

Magro, Massimiliano; Campos, René; Baratella, Davide; Lima, Giuseppina; Holà, Katerina; Divoky, Clemens; Stollberger, Rudolf; Malina, Ondrej; Aparicio, Claudia; Zoppellaro, Giorgio; Zbořil, Radek; Vianello, Fabio

2014-09-08

Curcumin possesses wide-ranging anti-inflammatory and anti-cancer properties and its biological activity can be linked to its potent antioxidant capacity. Superparamagnetic maghemite (γ-Fe2 O3 ), called surface-active maghemite nanoparticles (SAMNs) were surface-modified with curcumin molecules, due to the presence of under-coordinated Fe(III) atoms on the nanoparticle surface. The so-obtained curcumin-modified SAMNs (SAMN@curcumin) had a mean size of 13±4 nm. SAMN@curcumin was characterized by transmission and scanning electron microscopy, UV/Vis, FTIR, and Mössbauer spectroscopy, X-ray powder diffraction, bulk susceptibility (SQUID), and relaxometry measurements (MRI imaging). The high negative contrast proclivity of SAMN@curcumin to act as potential contrast agent in MRI screenings was also tested. Moreover, the redox properties of bound curcumin were probed by electrochemistry. SAMN@curcumin was studied in the presence of different electroactive molecules, namely hydroquinone, NADH and ferrocyanide, to assess its redox behavior. Finally, SAMN@curcumin was electrochemically probed in the presence of hydrogen peroxide, demonstrating the stability and reactivity of bound curcumin. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

αvß3-Integrin-Targeted Magnetic Resonance Imaging for the Assessment of Early Antiangiogenic Therapy Effects in Orthotopic Breast Cancer Xenografts.

PubMed

Kazmierczak, Philipp Maximilian; Schneider, Moritz; Habereder, Thomas; Hirner-Eppeneder, Heidrun; Eschbach, Ralf S; Moser, Matthias; Reiser, Maximilian F; Lauber, Kirsten; Nikolaou, Konstantin; Cyran, Clemens C

2016-11-01

The aim of this study was to investigate magnetic resonance imaging (MRI) with αvß3-integrin-targeted ultrasmall superparamagnetic iron oxide nanoparticles (RGD-USPIO) for the in vivo monitoring of early antiangiogenic therapy effects in experimental breast cancer. Orthotopic human breast cancer (MDA-MB-231) xenograft-bearing severe combined immunodeficiency mice were imaged before and after a 1-week therapy with the vascular endothelial growth factor receptor-antibody bevacizumab or placebo (n = 10 per group, daily intraperitoneal injections of bevacizumab or a volume-equivalent placebo solution, respectively) on a clinical 3 T scanner (Magnetom Skyra; Siemens Healthcare, Erlangen, Germany) before and 60 minutes after the intravenous injection of RGD-USPIO (P04000; Guerbet, Villepinte, France). R2 relaxometry employing a T2-weighted spin-echo sequence with 4 echo times (echo time, 20/40/60/80 milliseconds; repetition time, 3800 milliseconds; matrix, 128 × 128; field of view, 50 × 50; slice thickness, 1.2 mm; time to acquisition, 25 minutes) was used as semiquantitative measure to determine RGD-USPIO endothelial binding. In addition, the T2-weighted images were used to perform volumetric tumor response assessments. Imaging results were validated by ex vivo multiparametric immunohistochemistry with regard to αvß3-integrin expression, microvascular density (CD31), proliferation (Ki-67), and apoptosis (TUNEL). RGD-USPIO endothelial binding was significantly reduced after vascular endothelial growth factor inhibition, compared with the control group in which an increased endothelial binding was detected ([INCREMENT]R2Therapy = -0.80 ± 0.78 s; [INCREMENT]R2Control = +0.27 ± 0.59 s; P = 0.002). Correspondingly, immunohistochemistry revealed a significantly lower αvß3-integrin expression (91 ± 30 vs 357 ± 72; P < 0.001), microvascular density (CD31, 109 ± 46 vs 440 ± 208; P < 0.001), tumor cell proliferation (Ki-67, 4040 ± 1373 vs 6530 ± 1217; P < 0.001), as well as significantly higher apoptosis (TUNEL, 11186 ± 4387 vs 4017 ± 1191; P = 0.004) in the therapy compared with the control group. Contrary to the changes in αvß3-integrin expression detected by RGD-USPIO MRI, morphology-based tumor response assessments did not show a significant intergroup difference in tumor volume development over the course of the experiment (ΔVolTherapy +71 ± 40 μL vs ΔVolControl +125 ± 81 μL; P > 0.05). RGD-USPIO MRI allows for the noninvasive assessment of αvß3-integrin expression in the investigated breast cancer model. RGD-USPIO MRI may be applicable for the in vivo monitoring of early antiangiogenic therapy effects in experimental breast cancer, generating possible complementary molecular imaging biomarkers to morphology-based tumor response assessments.

Sewage sludge hydrochars: properties and agronomic impact as related to different production conditions

NASA Astrophysics Data System (ADS)

Paneque, Marina; María De la Rosa, José; Aragón, Carlos; Kern, Jürgen; Conte, Pellegrino; Knicker, Heike

2015-04-01

The huge amount of sewage sludge (SS) generated in wastewater treatment plants all over the world represents an environmental problem. Due to the high concentration of phosphorus and nitrogen in SS as well as other macro and micro nutrients it has been considered a suitable soil amendment. However, before being applied to soil a complete sterilization and elimination of pollutants should be carried out [1]. In this context, thermal treatments appear as a convenient methodology for producing SS byproducts useful for agronomic purposes. Hydrothermal carbonization (HTC) is a kind of pyrolysis characterized by the heating of the biomass in presence of water. This process shows an advantage compared to other thermal treatments for wet residues since dryness of the biomass prior to the thermal transformation is not necessary. The solid product which results from HTC is called hydrochar and it has been suggested to increase soil productivity [2]. However, the agronomic potential of hydrochars depends on the feedstock and production conditions. Additionally, possible toxic and risks have to be carefully evaluated. Thus, SS hydrochars appear as a potential soil amendment but further scientific research is needed to find its real capacity, optimal production conditions as well as possible environmental harmful effects. The aim of this study was to evaluate which are the most suitable production conditions, to transform SS into hydrochar. An additional goal of this work was to relate the hydrochars properties to its agronomic response. Therefore, hydrochars were produced from SS collected from the Experimental Wastewater Treatment plant of CENTA (http://www.centa.es/), located in Carrion de los Cespedes (Seville), under two different temperatures (200 and 260˚C) and residence times (30 min and 1h). With the hydrochars obtained, a greenhouse pot incubation study was carried out for 80 days. The pots contained 250 g of a Calcic Cambisol (IUSS Working Group WRB, 2007) and an amount of hydrochar equivalent to 5 and 25 t ha-1 were prepared in quadruplicate for each hydrochar using Lolium perenne as test plant (25 seeds per pot). Hydrochars were not washed before this experiment. Control pots, without hydrochar amendment, were also settled for comparison purposes (n=6). After adjusting the soil humidity to 60% of the maximum WHC, the pots were placed into a greenhouse under similar conditions than those reported by [3]. In this experiment germination, survival rates and biomass production per pot were measured periodically. Elemental analysis and the determination of several chemical properties of hydrochars such as pH, electrical conductivity and ash content were performed. Additionally, 13C solid-state nuclear magnetic resonance (NMR) was applied to elucidate the main chemical groups whereas fast field cycling (FFC) NMR relaxometry was valuable for investigating the porous structure and water dynamic in the different hydrochars. This work confirmed that production conditions of hydrochars vary their chemical properties and hence their agronomic effect. Biomass production raised significantly in presence of all hydrochars, being the response in presence of hydrochars produced at 200˚C significantly higher than the response in presence of hydrochars produced at 260˚C, whereas the residence time of the hydrochars in the reactor did not affect biomass productivity. Concerning the characterization data, hydrochars which showed the highest biomass production were those which contain the highest mineralized nitrogen content (NH4, NO2 and NO3) and a greater presence of alkyl carbons and carboxyl groups. Hydrochars FFC NMR relaxometry results show a lower T1 (longitudinal relaxation time) compared to the pure sewage sludge, which suggests that HTC processes reduced the average pore size of the system. This has further implications in the water and nutrient retention capacity of the hydrochars compared to the pure sewage sludge. Acknowledgements: The Marie Sklodowska-Curie actions of the EU 7th Framework People Programme (REA grant agreement PCIG12-GA-2012-333784-Biocharisma project) and the Spanish Ministry of Economy and Competitiveness (MINECO) (project PCGL2012-37041) are thanked for the financial support of the present study. The CSIC and the European Social Fund (ESF) are thanked for funding J.M. de la Rosa JAE-Doc contract. MINECO Spanish Ministry is thanked for funding the FPU fellowship (FPU 13/05831) of Marina Paneque. References: [1] Fytili D. and Zabaniotou A. (2008) Energy Reviews. 12, 116-140 [2] Libra JA, Ro KS, Kammann C, Funke A, Berge ND, Neubauer Y, Titirici MM, Fühner C, Bens O, Kern J, Emmerich KH (2011) Biofuels. 2, 89-124. [3] De la Rosa, Paneque M, Miller AZ, Knicker H (2014) Science of the Total Environment. 499, 175-184.

Drug-carrying microbubbles as a theranostic tool in convection-enhanced delivery for brain tumor therapy.

PubMed

Chen, Pin-Yuan; Yeh, Chih-Kuang; Hsu, Po-Hung; Lin, Chung-Yin; Huang, Chiung-Yin; Wei, Kuo-Chen; Liu, Hao-Li

2017-06-27

Convection-enhanced delivery (CED) is a promising technique for infusing a therapeutic agent through a catheter with a pressure gradient to create bulk flow for improving drug spread into the brain. So far, gadopentetate dimeglumine (Gd-DTPA) is the most commonly applied surrogate agent for predicting drug distribution through magnetic resonance imaging (MRI). However, Gd-DTPA provides only a short observation duration, and concurrent infusion provides an indirect measure of the exact drug distribution. In this study, we propose using microbubbles as a contrast agent for MRI monitoring, and evaluate their use as a drug-carrying vehicle to directly monitor the infused drug. Results show that microbubbles can provide excellent detectability through MRI relaxometry and accurately represent drug distribution during CED infusion. Compared with the short half-life of Gd-DTPA (1-2 hours), microbubbles allow an extended observation period of up to 12 hours. Moreover, microbubbles provide a sufficiently high drug payload, and glioma mice that underwent a CED infusion of microbubbles carrying doxorubicin presented considerable tumor growth suppression and a significantly improved survival rate. This study recommends microbubbles as a new theranostic tool for CED procedures.

Relaxometry model of strong dipolar perturbers for balanced-SSFP: application to quantification of SPIO loaded cells.

PubMed

Lebel, R Marc; Menon, Ravi S; Bowen, Chris V

2006-03-01

Magnetic resonance microscopy using magnetically labeled cells is an emerging discipline offering the potential for non-destructive studies targeting numerous cellular events in medical research. The present work develops a technique to quantify superparamagnetic iron-oxide (SPIO) loaded cells using fully balanced steady state free precession (b-SSFP) imaging. An analytic model based on phase cancellation was derived for a single particle and extended to predict mono-exponential decay versus echo time in the presence of multiple randomly distributed particles. Numerical models verified phase incoherence as the dominant contrast mechanism and evaluated the model using a full range of tissue decay rates, repetition times, and flip angles. Numerical simulations indicated a relaxation rate enhancement (DeltaR(2b)=0.412 gamma . LMD) proportional to LMD, the local magnetic dose (the additional sample magnetization due to the SPIO particles), a quantity related to the concentration of contrast agent. A phantom model of SPIO loaded cells showed excellent agreement with simulations, demonstrated comparable sensitivity to gradient echo DeltaR(*) (2) enhancements, and 14 times the sensitivity of spin echo DeltaR(2) measurements. We believe this model can be used to facilitate the generation of quantitative maps of targeted cell populations. Magn Reson Med, 2006. (c) 2006 Wiley-Liss, Inc.

NMR Investigations of Structure and Dynamics in Polymers for Energy Storage Applications

NASA Astrophysics Data System (ADS)

Greenbaum, Steven

Materials innovation is needed to realize major progress in energy storage capacity for lithium batteries and capacitors. Polymers hold considerable promise as ion conducting media in batteries and electrochemical capacitors and as dielectrics in thin film capacitors. Structural studies of materials utilized in lithium battery technology are hampered by the lack of long-range order found in well-defined crystalline phases. Powder x-ray diffraction yields structural parameters that have been averaged over hundreds of lattice sites, and is unable to provide structural information about amorphous phases. Our laboratory uses solid state nuclear magnetic resonance (NMR) methods to investigate structural and chemical aspects of lithium ion cathodes, anodes, electrolytes, interfaces and interphases. NMR is element- (nuclear-) specific and sensitive to small variations in the immediate environment of the ions being probed, for example Li+, and in most cases is a reliably quantitative spectroscopy in that the integrated intensity of a particular spectral component is directly proportional to the number of nuclei in the corresponding material phase. NMR is also a powerful tool for probing ionic and molecular motion in lithium battery electrolytes with a dynamic range spanning some ten orders of magnitude through spin-lattice relaxation and self-diffusion measurements. Broadband relaxometry based on Fast Field Cycling NMR (FFCNMR) methods can span three to four of these orders of magnitude in a single set of measurements. Results of several recent NMR investigations performed on our lab will be presented. We explore the ion transport mechanism in polyether-based and lithium polymer electrolytes and those based on other base polymers, in particular, the extent to which ionic motion is coupled to polymer segmental motion. Polycarbonates are being considered as a possible replacement for polypropylene in high power thin film capacitors due to their favorable dielectric properties. We investigate the effects of incorporation of two types of additives in the polymer film on the ring-flip motions corresponding to the γ relaxation: (i) high dielectric constant ceramic particles; (ii) polar organic diluent molecules, The low frequency realm of broadband relaxometry allows meaningful comparison with dielectric relaxation studies of these samples performed by collaborators. Work Supported in part by the U.S. Office of Naval Research.

Mediation of Developmental Risk Factors for Psychosis by White Matter Microstructure in Young Adults With Psychotic Experiences.

PubMed

Drakesmith, Mark; Dutt, Anirban; Fonville, Leon; Zammit, Stanley; Reichenberg, Abraham; Evans, C John; Lewis, Glyn; Jones, Derek K; David, Anthony S

2016-04-01

White matter (WM) abnormalities have been identified in schizophrenia at the earliest stages of the disorder. Individuals in the general population with psychotic experiences (PEs) may show similar changes, suggesting dysfunction due to aberrant neurodevelopment. Studying such people is a powerful means of understanding the nature of neurodevelopmental problems without the confound of clinical management and allows other potential risk factors associated with the schizophrenia spectrum to be taken into account. To compare WM microstructure and myelination in young adults with and without PEs identified from a population-based cohort using diffusion and relaxometry magnetic resonance imaging and to quantify potential mediating effects of WM on several known risk factors for psychosis. In this case-control study, participants were drawn from the UK Avon Longitudinal Study of Parents and Children. Psychotic experiences were assessed using a semistructured interview. Magnetic resonance imaging was carried out at age 20 years in 123 participants who had PEs and 124 individuals serving as controls. Participants with PEs were subdivided into those with operationally defined suspected PEs, definite PEs, and psychotic disorder. Diffusion tensor magnetic resonance imaging and relaxometry-derived myelin water fractions were used to measure WM microstructure and myelination, respectively. Differences in quantitative WM indices were assessed using tract-based spatial statistics. A binary model and a continuum-like ordinal model of PEs were tested. Among the 123 participants who had PEs (mean [SE] age, 20.01 [0.004] years), 37 were male and 86 were female. Among the 124 controls (mean [SE] age, 20.11 [0.004] years), 49 were male and 76 were female. Fractional anisotropy in left frontomedial WM was significantly reduced in individuals with PEs (Montreal Neurological Institute [MNI] coordinates, -18, 37, -2; P = .0046). The ordinal model identified a similar but more widespread effect, with a corresponding increase in radial diffusivity (MNI coordinates, -15, 29, 21; P = .0042). Low birth weight (ρ = -0.155; P = .015) and childhood IQ (ρ = -0.188; P = .003) were associated with the presence of PEs. Results of mediation analysis were consistent with the association between birth weight (21.1% mediation effect; P = 6.20 × 10-3) and childhood IQ (7.9% mediation effect; P = .041) and by PEs being mediated by fractional anisotropy changes in these regions. The results of the study imply the presence of abnormal WM microstructure in young adults with PEs. The results are consistent with the hypothesis that neurodevelopmental factors cause alterations in the cellular composition of WM circuits critical to higher cognitive function. Such alterations may first manifest in childhood as reduced IQ and later contribute to PEs in early adulthood.

Whole-brain ex-vivo quantitative MRI of the cuprizone mouse model

PubMed Central

Hurley, Samuel A.; Vernon, Anthony C.; Torres, Joel; Dell’Acqua, Flavio; Williams, Steve C.R.; Cash, Diana

2016-01-01

Myelin is a critical component of the nervous system and a major contributor to contrast in Magnetic Resonance (MR) images. However, the precise contribution of myelination to multiple MR modalities is still under debate. The cuprizone mouse is a well-established model of demyelination that has been used in several MR studies, but these have often imaged only a single slice and analysed a small region of interest in the corpus callosum. We imaged and analyzed the whole brain of the cuprizone mouse ex-vivo using high-resolution quantitative MR methods (multi-component relaxometry, Diffusion Tensor Imaging (DTI) and morphometry) and found changes in multiple regions, including the corpus callosum, cerebellum, thalamus and hippocampus. The presence of inflammation, confirmed with histology, presents difficulties in isolating the sensitivity and specificity of these MR methods to demyelination using this model. PMID:27833805

The quest for biocompatible phthalocyanines for molecular imaging: Photophysics, relaxometry and cytotoxicity studies.

PubMed

Pinto, Sara M A; Tomé, Vanessa A; Calvete, Mário J F; Pereira, Mariette M; Burrows, Hugh D; Cardoso, Ana M S; Pallier, Agnès; C A Castro, M Margarida; Tóth, Éva; Geraldes, Carlos F G C

2016-01-01

Water soluble phthalocyanines bearing either four PEG500 or four choline substituents in the macrocyclic structure, as well as their Zn(II) and Mn(III) complexes were synthesized. The metal-free and Zn(II) complexes present relatively high fluorescence quantum yields (up to 0.30), while the Mn(III) complexes show no fluorescence as a consequence of rapid non-radiative deactivation of the Mn(III) phthalocyanine excited states through low-lying metal based or charge-transfer states. The effect of DMSO on the aggregation of the phthalocyanines was studied. It was not possible to obtain the Mn(II) complexes by reduction of the corresponding Mn(III) complexes due to the presence of electron donating substituents at the periphery of the phthalocyanines. The (1)H NMRD plots of the PEG500 and choline substituted Mn(III)-phthalocyanine complexes are typical of self-aggregated Mn(III) systems with r1 relaxivities of 4.0 and 5.7mM(-1)s(-1) at 20MHz and 25°C. The Mn(III)-phthalocyanine-PEG4 complex shows no significant cytotoxicity to HeLa cell cultures after 2h of incubation up to 2mM concentration. After 24h of cell exposure to the compound, significant toxicity was observed for all the concentrations tested with IC50 of 1.105mM. Copyright © 2015 Elsevier Inc. All rights reserved.

Proton Relaxivity and Magnetic Hyperthermia Evaluation of Gadolinium Doped Nickel Ferrite Nanoparticles as Potential Theranostic Agents.

PubMed

Yadavalli, Tejabhiram; Raja, Paradeep; Ramaswamy, Shivaraman; Chandrasekharan, Gopalakrishnan; Chennakesavulu, Ramasamy

2017-02-01

This paper outlines the preparation of gadolinium doped nickel ferrite nanoparticles as potential magnetic carriers and longitudinal magnetic resonance imaging contrast agents using hydrothermal method with gadolinium concentration varying from 10% to 40%. A concise effect on the crystal structure was observed at 10% and 20% gadolinium doping, while gadolinium oxide was observed to leach at concentrations exceeding 20%. Further, gadolinium doped nickel ferrites were analyzed for their morphological, magnetic, proton relaxation and magnetic hyperthermia heating properties to understand their potential role as magnetic carrier agents. Low temperature and room temperature magnetic studies conducted on the samples showed comparatively high magnetic saturation with low remanent magnetization. Further, relaxometry studies revealed a high relaxation rate of 6.63 s−1 at a concentration of 0.1 mg/mL. Magnetic hyperthermia studies of the samples at a concentration of 1 mg/mL, assessed that the samples attained a temperature of 68 °C in 240 seconds.

Altered brain morphology and functional connectivity reflect a vulnerable affective state after cumulative multigenerational stress in rats.

PubMed

McCreary, J Keiko; Truica, L Sorina; Friesen, Becky; Yao, Youli; Olson, David M; Kovalchuk, Igor; Cross, Albert R; Metz, Gerlinde A S

2016-08-25

Prenatal stress is a risk factor for abnormal neuroanatomical, cognitive, behavioral and mental health outcomes with potentially transgenerational consequences. Females in general seem more resilient to the effects of prenatal stress than males. Here, we examined if repeated stress across generations may diminish stress resiliency and cumulatively enhance the susceptibility for adverse health outcomes in females. Pregnant female rats of three successive generations were exposed to stress from gestational days 12-18 to generate multigenerational prenatal stress (MPS) in the maternal lineage. Stress response was measured by plasma corticosterone levels and open-field exploration in each generation. Neuromorphological consequences of MPS were investigated in the F3 generation using in vivo manganese-enhanced magnetic resonance imaging (MEMRI), T2-relaxometry, and cytoarchitectonics in relation to candidate gene expression involved in brain plasticity and mental health. Each additional generation of prenatal stress incrementally elevated hypothalamic-pituitary-adrenal axis activation, anxiety-like and aversive behaviors in adult female offspring. Elevated stress responses in the MPS F3 generation were accompanied by reduced neural density in prefrontal cortex, hippocampus and whole brain along with altered brain activation patterns in in vivo MEMRI. MPS increased ephrin receptor A5 (Epha5), neuronal growth regulator (Negr1) and synaptosomal-associated protein 25 (Snap25) gene expression and reduced fibroblast growth factor 12 (Fgf12) in prefrontal cortex. These genes regulate neuronal maturation, arborization and synaptic plasticity and may explain altered brain cytoarchitectonics and connectivity. These findings emphasize that recurrent stress across generations may cumulatively increase stress vulnerability and the risk of adverse health outcomes through perinatal programing in females. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Nanometer-scale water- and proton-diffusion heterogeneities across water channels in polymer electrolyte membranes.

PubMed

Song, Jinsuk; Han, Oc Hee; Han, Songi

2015-03-16

Nafion, the most widely used polymer for electrolyte membranes (PEMs) in fuel cells, consists of a fluorocarbon backbone and acidic groups that, upon hydration, swell to form percolated channels through which water and ions diffuse. Although the effects of the channel structures and the acidic groups on water/ion transport have been studied before, the surface chemistry or the spatially heterogeneous diffusivity across water channels has never been shown to directly influence water/ion transport. By the use of molecular spin probes that are selectively partitioned into heterogeneous regions of the PEM and Overhauser dynamic nuclear polarization relaxometry, this study reveals that both water and proton diffusivity are significantly faster near the fluorocarbon and the acidic groups lining the water channels than within the water channels. The concept that surface chemistry at the (sub)nanometer scale dictates water and proton diffusivity invokes a new design principle for PEMs. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Osmoregulation in Methanogens (and Other Interesting Organisms)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roberts, Mary Fedarko

2014-12-03

Our research has been aimed at (i) identifying, (ii) determining mode of regulation, and (iii) understanding how different classes of compatible solutes (also termed osmolytes) affect macromolecular stability in response to osmotic and thermal stress. For solutes we have identified (e.g., di-inositol-1,1’-phosphate (DIP)), we used NMR to elucidate biosynthetic pathways and then cloned suspected enzymes in the pathway to explore how they are regulated. Compatible solutes are thought to protect proteins from thermal and osmotic stresses by being excluded from the surface, allowing critical water molecules to interact with the protein. This implies there are no specific binding interactions betweenmore » osmolytes and proteins. However, we and others have often observed very specific solute effects for proteins that suggest a more direct interaction between solute and protein is likely can occur. Measuring such a weak interaction is extremely difficult. We have developed a solution NMR method, high-resolution field cycling relaxometry, that can measure spin-lattice relaxation rates as a function of magnetic field from 11.7 (the field of a 500 MHz spectrometer) to 0.003 T. The methodology is ideal for nuclei in small molecules with moderately long relaxation times at high fields – phosphate groups (31P), enriched carbonyls (13C), or methyl groups (1H). The protein of interest is spin-labeled to introduce a large dipole on it that will dominate the relaxation of nuclei on any small molecules that bind transiently. The key is to measure relaxation below 1-2 T (and extract nuclei-spin label distances in the bound complex) where the small molecule relaxation will be dominated by dipolar mechanisms with a correlation time indicative of the large protein complex. Our explorations of an inositol monophosphatase (the last step in DIP generation) localized four discrete binding sides for the thermoprotectant α-glutamate. This is a novel approach, and while the work did not fully explain how this solute protected the IMPase from thermal denaturation, it did showcase a new and exciting method to monitor weak binding in biological systems.« less

Composting-derived organic coating on biochar enhances its affinity to nitrate

NASA Astrophysics Data System (ADS)

Hagemann, Nikolas; Joseph, Stephen; Conte, Pellegrino; Albu, Mihaela; Obst, Martin; Borch, Thomas; Orsetti, Silvia; Subdiaga, Edisson; Behrens, Sebastian; Kappler, Andreas

2017-04-01

Biochar is defined charcoal that is produced by the thermal treatment of biomass in the (partial) absence of oxygen (pyrolysis) for non-oxidative applications, especially in agriculture. Due to its high surface area and porous structure, it is suggested as a beneficial soil amendment to increase crop yields and to tailor biogeochemical cycles in agro-ecosystems to reduce both greenhouse gas emissions and nutrient leaching. While early research focused on single applications of large amounts of biochar (>10 t ha-1), economic and ecological boundaries as well as practical considerations and recent findings shifted the focus towards low-dose (˜1 t ha-1) and potentially repeated applications of nutrient-enriched biochars, i.e. biochar-based fertilizers in the root-zone. Thus, biochar must be "loaded" with nutrients prior to its use as a root-zone amendment. Co-composting is suggested as a superior method, as co-composted biochar was shown to promote plant growth and showed the desired slow release of nutrients such as nitrate ("nitrate capture", Kammann et al., 2015 SR5:11080). However, the underlying mechanisms are not understood and nitrate capture has been quantified only for isolated biochars but not for e.g. biochar-amended composts without prior separation of the biochar. In the present study, we used repeated extractions with 2 M KCl and found that up to 30% of the nitrate present in a biochar-amended compost is captured in biochar, although biochar was amended to the initial composting feedstock (manure) only at 4% (w/w). Additionally, we quantified nitrate capture by pristine biochar after soaking the biochar in NH4NO3 solution in the absence of any additional organic carbon and nitrate capture of separated co-composted biochar. Assuming pseudo-first order kinetics for biochar nitrate release, we found an increase of biochar's affinity to nitrate after co-composting. Spectro-microscopical investigations (scanning transmission electron microscopy with electron energy loss spectroscopy - STEM-EELS, scanning transmission X-ray microscopy STXM) revealed the formation of a nano-porous organic coating on co-composted biochar. This coating alters the interaction of biochar with water as evidenced by proton fast field cycling nuclear magnetic resonance (1H FFC NMR) relaxometry and might explain its distinct characteristics. Our findings offer a roadmap for future research to design sustainable slow-release nitrogen fertilizers based on biochar to reduce the environmental impact of agriculture. Further microscopic studies are necessary to understand the preconditions of the formation of organic coatings on biochar on a holistic basis to design biochar post-production treatments.

The influence of silanized nano-SiO{sub 2} on the hydration of cement paste: NMR investigations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bede, A., E-mail: Andrea.Bede@phys.utcluj.ro; Pop, A.; Ardelean, I.

2015-12-23

It is known that by adding a small amount of nanoparticles to the cement-based materials a strong influence on the workability, strength and durability is obtained. These characteristics of the material are fundamentally determined by the hydration process taking place after mixing the cement grains with water. In the present study the influence introduced by the addition of nano-silica with silanized surfaces on the hydration process was investigated using low-field nuclear magnetic resonance (NMR) relaxometry. The cement samples were prepared using gray cement at a water-to-cement ratio of 0.4 and a 5% addition of nanosilica. The surface of the nanoparticlesmore » was modified using a coating of Silane A174. The cement pastes were monitored during their standard curing time of 28 days. It was established that, by using unmodified nanosilica particles, an acceleration of the hydration process takes place as compared with the pure cement paste. On the other side, by adding silanized nanoparticles, the dormancy stage significantly extends and the hydration process is slower. This slowing down process could enhance the mechanical strength of cement based materials as a result of a better compaction of the hydrated samples.« less

Quantifying Contributions to Transport in Ionic Polymers Across Multiple Length Scales

NASA Astrophysics Data System (ADS)

Madsen, Louis

Self-organized polymer membranes conduct mobile species (ions, water, alcohols, etc.) according to a hierarchy of structural motifs that span sub-nm to >10 μm in length scale. In order to comprehensively understand such materials, our group combines multiple types of NMR dynamics and transport measurements (spectroscopy, diffusometry, relaxometry, imaging) with structural information from scattering and microscopy as well as with theories of porous media,1 electrolytic transport, and oriented matter.2 In this presentation, I will discuss quantitative separation of the phenomena that govern transport in polymer membranes, from intermolecular interactions (<= 2 nm),3 to locally ordered polymer nanochannels (a few to 10s of nm),2 to larger polymer domain structures (10s of nm and larger).1 Using this multi-scale information, we seek to give informed feedback on the design of polymer membranes for use in, e . g . , efficient batteries, fuel cells, and mechanical actuators. References: [1] J. Hou, J. Li, D. Mountz, M. Hull, and L. A. Madsen. Journal of Membrane Science448, 292-298 (2013). [2] J. Li, J. K. Park, R. B. Moore, and L. A. Madsen. Nature Materials 10, 507-511 (2011). [3] M. D. Lingwood, Z. Zhang, B. E. Kidd, K. B. McCreary, J. Hou, and L. A. Madsen. Chemical Communications 49, 4283 - 4285 (2013).

Osmotic dehydration of organic kiwifruit pre-treated by pulsed electric fields and monitored by NMR.

PubMed

Traffano-Schiffo, Maria Victoria; Laghi, Luca; Castro-Giraldez, Marta; Tylewicz, Urszula; Rocculi, Pietro; Ragni, Luigi; Dalla Rosa, Marco; Fito, Pedro J

2017-12-01

Osmotic dehydration (OD) is a widely used preservation technique that consists in the reduction in food water activity by the immersion of the biological tissue in hypertonic solutions. The aim of this work was to analyze the effect of pulsed electric fields (PEF) in mass transfer as a pre-treatment of the OD using NMR. In this sense, PEF pre-treatments were done using three different voltages (100, 250 and 400V/cm) and 60 number of pulse. The OD of kiwifruit was carried out in 61.5% of sucrose solution at 25°C, for a contact period from 0 to 120min. The water distribution into the cellular tissue was studied by NMR relaxometry. In conclusion, NMR is an excellent technique for quantifying water molecules according to their interactions in the fruit tissue, obtaining the adsorbed water and opening the possibility to apply the BET model to fit the adsorbed isotherm over the whole range of water activity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Metabolism variation and better storability of dark- versus light-coloured soybean (Glycine max L. Merr.) seeds.

PubMed

Liu, Jiang; Qin, Wen-Ting; Wu, Hai-Jun; Yang, Cai-Qiong; Deng, Jun-Cai; Iqbal, Nasir; Liu, Wei-Guo; Du, Jun-Bo; Shu, Kai; Yang, Feng; Wang, Xiao-Chun; Yong, Tai-Wen; Yang, Wen-Yu

2017-05-15

The effects of storage duration on the seed germination and metabolite profiling of soybean seeds with five different coloured coats were studied. Their germination, constituents and transcript expressions of isoflavones and free fatty acids (FFAs) were compared using chromatographic metabolomic profiling and transcriptome sequencing. The seed water content was characterized using nuclear magnetic resonance (NMR) relaxometry. Results showed that dark-coloured seeds were less inactivated than light-coloured seeds. The aglycone and β-glucoside concentrations of upstream constituents increased significantly, whereas the acetylglucosides and malonylglucosides of downstream constituents decreased with an increase in the storage period. FFAs increased considerably in the soybean seeds as a result of storage. These results indicate that dark-coloured soybean seeds have better storability than light-coloured seeds, and seed water content plays a role in seed inactivation. It was concluded that there are certain metabolic regularities that are associated with different coloured seed coats of soybeans under storage conditions. Copyright © 2016 Elsevier Ltd. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Braun, Efrem; Chen, Joseph J.; Schnell, Sondre K.

Molecular simulations and NMR relaxometry experiments demonstrate that pure benzene or xylene confined in isoreticular metal–organic frameworks (IRMOFs) exhibit true vapor–liquid phase equilibria where the effective critical point may be reduced by tuning the structure of the MOF. Our results are consistent with vapor and liquid phases extending over many MOF unit cells. These results are counterintuitive since the MOF pore diameters are approximately the same length scale as the adsorbate molecules. As applications of these materials in catalysis, separations, and gas storage rely on the ability to tune the properties of adsorbed molecules, we anticipate that the ability tomore » systematically control the critical point, thereby preparing spatially inhomogeneous local adsorbate densities, could add a new design tool for MOF applications.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Braun, Efrem; Chen, Joseph J.; Schnell, Sondre K.

Molecular simulations and NMR relaxometry experiments demonstrate that pure benzene or xylene confined in isoreticular metal–organic frameworks (IRMOFs) exhibit true vapor–liquid phase equilibria where the effective critical point may be reduced by tuning the structure of the MOF. Our results are consistent with vapor and liquid phases extending over many MOF unit cells. These results are counterintuitive since the MOF pore diameters are approximately the same length scale as the adsorbate molecules. Lastly, as applications of these materials in catalysis, separations, and gas storage rely on the ability to tune the properties of adsorbed molecules, we anticipate that the abilitymore » to systematically control the critical point, thereby preparing spatially inhomogeneous local adsorbate densities, could add a new design tool for MOF applications.« less

Association of Amyloid Pathology With Myelin Alteration in Preclinical Alzheimer Disease.

PubMed

Dean, Douglas C; Hurley, Samuel A; Kecskemeti, Steven R; O'Grady, J Patrick; Canda, Cristybelle; Davenport-Sis, Nancy J; Carlsson, Cynthia M; Zetterberg, Henrik; Blennow, Kaj; Asthana, Sanjay; Sager, Mark A; Johnson, Sterling C; Alexander, Andrew L; Bendlin, Barbara B

2017-01-01

The accumulation of aggregated β-amyloid and tau proteins into plaques and tangles is a central feature of Alzheimer disease (AD). While plaque and tangle accumulation likely contributes to neuron and synapse loss, disease-related changes to oligodendrocytes and myelin are also suspected of playing a role in development of AD dementia. Still, to our knowledge, little is known about AD-related myelin changes, and even when present, they are often regarded as secondary to concomitant arteriosclerosis or related to aging. To assess associations between hallmark AD pathology and novel quantitative neuroimaging markers while being sensitive to white matter myelin content. Magnetic resonance imaging was performed at an academic research neuroimaging center on a cohort of 71 cognitively asymptomatic adults enriched for AD risk. Lumbar punctures were performed and assayed for cerebrospinal fluid (CSF) biomarkers of AD pathology, including β-amyloid 42, total tau protein, phosphorylated tau 181, and soluble amyloid precursor protein. We measured whole-brain longitudinal and transverse relaxation rates as well as the myelin water fraction from each of these individuals. Automated brain mapping algorithms and statistical models were used to evaluate the relationships between age, CSF biomarkers of AD pathology, and quantitative magnetic resonance imaging relaxometry measures, including the longitudinal and transverse relaxation rates and the myelin water fraction. The mean (SD) age for the 19 male participants and 52 female participants in the study was 61.6 (6.4) years. Widespread age-related changes to myelin were observed across the brain, particularly in late myelinating brain regions such as frontal white matter and the genu of the corpus callosum. Quantitative relaxometry measures were negatively associated with levels of CSF biomarkers across brain white matter and in areas preferentially affected in AD. Furthermore, significant age-by-biomarker interactions were observed between myelin water fraction and phosphorylated tau 181/β-amyloid 42, suggesting that phosphorylated tau 181/β-amyloid 42 levels modulate age-related changes in myelin water fraction. These findings suggest amyloid pathologies significantly influence white matter and that these abnormalities may signify an early feature of the disease process. We expect that clarifying the nature of myelin damage in preclinical AD may be informative on the disease's course and lead to new markers of efficacy for prevention and treatment trials.

Association of Amyloid Pathology With Myelin Alteration in Preclinical Alzheimer Disease

PubMed Central

Dean, Douglas C.; Hurley, Samuel A.; Kecskemeti, Steven R.; O’Grady, J. Patrick; Canda, Cristybelle; Davenport-Sis, Nancy J.; Carlsson, Cynthia M.; Zetterberg, Henrik; Blennow, Kaj; Asthana, Sanjay; Sager, Mark A.; Johnson, Sterling C.; Alexander, Andrew L.; Bendlin, Barbara B.

2016-01-01

IMPORTANCE The accumulation of aggregated β-amyloid and tau proteins into plaques and tangles is a central feature of Alzheimer disease (AD). While plaque and tangle accumulation likely contributes to neuron and synapse loss, disease-related changes to oligodendrocytes and myelin are also suspected of playing a role in development of AD dementia. Still, to our knowledge, little is known about AD-related myelin changes, and even when present, they are often regarded as secondary to concomitant arteriosclerosis or related to aging. OBJECTIVE To assess associations between hallmark AD pathology and novel quantitative neuroimaging markers while being sensitive to white matter myelin content. DESIGN, SETTING, AND PARTICIPANTS Magnetic resonance imaging was performed at an academic research neuroimaging center on a cohort of 71 cognitively asymptomatic adults enriched for AD risk. Lumbar punctures were performed and assayed for cerebrospinal fluid (CSF) biomarkers of AD pathology, including β-amyloid 42, total tau protein, phosphorylated tau 181, and soluble amyloid precursor protein. We measured whole-brain longitudinal and transverse relaxation rates as well as the myelin water fraction from each of these individuals. MAIN OUTCOMES AND MEASURES Automated brain mapping algorithms and statistical models were used to evaluate the relationships between age, CSF biomarkers of AD pathology, and quantitative magnetic resonance imaging relaxometry measures, including the longitudinal and transverse relaxation rates and the myelin water fraction. RESULTS The mean (SD) age for the 19 male participants and 52 female participants in the study was 61.6 (6.4) years. Widespread age-related changes to myelin were observed across the brain, particularly in late myelinating brain regions such as frontal white matter and the genu of the corpus callosum. Quantitative relaxometry measures were negatively associated with levels of CSF biomarkers across brain white matter and in areas preferentially affected in AD. Furthermore, significant age-by-biomarker interactions were observed between myelin water fraction and phosphorylated tau 181/β-amyloid 42, suggesting that phosphorylated tau 181/β-amyloid 42 levels modulate age-related changes in myelin water fraction. CONCLUSIONS AND RELEVANCE These findings suggest amyloid pathologies significantly influence white matter and that these abnormalities may signify an early feature of the disease process. We expect that clarifying the nature of myelin damage in preclinical AD may be informative on the disease’s course and lead to new markers of efficacy for prevention and treatment trials. PMID:27842175

Advances in multiphase flow measurements using magnetic resonance relaxometry

NASA Astrophysics Data System (ADS)

Kantzas, Apostolos; Kryuchkov, Sergey; Chandrasekaran, Blake

2009-02-01

When it comes to the measurement of bitumen and water content as they are produced from thermally exploited reservoirs (cyclic steam stimulation or steam assisted gravity drainage) most of the current tools that are available in the market fail. This was demonstrated previously when our group introduced the first concept of a magnetic resonance based water-cut meter. The use of magnetic resonance as a potential tool for fluid cut metering from thermally produced heavy oil and bitumen reservoirs is revisited. At first a review of the work to date is presented. Our recent approach in the tackling of this problem follows. A patented process is coupled with a patented pipe design that can be used inside a magnetic field and can capture fluids up to 260°C and 4.2MPa. The paper describes the technical advances to this goal and offers a first glimpse of field data from an actual thermal facility for bitumen production. The paper also addresses an approach for converting the current discrete measurement device into a continuous measurement system. Preliminary results for this new concept are also presented.

Thermodynamic stability and relaxation studies of small, triaza-macrocyclic Mn(II) chelates.

PubMed

de Sá, Arsénio; Bonnet, Célia S; Geraldes, Carlos F G C; Tóth, Éva; Ferreira, Paula M T; André, João P

2013-04-07

Due to its favorable relaxometric properties, Mn(2+) is an appealing metal ion for magnetic resonance imaging (MRI) contrast agents. This paper reports the synthesis and characterization of three new triazadicarboxylate-type ligands and their Mn(2+) chelates (NODAHep, 1,4,7-triazacyclononane-1,4-diacetate-7-heptanil; NODABA, 1,4,7-triazacyclononane-1,4-diacetate-7-benzoic acid; and NODAHA, 1,4,7-triazacyclononane-1,4-diacetate-7-hexanoic acid). The protonation constants of the ligands and the stability constants of the chelates formed with Mn(2+) and the endogenous Zn(2+) ion have been determined by potentiometry. In overall, the thermodynamic stability of the chelates is lower than that of the corresponding NOTA analogues (NOTA = 1,4,7-triazacyclononane-1,4,7-triacetate), consistent with the decreased number of coordinating carboxylate groups. Variable temperature (1)H NMRD and (17)O NMR measurements have been performed on the paramagnetic chelates to provide information on the water exchange rates and the rotational dynamics. The values of the (17)O chemical shifts are consistent with the presence of one water molecule in the first coordination sphere of Mn(2+). The three complexes are in the slow to intermediate regime for the water exchange rate, and they all display relatively high rotational correlation times, which explain the relaxivity values between 4.7 and 5.8 mM(-1) s(-1) (20 MHz and 298 K). These relaxivities are higher than expected for Mn(2+) chelates of such size and comparable to those of small monohydrated Gd(3+) complexes. The amphiphilic [Mn(NODAHep)] forms micelles above 22 mM (its critical micellar concentration was determined by relaxometry and fluorescence), and interacts with HSA via its alkylic carbon chain providing a 60% relaxivity increase at 20 MHz due to a longer tumbling time.

Mechanism of drug release from silica-gelatin aerogel-Relationship between matrix structure and release kinetics.

PubMed

Veres, Péter; Kéri, Mónika; Bányai, István; Lázár, István; Fábián, István; Domingo, Concepción; Kalmár, József

2017-04-01

Specific features of a silica-gelatin aerogel (3 wt.% gelatin content) in relation to drug delivery has been studied. It was confirmed that the release of both ibuprofen (IBU) and ketoprofen (KET) is about tenfold faster from loaded silica-gelatin aerogel than from pure silica aerogel, although the two matrices are structurally very similar. The main goal of the study was to understand the mechanistic background of the striking difference between the delivery properties of these closely related porous materials. Hydrated and dispersed silica-gelatin aerogel has been characterized by NMR cryoporometry, diffusiometry and relaxometry. The pore structure of the silica aerogel remains intact when it disintegrates in water. In contrast, dispersed silica-gelatin aerogel develops a strong hydration sphere, which reshapes the pore walls and deforms the pore structure. The drug release kinetics was studied on a few minutes time scale with 1s time resolution. Simultaneous evaluation of all relevant kinetic and structural information confirmed that strong hydration of the silica-gelatin skeleton facilitates the rapid desorption and dissolution of the drugs from the loaded aerogel. Such a driving force is not operative in pure silica aerogels. Copyright © 2017 Elsevier B.V. All rights reserved.

An investigation into the effects of pore connectivity on T2 NMR relaxation

NASA Astrophysics Data System (ADS)

Ghomeshi, Shahin; Kryuchkov, Sergey; Kantzas, Apostolos

2018-04-01

Nuclear Magnetic Resonance (NMR) is a powerful technique used to characterize fluids and flow in porous media. The NMR relaxation curves are closely related to pore geometry, and the inversion of the NMR relaxometry data is known to give useful information with regards to pore size distribution (PSD) through the relative amplitudes of the fluids stored in the small and large pores. While this information is crucial, the main challenge for the successful use of the NMR measurements is the proper interpretation of the measured signals. Natural porous media patterns consist of complex pore structures with many interconnected or "coupled" regions, as well as isolated pores. This connectivity along the throats changes the relaxation distribution and in order to properly interpret this data, a thorough understanding of the effects of pore connectivity on the NMR relaxation distribution is warranted. In this paper we address two main points. The first pertains to the fact that there is a discrepancy between the relaxation distribution obtained from experiments, and the ones obtained from solving the mathematical models of diffusion process in the digitized images of the pore space. There are several reasons that may attribute to this such as the lack of a proper incorporation of surface roughness into the model. However, here we are more interested in the effects of pore connectivity and to understand why the typical NMR relaxation distribution obtained from experiments are wider, while the numerical simulations predict that a wider NMR relaxation distribution may indicate poor connectivity. Secondly, by not taking into account the pore coupling effects, from our experience in interpreting the data, we tend to underestimate the pore volume of small pores and overestimate the amplitudes in the large pores. The role of pore coupling becomes even more prominent in rocks with small pore sizes such as for example in shales, clay in sandstones, and in the microstructures of carbonates.

Nanoporous Materials Can Tune the Critical Point of a Pure Substance

DOE PAGES

Braun, Efrem; Chen, Joseph J.; Schnell, Sondre K.; ...

2015-09-30

Molecular simulations and NMR relaxometry experiments demonstrate that pure benzene or xylene confined in isoreticular metal–organic frameworks (IRMOFs) exhibit true vapor–liquid phase equilibria where the effective critical point may be reduced by tuning the structure of the MOF. Our results are consistent with vapor and liquid phases extending over many MOF unit cells. These results are counterintuitive since the MOF pore diameters are approximately the same length scale as the adsorbate molecules. Lastly, as applications of these materials in catalysis, separations, and gas storage rely on the ability to tune the properties of adsorbed molecules, we anticipate that the abilitymore » to systematically control the critical point, thereby preparing spatially inhomogeneous local adsorbate densities, could add a new design tool for MOF applications.« less

The gelation influence on diffusion and conductivity enhancement effect in renewable ionic gels based on a LMWG.

PubMed

Bielejewski, M; Rachocki, A; Kaszyńska, J; Tritt-Goc, J

2018-02-21

This paper reports the interdisciplinary study on molecular dynamics, ionic interactions and electrical conductivity in a quaternary ammonium salt (TMABr) ionogel based on a low molecular weight gelator (LMWG) in a wide range of electrolyte molar concentrations. The thermal scanning conductometry (TSC) was used to investigate the electric properties of the ionogels. The prepared TMABr/H 2 O/LMWG ionogel exhibits better ion transport properties than the dissociated TMA + cation in solution. The enhanced ionic conductivity effect (EICE) was observed in the concentration range of the TMABr salt up to 1 M. To investigate the transport properties of the TMA + cation and solvent molecules in the gel and sol phase, the NMR diffusiometry method was used. The field-cycling relaxometry method (FFC NMR) was applied to study the local motions of the electrolyte at the surface of the gelator matrix. On the basis of the obtained data, the higher ionic conductivity observed in the gel phase has been related to the microstructure of the gel matrix. The possible explanation for the origin of this effect has been given. The investigated system is a thermally reversible physical gel, all registered data were reproducible upon transforming the sample from gel to sol and back to the gel state, confirming the enhancement effect as a permanent property of the investigated ionogels. Therefore, the EICE has been proposed to be used as an internal sensor to monitor the condition of the ionogel phase, thus making them smart materials.

Isotope effects associated with tunneling and double proton transfer in the hydrogen bonds of benzoic acid

NASA Astrophysics Data System (ADS)

Xue, Q.; Horsewill, A. J.; Johnson, M. R.; Trommsdorff, H. P.

2004-06-01

The isotope effects associated with double proton transfer in the hydrogen bonds of benzoic acid (BA) dimers have been measured using field-cycling 1H NMR relaxometry and quasielastic neutron scattering. By studying mixed isotope (hydrogen and deuterium) samples, the dynamics of three isotopologues, BA-HH, BA-HD, and BA-DD, have been investigated. Low temperature measurements provide accurate measurements of the incoherent tunneling rate, k0. This parameter scales accurately with the mass number, m, according to the formula k0=(E/m)e-F√m providing conclusive evidence that the proton transfer process is a strongly correlated motion of two hydrons. Furthermore, we conclude that the tunneling pathway is the same for the three isotopologue species. Measurements at higher temperatures illuminate the through barrier processes that are mediated via intermediate or excited vibrational states. In parallel with the investigation of proton transfer dynamics, the theoretical and experimental aspects of studying spin-lattice relaxation in single crystals of mixed isotope samples are investigated in depth. Heteronuclear dipolar interactions between 1H and 2H isotopes contribute significantly to the overall proton spin-lattice relaxation and it is shown that these must be modeled correctly to obtain accurate values for the proton transfer rates. Since the sample used in the NMR measurements was a single crystal, full account of the orientation dependence of the spin-lattice relaxation with respect to the applied B field was incorporated into the data analysis.

NMR relaxometric properties and cytotoxicity of Gd2O3 nanoparticle suspensions in an organic liquid

NASA Astrophysics Data System (ADS)

Babić-Stojić, Branka; Jokanović, Vukoman; Milivojević, Dušan; Požek, Miroslav; Jagličić, Zvonko; Makovec, Darko; Arsikin, Katarina; Paunović, Verica

2014-10-01

Gd2O3 nanoparticles and their agglomerates from approximately 10 to 80 nm in size suspended in an organic liquid were synthesized via polyol route. The reaction between diethylene glycol and added acetic acid, which occurred simultaneously with the synthesis of Gd2O3 nanoparticles, was catalyzed by sodium bisulfate to transform as much as possible diethylene glycol in corresponding ester at the end of complete reaction. The produced nanosized material of gadolinium oxide was investigated by TEM, DLS, FTIR spectroscopy, and NMR relaxometry. Biological evaluation of this material was done by MTT and crystal violet assays to determine the cell viability. Longitudinal and transverse relaxivities of water-diluted Gd2O3 nanoparticle suspensions estimated to be r 1 = 13.6 and r 2 = 14.7 s-1 mM-1 are about three times higher compared to the relaxivities obtained for standard contrast agent Gd-DTPA (Magnevist). Good MRI signal intensities of the water-diluted Gd2O3 nanoparticle suspensions were recorded in the Gd concentration range 0.2-0.3 mM for which the suspensions were not toxic exhibiting simultaneously higher signal intensities than those for Magnevist in the Gd concentration range 0.4-1 mM for which this standard contrast agent was not toxic. These properties make the produced Gd2O3 nanoparticle material promising for potential application as MRI contrast agent.

An NMR relaxometry and gravimetric study of gelatin-free aqueous polyacrylamide dosimeters

NASA Astrophysics Data System (ADS)

Babic, Steven; Schreiner, L. John

2006-09-01

In conformal radiation therapy, a high dose of radiation is given to a target volume to increase the probability of cure, and care is taken to minimize the dose to surrounding healthy tissue. The techniques used to achieve this are very complicated and the precise verification of the resulting three-dimensional (3D) dose distribution is required. Polyacrylamide gelatin (PAG) dosimeters with magnetic resonance imaging and optical computed tomography scanning provide the required 3D dosimetry with high spatial resolution. Many basic studies have characterized these chemical dosimeters that polymerize under irradiation. However, the investigation of the fundamental properties of the radiation-induced polymerization in PAG dosimeters is complicated by the presence of the background gelatin matrix. In this work, a gelatin-free model system for the study of the basic radiation-induced polymerization in PAG dosimeters has been developed. Experiments were performed on gelatin-free dosimeters, named aqueous polyacrylamide (APA) dosimeters, containing equal amounts of acrylamide and N,N'-methylene-bisacrylamide. The APA dosimeters were prepared with four different total monomer concentrations (2, 4, 6 and 8% by weight). Nuclear magnetic resonance (NMR) spin-spin and spin-lattice proton relaxation measurements at 20 MHz, and gravimetric analyses performed on all four dosimeters, show a continuous degree of polymerization over the dose range of 0-25 Gy. The developed NMR model explains the relationship observed between the relaxation data and the amount of crosslinked polymer formed at each dose. This model can be extended with gelatin relaxation data to provide a fundamental understanding of radiation-induced polymerization in the conventional PAG dosimeters.

Delineation of early brain development from fetuses to infants with diffusion MRI and beyond.

PubMed

Ouyang, Minhui; Dubois, Jessica; Yu, Qinlin; Mukherjee, Pratik; Huang, Hao

2018-04-12

Dynamic macrostructural and microstructural changes take place from the mid-fetal stage to 2 years after birth. Delineating structural changes of the brain during early development provides new insights into the complicated processes of both typical development and the pathological mechanisms underlying various psychiatric and neurological disorders including autism, attention deficit hyperactivity disorder and schizophrenia. Decades of histological studies have identified strong spatial and functional maturation gradients in human brain gray and white matter. The recent improvements in magnetic resonance imaging (MRI) techniques, especially diffusion MRI (dMRI), relaxometry imaging, and magnetization transfer imaging (MTI) have provided unprecedented opportunities to non-invasively quantify and map the early developmental changes at whole brain and regional levels. Here, we review the recent advances in understanding early brain structural development during the second half of gestation and the first two postnatal years using modern MR techniques. Specifically, we review studies that delineate the emergence and microstructural maturation of white matter tracts, as well as dynamic mapping of inhomogeneous cortical microstructural organization unique to fetuses and infants. These imaging studies converge into maturational curves of MRI measurements that are distinctive across different white matter tracts and cortical regions. Furthermore, contemporary models offering biophysical interpretations of the dMRI-derived measurements are illustrated to infer the underlying microstructural changes. Collectively, this review summarizes findings that contribute to charting spatiotemporally heterogeneous gray and white matter structural development, offering MRI-based biomarkers of typical brain development and setting the stage for understanding aberrant brain development in neurodevelopmental disorders. Copyright © 2018 Elsevier Inc. All rights reserved.

An NMR relaxometry and gravimetric study of gelatin-free aqueous polyacrylamide dosimeters.

PubMed

Babic, Steven; Schreiner, L John

2006-09-07

In conformal radiation therapy, a high dose of radiation is given to a target volume to increase the probability of cure, and care is taken to minimize the dose to surrounding healthy tissue. The techniques used to achieve this are very complicated and the precise verification of the resulting three-dimensional (3D) dose distribution is required. Polyacrylamide gelatin (PAG) dosimeters with magnetic resonance imaging and optical computed tomography scanning provide the required 3D dosimetry with high spatial resolution. Many basic studies have characterized these chemical dosimeters that polymerize under irradiation. However, the investigation of the fundamental properties of the radiation-induced polymerization in PAG dosimeters is complicated by the presence of the background gelatin matrix. In this work, a gelatin-free model system for the study of the basic radiation-induced polymerization in PAG dosimeters has been developed. Experiments were performed on gelatin-free dosimeters, named aqueous polyacrylamide (APA) dosimeters, containing equal amounts of acrylamide and N,N'-methylene-bisacrylamide. The APA dosimeters were prepared with four different total monomer concentrations (2, 4, 6 and 8% by weight). Nuclear magnetic resonance (NMR) spin-spin and spin-lattice proton relaxation measurements at 20 MHz, and gravimetric analyses performed on all four dosimeters, show a continuous degree of polymerization over the dose range of 0-25 Gy. The developed NMR model explains the relationship observed between the relaxation data and the amount of crosslinked polymer formed at each dose. This model can be extended with gelatin relaxation data to provide a fundamental understanding of radiation-induced polymerization in the conventional PAG dosimeters.

Effect of Rubber Polarity on Cluster Formation in Rubbers Cross-Linked with Diels–Alder Chemistry

PubMed Central

2017-01-01

Diels–Alder chemistry has been used for the thermoreversible cross-linking of furan-functionalized ethylene/propylene (EPM) and ethylene/vinyl acetate (EVM) rubbers. Both furan-functionalized elastomers were successfully cross-linked with bismaleimide to yield products with a similar cross-link density. NMR relaxometry and SAXS measurements both show that the apolar EPM-g-furan precursor contains phase-separated polar clusters and that cross-linking with polar bismaleimide occurs in these clusters. The heterogeneously cross-linked network of EPM-g-furan contrasts with the homogeneous network in the polar EVM-g-furan. The heterogeneous character of the cross-links in EPM-g-furan results in a relatively high Young’s modulus, whereas the more uniform cross-linking in EVM-g-furan results in a higher tensile strength and elongation at break. PMID:29213149

Mapping an index of the myelin g-ratio in infants using magnetic resonance imaging

PubMed Central

Dean, Douglas C.; O'Muircheartaigh, Jonathan; Dirks, Holly; Travers, Brittany G.; Adluru, Nagesh; Alexander, Andrew L.; Deoni, Sean C.L.

2016-01-01

Optimal myelination of neuronal axons is essential for effective brain and cognitive function. The ratio of the axon diameter to the outer fiber diameter, known as the g-ratio, is a reliable measure to assess axonal myelination and is an important index reflecting the efficiency and maximal conduction velocity of white matter pathways. Although advanced neuroimaging techniques including multicomponent relaxometry (MCR) and diffusion tensor imaging afford insight into the microstructural characteristics of brain tissue, by themselves they do not allow direct analysis of the myelin g-ratio. Here, we show that by combining myelin content information (obtained with mcDESPOT MCR) with neurite density information (obtained through NODDI diffusion imaging) an index of the myelin g-ratio may be estimated. Using this framework, we present the first quantitative study of myelin g-ratio index changes across childhood, examining 18 typically developing children 3 months to 7.5 years of age. We report a spatio-temporal pattern of maturation that is consistent with histological and developmental MRI studies, as well as theoretical studies of the myelin g-ratio. This work represents the first ever in vivo visualization of the evolution of white matter g-ratio indices throughout early childhood. PMID:26908314

Time domain para hydrogen induced polarization.

PubMed

Ratajczyk, Tomasz; Gutmann, Torsten; Dillenberger, Sonja; Abdulhussaein, Safaa; Frydel, Jaroslaw; Breitzke, Hergen; Bommerich, Ute; Trantzschel, Thomas; Bernarding, Johannes; Magusin, Pieter C M M; Buntkowsky, Gerd

2012-01-01

Para hydrogen induced polarization (PHIP) is a powerful hyperpolarization technique, which increases the NMR sensitivity by several orders of magnitude. However the hyperpolarized signal is created as an anti-phase signal, which necessitates high magnetic field homogeneity and spectral resolution in the conventional PHIP schemes. This hampers the application of PHIP enhancement in many fields, as for example in food science, materials science or MRI, where low B(0)-fields or low B(0)-homogeneity do decrease spectral resolution, leading to potential extinction if in-phase and anti-phase hyperpolarization signals cannot be resolved. Herein, we demonstrate that the echo sequence (45°-τ-180°-τ) enables the acquisition of low resolution PHIP enhanced liquid state NMR signals of phenylpropiolic acid derivatives and phenylacetylene at a low cost low-resolution 0.54 T spectrometer. As low field TD-spectrometers are commonly used in industry or biomedicine for the relaxometry of oil-water mixtures, food, nano-particles, or other systems, we compare two variants of para-hydrogen induced polarization with data-evaluation in the time domain (TD-PHIP). In both TD-ALTADENA and the TD-PASADENA strong spin echoes could be detected under conditions when usually no anti-phase signals can be measured due to the lack of resolution. The results suggest that the time-domain detection of PHIP-enhanced signals opens up new application areas for low-field PHIP-hyperpolarization, such as non-invasive compound detection or new contrast agents and biomarkers in low-field Magnetic Resonance Imaging (MRI). Finally, solid-state NMR calculations are presented, which show that the solid echo (90y-τ-90x-τ) version of the TD-ALTADENA experiment is able to convert up to 10% of the PHIP signal into visible magnetization. Copyright © 2012 Elsevier Inc. All rights reserved.

Biomass-water interactions correlate to recalcitrance and are intensified by pretreatment: An investigation of water constraint and retention in pretreated spruce using low field NMR and water retention value techniques.

PubMed

Weiss, Noah D; Thygesen, Lisbeth Garbrecht; Felby, Claus; Roslander, Christian; Gourlay, Keith

2017-01-01

The underlying mechanisms of the recalcitrance of biomass to enzymatic deconstruction are still not fully understood, and this hampers the development of biomass based fuels and chemicals. With water being necessary for most biological processes, it is suggested that interactions between water and biomass may be key to understanding and controlling biomass recalcitrance. This study investigates the correlation between biomass recalcitrance and the constraint and retention of water by the biomass, using SO 2 pretreated spruce, a common feedstock for lignocellulosic biofuel production, as a substrate to evaluate this relationship. The water retention value (WRV) of the pretreated materials was measured, and water constraint was assessed using time domain Low Field Nuclear Magnetic Resonance (LFNMR) relaxometry. WRV increased with pretreatment severity, correlating to reduced recalcitrance, as measured by hydrolysis of cellulose using commercial enzyme preparations. Water constraint increased with pretreatment severity, suggesting that a higher level of biomass-water interaction is indicative of reduced recalcitrance in pretreated materials. Both WRV and water constraint increased significantly with reductions in particle size when pretreated materials were further milled, suggesting that particle size plays an important role in biomass water interactions. It is suggested that WRV may be a simple and effective method for measuring and comparing biomass recalcitrance. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 33:146-153, 2017. © 2016 American Institute of Chemical Engineers.

Dynamic nuclear magnetic resonance field sensing with part-per-trillion resolution

NASA Astrophysics Data System (ADS)

Gross, Simon; Barmet, Christoph; Dietrich, Benjamin E.; Brunner, David O.; Schmid, Thomas; Pruessmann, Klaas P.

2016-12-01

High-field magnets of up to tens of teslas in strength advance applications in physics, chemistry and the life sciences. However, progress in generating such high fields has not been matched by corresponding advances in magnetic field measurement. Based mostly on nuclear magnetic resonance, dynamic high-field magnetometry is currently limited to resolutions in the nanotesla range. Here we report a concerted approach involving tailored materials, magnetostatics and detection electronics to enhance the resolution of nuclear magnetic resonance sensing by three orders of magnitude. The relative sensitivity thus achieved amounts to 1 part per trillion (10-12). To exemplify this capability we demonstrate the direct detection and relaxometry of nuclear polarization and real-time recording of dynamic susceptibility effects related to human heart function. Enhanced high-field magnetometry will generally permit a fresh look at magnetic phenomena that scale with field strength. It also promises to facilitate the development and operation of high-field magnets.

Optical imaging of localized chemical events using programmable diamond quantum nanosensors

NASA Astrophysics Data System (ADS)

Rendler, Torsten; Neburkova, Jitka; Zemek, Ondrej; Kotek, Jan; Zappe, Andrea; Chu, Zhiqin; Cigler, Petr; Wrachtrup, Jörg

2017-03-01

Development of multifunctional nanoscale sensors working under physiological conditions enables monitoring of intracellular processes that are important for various biological and medical applications. By attaching paramagnetic gadolinium complexes to nanodiamonds (NDs) with nitrogen-vacancy (NV) centres through surface engineering, we developed a hybrid nanoscale sensor that can be adjusted to directly monitor physiological species through a proposed sensing scheme based on NV spin relaxometry. We adopt a single-step method to measure spin relaxation rates enabling time-dependent measurements on changes in pH or redox potential at a submicrometre-length scale in a microfluidic channel that mimics cellular environments. Our experimental data are reproduced by numerical simulations of the NV spin interaction with gadolinium complexes covering the NDs. Considering the versatile engineering options provided by polymer chemistry, the underlying mechanism can be expanded to detect a variety of physiologically relevant species and variables.

Relaxometry imaging of superparamagnetic magnetite nanoparticles at ambient conditions

NASA Astrophysics Data System (ADS)

Finkler, Amit; Schmid-Lorch, Dominik; Häberle, Thomas; Reinhard, Friedemann; Zappe, Andrea; Slota, Michael; Bogani, Lapo; Wrachtrup, Jörg

We present a novel technique to image superparamagnetic iron oxide nanoparticles via their fluctuating magnetic fields. The detection is based on the nitrogen-vacancy (NV) color center in diamond, which allows optically detected magnetic resonance (ODMR) measurements on its electron spin structure. In combination with an atomic-force-microscope, this atomic-sized color center maps ambient magnetic fields in a wide frequency range from DC up to several GHz, while retaining a high spatial resolution in the sub-nanometer range. We demonstrate imaging of single 10 nm sized magnetite nanoparticles using this spin noise detection technique. By fitting simulations (Ornstein-Uhlenbeck process) to the data, we are able to infer additional information on such a particle and its dynamics, like the attempt frequency and the anisotropy constant. This is of high interest to the proposed application of magnetite nanoparticles as an alternative MRI contrast agent or to the field of particle-aided tumor hyperthermia.

Synthesis and characterization of polyethylenimine-based iron oxide composites as novel contrast agents for MRI.

PubMed

Masotti, A; Pitta, A; Ortaggi, G; Corti, M; Innocenti, C; Lascialfari, A; Marinone, M; Marzola, P; Daducci, A; Sbarbati, A; Micotti, E; Orsini, F; Poletti, G; Sangregorio, C

2009-04-01

Use of polyethylenimines (PEIs) of different molecular weight and selected carboxylated-PEI derivatives (PEI-COOH) in the synthesis and stabilization of iron oxide nanoparticles, to obtain possible multifunctional contrast agents. Oxidation of Fe(II) at slightly elevated pH and temperature resulted in the formation of highly soluble and stable nanocomposites of iron oxides and polymer. Composites were characterized and studied by atomic force microscopy (AFM), transmission electron microscopy (TEM), X-ray diffractometry, AC and DC magnetometry, NMR relaxometry and magnetic resonance imaging (MRI). From AFM the dimensions of the aggregates were found to be in the ~150-250 nm size region; the mean diameter of the magnetic core of the compounds named PEI-25, PEI-500 and PEI-COOH60 resulted d approximately 20 +/- 5 nm for PEI-25, d approximately 9.5 +/- 1.0 nm for PEI-500 and d approximately 6.8 +/- 1.0 nm for PEI-COOH60. In PEI-COOH60 TEM and X-ray diffractometry revealed small assemblies of mineral magnetic cores with clear indications that the main constituents are maghemite and/or magnetite as confirmed by AC and DC SQUID magnetometry. For PEI-COOH60, the study of NMR-dispersion profiles revealed r (1) and r (2) relaxivities comparable to superparamagnetic iron-oxide commercial compounds in the whole investigated frequency range 7 < or = nu < or = 212 MHz. PEI-25 was studied as possible MRI contrast agent (CA) to map the cerebral blood volume (CBV) and cerebral blood flow (CBF) in an animal model obtaining promising results. The reported compounds may be further functionalized to afford novel multifunctional systems for biomedical applications.

Dynamic nuclear magnetic resonance field sensing with part-per-trillion resolution

PubMed Central

Gross, Simon; Barmet, Christoph; Dietrich, Benjamin E.; Brunner, David O.; Schmid, Thomas; Pruessmann, Klaas P.

2016-01-01

High-field magnets of up to tens of teslas in strength advance applications in physics, chemistry and the life sciences. However, progress in generating such high fields has not been matched by corresponding advances in magnetic field measurement. Based mostly on nuclear magnetic resonance, dynamic high-field magnetometry is currently limited to resolutions in the nanotesla range. Here we report a concerted approach involving tailored materials, magnetostatics and detection electronics to enhance the resolution of nuclear magnetic resonance sensing by three orders of magnitude. The relative sensitivity thus achieved amounts to 1 part per trillion (10−12). To exemplify this capability we demonstrate the direct detection and relaxometry of nuclear polarization and real-time recording of dynamic susceptibility effects related to human heart function. Enhanced high-field magnetometry will generally permit a fresh look at magnetic phenomena that scale with field strength. It also promises to facilitate the development and operation of high-field magnets. PMID:27910860

[Initial diagnosis of Parkinson's disease - neuroradiological diagnosis].

PubMed

Orimo, Satoshi

2013-01-01

Brain MRI is essential for differentiating Parkinson's disease (PD) from other parkinsonian syndromes. The purpose of performing brain MRI is not to make a diagnosis of PD but is to exclude other parkinsonian syndromes. Recently, several new MRI techniques such as voxel based morphometry, relaxometry, magnetization transfer, spectroscopy, tractography, and functional MRI have been introduced in the diagnosis of PD. Neuromelanin imaging is one of the new techniques and can be useful to make an initial diagnosis of PD. MIBG myocardial scintigraphy is a sensitive imaging tool to differentiate PD from other parkinsonian syndromes and is one of the good tools to make an initial diagnosis of PD. Brain perfusion imaging is sometimes useful to make an initial diagnosis of PD, because reduced brain perfusion area can be detected before brain MRI detects morphological changes of the brain. Dopamine transporter imaging, not available in Japan, is a sensitive tool to detect very early parkinsonism and is useful to make an initial diagnosis of PD. However, it is difficult to differentiate PD from other parkinsonian syndromes.

Transverse signal decay under the weak field approximation: Theory and validation.

PubMed

Berman, Avery J L; Pike, G Bruce

2018-07-01

To derive an expression for the transverse signal time course from systems in the motional narrowing regime, such as water diffusing in blood. This was validated in silico and experimentally with ex vivo blood samples. A closed-form solution (CFS) for transverse signal decay under any train of refocusing pulses was derived using the weak field approximation. The CFS was validated via simulations of water molecules diffusing in the presence of spherical perturbers, with a range of sizes and under various pulse sequences. The CFS was compared with more conventional fits assuming monoexponential decay, including chemical exchange, using ex vivo blood Carr-Purcell-Meiboom-Gill data. From simulations, the CFS was shown to be valid in the motional narrowing regime and partially into the intermediate dephasing regime, with increased accuracy with increasing Carr-Purcell-Meiboom-Gill refocusing rate. In theoretical calculations of the CFS, fitting for the transverse relaxation rate (R 2 ) gave excellent agreement with the weak field approximation expression for R 2 for Carr-Purcell-Meiboom-Gill sequences, but diverged for free induction decay. These same results were confirmed in the ex vivo analysis. Transverse signal decay in the motional narrowing regime can be accurately described analytically. This theory has applications in areas such as tissue iron imaging, relaxometry of blood, and contrast agent imaging. Magn Reson Med 80:341-350, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

Effects of iron oxide contrast agent in combination with various transfection agents during mesenchymal stem cells labelling: An in vitro toxicological evaluation.

PubMed

Mishra, Sushanta Kumar; Khushu, Subash; Gangenahalli, Gurudutta

2018-03-22

The use of iron oxide nanoparticles for different biomedical applications, hold immense promise to develop negative tissue contrast in magnetic resonance imaging (MRI). Previously, we have optimized the labelling of mesenchymal stem cells (MSCs) with iron oxide nanoparticles complexed to different transfection agents like poly-l-lysine (IO-PLL) and protamine sulfate (Fe-Pro) on the basis of relaxation behaviour and its biological expressions. However, there is a distinct need to investigate the biocompatibility and biosafety concerns coupled with its cytotoxicity and genotoxicity. This study was prepared to evaluate the viability of cells, generation of ROS, changes in actin cytoskeleton, investigation of cell death, level of GSH and TAC, activities of SOD and GPx, and stability of DNA in MSCs after labelling. Results demonstrated a marginal alteration in toxicological parameters like ROS generation, cell length, actin cytoskeleton, total apoptosis and DNA damage was detected after stem cell labelling. Insignificant depletion of GSH and SOD level, and increase in GPx and TAC level in MSCs were measured after labelling with IO-PLL and Fe-Pro complexes, which later on recovered and normalized to its baseline. This MSCs labelling could provide a reference guideline for toxicological analysis and relaxometry based in vivo MRI detection. Copyright © 2018. Published by Elsevier Ltd.

Influence of Medium Viscosity and Intracellular Environment on the Magnetization of Superparamagnetic Nanoparticles in Silk Fibroin Solutions and 3T3 Mouse Fibroblast Cell Cultures.

PubMed

Urbano Bojorge, Ana Lorena; Casanova Carvajal, Oscar Ernesto; Félix González, Nazario; García, Laura Fernandez; Madurga, Rodrigo; Sanchez, Santiago; Aznar, Elena; Ramos, Milagros; Serrano Olmedo, José Javier

2018-06-27

Biomedical applications based on the magnetic properties of superparamagnetic iron oxide nanoparticles may be altered by the mechanical attachment or cellular uptake of these nanoparticles. When nanoparticles interact with living cells, nanoparticles are captured and internalized into intracellular compartments. Consequently, the magnetic behavior of the nanoparticles is modified. In this paper, we investigated the change in the magnetic response of 14 nm magnetic nanoparticles (Fe3O4) in solutions, both as a stable liquid suspension (one of them mimicking the cellular cytoplasm) and when associated with cells. The field-dependent magnetization curves from inert fluids and cell cultures were determined by using a MicroMagTM 2900 alternating gradient magnetometer (AGM system). The equipment was adapted to measure liquid samples because it was originally designed only for solids. In order to achieve this goal, custom sample holders were manufactured. Likewise, the nuclear magnetic relaxation dispersion (NMRD) profiles for the inert fluid were also measured by fast field cycling NMR relaxometry (FFCNMR). The results show that superparamagnetic iron oxide nanoparticles magnetization in inert fluids was affected by the carrier liquid viscosity and the concentration. In cell cultures, the mechanical attachment or confinement of superparamagnetic iron oxide naoparticles inside cells accounted for the change in the dynamic magnetic behavior of the nanoparticles. Nevertheless, the magnetization value in cell cultures was slightly lower than that of the fluid simulating the viscosity of cytoplasm, suggesting that magnetization loss was not only due to medium viscosity but also to a reduction in the mechanical degrees of freedom of superparamagnetic iron oxide nanoparticles rotation and translation inside cells. The findings presented here provide information on the loss of magnetic properties when nanoparticles are suspended in viscous fluids or internalized in cells. This information could be exploited to improve biomedical applications based on magnetic properties as magnetic hyperthermia, contrast agents and drug delivery. . © 2018 IOP Publishing Ltd.

Association between thyroid hormone parameters and dyslipidemia among type 2 diabetes mellitus patients: Comparative cross-sectional study.

PubMed

Wolide, Amare Desalegn; Zawdie, Belay; Alemayehu, Tilahun; Tadesse, Samuel

2017-11-01

The relationship between thyroid function and lipid profile has been documented in T2DM and healthy subjects. The aim of the current study was to assess the association between thyroid hormone parameters and dyslipidemia in T2DM and non-diabetic study participants. In this comparative cross-sectional study, 214 type 2 diabetic and 214 non-diabetic study participants were enrolled. Clinical and anthropometric data were collected from all study participants. After overnight fasting, 10ml of whole blood samples were drawn for the measurement of serum TSH, free thyroxine (fT4), free triiodothyronine (fT3), serum reactive C-protein levels, as well as for lipid profile test and glucose. The burden of hypothyroidism and subclinical hypothyroidism among T2DM study participants were 73 (17.05%) and 13 (3.04%) respectively. Comparatively, T2DM study participants had significantly higher serum lipid level than non-diabetics. Stratified by TSH, hypothyroid T2DM study participants had increased lipid level than euthyroid subjects. T2DM serum TSH have shown a positive significant correlation with all lipid profile parameters except HDL-C. In the final model (multivariate linear regression), diabetics serum TSH significantly and positively associated with TG and BMI. Diabetic serum fT3 and fT4 negatively associated with body mass index. In addition, diabetics serum fT3 negatively and serum fT4 positively associated with TC and HDL-C respectively. T2DM study subjects had significantly higher lipid level than nondiabetic and We identified that TSH was positively associated with serum TG and BMI among T2DM study participants. Copyright © 2016 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Model for the interpretation of nuclear magnetic resonance relaxometry of hydrated porous silicate materials

NASA Astrophysics Data System (ADS)

Faux, D. A.; Cachia, S.-H. P.; McDonald, P. J.; Bhatt, J. S.; Howlett, N. C.; Churakov, S. V.

2015-03-01

Nuclear magnetic resonance (NMR) relaxation experimentation is an effective technique for probing the dynamics of proton spins in porous media, but interpretation requires the application of appropriate spin-diffusion models. Molecular dynamics (MD) simulations of porous silicate-based systems containing a quasi-two-dimensional water-filled pore are presented. The MD simulations suggest that the residency time of the water on the pore surface is in the range 0.03-12 ns, typically 2-5 orders of magnitude less than values determined from fits to experimental NMR measurements using the established surface-layer (SL) diffusion models of Korb and co-workers [Phys. Rev. E 56, 1934 (1997), 10.1103/PhysRevE.56.1934]. Instead, MD identifies four distinct water layers in a tobermorite-based pore containing surface Ca2 + ions. Three highly structured water layers exist within 1 nm of the surface and the central region of the pore contains a homogeneous region of bulklike water. These regions are referred to as layer 1 and 2 (L1, L2), transition layer (TL), and bulk (B), respectively. Guided by the MD simulations, a two-layer (2L) spin-diffusion NMR relaxation model is proposed comprising two two-dimensional layers of slow- and fast-moving water associated with L2 and layers TL+B, respectively. The 2L model provides an improved fit to NMR relaxation times obtained from cementitious material compared to the SL model, yields diffusion correlation times in the range 18-75 ns and 28-40 ps in good agreement with MD, and resolves the surface residency time discrepancy. The 2L model, coupled with NMR relaxation experimentation, provides a simple yet powerful method of characterizing the dynamical properties of proton-bearing porous silicate-based systems such as porous glasses, cementitious materials, and oil-bearing rocks.

Pancreatic size and fat content in diabetes: A systematic review and meta-analysis of imaging studies.

PubMed

Garcia, Tiago Severo; Rech, Tatiana Helena; Leitão, Cristiane Bauermann

2017-01-01

Imaging studies are expected to produce reliable information regarding the size and fat content of the pancreas. However, the available studies have produced inconclusive results. The aim of this study was to perform a systematic review and meta-analysis of imaging studies assessing pancreas size and fat content in patients with type 1 diabetes (T1DM) and type 2 diabetes (T2DM). Medline and Embase databases were performed. Studies evaluating pancreatic size (diameter, area or volume) and/or fat content by ultrasound, computed tomography, or magnetic resonance imaging in patients with T1DM and/or T2DM as compared to healthy controls were selected. Seventeen studies including 3,403 subjects (284 T1DM patients, 1,139 T2DM patients, and 1,980 control subjects) were selected for meta-analyses. Pancreas diameter, area, volume, density, and fat percentage were evaluated. Pancreatic volume was reduced in T1DM and T2DM vs. controls (T1DM vs. controls: -38.72 cm3, 95%CI: -52.25 to -25.19, I2 = 70.2%, p for heterogeneity = 0.018; and T2DM vs. controls: -12.18 cm3, 95%CI: -19.1 to -5.25, I2 = 79.3%, p for heterogeneity = 0.001). Fat content was higher in T2DM vs. controls (+2.73%, 95%CI 0.55 to 4.91, I2 = 82.0%, p for heterogeneity<0.001). Individuals with T1DM and T2DM have reduced pancreas size in comparison with control subjects. Patients with T2DM have increased pancreatic fat content.

Quantitative T1 and T2* carotid atherosclerotic plaque imaging using a three-dimensional multi-echo phase-sensitive inversion recovery sequence: a feasibility study.

PubMed

Fujiwara, Yasuhiro; Maruyama, Hirotoshi; Toyomaru, Kanako; Nishizaka, Yuri; Fukamatsu, Masahiro

2018-06-01

Magnetic resonance imaging (MRI) is widely used to detect carotid atherosclerotic plaques. Although it is important to evaluate vulnerable carotid plaques containing lipids and intra-plaque hemorrhages (IPHs) using T 1 -weighted images, the image contrast changes depending on the imaging settings. Moreover, to distinguish between a thrombus and a hemorrhage, it is useful to evaluate the iron content of the plaque using both T 1 -weighted and T 2 *-weighted images. Therefore, a quantitative evaluation of carotid atherosclerotic plaques using T 1 and T 2 * values may be necessary for the accurate evaluation of plaque components. The purpose of this study was to determine whether the multi-echo phase-sensitive inversion recovery (mPSIR) sequence can improve T 1 contrast while simultaneously providing accurate T 1 and T 2 * values of an IPH. T 1 and T 2 * values measured using mPSIR were compared to values from conventional methods in phantom and in vivo studies. In the phantom study, the T 1 and T 2 * values estimated using mPSIR were linearly correlated with those of conventional methods. In the in vivo study, mPSIR demonstrated higher T 1 contrast between the IPH phantom and sternocleidomastoid muscle than the conventional method. Moreover, the T 1 and T 2 * values of the blood vessel wall and sternocleidomastoid muscle estimated using mPSIR were correlated with values measured by conventional methods and with values reported previously. The mPSIR sequence improved T 1 contrast while simultaneously providing accurate T 1 and T 2 * values of the neck region. Although further study is required to evaluate the clinical utility, mPSIR may improve carotid atherosclerotic plaque detection and provide detailed information about plaque components.

Nanomaterials-based biosensors for detection of microorganisms and microbial toxins.

PubMed

Sutarlie, Laura; Ow, Sian Yang; Su, Xiaodi

2017-04-01

Detection of microorganisms and microbial toxins is important for health and safety. Due to their unique physical and chemical properties, nanomaterials have been extensively used to develop biosensors for rapid detection of microorganisms with microbial cells and toxins as target analytes. In this paper, the design principles of nanomaterials-based biosensors for four selected analyte categories (bacteria cells, toxins, mycotoxins, and protozoa cells), closely associated with the target analytes' properties is reviewed. Five signal transducing methods that are less equipment intensive (colorimetric, fluorimetric, surface enhanced Raman scattering, electrochemical, and magnetic relaxometry methods) is described and compared for their sensory performance (in term oflimit of detection, dynamic range, and response time) for all analyte categories. In the end, the suitability of these five sensing principles for on-site or field applications is discussed. With a comprehensive coverage of nanomaterials, design principles, sensing principles, and assessment on the sensory performance and suitability for on-site application, this review offers valuable insight and perspective for designing suitable nanomaterials-based microorganism biosensors for a given application. Copyright © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The development of form two mathematics i-Think module (Mi-T2)

NASA Astrophysics Data System (ADS)

Yao, Foo Jing; Abdullah, Mohd Faizal Nizam Lee; Tien, Lee Tien

2017-05-01

This study aims to develop a training module i-THINK Mathematics Form Two (Mi-T2) to increase the higher-order thinking skills of students. The Mi-T2 training module was built based on the Sidek Module Development Model (2001). Constructivist learning theory, cognitive learning theory, i-THINK map and higher order thinking skills were the building blocks of the module development. In this study, researcher determined the validity and reliability of Mi-T2 module. The design being used in this study was descriptive study. To determine the needs of Mi-T2 module, questionnaires and literature review were used to collect data. When the need of the module was determined, the module was built and a pilot study was conducted to test the reliability of the Mi-T2 module. The pilot study was conducted at a secondary school in North Kinta, Perak. A Form Two class was selected to be the sample study through clustered random sampling. The pilot study was conducted for two months and one topic had been studied. The Mi-T2 module was evaluated by five expert panels to determine the content validity of the module. The instruments being used in the study were questionnaires about the necessity of the Mi-T2 module for guidance, questionnaires about the validity of the module and questionnaires concerning the reliability of the module. Statistical analysis was conducted to determine the validity and reliability coefficients of the Mi-T2 module. The content validity of Mi-T2 module was determined by Cohen's Kappa's (1968) agreement coefficient and the reliability of Mi-T2 module was determined by Cronbach Alpha's value scale. The content validity of Mi-T2 module was 0.89 and the Cronbach Alpha's value of Mi-T2 module was 0.911.

Spatial Distribution and Relationship of T1ρ and T2 Relaxation Times in Knee Cartilage With Osteoarthritis

PubMed Central

Li, Xiaojuan; Pai, Alex; Blumenkrantz, Gabrielle; Carballido-Gamio, Julio; Link, Thomas; Ma, Benjamin; Ries, Michael; Majumdar, Sharmila

2009-01-01

T1ρ and T2 relaxation time constants have been proposed to probe biochemical changes in osteoarthritic cartilage. This study aimed to evaluate the spatial correlation and distribution of T1ρ and T2 values in osteoarthritic cartilage. Ten patients with osteoarthritis (OA) and 10 controls were studied at 3T. The spatial correlation of T1ρ and T2 values was investigated using Z-scores. The spatial variation of T1ρ and T2 values in patellar cartilage was studied in different cartilage layers. The distribution of these relaxation time constants was measured using texture analysis parameters based on gray-level co-occurrence matrices (GLCM). The mean Z-scores for T1ρ and T2 values were significantly higher in OA patients vs. controls (P < 0.05). Regional correlation coefficients of T1ρ and T2 Z-scores showed a large range in both controls and OA patients (0.2– 0.7). OA patients had significantly greater GLCM contrast and entropy of T1ρ values than controls (P < 0.05). In summary, T1ρ and T2 values are not only increased but are also more heterogeneous in osteoarthritic cartilage. T1ρ and T2 values show different spatial distributions and may provide complementary information regarding cartilage degeneration in OA. PMID:19319904

Evaluating the Effectiveness of a Health Promotion Intervention Program Among Physiotherapy Undergraduate Students

PubMed Central

Korn, Liat; Ben-Ami, Noa; Azmon, Michal; Einstein, Ofira; Lotan, Meir

2017-01-01

This study evaluated the effectiveness of a health promotion (HP) intervention program among physiotherapy undergraduate students in an academic institution by examining pre- and post-intervention health perceptions and behaviors compared to a control group (non-physiotherapy students). Participants completed questionnaires on their health perceptions and behaviors at T1 (April 2009–May 2009) before the intervention program was initiated, and at T2 (April 2015–May 2015) after the intervention program was implemented for several years. At T1, 1,087 undergraduate students, including 124 physiotherapy students, participated. At T2, 810 undergraduate students, including 133 physiotherapy students participated. Self-reported health-related perceptions and behaviors were compared in the study group (physiotherapy students) over time (T1 versus T2), and between the study group and the control group (non-physiotherapy students) pre-intervention (T1) and post-intervention (T2). Findings showed more positive perceptions and behaviors at T2 compared to T1 in the study group (51.0% at T2 versus 35.2% at T1; p<0.05). There was no significant difference at T2 compared to T1 in health perceptions reported by the control group (37.8% at T2 versus 32.8% at T1; non-significant difference). Our findings demonstrated the effectiveness of the intervention program. PMID:28735335

[Coexistence of risky behaviors amongst group of students. Tendencies of changes between 2009-2012. Prospective studies].

PubMed

Sałacińska, Izabela; Binkowska-Bury, Monika; Wiech, Paweł; Januszewicz, Paweł

2015-01-01

Aim of conducted studies was to asses changes in time and coexistence of improper behavior patterns among students in year 2009 and 2012. The study included 905 students of the University of Rzeszow and Rzeszow University of Technology who have studied on medical, humanistic and science fields. Research was conducted by diagnostic sounding with usage of survey technique. In statistical elaboration squared-chi test and logical regression models were used. The study was conducted between October and December 2009 (study T1). It was repeated in 2012 among the same group of students (T2). Conducted in year 2009 and 2012 studies indicated that over half of surveyed students did not smoke cigarettes (T1 67.8%; T2 66.5%) and that daily smoking was declared only by 11.5% (T1) and 10.9% (T2) of asked youths. Majority of examined youth academic people drank alcohol once a month (T1 30.7%; T2 32.1%). Only 4.7% (T1) i 6.3% (T2) declared themselves as abstainers. Research pointed on significant increase of systematic drugs use (T1 0.4%; T2 1.7%). Vast majority of surveyed youths did not use legal highs in both research periods (89.3%--T2 and 91.5%--T2). There were no differences shown on the level of statistical significance in neither category (tobacco smoking, alcohol drinking, usage of drugs and legal highs). Students who smokes have bigger chance to addict themselves to alcohol, legal highs and drugs then the ones who do not smoke cigarettes. Conducted studies shows that tobacco smoking is a predictor of risky behaviors. Students who smoke are more exposed to addiction to alcohol, drugs and legal highs then those who reject tobacco.

Association between type 1 and type 2 diabetes with periodontal disease and tooth loss.

PubMed

Kaur, Gaganpreet; Holtfreter, Birte; Rathmann, Wolfgang; Rathmann, Wolfgan G; Schwahn, Christian; Wallaschofski, Henry; Schipf, Sabine; Nauck, Matthias; Kocher, Thomas

2009-09-01

The aim of this study was to determine whether both type 1 (T1DM) and type 2 diabetes mellitus (T2DM) are associated with increased prevalence and extent of periodontal disease and tooth loss compared with non-diabetic subjects within a homogeneous adult study population. T1DM, T2DM and non-diabetic subjects were recruited from the population-based Study of Health in Pomerania. Additionally, T1DM subjects were retrieved from a Diabetes Centre. The total study population comprised 145 T1DM and 2647 non-diabetic subjects aged 20-59 years, and 182 T2DM and 1314 non-diabetic subjects aged 50-81 years. Periodontal disease was assessed by attachment loss (AL) and the number of missing teeth. Multivariable regression revealed an association between T1DM (p<0.001) and T2DM (p<0.01) with mean AL after full adjustment. After age stratification (p=0.04 for interaction), the effect of T2DM was only statistically significant in the 60-69-year-old subjects (B=0.90 (95% confidence intervals [95% CI]; 0.49, 1.31). T1DM was positively associated with tooth loss (adjusted, p<0.001). The association between T2DM and tooth loss was statistically significant only for females (odds ratios=1.60 [95% CI: 1.10, 2.33]). Our study confirmed an association between both T1DM and T2DM with periodontitis and tooth loss. Therefore, oral health education should be promoted in diabetic subjects.

The impact of acute high-intensity interval exercise on biomarkers of cardiovascular health in type 2 diabetes.

PubMed

Francois, Monique E; Little, Jonathan P

2017-08-01

High-intensity interval training (HIIT) interventions improve cardiovascular health, yet the acute effects on circulating and functional biomarkers of cardiovascular function are unclear in individuals with type 2 diabetes (T2D). To explore this, we conducted two investigations to examine the acute response to HIIT in individuals with T2D. Study 1 measured blood pressure, endothelial-dependent dilation, circulating measures of endothelial activation, and troponin T, 30 min and 2 h after HIIT (7 × 1-min intervals) in T2D (n = 8) and age-matched normoglycemic controls (CTL; n = 8). Study 2 assessed circulating measures of endothelial activation and troponin T, 30 min, and 24 h after HIIT (10 × 1-min intervals) in ten previously trained T2D men. In study 1, markers of endothelial function and activation within the first 2 h after HIIT did not differ from baseline between T2D and CTL participants, except at 30 min after HIIT for glucose, which was reduced more in T2D than CTL (by -0.8 ± 1.2 mmol/L, p = 0.04), and VCAM-1, which was reduced more 30 min after HIIT in CTL compared to T2D (by -187 ± 221 ng/mL, p = 0.05). Study 2 saw no significant difference in any circulating markers of endothelial activation and troponin T, 30 min, and 24 h after HIIT in trained T2D males. Exploratory findings from these two studies suggest that acute HIIT does not substantially alter circulating and functional markers of cardio(vascular) health in individuals with T2D who are unaccustomed (study 1) and accustomed to HIIT (study 2).

An Ultra-High Field Study of Cerebellar Pathology in Early Relapsing-Remitting Multiple Sclerosis Using MP2RAGE.

PubMed

Fartaria, Mário João; OʼBrien, Kieran; Şorega, Alexandra; Bonnier, Guillaume; Roche, Alexis; Falkovskiy, Pavel; Krueger, Gunnar; Kober, Tobias; Bach Cuadra, Meritxell; Granziera, Cristina

2017-05-01

The aim of this study was to study focal cerebellar pathology in early stages of multiple sclerosis (MS) using ultra-high-field magnetization-prepared 2 inversion-contrast rapid gradient-echo (7T MP2RAGE). Twenty early-stage relapsing-remitting MS patients underwent an MP2RAGE acquisition at 7 T magnetic resonance imaging (MRI) (images acquired at 2 different resolutions: 0.58 × 0.58 × 0.58 mm, 7T_0.58, and 0.75 × 0.75 × 0.90 mm, 7T_0.75) and 3 T MRI (1.0 × 1.0 × 1.2 mm, 3T_1.0). Total cerebellar lesion load and volume and mean cerebellar lesion volume were compared across images using a Wilcoxon signed-rank test. Mean T1 relaxation times in lesions and normal-appearing tissue as well as contrast-to-noise ratio (CNR) measurements were also compared using a Wilcoxon signed-rank test. A multivariate analysis was applied to assess the contribution of MRI metrics to clinical performance in MS patients. Both 7T_0.58 and 7T_0.75 MP2RAGE showed significantly higher lesion load compared with 3T_1.0 MP2RAGE (P < 0.001). Plaques that were judged as leukocortical in 7T_0.75 and 3T_1.0 MP2RAGEs were instead identified as WM lesions in 7T_0.58 MP2RAGE. Cortical lesion CNR was significantly higher in MP2RAGEs at 7 T than at 3 T. Total lesion load as well as total and mean lesion volume obtained at both 7 T and 3 T MP2RAGE significantly predicted attention (P < 0.05, adjusted R = 0.5), verbal fluency (P < 0.01, adjusted R = 0.6), and motor performance (P = 0.01, adjusted R = 0.7). This study demonstrates the value of 7 T MP2RAGE to study the cerebellum in early MS patients. 7T_0.58 MP2RAGE provides a more accurate anatomical description of white and gray matter pathology compared with 7T_0.75 and 3T_1.0 MP2RAGE, likely due to the improved spatial resolution, lower partial volume effects, and higher CNR.

Exploration of Morbidity in a Serial Study of Long-Term Brain Tumor Survivors: A Focus on Pain.

PubMed

Nayiager, Trishana; Duckworth, JoAnn; Pullenayegum, Eleanor; Whitton, Anthony; Hollenberg, Robert; Horsman, John; Furlong, William; Spitzer, Rachel; Barr, Ronald

2015-09-01

Children surviving brain tumors are frequently identified as having substantially decreased health-related quality of life (HRQL) in cross-sectional studies. This study explored the HRQL of a cohort of such survivors, who were recruited as adolescents and followed for a decade, in order to determine the trajectory of their morbidities. Children diagnosed between January 1, 1985, and December 31, 1998, more than 2 years from diagnosis (N = 40), were recruited in 2000/2001 (T1) aged 16.74 ± 4.23 years. Health Utilities Index questionnaires (HUI2/3) were completed in 2000/2001 and again at 5 years (T2) and 10 years (T3), with 37 and 25 participants then aged 21.54 ± 4.29 and 27.97 ± 4.07 years, respectively. In addition to study subjects, parental proxies completed questionnaires at T1 and T2, while study subjects selected proxies at T3. Single attributes (domains/dimensions) of HRQL and details of pain were analyzed. Cognition was the attribute compromised most often (T1 = 66.7% of participants, T2 = 62.2%, T3 = 60.0%). Pain was also reported frequently (T1 = 35%, T2 = 25%, T3 = 52%), and at T3 correlated moderately with HUI2 sensation (0.77) and HUI3 vision (0.44), speech (0.51), and ambulation (0.50). The lower median utility score for pain at T3 than at T1/T2 was a clinically important difference. Severe pain was identified in the lower extremities, back, upper extremities, and abdomen. Morbidity was observed also in emotion (worry HUI2 and unhappiness HUI3), sensation, and vision. Decreased HRQL in survivors of brain tumors in childhood is multifaceted. Pain is a prominent burden, along with morbidity in cognition, emotion, sensation, and vision. Further studies should explore pain and neurologic deficits, and potential opportunities for therapeutic intervention.

Association between anorexia nervosa and type 2 diabetes in Sweden: Etiological clue for the primary prevention of type 2 diabetes.

PubMed

Ji, Jianguang; Sundquist, Jan; Sundquist, Kristina

2016-11-01

Caloric restriction has been found to be protective against the development of type 2 diabetes mellitus (T2D) in experimental animal studies. However, studies examining this association in humans are limited. In the present study, we examined whether individuals with anorexia nervosa, one marker of severe caloric restriction in humans, have a low incidence of T2D by using several Swedish registries. Individuals with anorexia nervosa were identified from the Swedish Hospital Discharge Register and Outpatient Register between 1964 and 2010. Standardized incidence ratios (SIRs) for T2D were studied among individuals with anorexia nervosa compared to those without the disorder. A total of 17,135 individuals were identified with anorexia nervosa in Sweden. From this tally, 34 of them developed T2D, demonstrating a reduced risk of T2D with a SIR of 0.70, compared to individuals without anorexia nervosa. Patients with severe anorexia, indicated by more frequent hospitalizations, had a statistically non-significant lower incidence of T2D than those with fewer hospitalizations. A sibling study, controlled for familial confounding, found a statistically non-significant association between anorexia nervosa and T2D. Our study found that severe caloric restriction by using individuals with anorexia nervosa as a proxy was negatively associated with T2D, which might provide a biological basis for the primary prevention of T2D. Further studies are needed to explore whether moderate caloric restriction can effectively prevent the development of T2D in general population.

Meta-analyses of structural regional cerebral effects in type 1 and type 2 diabetes.

PubMed

Moulton, Calum D; Costafreda, Sergi G; Horton, Paul; Ismail, Khalida; Fu, Cynthia H Y

2015-12-01

Diabetes is associated with macrovascular and microvascular complications and is a major risk factor for neurological and psychiatric disorders, such as dementia and depression. Type 1 diabetes (T1DM) and type 2 diabetes (T2DM) have distinct etiologies and pathophysiological effects while sharing a common endpoint of persistent hyperglycemia. Neuroimaging studies in T1DM have revealed reductions in numerous regions, including the parahippocampal and occipital regions, while in T2DM there have been numerous reports of hippocampal atrophy. This meta-analysis aimed to identify consistent regional abnormalities in cerebral structures in T1DM and T2DM respectively, and also to examine the impact of potential confounds, including age, depression and vascular risk factors. Neuroimaging studies of both voxel-based morphometry (VBM) data and volumetric data were included. Ten T1DM studies (n = 613 patients) and 23 T2DM studies (n = 1364 patients) fulfilled inclusion criteria. The T1DM meta-analysis revealed reduced bilateral thalamus grey matter density in adults. The T2DM meta-analysis revealed reduced global brain volume and regional atrophy in the hippocampi, basal ganglia, and orbitofrontal and occipital lobes. Moreover, hippocampal atrophy in T2DM was not modified by hypertension, although there were more marked reductions in younger patients relative to healthy controls. In conclusion, T1DM and T2DM demonstrated distinct cerebral effects with generalised and specific target areas of grey matter reduction. Thalamic atrophy in T1DM may be a substrate of associated cognitive deficits. In T2DM, global cerebral atrophy may reflect atherosclerotic factors, while hippocampal atrophy was an independent effect providing a potential common neuropathological etiology for the comorbidity of T2DM with dementia and depression.

Retracted: Association of ACE I/D gene polymorphism with T2DN susceptibility and the risk of T2DM developing into T2DN in a Caucasian population.

PubMed

Liu, Guohui; Zhou, Tian-Biao; Jiang, Zongpei; Zheng, Dongwen

2015-03-01

The association of the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism with type-2 diabetic nephropathy (T2DN) susceptibility and the risk of type-2 diabetes mellitus (T2DM) developing into T2DN in Caucasian populations is still controversial. A meta-analysis was performed to evaluate the association of ACE I/D gene polymorphism with T2DN susceptibility and the risk of T2DM developing into T2DN in Caucasian populations. A predefined literature search and selection of eligible relevant studies were performed to collect data from electronic databases. Sixteen articles were identified for the analysis of the association of ACE I/D gene polymorphism with T2DN susceptibility and the risk of T2DM developing into T2DN in Caucasian populations. ACE I/D gene polymorphism was not associated with T2DN susceptibility and the risk of patients with T2DM developing T2DN in Caucasian populations. Sensitivity analysis according to sample size of case (<100 vs. ≥100) was also performed, and the results were similar to the non-sensitivity analysis. ACE I/D gene polymorphism was not associated with T2DN susceptibility and the risk of patients with T2DM developing T2DN in Caucasian populations. However, more studies should be performed in the future. © The Author(s) 2014.

A longitudinal study on anxiety, depressive and adjustment disorder, suicide ideation and symptoms of emotional distress in patients with cancer undergoing radiotherapy.

PubMed

Hernández Blázquez, Manuel; Cruzado, Juan Antonio

2016-08-01

The aim of this study is to evaluate the presence of anxiety, depressive and adjustment disorders, suicide ideation, and symptoms of anxiety and depression in patients with cancer before (T1), and after radiotherapy (T2) and at the 1-month follow-up (T3). A longitudinal study on 103 patients with cancer treated as outpatients undergoing radiotherapy was carried out, evaluating them three times (T1-T2-T3) according to DSM-IV criteria with the Mini-International Neuropsychiatric Interview and the Hospital Anxiety and Depression Scale. Prevalence of the depressive disorders was: T1=6.8%, T2=3.9% and T3=3.9%; for anxiety disorders: T1=16.5%, T2=18.4% and T3=16.5%; for adjustment disorder: 10.7%, 5.8% and 7.8%; and for suicide ideation: T1=11.7%, T2=7.8% and T3=7.8%. In all, the presence of disorders was: T1=35%, T2=26.2%0.4% and T3=29.1%. At least one mental disorder was diagnosed in 46.6% of patients in one of the three times of the study. In relation to the symptoms, the prevalence of the possible cases of clinical anxiety was: T1=35.9%, T2=18.4% and T3=22.3%; the prevalence of possible cases of clinical depression was 19.4%, 16.5% and 10.7%, respectively; and the prevalence of emotional distress was 27.2%, 17.5% and 18.4%, respectively. All symptoms decreased significantly from T1 to T2 and from T1 to T3, with moderate effect sizes. No changes were observed between the end of the radiotherapy and the follow-up period. High prevalence of mental disorders and symptoms of anxiety, depression and distress were observed in the patients with cancer before finishing radiotherapy treatment and during the follow-up. Basurto University Hospital and Basque Foundation for Innovation and Research in Health-BIOEF. Copyright © 2016 Elsevier Inc. All rights reserved.

Study on impact of parasite (Nosema species) on characters of tropical tasar silkworm Anthereae mylitta drury.

PubMed

Velide, Lakshmi; Bhagavanulu, M V K; Rao, A Purushotham

2013-01-01

Infection of the pebrine disease has been found to be highly virulent and harm the cocoon yield as well as characters of silkworm Anthereae mylitta. Therefore, an attempt was made to evaluate the impact of parasite Nosema species on the ecorace (Sukinda) of A. mylitta in respect of transovarial transmitted (T1), secondary infection (T2) and healthy silkworm (T3). In comparison to T3, the number of larval mortality was 16 and 11 in T1 and T2 respectively; whereas as number of pupal mortality was 6 and 5 in T1 and T2 respectivelyThe larval weight, number of moths emerged, number of eggs laid and percent hatchability were reduced in T1 and T2 in comparison to T3.The infected layings were high in T1 (51%) and T2 (42%) as against T3 (0%). Similarly, the infected moths were 34% in T1 and 15% in T2 as against 0 percent in T3. All the characteristics parameters of cocoon were reduced in T1 and T2 against T3. The study explains that there was no significant variation between T1 and T2 on different parameters of larva, pupa and cocoon characters.

A comparison study between 3D T2-weighted SPACE and conventional 2D T2-weighted turbo spin echo in assessment of carotid plaque.

PubMed

Lv, Peng; Dai, Yuanyuan; Lin, Jiang; Zhang, Weisheng; Liu, Hao; Liu, Hui; Tang, Xiao

2017-03-01

The aim of this study was to compare 3D T2-weighted sampling perfection with application optimized contrast using different flip angle evolutions (T2w SPACE) with conventional 2D T2w turbo-spin echo (TSE) in plaque imaging of carotid artery. 45 patients underwent 3.0-T MRI for carotid arteries imaging. MR sequences included T2w SPACE, T2w TSE, Time of flight (TOF) and T1-weighted (T1w) TSE. The signal intensity of intra-plaque hemorrhage (IPH), lipid-rich necrotic core (LRNC), and loose matrix (LM) were measured and their contrast ratios (CRs) against adjacent muscle were calculated. CRs from T2w SPACE and T2w TSE were compared to each other. CRs of LM, LRNC, and IPH measured on T2w SPACE were 1.74-3.04 (2.44), 0.98-1.66 (1.39), and 1.91-2.93 (2.51), respectively. CRs of LM, LRNC, and IPH on T2w TSE were 1.97-3.41 (2.44), 1.18-1.73 (1.43), and 2.26-3.75 (2.26), respectively. There was no significant difference of CR of the carotid plaques between T2w SPACE and T2w TSE (p = 0.455). Markedly significant differences of CRs were found between LM and LRNC (p < 0.001), and between LRNC and IPH (p < 0.001) on T2w SPACE and T2w TSE. T2w SPACE was comparable with conventional T2w TSE in characterization of carotid plaque.

(1)H nuclear magnetic resonance (NMR) as a tool to measure dehydration in mice.

PubMed

Li, Matthew; Vassiliou, Christophoros C; Colucci, Lina A; Cima, Michael J

2015-08-01

Dehydration is a prevalent pathology, where loss of bodily water can result in variable symptoms. Symptoms can range from simple thirst to dire scenarios involving loss of consciousness. Clinical methods exist that assess dehydration from qualitative weight changes to more quantitative osmolality measurements. These methods are imprecise, invasive, and/or easily confounded, despite being practiced clinically. We investigate a non-invasive, non-imaging (1)H NMR method of assessing dehydration that attempts to address issues with existing clinical methods. Dehydration was achieved by exposing mice (n = 16) to a thermally elevated environment (37 °C) for up to 7.5 h (0.11-13% weight loss). Whole body NMR measurements were made using a Bruker LF50 BCA-Analyzer before and after dehydration. Physical lean tissue, adipose, and free water compartment approximations had NMR values extracted from relaxation data through a multi-exponential fitting method. Changes in before/after NMR values were compared with clinically practiced metrics of weight loss (percent dehydration) as well as blood and urine osmolality. A linear correlation between tissue relaxometry and both animal percent dehydration and urine osmolality was observed in lean tissue, but not adipose or free fluids. Calculated R(2) values for percent dehydration were 0.8619 (lean, P < 0.0001), 0.5609 (adipose, P = 0.0008), and 0.0644 (free fluids, P = 0.3445). R(2) values for urine osmolality were 0.7760 (lean, P < 0.0001), 0.5005 (adipose, P = 0.0022), and 0.0568 (free fluids, P = 0.3739). These results suggest that non-imaging (1)H NMR methods are capable of non-invasively assessing dehydration in live animals. Copyright © 2015 John Wiley & Sons, Ltd.

Magnetic response of a viscoelastic ferrodispersion: From a nearly Newtonian ferrofluid to a Jeffreys ferrogel.

PubMed

Rusakov, V V; Raikher, Yu L

2017-09-28

The theory of orientational motion of a Brownian magnetic nanoparticle embedded in a viscoelastic medium and subjected to a time-dependent uniform magnetic field is developed. The rheology of the viscoelastic environment of the particle is modeled by the Jeffreys scheme, which under variation of a minimal number of parameters is able to resemble a wide range of soft materials: from a weakly structured (nearly Newtonian) polymer solution to a gel. It is shown that in the Jeffreys model, the diffusional orientational motion of a particle is a combination of two modes, which could be associated with a fast motion within the polymer mesh cell and a slow displacement that involves deformation of the mesh, respectively. The dependencies of the reference times of both relaxation modes on the Jeffreys viscous and elastic parameters and temperature are found. It turns out that in substantially viscoelastic media, the rate of the slow mode (it dominates in relaxation) quadratically depends on the matrix temperature. This effect does not have analogs in linearly viscous systems. For an ensemble of magnetic nanoparticles in viscoelastic and gel Jeffreys matrices: (1) the dynamic magnetic susceptibility is derived and evaluated both within an exact approach and in a simple approximation; (2) the problem of magnetic relaxometry, i.e., evolution of magnetization after step-wise turning off the field, is solved; (3) the specific power loss caused by viscous dissipation generated by the particles under an ac field is analyzed as a function of the rheological parameters. Results (1) and (2) provide simple models for magnetic nanorheology; consideration (3) advances the physics of magnetic hyperthermia in viscoelastic and gel-like media.

Cardiac Iron Determines Cardiac T2*, T2, and T1 in the Gerbil Model of Iron Cardiomyopathy

PubMed Central

Wood, John C.; Otto-Duessel, Maya; Aguilar, Michelle; Nick, Hanspeter; Nelson, Marvin D.; Coates, Thomas D.; Pollack, Harvey; Moats, Rex

2010-01-01

Background Transfusional therapy for thalassemia major and sickle cell disease can lead to iron deposition and damage to the heart, liver, and endocrine organs. Iron causes the MRI parameters T1, T2, and T2* to shorten in these organs, which creates a potential mechanism for iron quantification. However, because of the danger and variability of cardiac biopsy, tissue validation of cardiac iron estimates by MRI has not been performed. In this study, we demonstrate that iron produces similar T1, T2, and T2* changes in the heart and liver using a gerbil iron-overload model. Methods and Results Twelve gerbils underwent iron dextran loading (200 mg · kg−1 · wk−1) from 2 to 14 weeks; 5 age-matched controls were studied as well. Animals had in vivo assessment of cardiac T2* and hepatic T2 and T2* and postmortem assessment of cardiac and hepatic T1 and T2. Relaxation measurements were performed in a clinical 1.5-T magnet and a 60-MHz nuclear magnetic resonance relaxometer. Cardiac and liver iron concentrations rose linearly with administered dose. Cardiac 1/T2*, 1/T2, and 1/T1 rose linearly with cardiac iron concentration. Liver 1/T2*, 1/T2, and 1/T1 also rose linearly, proportional to hepatic iron concentration. Liver and heart calibrations were similar on a dry-weight basis. Conclusions MRI measurements of cardiac T2 and T2* can be used to quantify cardiac iron. The similarity of liver and cardiac iron calibration curves in the gerbil suggests that extrapolation of human liver calibration curves to heart may be a rational approximation in humans. PMID:16027257

Role of exercise in the management of diabetes mellitus: the global scenario.

PubMed

Thent, Zar Chi; Das, Srijit; Henry, Leonard Joseph

2013-01-01

Exercise training programs have emerged as a useful therapeutic regimen for the management of type 2 diabetes mellitus (T2DM). Majority of the Western studies highlighted the effective role of exercise in T2DM. Therefore, the main aim was to focus on the extent, type of exercise and its clinical significance in T2DM in order to educate the clinicians from developing countries, especially in Asians. Pubmed, Science Direct, Scopus, ISI Web of Knowledge and Google scholar were searched using the terms "type 2 diabetes mellitus," "type 2 DM," "exercise," and/or "physical activity," and "type 2 diabetes mellitus with exercise." Only clinical or human studies published in English language between 2000 and 2012 were included. Certain criteria were assigned to achieve appropriate results. Twenty five studies met the selected criteria. The majority of the studies were randomized controlled trial study design (65%). Most of the aerobic exercise based studies showed a beneficial effect in T2DM. Resistance exercise also proved to have positive effect on T2DM patients. Minimal studies related to other types of exercises such as yoga classes, joba riding and endurance-type exercise were found. On the other hand, United States of America (USA) showed strong interest of exercise management towards T2DM. Aerobic exercise is more common in clinical practice compared to resistance exercise in managing T2DM. Treatment of T2DM with exercise training showed promising role in USA. A large number of researches are mandatory in the developing countries for incorporating exercise in the effective management of T2DM.

Direct and indirect health economic impact of hypoglycaemia in a global population of patients with insulin-treated diabetes.

PubMed

Aronson, Ronnie; Galstyan, Gagik; Goldfracht, Margalit; Al Sifri, Saud; Elliott, Lisa; Khunti, Kamlesh

2018-04-01

The Hypoglycaemia Assessment Tool (HAT) study investigated the health economic impact of hypoglycaemic events in 24 countries, including countries without previously published data on hypoglycaemia. Self-assessment questionnaires and patient diaries (4-week prospective period) were completed by adults with type 1 (T1D) or type 2 diabetes (T2D) treated with insulin for more than 12 months (N = 27,585). Direct economic impacts of hypoglycaemia during the 4-week prospective period, included increased blood glucose monitoring (reported by 69.7% [T1D] and 60.9% [T2D] of patients), hospitalisation (T1D 2.1%; T2D 3.4% of patients) and medical contact (clinic or telephone; T1D 3.8%; T2D 6.8% of patients). Regional variation in medical contact and hospitalisation was found, with the highest usage in Russia (T1D 17.1%; T2D 17.3%), and Latin America (T1D 5.2%; T2D 6.8%) respectively. Indirect economic impacts following hypoglycaemia included loss of productivity due to absence from work or study; 3.9% (T1D) and 6.2% (T2D) of patients. Regional differences in work productivity were noted among patients with T2D, with a low prevalence in Northern Europe and Canada (0.9%) and high in Southeast Asia (14.6%). This study shows that hypoglycaemia has a significant but variable impact on the economics of diabetes healthcare globally. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

The Attentional Blink Is Not Affected by Backward Masking of T2, T2-Mask SOA, or Level of T2 Impoverishment

ERIC Educational Resources Information Center

Jannati, Ali; Spalek, Thomas M.; Lagroix, Hayley E. P.; Di Lollo, Vincent

2012-01-01

Identification of the second of two targets (T2) is impaired when presented shortly after the first (T1). This "attentional blink" (AB) is thought to arise from a delay in T2 processing during which T2 is vulnerable to masking. Conventional studies have measured T2 accuracy which is constrained by the 100% ceiling. We avoided this problem by using…

A systematic evaluation of three different cardiac T2-mapping sequences at 1.5 and 3T in healthy volunteers.

PubMed

Baeßler, Bettina; Schaarschmidt, Frank; Stehning, Christian; Schnackenburg, Bernhard; Maintz, David; Bunck, Alexander C

2015-11-01

Previous studies showed that myocardial T2 relaxation times measured by cardiac T2-mapping vary significantly depending on sequence and field strength. Therefore, a systematic comparison of different T2-mapping sequences and the establishment of dedicated T2 reference values is mandatory for diagnostic decision-making. Phantom experiments using gel probes with a range of different T1 and T2 times were performed on a clinical 1.5T and 3T scanner. In addition, 30 healthy volunteers were examined at 1.5 and 3T in immediate succession. In each examination, three different T2-mapping sequences were performed at three short-axis slices: Multi Echo Spin Echo (MESE), T2-prepared balanced SSFP (T2prep), and Gradient Spin Echo with and without fat saturation (GraSEFS/GraSE). Segmented T2-Maps were generated according to the AHA 16-segment model and statistical analysis was performed. Significant intra-individual differences between mean T2 times were observed for all sequences. In general, T2prep resulted in lowest and GraSE in highest T2 times. A significant variation with field strength was observed for mean T2 in phantom as well as in vivo, with higher T2 values at 1.5T compared to 3T, regardless of the sequence used. Segmental T2 values for each sequence at 1.5 and 3T are presented. Despite a careful selection of sequence parameters and volunteers, significant variations of the measured T2 values were observed between field strengths, MR sequences and myocardial segments. Therefore, we present segmental T2 values for each sequence at 1.5 and 3T with the inherent potential to serve as reference values for future studies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Arachidonic acid and lipoxinA4 attenuate streptozotocin-induced cytotoxicity to RIN5 F cells in vitro and type 1 and type 2 diabetes mellitus in vivo.

PubMed

Gundala, Naveen K V; Naidu, Vegi G M; Das, Undurti N

2017-03-01

The aim of this study was to observe whether polyunsaturated fatty acids (PUFAs) can protect rat insulinoma (RIN5 F) cells against streptozotocin (STZ)-induced apoptosis in vitro and type 1 diabetes mellitus (T1DM) and type 2 DM (T2DM) in vivo and if so, what would be the mechanism of this action. RIN5 F cells were used for the in vitro study, whereas the in vivo study was performed in Wistar rats. STZ was used to induce apoptosis of RIN5 F cells in vitro and T1- and T2DM in vivo. The effect of PUFAs: γ-linolenic acid (GLA), arachidonic acid (AA) of ω-6 series, and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) of ω-3 series; cyclooxygenase (COX) and lipoxygenase (LOX) inhibitors and antiinflammatory metabolite of AA and DHA, lipoxin A4 (LXA4), and resolvin D2 and protectin, respectively against STZ-induced cytotoxicity to RIN5 F cells in vitro and LXA4 against T1- and T2DM in vivo was studied. Changes in the antioxidant content, lipid peroxides, nitric oxide, and expression of PDX1, P65, nuclear factor-κb (NF-κb), and IKB genes in STZ-treated RIN5 F cells in vitro and Nrf2, GLUT2, COX2, iNOS protein levels in the pancreatic tissue of T1- and T2DM and LPCLN2 (lipocalin 2), NF-κb, IKB I in adipose tissue of T2DM after LXA4 treatment were studied. Plasma glucose, insulin, and tumor necrosis factor (TNF)-α levels also were measured in STZ-induced T1- and T2DM Wistar rats. Among all PUFAs tested, AA and EPA are the most effective against STZ-induced cytotoxicity to RIN5 F cells in vitro. Neither COX nor LOX inhibitors blocked the cytoprotective action of AA in vitro and T1- and T2DM by STZ. LXA4 production by RIN5 F cells in vitro and plasma LXA4 levels in STZ-induced T1- and T2DM animals were decreased by STZ that reverted to normal after AA treatment. AA prevented both T1- and T2DM induced by STZ. Antiinflammatory metabolite of AA and LXA4 prevented both T1- and T2DM induced by STZ. The expression of Pdx1, NF-κb, IKB genes in the pancreas and plasma TNF-α levels in T1- and T2DM; Nrf2, Glut2, COX2, and iNOS proteins in pancreatic tissue of T1DM and LPCLN2, NF-κb, IKB I in adipose tissue of T2DM reverted to normal in LXA4-treated animals. Both AA and LXA4 prevented STZ-induced cytotoxicity to RIN5 F cells in vitro and T1- and T2DM in vivo, suggesting that these two bioactive lipids may function as antidiabetic molecules. AA is beneficial against STZ-induced cytotoxicity and T1- and T2DM by enhancing the production of LXA4. Copyright © 2016 Elsevier Inc. All rights reserved.

T2 Mapping of the Sacroiliac Joints With 3-T MRI: A Preliminary Study.

PubMed

Lefebvre, Guillaume; Bergère, Antonin; Rafei, Mazen El; Duhamel, Alain; Teixeira, Pedro; Cotten, Anne

2017-08-01

The objective of this study was to assess the feasibility of T2 relaxation time measurements of the sacroiliac joints. The sacroiliac joints of 40 patients were imaged by 3-T MRI using an oblique axial multislice multiecho spin-echo T2-weighted sequence. Manual plotting and automatic subdivision of ROIs allowed us to obtain T2 values for up to 48 different areas per patient (posterior and anterior parts, sacral, intermediate, and iliac parts). Intraand interobserver reproducibility of T2 values were calculated after independent assessment by two musculoskeletal radiologists. A total of 1656 measurement sites could be analyzed. Mean (± SD) T2 values were 40.6 ± 6.7 ms and 41.2 ± 6.3 ms for observer 1 and 39.9 ± 6.6 ms for observer 2. The intraobserver intraclass correlation coefficient was 0.72 (95% CI, 0.70-0.74), and the interobserver intraclass correlation coefficient was 0.71 (95% CI, 0.68-0.72). Our study shows the feasibility of T2 relaxation time measurements at the sacroiliac joints.

Dose-Response Relationship between Dietary Magnesium Intake and Risk of Type 2 Diabetes Mellitus: A Systematic Review and Meta-Regression Analysis of Prospective Cohort Studies.

PubMed

Fang, Xin; Han, Hedong; Li, Mei; Liang, Chun; Fan, Zhongjie; Aaseth, Jan; He, Jia; Montgomery, Scott; Cao, Yang

2016-11-19

The epidemiological evidence for a dose-response relationship between magnesium intake and risk of type 2 diabetes mellitus (T2D) is sparse. The aim of the study was to summarize the evidence for the association of dietary magnesium intake with risk of T2D and evaluate the dose-response relationship. We conducted a systematic review and meta-analysis of prospective cohort studies that reported dietary magnesium intake and risk of incident T2D. We identified relevant studies by searching major scientific literature databases and grey literature resources from their inception to February 2016. We included cohort studies that provided risk ratios, i.e., relative risks (RRs), odds ratios (ORs) or hazard ratios (HRs), for T2D. Linear dose-response relationships were assessed using random-effects meta-regression. Potential nonlinear associations were evaluated using restricted cubic splines. A total of 25 studies met the eligibility criteria. These studies comprised 637,922 individuals including 26,828 with a T2D diagnosis. Compared with the lowest magnesium consumption group in the population, the risk of T2D was reduced by 17% across all the studies; 19% in women and 16% in men. A statistically significant linear dose-response relationship was found between incremental magnesium intake and T2D risk. After adjusting for age and body mass index, the risk of T2D incidence was reduced by 8%-13% for per 100 mg/day increment in dietary magnesium intake. There was no evidence to support a nonlinear dose-response relationship between dietary magnesium intake and T2D risk. The combined data supports a role for magnesium in reducing risk of T2D, with a statistically significant linear dose-response pattern within the reference dose range of dietary intake among Asian and US populations. The evidence from Europe and black people is limited and more prospective studies are needed for the two subgroups.

Flavonoids intake and risk of type 2 diabetes mellitus: A meta-analysis of prospective cohort studies.

PubMed

Xu, Hui; Luo, Jia; Huang, Jia; Wen, Qian

2018-05-01

Epidemiological studies exploring the role of flavonoids intake in preventing type 2 diabetes mellitus (T2DM) showed inconsistent results. Therefore, we performed a meta-analysis of relevant studies to examine the relationship between flavonoids intake and risk of T2DM. We hypothesized that flavonoids intake may decrease the risk of developing T2DM.A systematical search in PubMed and Embase until September 2017 was performed to identify eligible prospective cohort studies. The summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated using random-effect models. Dose-response pattern between total flavonoids intake and T2DM risk was also estimated.Eight prospective studies were included with 312,015 participants, of whom 19,953 developed T2DM during the follow-up periods of 4 to 28 years. Compared with lower consumption, high intake of total flavonoids was associated with a decreased risk of T2DM (RR: 0.89, 95% CI: 0.82-0.96). Among flavonoid subclasses, inverse correlations with T2DM were achieved for intakes of anthocyanidins, flavan-3-ols, flavonols, and isoflavones. Dose-response meta-analysis indicated a curvilinear relationship between total flavonoids intake and incident T2DM (P for nonlinearity = .042), with a significant risk reduction at an intake of ≥550 mg/day. When assuming a linear pattern, the risk of T2DM was decreased by 5% for each 300-mg/day increment in total flavonoids intake (RR: 0.95, 95% CI: 0.93-0.97).Our study suggests that higher intakes of total flavonoids and subclasses (anthocyanidins, flavan-3-ols, flavonols, and isoflavones) are associated with lower risk of T2DM.

Role of Exercise in the Management of Diabetes Mellitus: the Global Scenario

PubMed Central

Thent, Zar Chi; Das, Srijit; Henry, Leonard Joseph

2013-01-01

Background Exercise training programs have emerged as a useful therapeutic regimen for the management of type 2 diabetes mellitus (T2DM). Majority of the Western studies highlighted the effective role of exercise in T2DM. Therefore, the main aim was to focus on the extent, type of exercise and its clinical significance in T2DM in order to educate the clinicians from developing countries, especially in Asians. Methods Pubmed, Science Direct, Scopus, ISI Web of Knowledge and Google scholar were searched using the terms “type 2 diabetes mellitus,” “type 2 DM,” “exercise,” and/or “physical activity,” and “type 2 diabetes mellitus with exercise.” Only clinical or human studies published in English language between 2000 and 2012 were included. Certain criteria were assigned to achieve appropriate results. Results Twenty five studies met the selected criteria. The majority of the studies were randomized controlled trial study design (65%). Most of the aerobic exercise based studies showed a beneficial effect in T2DM. Resistance exercise also proved to have positive effect on T2DM patients. Minimal studies related to other types of exercises such as yoga classes, joba riding and endurance-type exercise were found. On the other hand, United States of America (USA) showed strong interest of exercise management towards T2DM. Conclusion Aerobic exercise is more common in clinical practice compared to resistance exercise in managing T2DM. Treatment of T2DM with exercise training showed promising role in USA. A large number of researches are mandatory in the developing countries for incorporating exercise in the effective management of T2DM. PMID:24236181

Nitric oxide levels in patients with diabetes mellitus: A systematic review and meta-analysis.

PubMed

Assmann, Taís S; Brondani, Letícia A; Bouças, Ana P; Rheinheimer, Jakeline; de Souza, Bianca M; Canani, Luís H; Bauer, Andrea C; Crispim, Daisy

2016-12-30

Altered serum nitric oxide (NO) levels in patients with diabetes mellitus (DM) have been reported by different studies; however, results are still controversial. Until this date, no meta-analysis evaluated the association of NO levels with DM. Thus, this paper describes a meta-analysis conducted to evaluate if there is a relationship between NO levels and type 1 DM (T1DM) or type 2 DM (T2DM). A literature search was done to identify all studies that investigated NO levels between T1DM or T2DM patients (cases) and non-diabetic subjects (controls). Measurement of nitrate and nitrite (NOx - the stable NO products) were used to estimate NO concentrations because they closely reflect NO bioavailability. Weighted mean differences (WMD) of NOx levels between case and control samples were calculated for T1DM and T2DM groups. Thirty studies were eligible for inclusion in the meta-analysis (8 in T1DM samples and 22 in T2DM samples). NOx levels were increased in European T1DM patients compared with controls [random effect model (REM) WMD = 8.55, 95% CI 2.88 - 14.21]. No other ethnicity was evaluated in T1DM studies. NOx levels were also increased in both European (REM WMD = 18.76, 95% CI 1.67 - 35.85) and Asian (REM WMD = 18.41, 95% CI 8.01 - 28.81) T2DM patients, but not in Latin American patients compared with controls. This meta-analysis detected a significant increase in NOx levels in European T1DM patients as well as European and Asian T2DM patients. Further studies in other ethnicities are necessary to confirm these data. Copyright © 2016 Elsevier Inc. All rights reserved.

Quantitative Relationship Between Cumulative Risk Alleles Based on Genome-Wide Association Studies and Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis.

PubMed

Kodama, Satoru; Fujihara, Kazuya; Ishiguro, Hajime; Horikawa, Chika; Ohara, Nobumasa; Yachi, Yoko; Tanaka, Shiro; Shimano, Hitoshi; Kato, Kiminori; Hanyu, Osamu; Sone, Hirohito

2018-01-05

Many epidemiological studies have assessed the genetic risk of having undiagnosed or of developing type 2 diabetes mellitus (T2DM) using several single nucleotide polymorphisms (SNPs) based on findings of genome-wide association studies (GWAS). However, the quantitative association of cumulative risk alleles (RAs) of such SNPs with T2DM risk has been unclear. The aim of this meta-analysis is to review the strength of the association between cumulative RAs and T2DM risk. Systematic literature searches were conducted for cross-sectional or longitudinal studies that examined odds ratios (ORs) for T2DM in relation to genetic profiles. Logarithm of the estimated OR (log OR) of T2DM for 1 increment in RAs carried (1-ΔRA) in each study was pooled using a random-effects model. There were 46 eligible studies that included 74,880 cases among 249,365 participants. In 32 studies with a cross-sectional design, the pooled OR for T2DM morbidity for 1-ΔRA was 1.16 (95% confidence interval [CI], 1.13-1.19). In 15 studies that had a longitudinal design, the OR for incident T2DM was 1.10 (95% CI, 1.08-1.13). There was large heterogeneity in the magnitude of log OR (P < 0.001 for both cross-sectional studies and longitudinal studies). The top 10 commonly used genes significantly explained the variance in the log OR (P = 0.04 for cross-sectional studies; P = 0.006 for longitudinal studies). The current meta-analysis indicated that carrying 1-ΔRA in T2DM-associated SNPs was associated with a modest risk of prevalent or incident T2DM, although the heterogeneity in the used genes among studies requires us to interpret the results with caution.

Quantitative Relationship Between Cumulative Risk Alleles Based on Genome-Wide Association Studies and Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis

PubMed Central

Kodama, Satoru; Fujihara, Kazuya; Ishiguro, Hajime; Horikawa, Chika; Ohara, Nobumasa; Yachi, Yoko; Tanaka, Shiro; Shimano, Hitoshi; Kato, Kiminori; Hanyu, Osamu; Sone, Hirohito

2018-01-01

Many epidemiological studies have assessed the genetic risk of having undiagnosed or of developing type 2 diabetes mellitus (T2DM) using several single nucleotide polymorphisms (SNPs) based on findings of genome-wide association studies (GWAS). However, the quantitative association of cumulative risk alleles (RAs) of such SNPs with T2DM risk has been unclear. The aim of this meta-analysis is to review the strength of the association between cumulative RAs and T2DM risk. Systematic literature searches were conducted for cross-sectional or longitudinal studies that examined odds ratios (ORs) for T2DM in relation to genetic profiles. Logarithm of the estimated OR (log OR) of T2DM for 1 increment in RAs carried (1-ΔRA) in each study was pooled using a random-effects model. There were 46 eligible studies that included 74,880 cases among 249,365 participants. In 32 studies with a cross-sectional design, the pooled OR for T2DM morbidity for 1-ΔRA was 1.16 (95% confidence interval [CI], 1.13–1.19). In 15 studies that had a longitudinal design, the OR for incident T2DM was 1.10 (95% CI, 1.08–1.13). There was large heterogeneity in the magnitude of log OR (P < 0.001 for both cross-sectional studies and longitudinal studies). The top 10 commonly used genes significantly explained the variance in the log OR (P = 0.04 for cross-sectional studies; P = 0.006 for longitudinal studies). The current meta-analysis indicated that carrying 1-ΔRA in T2DM-associated SNPs was associated with a modest risk of prevalent or incident T2DM, although the heterogeneity in the used genes among studies requires us to interpret the results with caution. PMID:29093303

Combined effects of 19 common variations on type 2 diabetes in Chinese: results from two community-based studies.

PubMed

Xu, Min; Bi, Yufang; Xu, Yu; Yu, Bing; Huang, Yun; Gu, Lina; Wu, Yaohua; Zhu, Xiaolin; Li, Mian; Wang, Tiange; Song, Aiyun; Hou, Jianing; Li, Xiaoying; Ning, Guang

2010-11-17

Many susceptible loci for type 2 diabetes mellitus (T2DM) have recently been identified from Caucasians through genome wide association studies (GWAS). We aimed to determine the association of 11 known loci with T2DM and impaired glucose regulation (IGR), individually and in combination, in Chinese. Subjects were enrolled in: (1) a case-control study including 1825 subjects with T2DM, 1487 with IGR and 2200 with normal glucose regulation; and (2) a prospective cohort with 734 non-diabetic subjects at baseline. The latter was followed up for 3.5 years, in which 67 subjects developed T2DM. Nineteen single nucleotide polymorphisms (SNPs) were selected to replicate in both studies. We found that CDKAL1 (rs7756992), SLC30A8 (rs13266634, rs2466293), CDKN2A/2B (rs10811661) and KCNQ1 (rs2237892) were associated with T2DM with odds ratio from 1.21 to 1.35. In the prospective study, the fourth quartile of risk scores based on the combined effects of the risk alleles had 3.05 folds (95% CI, 1.31-7.12) higher risk for incident T2DM as compared with the first quartile, after adjustment for age, gender, body mass index and diabetes family history. This combined effect was confirmed in the case-control study after the same adjustments. The addition of the risk scores to the model of clinical risk factors modestly improved discrimination for T2DM by 1.6% in the case-control study and 2.9% in the prospective study. Our study provided further evidence for these GWAS derived SNPs as the genetic susceptible loci for T2DM in Chinese and extended this association to IGR.

Olfaction and incident Parkinson disease in US white and black older adults.

PubMed

Chen, Honglei; Shrestha, Srishti; Huang, Xuemei; Jain, Samay; Guo, Xuguang; Tranah, Gregory J; Garcia, Melissa E; Satterfield, Suzanne; Phillips, Caroline; Harris, Tamara B

2017-10-03

To investigate olfaction in relation to incident Parkinson disease (PD) in US white and black older adults. The study included 1,510 white (mean age 75.6 years) and 952 black (75.4 years) participants of the Health, Aging, and Body Composition study. We evaluated the olfaction of study participants with the Brief Smell Identification Test (BSIT) in 1999-2000. We retrospectively adjudicated PD cases identified through August 31, 2012, using multiple data sources. We used multivariable Cox models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). During an average of 9.8 years of follow-up, we identified a total of 42 incident PD cases, including 30 white and 12 black participants. Overall, poor sense of smell, as indicated by a lower BSIT score, was associated with higher risk of PD. Compared with the highest tertile of BSIT (t3), the HR was 1.3 (95% CI 0.5-3.6) for the second tertile (t2) and 4.8 (95% CI 2.0-11.2) for the lowest tertile (t1) ( p trend < 0.00001). Further analyses revealed significant associations for incident PD in both the first 5 years of follow-up (HR t1/[t2+t3] 4.2, 95% CI 1.7-10.8) and thereafter (HR t1/[t2+t3] 4.1, 95% CI 1.7-9.8). This association appeared to be stronger in white (HR t1/[t2+t3] 4.9, 95% CI 2.3-10.5) than in black participants (HR t1/[t2+t3] 2.5, 95% CI 0.8-8.1), and in men (HR t1/[t2+t3] 5.4, 95% CI 2.3-12.9) than in women (HR t1/[t2+t3] 2.9, 95% CI 1.1-7.8). Poor olfaction predicts PD in short and intermediate terms; the possibility of stronger associations among men and white participants warrants further investigation. © 2017 American Academy of Neurology.

Changes of immunocytochemical localization of vesicular glutamate transporters in the rat visual system after the retinofugal denervation.

PubMed

Fujiyama, Fumino; Hioki, Hiroyuki; Tomioka, Ryohei; Taki, Kousuke; Tamamaki, Nobuaki; Nomura, Sakashi; Okamoto, Keiko; Kaneko, Takeshi

2003-10-13

To clarify which vesicular glutamate transporter (VGluT) is used by excitatory axon terminals of the retinofugal system, we examined immunoreactivities and mRNA signals for VGluT1 and VGluT2 in the rat retina and compared immunoreactivities for VGluT1 and VGluT2 in the retinorecipient regions using double immunofluorescence method, anterograde tracing, and immunoelectron microscopy. Furthermore, the changes of VGluT1 and VGluT2 immunoreactivities were studied after eyeball enucleation. Intense immunoreactivity and mRNA signal for VGluT2, but not for VGluT1 immunoreactivity, were observed in most perikarya of ganglion cells in the retina. Immunoelectron microscopy revealed that VGluT1- and VGluT2-immunolabeled terminals made asymmetrical synapses, suggesting that they were excitatory synapses, and that VGluT1-immunolabeled terminals were smaller than VGluT2-labeled ones in many retinorecipient regions, such as the dorsal lateral geniculate nucleus (LGd) and superior colliculus (SC). Double immunofluorescence study further revealed that almost no VGluT2 immunoreactivity was colocalized with VGluT1 in the retinorecipient regions. After wheat germ agglutinin (WGA) injection into the eyeballs, WGA immunoreactivity was colocalized in the single axon terminals of LGd and SC with VGluT2 but not VGluT1 immunoreactivity. After unilateral enucleation, VGluT2 immunoreactivity in the LGd, SC, nucleus of the optic tract, and nuclei of the accessory optic tract in the contralateral side of the enucleated eye was clearly decreased. Although only a small change of VGluT2 immunoreactivity was observed in the contra- and ipsilateral suprachiasmatic nuclei, olivary pretectal nucleus, anterior pretectal nucleus, and posterior pretectal nucleus, moderate reduction of VGluT2 was found in these regions after bilateral enucleation. On the other hand, almost no change in VGluT1 immunoreactivity was found in the structures examined in the present enucleation study. Thus, the present results support the notion that the retinofugal pathways are glutamatergic, and indicate that VGluT2, but not VGluT1, is employed for accumulating glutamate into synaptic vesicles of retinofugal axons. Copyright 2003 Wiley-Liss, Inc.

Contribution of type 2 diabetes associated loci in the Arabic population from Tunisia: a case-control study

PubMed Central

Ezzidi, Intissar; Mtiraoui, Nabil; Cauchi, Stéphane; Vaillant, Emmanuel; Dechaume, Aurélie; Chaieb, Molka; Kacem, Maha; Almawi, Wassim Y; Froguel, Philippe; Mahjoub, Touhami; Vaxillaire, Martine

2009-01-01

Background Candidate gene and genome-wide association studies have both reproducibly identified several common Single Nucleotide Polymorphisms (SNPs) that confer type 2 diabetes (T2D) risk in European populations. Our aim was to evaluate the contribution to T2D of five of these established T2D-associated loci in the Arabic population from Tunisia. Methods A case-control design comprising 884 type 2 diabetic patients and 513 control subjects living in the East-Center of Tunisia was used to analyze the contribution to T2D of the following SNPs: E23K in KCNJ11/Kir6.2, K121Q in ENPP1, the -30G/A variant in the pancreatic β-cell specific promoter of Glucokinase, rs7903146 in TCF7L2 encoding transcription factor 7-like2, and rs7923837 in HHEX encoding the homeobox, hematopoietically expressed transcription factor. Results TCF7L2-rs7903146 T allele increased susceptibility to T2D (OR = 1.25 [1.06–1.47], P = 0.006) in our study population. This risk was 56% higher among subjects carrying the TT genotype in comparison to those carrying the CC genotype (OR = 1.56 [1.13–2.16], P = 0.002). No allelic or genotypic association with T2D was detected for the other studied polymorphisms. Conclusion In the Tunisian population, TCF7L2-rs7903146 T allele confers an increased risk of developing T2D as previously reported in the European population and many other ethnic groups. In contrast, none of the other tested SNPs that influence T2D risk in the European population was associated with T2D in the Tunisian Arabic population. An insufficient power to detect minor allelic contributions or genetic heterogeneity of T2D between different ethnic groups can explain these findings. PMID:19368707

[Hypoglycaemia in patients with type 1 and type 2 diabetes mellitus on insulin therapy. Results of the global HAT study in Argentina].

PubMed

Costa Gil, José E; Linari, María A; Pugnaloni, Natalia; Zambon, Fabio G; Pérez Manghi, Federico; Rezzónico, Mariana

2017-01-01

We describe the results of the HAT study in 433 Argentinean patients with type 1 diabetes (T1D) and 823 with type 2 diabetes (T2D). HAT was an international non-interventional study assessing severe and non-severe hypoglycaemia in patients with T1D and T2D under insulin treatment through a two-part self-assessment questionnaire (retrospective and prospective). The annual incidence of at least one hypoglycaemic episode was 46 episode/patient/year in T1D and 14.2 in T2D (retrospective), 96.5 and 24.6 episode/patient/year in T1D and T2D, respectively (prospective). Hypoglycaemia affected quality of life (on a scale of 0-10 for fear of hypoglycaemia: 60% in T1D and 37.6% in T2D scored 5 to 10), daily life, occupational or academic performance (2.1% with T1D and 3.2% with T2D did not attend to their work after hypoglycaemia), and induced an increased use of health resources (T1D: 66.1% increased glucose monitoring, 60.5% food intake, 51% consultations, 3.5% hospital admissions; 60.5% reduced insulin and 20.9% exercises; T2D increased 46.2% glucose monitoring, 43.8% consultations, 38.6% food intake, 24.1% reduced and 13.9% skipped the insulin dose and 14.3% suspended exercises). Greater numbers of episodes were recorded in the prospective period. An instrument to assess hypoglycaemia in clinical practice and strategies to reduce their risk are required. It is also important to ask about the episodes and reinforce the education of patients and close relatives on hypoglycaemia prevention and treatment.

Indonesia Cohort of IO HAT Study to Evaluate Diabetes Management, Control, and Complications in Retrospective and Prospective Periods Among Insulin-Treated Patients with Type 1 and Type 2 Diabetes.

PubMed

Rudijanto, Achmad; Saraswati, Made R; Yunir, Em; Kumala, Poppy; Puteri, Happy Hs; Mandang, Veny Vv

2018-01-01

hypoglycemia is a major adverse event of insulin therapy for diabetes mellitus patients. The study was conducted to evaluate the incidence of hypoglycemia among insulin treated patients with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) in the Indonesian cohort. this Indonesian cohort study consisted of retrospective and prospective evaluation of hypoglycemic episodes, using International Operations Hypoglycemia Assessment Tool (IO HAT) in 374 patients with diabetes (T1DM; n=17 or T2DM; n=357). The patients of ≥18 years of age and treated with insulin for >12 months were selected for this study (ClinicalTrials.gov number: NCT02306681). a total of 374 patients were enrolled in this study and completed SAQ1. All patients with T1DM (17 [100%]), and 347 (97.2%) patients with T2DM completed SAQ2. Almost all the patients in the 4-week prospective period reported at least one hypoglycemic event (T1DM 100%, T2DM 99.4%) and the incidence rate of any hypoglycemia was 67.5 events per patient-year (PPY) and 25.7 events PPY for T1DM and T2DM patients, respectively. Among patients with T1DM and T2DM, 5.9% and 36.4%, respectively, did not know what hypoglycemia was at baseline, also high proportion of patients had impaired hypoglycemic awareness in the study (82.4% and 62.7%, respectively). overall, high proportion of patients reported hypoglycemic events in the prospective period indicating under reporting during the retrospective period due to recall bias. Therefore, there is a need for patient education program to improve the awareness of hypoglycemia in diabetes patient in Indonesia.

[Burnout and job satisfaction among nursing professionals].

PubMed

Figueiredo-Ferraz, Hugo; Grau-Alberola, Ester; Gil-Monte, Pedro R; García-Juesas, Juan A

2012-05-01

The purpose of this study was to examine the relationship between burnout and job satisfaction among nursing professionals. The sample consisted of 316 staff nurses. The study was longitudinal, and not randomized. The gap between Time 1 (T1) and Time 2 (T2) was one year. Hierarchical regression analysis showed empirical evidence of the significant and negative effect of burnout (i.e., Emotional exhaustion and Depersonalization dimensions) at T1 on job satisfaction in T2. Significant results were also obtained that showed the influence of job satisfaction at T1 on burnout at T2 (i.e., Depersonalization dimension). The study concludes that there is a bidirectional and longitudinal relationship between burnout and job satisfaction. However, longitudinal effects of burnout at T1 on job satisfaction on T2 (i.e., burnout as antecedent of job satisfaction) are stronger than vice-versa (i.e., job satisfaction as antecedent of burnout).

A Reference Database of Cartilage 3 Tesla MRI T2 Values in Knees without Diagnostic Evidence of Cartilage Degeneration: Data from the Osteoarthritis Initiative

PubMed Central

Joseph, Gabby B.; McCulloch, Charles E.; Nevitt, Michael C.; Heilmeier, Ursula; Nardo, Lorenzo; Lynch, John A.; Liu, Felix; Baum, Thomas; Link, Thomas M.

2015-01-01

Objective The purpose of this study was 1) to establish a gender- and BMI-specific reference database of cartilage T2 values, and 2) to assess the associations between cartilage T2 values and gender, age, and BMI in knees without radiographic osteoarthritis or MRI-based (WORMS 0/1) evidence of cartilage degeneration. Design 481 subjects between the ages of 45-65 years with Kellgren-Lawrence Scores 0/1 in the study knee were selected from the Osteoarthritis Initiative database. Baseline morphologic cartilage 3T MRI readings (WORMS scoring) and T2 measurements (resolution=0.313mmx0.446mm) were performed in the medial femur, lateral femur, medial tibia, lateral tibia, and patella compartments. In order to create a reference database, a logarithmic transformation was applied to the data to obtain the 5th-95th percentile values for T2. Results Significant differences in mean cartilage T2 values were observed between joint compartments. Although females had slightly higher T2 values than males in a majority of compartments, the differences were only significant in the medial femur (p<0.0001). A weak positive association was seen between age and T2 in all compartments, and was most pronounced in the patella (3.27% increase in median T2/10 years, p=0.009). Significant associations between BMI and T2 were observed, and were most pronounced in the lateral tibia (5.33% increase in median T2/5 kg/m2 increase in BMI, p<0.0001), and medial tibia (4.81% increase in median T2 /5 kg/m2 increase in BMI, p<0.0001). Conclusions This study established the first reference database of T2 values in a large sample of morphologically normal cartilage plates in knees without radiographic knee osteoarthritis. While cartilage T2 values were weakly associated with age and gender, they had the highest correlations with BMI. PMID:25680652

Identification of unknown spatial load distributions in a vibrating Euler-Bernoulli beam from limited measured data

NASA Astrophysics Data System (ADS)

Hasanov, Alemdar; Kawano, Alexandre

2016-05-01

Two types of inverse source problems of identifying asynchronously distributed spatial loads governed by the Euler-Bernoulli beam equation ρ (x){w}{tt}+μ (x){w}t+{({EI}(x){w}{xx})}{xx}-{T}r{u}{xx}={\\sum }m=1M{g}m(t){f}m(x), (x,t)\\in {{{Ω }}}T := (0,l)× (0,T), with hinged-clamped ends (w(0,t)={w}{xx}(0,t)=0,w(l,t) = {w}x(l,t)=0,t\\in (0,T)), are studied. Here {g}m(t) are linearly independent functions, describing an asynchronous temporal loading, and {f}m(x) are the spatial load distributions. In the first identification problem the values {ν }k(t),k=\\bar{1,K}, of the deflection w(x,t), are assumed to be known, as measured output data, in a neighbourhood of the finite set of points P:= \\{{x}k\\in (0,l),k=\\bar{1,K}\\}\\subset (0,l), corresponding to the internal points of a continuous beam, for all t\\in ]0,T[. In the second identification problem the values {θ }k(t),k=\\bar{1,K}, of the slope {w}x(x,t), are assumed to be known, as measured output data in a neighbourhood of the same set of points P for all t\\in ]0,T[. These inverse source problems will be defined subsequently as the problems ISP1 and ISP2. The general purpose of this study is to develop mathematical concepts and tools that are capable of providing effective numerical algorithms for the numerical solution of the considered class of inverse problems. Note that both measured output data {ν }k(t) and {θ }k(t) contain random noise. In the first part of the study we prove that each measured output data {ν }k(t) and {θ }k(t),k=\\bar{1,K} can uniquely determine the unknown functions {f}m\\in {H}-1(]0,l[),m=\\bar{1,M}. In the second part of the study we will introduce the input-output operators {{ K }}d :{L}2(0,T)\\mapsto {L}2(0,T),({{ K }}df)(t):= w(x,t;f),x\\in P, f(x) := ({f}1(x),\\ldots ,{f}M(x)), and {{ K }}s :{L}2(0,T)\\mapsto {L}2(0,T), ({{ K }}sf)(t):= {w}x(x,t;f), x\\in P , corresponding to the problems ISP1 and ISP2, and then reformulate these problems as the operator equations: {{ K }}df=ν and {{ K }}sf=θ , where ν (t):= ({ν }1(t),\\ldots ,{ν }K(t)) and {θ }k(t):= ({θ }1(t),\\ldots ,{θ }K(t)). Since both measured output data contain random noise, we use the most prominent regularisation method, Tikhonov regularisation, introducing the regularised cost functionals {J}1α (f):= (1/2)\\parallel {{ K }}df-ν {\\parallel }{L2(0,T)}2+(1/2)α \\parallel f{\\parallel }{L2(0,T)}2 and {J}2α (f):= (1/2)\\parallel {{ K }}sf-θ {\\parallel }{L2(0,T)}2+(1/2)α \\parallel f{\\parallel }{L2(0,T)}2. Using a priori estimates for the weak solution of the direct problem and the Tikhonov regularisation method combined with the adjoint problem approach, we prove that the Fréchet gradients {J}1\\prime (f) and {J}2\\prime (f) of both cost functionals can explicitly be derived via the corresponding weak solutions of adjoint problems and the known temporal loads {g}m(t). Moreover, we show that these gradients are Lipschitz continuous, which allows the use of gradient type iteration convergent algorithms. Two applications of the proposed theory are presented. It is shown that solvability results for inverse source problems related to the synchronous loading case, with a single interior measured data, are special cases of the obtained results for asynchronously distributed spatial load cases.

Evaluation of a combination tumor treatment using thermo-triggered liposomal drug delivery and carbon ion irradiation.

PubMed

Kokuryo, Daisuke; Aoki, Ichio; Yuba, Eiji; Kono, Kenji; Aoshima, Sadahito; Kershaw, Jeff; Saga, Tsuneo

2017-07-01

The combination of radiotherapy with chemotherapy is one of the most promising strategies for cancer treatment. Here, a novel combination strategy utilizing carbon ion irradiation as a high-linear energy transfer (LET) radiotherapy and a thermo-triggered nanodevice is proposed, and drug accumulation in the tumor and treatment effects are evaluated using magnetic resonance imaging relaxometry and immunohistology (Ki-67, n = 15). The thermo-triggered liposomal anticancer nanodevice was administered into colon-26 tumor-grafted mice, and drug accumulation and efficacy was compared for 6 groups (n = 32) that received or did not receive the radiotherapy and thermo trigger. In vivo quantitative R 1 maps visually demonstrated that the multimodal thermosensitive polymer-modified liposomes (MTPLs) can accumulate in the tumor tissue regardless of whether the region was irradiated by carbon ions or not. The tumor volume after combination treatment with carbon ion irradiation and MTPLs with thermo-triggering was significantly smaller than all the control groups at 8 days after treatment. The proposed strategy of combining high-LET irradiation and the nanodevice provides an effective approach for minimally invasive cancer treatment. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

White Matter Fiber-based Analysis of T1w/T2w Ratio Map.

PubMed

Chen, Haiwei; Budin, Francois; Noel, Jean; Prieto, Juan Carlos; Gilmore, John; Rasmussen, Jerod; Wadhwa, Pathik D; Entringer, Sonja; Buss, Claudia; Styner, Martin

2017-02-01

To develop, test, evaluate and apply a novel tool for the white matter fiber-based analysis of T1w/T2w ratio maps quantifying myelin content. The cerebral white matter in the human brain develops from a mostly non-myelinated state to a nearly fully mature white matter myelination within the first few years of life. High resolution T1w/T2w ratio maps are believed to be effective in quantitatively estimating myelin content on a voxel-wise basis. We propose the use of a fiber-tract-based analysis of such T1w/T2w ratio data, as it allows us to separate fiber bundles that a common regional analysis imprecisely groups together, and to associate effects to specific tracts rather than large, broad regions. We developed an intuitive, open source tool to facilitate such fiber-based studies of T1w/T2w ratio maps. Via its Graphical User Interface (GUI) the tool is accessible to non-technical users. The framework uses calibrated T1w/T2w ratio maps and a prior fiber atlas as an input to generate profiles of T1w/T2w values. The resulting fiber profiles are used in a statistical analysis that performs along-tract functional statistical analysis. We applied this approach to a preliminary study of early brain development in neonates. We developed an open-source tool for the fiber based analysis of T1w/T2w ratio maps and tested it in a study of brain development.

White matter fiber-based analysis of T1w/T2w ratio map

NASA Astrophysics Data System (ADS)

Chen, Haiwei; Budin, Francois; Noel, Jean; Prieto, Juan Carlos; Gilmore, John; Rasmussen, Jerod; Wadhwa, Pathik D.; Entringer, Sonja; Buss, Claudia; Styner, Martin

2017-02-01

Purpose: To develop, test, evaluate and apply a novel tool for the white matter fiber-based analysis of T1w/T2w ratio maps quantifying myelin content. Background: The cerebral white matter in the human brain develops from a mostly non-myelinated state to a nearly fully mature white matter myelination within the first few years of life. High resolution T1w/T2w ratio maps are believed to be effective in quantitatively estimating myelin content on a voxel-wise basis. We propose the use of a fiber-tract-based analysis of such T1w/T2w ratio data, as it allows us to separate fiber bundles that a common regional analysis imprecisely groups together, and to associate effects to specific tracts rather than large, broad regions. Methods: We developed an intuitive, open source tool to facilitate such fiber-based studies of T1w/T2w ratio maps. Via its Graphical User Interface (GUI) the tool is accessible to non-technical users. The framework uses calibrated T1w/T2w ratio maps and a prior fiber atlas as an input to generate profiles of T1w/T2w values. The resulting fiber profiles are used in a statistical analysis that performs along-tract functional statistical analysis. We applied this approach to a preliminary study of early brain development in neonates. Results: We developed an open-source tool for the fiber based analysis of T1w/T2w ratio maps and tested it in a study of brain development.

Adoptive transfer of autologous, HER2-specific, cytotoxic T lymphocytes for the treatment of HER2-overexpressing breast cancer.

PubMed

Bernhard, Helga; Neudorfer, Julia; Gebhard, Kerstin; Conrad, Heinke; Hermann, Christine; Nährig, Jörg; Fend, Falko; Weber, Wolfgang; Busch, Dirk H; Peschel, Christian

2008-02-01

The human epidermal growth factor receptor 2 (HER2) has been targeted as a breast cancer-associated antigen by immunotherapeutical approaches based on HER2-directed monoclonal antibodies and cancer vaccines. We describe the adoptive transfer of autologous HER2-specific T-lymphocyte clones to a patient with metastatic HER2-overexpressing breast cancer. The HLA/multimer-based monitoring of the transferred T lymphocytes revealed that the T cells rapidly disappeared from the peripheral blood. The imaging studies indicated that the T cells accumulated in the bone marrow (BM) and migrated to the liver, but were unable to penetrate into the solid metastases. The disseminated tumor cells in the BM disappeared after the completion of adoptive T-cell therapy. This study suggests the therapeutic potential for HER2-specific T cells for eliminating disseminated HER2-positive tumor cells and proposes the combination of T cell-based therapies with strategies targeting the tumor stroma to improve T-cell infiltration into solid tumors.

Mapping of the minimal inorganic phosphate transporting unit of human PiT2 suggests a structure universal to PiT-related proteins from all kingdoms of life

PubMed Central

2011-01-01

Background The inorganic (Pi) phosphate transporter (PiT) family comprises known and putative Na+- or H+-dependent Pi-transporting proteins with representatives from all kingdoms. The mammalian members are placed in the outer cell membranes and suggested to supply cells with Pi to maintain house-keeping functions. Alignment of protein sequences representing PiT family members from all kingdoms reveals the presence of conserved amino acids and that bacterial phosphate permeases and putative phosphate permeases from archaea lack substantial parts of the protein sequence when compared to the mammalian PiT family members. Besides being Na+-dependent Pi (NaPi) transporters, the mammalian PiT paralogs, PiT1 and PiT2, also are receptors for gamma-retroviruses. We have here exploited the dual-function of PiT1 and PiT2 to study the structure-function relationship of PiT proteins. Results We show that the human PiT2 histidine, H502, and the human PiT1 glutamate, E70, - both conserved in eukaryotic PiT family members - are critical for Pi transport function. Noticeably, human PiT2 H502 is located in the C-terminal PiT family signature sequence, and human PiT1 E70 is located in ProDom domains characteristic for all PiT family members. A human PiT2 truncation mutant, which consists of the predicted 10 transmembrane (TM) domain backbone without a large intracellular domain (human PiT2ΔR254-V483), was found to be a fully functional Pi transporter. Further truncation of the human PiT2 protein by additional removal of two predicted TM domains together with the large intracellular domain created a mutant that resembles a bacterial phosphate permease and an archaeal putative phosphate permease. This human PiT2 truncation mutant (human PiT2ΔL183-V483) did also support Pi transport albeit at very low levels. Conclusions The results suggest that the overall structure of the Pi-transporting unit of the PiT family proteins has remained unchanged during evolution. Moreover, in combination, our studies of the gene structure of the human PiT1 and PiT2 genes (SLC20A1 and SLC20A2, respectively) and alignment of protein sequences of PiT family members from all kingdoms, along with the studies of the dual functions of the human PiT paralogs show that these proteins are excellent as models for studying the evolution of a protein's structure-function relationship. PMID:21586110

Mapping of the minimal inorganic phosphate transporting unit of human PiT2 suggests a structure universal to PiT-related proteins from all kingdoms of life.

PubMed

Bøttger, Pernille; Pedersen, Lene

2011-05-17

The inorganic (Pi) phosphate transporter (PiT) family comprises known and putative Na(+)- or H(+)-dependent Pi-transporting proteins with representatives from all kingdoms. The mammalian members are placed in the outer cell membranes and suggested to supply cells with Pi to maintain house-keeping functions. Alignment of protein sequences representing PiT family members from all kingdoms reveals the presence of conserved amino acids and that bacterial phosphate permeases and putative phosphate permeases from archaea lack substantial parts of the protein sequence when compared to the mammalian PiT family members. Besides being Na(+)-dependent P(i) (NaP(i)) transporters, the mammalian PiT paralogs, PiT1 and PiT2, also are receptors for gamma-retroviruses. We have here exploited the dual-function of PiT1 and PiT2 to study the structure-function relationship of PiT proteins. We show that the human PiT2 histidine, H(502), and the human PiT1 glutamate, E(70),--both conserved in eukaryotic PiT family members--are critical for P(i) transport function. Noticeably, human PiT2 H(502) is located in the C-terminal PiT family signature sequence, and human PiT1 E(70) is located in ProDom domains characteristic for all PiT family members.A human PiT2 truncation mutant, which consists of the predicted 10 transmembrane (TM) domain backbone without a large intracellular domain (human PiT2ΔR(254)-V(483)), was found to be a fully functional P(i) transporter. Further truncation of the human PiT2 protein by additional removal of two predicted TM domains together with the large intracellular domain created a mutant that resembles a bacterial phosphate permease and an archaeal putative phosphate permease. This human PiT2 truncation mutant (human PiT2ΔL(183)-V(483)) did also support P(i) transport albeit at very low levels. The results suggest that the overall structure of the P(i)-transporting unit of the PiT family proteins has remained unchanged during evolution. Moreover, in combination, our studies of the gene structure of the human PiT1 and PiT2 genes (SLC20A1 and SLC20A2, respectively) and alignment of protein sequences of PiT family members from all kingdoms, along with the studies of the dual functions of the human PiT paralogs show that these proteins are excellent as models for studying the evolution of a protein's structure-function relationship. © 2011 Bøttger and Pedersen; licensee BioMed Central Ltd.

Thyroid hormone therapy in the management of 63,593 brain-dead organ donors: a retrospective analysis.

PubMed

Novitzky, Dimitri; Mi, Zhibao; Sun, Qing; Collins, Joseph F; Cooper, David K C

2014-11-27

Hormonal therapy to the brain-dead potential organ donor can include thyroid hormone (triiodothyronine [T3] or levothyroxine [T4]), corticosteroids, antidiuretic hormone, and insulin. Data on 66,629 donors (2000-2009) were retrospectively reviewed. Documentation on T3/T4 was available in 63,593 (study 1), but 23,469 had incomplete documentation of other hormones. In 40,124, details of all four hormones were recorded (study 2). In this cohort, group A (received T3/T4) consisted of 23,022, and group B (no T3/T4) consisted of 17,102 donors. A multivariate analysis was performed to determine whether age, sex, ethnicity, cause of death, body mass index, Organ Procurement Organization region, or other hormonal therapy influenced procurement. Posttransplantation organ graft survival at 1 and 12 months was compared. In study 1, 30,962 (48.69%) received T3/T4, providing a mean of 3.35 organs per donor, and 32,631 (51.31%) did not receive T3/T4, providing a mean of 2.97 organs per donor, an increase of 12.8% of organs from T3/T4-treated donors (P<0.0001). In study 2, group A provided a mean of 3.31 organs per donor and group B provided a mean of 2.87 organs per donor, an increase of 15.3% in group A (P<0.0001). T3/T4 therapy was associated with procurement of significantly greater numbers of hearts, lungs, kidneys, pancreases, and intestines, but not livers. Multivariate analysis indicated a beneficial effect of T3/T4 independent of other factors (P<0.0001). T3/T4 therapy of the donor was associated with improved posttransplantation graft survival or no difference in survival, except for pancreas recipient (but not graft) survival at 12 months in study 2. T3/T4 therapy results in more transplantable organs, with no detriment to posttransplantation graft survival.

The influence of unmet supportive care needs on anxiety and depression during cancer treatment and beyond: a longitudinal study of survivors of haematological cancers.

PubMed

Oberoi, Devesh; White, Victoria M; Seymour, John F; Miles Prince, H; Harrison, Simon; Jefford, Michael; Winship, Ingrid; Hill, David; Bolton, Damien; Kay, Anne; Millar, Jeremy; Doo, Nicole Wong; Giles, Graham

2017-11-01

This paper aims to examine the cross-sectional and longitudinal associations between patient-reported unmet needs and anxiety and depression for survivors of diffuse large B cell lymphoma (DLBCL) and multiple myeloma (MM). In a longitudinal study design, self-reported data were collected through telephone interviews at two time points approximately 7 (T1) and 15 (T2) months post-diagnosis. The sample was recruited through the population-based Victorian Cancer Registry. At T1 and T2, the study outcomes, anxiety and depression, were assessed using the Hospital Anxiety and Depression Scale (HADS) and unmet needs were measured using the Supportive Care Needs Survey (SCNS-SF34). Questions related to social/family problems, relationship problems and financial problems were also asked. A three-step multivariable hierarchical logistic regression analysis examined the relative role of T1 anxiety and depression, T1 and T2 unmet needs and other psychosocial factors with T2 anxiety and depression. Both cross-sectional and longitudinal associations were observed between unmet needs and psychological distress. T2 anxiety was associated with T1 anxiety (OR 4.75, 95% CI 1.86-11.09), T2 psychological needs (OR 1.68, 95% CI 1.34-2.11) and with T1 social problems (OR 2.33, 95% CI 1.03-5.05) in multivariate analysis. T2 depression was associated with both T1 (OR 1.28, 95% CI 1.06-1.57) and T2 psychological needs (OR 1.35, 95% CI 1.06-1.70), T2 physical needs (OR 1.89, 95% CI 1.27-2.81) and T1 depression (OR 4.52, 95% CI 1.88-10.86). Unmet needs that manifest following diagnosis and treatment may persist into early survivorship and contribute to psychological distress. Addressing these needs during treatment may diminish the risk of current and future anxiety and depression.

Efficacy of T2 Magnetic Resonance Assay in Monitoring Candidemia after Initiation of Antifungal Therapy: the Serial Therapeutic and Antifungal Monitoring Protocol (STAMP) Trial

PubMed Central

2018-01-01

ABSTRACT The performance of blood culture for monitoring candidemia clearance is hampered by its low sensitivity, especially during antifungal therapy. The T2 magnetic resonance (T2MR) assay combines magnetic resonance with nanotechnology to identify whole Candida species cells. A multicenter clinical trial studied the performance of T2MR in monitoring candidemia clearance compared to blood culture. Adults with a blood culture positive for yeast were enrolled and had blood cultures and T2MR testing performed on prespecified days. Thirty-one patients completed the trial. Thirteen of the 31 patients (41.9%) had at least one positive surveillance T2MR and/or blood culture result. All positive blood cultures (7/7 [100%]) had an accompanying positive T2MR result with concordance in the identified Candida sp., while only 7/23 (30.4%) T2MR results had an accompanying positive blood culture. There was one case of discordance in species identification between T2MR and the preenrollment blood culture with evidence to support deep-seated infection by the Candida spp. detected by the T2MR assay. Based on the log rank test, there was a statistically significant improvement in posttreatment surveillance using the T2MR assay compared to blood culture (P = 0.004). Limitations of the study include the small sample size and lack of outcome data. In conclusion, the T2MR assay significantly outperformed blood cultures for monitoring the clearance of candidemia in patients receiving antifungal therapy and may be useful in determining adequate source control, timing for deescalation, and optimal duration of treatment. However, further studies are needed to determine the viability of Candida species cells detected by the T2MR assay and correlate the results with patient outcomes. (This study is registered at ClinicalTrials.gov under registration number NCT02163889.) PMID:29367293

Efficacy of T2 Magnetic Resonance Assay in Monitoring Candidemia after Initiation of Antifungal Therapy: the Serial Therapeutic and Antifungal Monitoring Protocol (STAMP) Trial.

PubMed

Mylonakis, Eleftherios; Zacharioudakis, Ioannis M; Clancy, Cornelius J; Nguyen, M Hong; Pappas, Peter G

2018-04-01

The performance of blood culture for monitoring candidemia clearance is hampered by its low sensitivity, especially during antifungal therapy. The T2 magnetic resonance (T2MR) assay combines magnetic resonance with nanotechnology to identify whole Candida species cells. A multicenter clinical trial studied the performance of T2MR in monitoring candidemia clearance compared to blood culture. Adults with a blood culture positive for yeast were enrolled and had blood cultures and T2MR testing performed on prespecified days. Thirty-one patients completed the trial. Thirteen of the 31 patients (41.9%) had at least one positive surveillance T2MR and/or blood culture result. All positive blood cultures (7/7 [100%]) had an accompanying positive T2MR result with concordance in the identified Candida sp., while only 7/23 (30.4%) T2MR results had an accompanying positive blood culture. There was one case of discordance in species identification between T2MR and the preenrollment blood culture with evidence to support deep-seated infection by the Candida spp. detected by the T2MR assay. Based on the log rank test, there was a statistically significant improvement in posttreatment surveillance using the T2MR assay compared to blood culture ( P = 0.004). Limitations of the study include the small sample size and lack of outcome data. In conclusion, the T2MR assay significantly outperformed blood cultures for monitoring the clearance of candidemia in patients receiving antifungal therapy and may be useful in determining adequate source control, timing for deescalation, and optimal duration of treatment. However, further studies are needed to determine the viability of Candida species cells detected by the T2MR assay and correlate the results with patient outcomes. (This study is registered at ClinicalTrials.gov under registration number NCT02163889.). Copyright © 2018 Mylonakis et al.

* A 3D Tissue-Printing Approach for Validation of Diffusion Tensor Imaging in Skeletal Muscle.

PubMed

Berry, David B; You, Shangting; Warner, John; Frank, Lawrence R; Chen, Shaochen; Ward, Samuel R

2017-09-01

The ability to noninvasively assess skeletal muscle microstructure, which predicts function and disease, would be of significant clinical value. One method that holds this promise is diffusion tensor magnetic resonance imaging (DT-MRI), which is sensitive to the microscopic diffusion of water within tissues and has become ubiquitous in neuroimaging as a way of assessing neuronal structure and damage. However, its application to the assessment of changes in muscle microstructure associated with injury, pathology, or age remains poorly defined, because it is difficult to precisely control muscle microstructural features in vivo. However, recent advances in additive manufacturing technologies allow precision-engineered diffusion phantoms with histology informed skeletal muscle geometry to be manufactured. Therefore, the goal of this study was to develop skeletal muscle phantoms at relevant size scales to relate microstructural features to MRI-based diffusion measurements. A digital light projection based rapid 3D printing method was used to fabricate polyethylene glycol diacrylate based diffusion phantoms with (1) idealized muscle geometry (no geometry; fiber sizes of 30, 50, or 70 μm or fiber size of 50 μm with 40% of walls randomly deleted) or (2) histology-based geometry (normal and after 30-days of denervation) containing 20% or 50% phosphate-buffered saline (PBS). Mean absolute percent error (8%) of the printed phantoms indicated high conformity to templates when "fibers" were >50 μm. A multiple spin-echo echo planar imaging diffusion sequence, capable of acquiring diffusion weighted data at several echo times, was used in an attempt to combine relaxometry and diffusion techniques with the goal of separating intracellular and extracellular diffusion signals. When fiber size increased (30-70 μm) in the 20% PBS phantom, fractional anisotropy (FA) decreased (0.32-0.26) and mean diffusivity (MD) increased (0.44 × 10 -3 mm 2 /s-0.70 × 10 -3 mm 2 /s). Similarly, when fiber size increased from 30 to 70 μm in the 50% PBS diffusion phantoms, a small change in FA was observed (0.18-0.22), but MD increased from 0.86 × 10 -3 mm 2 /s to 1.79 × 10 -3 mm 2 /s. This study demonstrates a novel application of tissue engineering to understand complex diffusion signals in skeletal muscle. Through this work, we have also demonstrated the feasibility of 3D printing for skeletal muscle with relevant matrix geometries and physiologically relevant tissue characteristics.

Linkage of Type 2 Diabetes on Chromosome 9p24 in Mexican Americans: Additional Evidence from the Veterans Administration Genetic Epidemiology Study (VAGES)

PubMed Central

Farook, Vidya S.; Coletta, Dawn K.; Puppala, Sobha; Schneider, Jennifer; Chittoor, Geetha; Hu, Shirley L.; Winnier, Deidre A.; Norton, Luke; Dyer, Thomas D.; Arya, Rector; Cole, Shelley A.; Carless, Melanie; Göring, Harald H.; Almasy, Laura; Mahaney, Michael C.; Comuzzie, Anthony G.; Curran, Joanne E.; Blangero, John; Duggirala, Ravindranath; Lehman, Donna M.; Jenkinson, Christopher P.; DeFronzo, Ralph A.

2014-01-01

Objective Type 2 diabetes (T2DM) is a complex metabolic disease and is more prevalent in certain ethnic groups such as the Mexican Americans. The goal of our study was to perform a genome-wide linkage analysis to localize T2DM susceptibility loci in Mexican Americans. Methods We used the phenotypic and genotypic data from 1,122 Mexican American individuals (307 families) who participated in the Veterans Administration Genetic Epidemiology Study (VAGES). Genome-wide linkage analysis was performed, using the variance components approach. Data from two additional Mexican American family studies, the San Antonio Family Heart Study (SAFHS) and the San Antonio Family Diabetes/Gallbladder Study (SAFDGS), were combined with the VAGES data to test for improved linkage evidence. Results After adjusting for covariate effects, T2DM was found to be under significant genetic influences (h2 = 0.62, P = 2.7 × 10−6). The strongest evidence for linkage of T2DM occurred between markers D9S1871 and D9S2169 on chromosome 9p24.2-p24.1 (LOD = 1.8). Given that we previously reported suggestive evidence for linkage of T2DM at this region in SAFDGS also, we found the significant and increased linkage evidence (LOD = 4.3, empirical P = 1.0 × 10−5, genome-wide P = 1.6 × 10−3) for T2DM at the same chromosomal region when we performed genome-wide linkage analysis of the VAGES data combined with SAFHS and SAFDGS data. Conclusion Significant T2DM linkage evidence was found on chromosome 9p24 in Mexican Americans. Importantly, the chromosomal region of interest in this study overlaps with several recent genome-wide association studies (GWASs) involving T2DM related traits. Given its overlap with such findings and our own initial T2DM association findings in the 9p24 chromosomal region, high throughput sequencing of the linked chromosomal region could identify the potential causal T2DM genes. PMID:24060607

Ex vivo T2 relaxation: Associations with age-related neuropathology and cognition

PubMed Central

Dawe, Robert J.; Bennett, David A.; Schneider, Julie A.; Leurgans, Sue E.; Kotrotsou, Aikaterini; Boyle, Patricia A.; Arfanakis, Konstantinos

2014-01-01

The transverse relaxation time constant, T2, is sensitive to brain tissue’s free water content and the presence of paramagnetic materials such as iron. In this study, ex vivo MRI was employed to investigate alterations in T2 related to Alzheimer’s disease (AD) pathology and other types of neuropathology common in old age, as well as the relationship between T2 alterations and cognition. Cerebral hemispheres were obtained from 371 deceased older adults. Using fast spin-echo imaging with multiple echo times, T2 maps were produced and warped to a study-specific template. Hemispheres underwent neuropathologic examination for identification of AD pathology and other common age-related neuropathologies. Voxelwise linear regression was carried out to detect regions of pathology-related T2 alterations and, in separate analyses, regions in which T2 alterations were linked to antemortem cognitive performance. AD pathology was associated with T2 prolongation in white matter of all lobes and T2 shortening in the basal ganglia and insula. Gross infarcts were associated with T2 prolongation in white matter of all lobes, and in the thalamus and basal ganglia. Hippocampal sclerosis was associated with T2 prolongation in the hippocampus and white matter of the temporal lobe. After controlling for neuropathology, T2 prolongation in the frontal lobe white matter was associated with lower performance in the episodic, semantic, and working memory domains. In addition, voxelwise analysis of in vivo and ex vivo T2 values indicated a positive relationship between the two, though further investigation is necessary to accurately translate findings of the current study to the in vivo case. PMID:24582637

Lack of association between uncoupling protein-2 Ala55Val polymorphism and incident diabetes in the atherosclerosis risk in communities study.

PubMed

Bielinski, Suzette J; Pankow, James S; Boerwinkle, Eric; Bray, Molly S; Kao, W H Linda; Folsom, Aaron R

2008-09-01

Type 2 diabetes mellitus (T2DM) is characterized by impaired insulin secretion, peripheral insulin resistance, and increased hepatic glucose production. Genes that contribute to genetic susceptibility to T2DM function in numerous biochemical pathways. Uncoupling protein-2 (UCP2) functions as a negative regulator of insulin secretion. Animal studies show induction of UCP2 plays a pathogenic role in the progression of obesity-induced T2DM and some human studies have shown an association between a common UCP2 polymorphism, Ala55Val (rs660339), and T2DM, obesity, and resting metabolic rate with the Val/Val genotype conferring increased risk. We investigated the relationship between the Ala55Val variant and incidence of T2DM among 12,056 participants in the Atherosclerosis Risk in Communities (ARIC) Study aged 45-64 years at baseline. Incident T2DM (n = 1,406) cases were identified over 9 years of follow-up. The Val55 allele frequency was 44% in blacks and 41% in whites. The rate of T2DM per 1,000 person was 15.0, 15.6, and 15.6 yearsfor Ala/Ala, Ala/Val, and Val/Val genotypes, respectively. We found no significant association between UCP2 genotypes and incident T2DM in the whole cohort, in race-gender subgroups, or in categories of body mass index (normal, overweight and obese). The Ala55Val polymorphism of UCP2 was not associated with incident T2DM in the ARIC cohort.

Type 2 diabetes mellitus susceptibility gene TCF7L2 is strongly associated with hyperglycemia in the Saudi Arabia Population of the eastern province of Saudi Arabia.

PubMed

Acharya, S; Al-Elq, A; Al-Nafaie, A; Muzaheed, M; Al-Ali, A

2015-08-01

We studied the association of single nucleotide polymorphisms (SNPs) rs7903146, rs12255372 and rs4506565 in type 2 diabetes mellitus (T2DM) susceptibility gene, transcription factor 7 like 2 (TCF7L2) with T2DM among the population of the Eastern Province of Saudi Arabia. In a case-control study, blood samples were collected from 359 T2DM patients and 351 age and sex-matched normoglycemic controls. Genotyping was done by allele specific PCR assay. Our results revealed a strong association between risk T alleles in variants rs12255372 (OR: G/T=1.4233; T/T=2.0395) and rs4506565 (OR: A/T=1.6066; T/T=3.1301) and T2DM among the Saudi population of the Eastern Province of Saudi Arabia. This is the first time that this association has been identified in a Saudi population. However, a common variant, rs7903146, often found to be associated with T2DM in other populations failed to demonstrate any association to T2DM with the present population. These data further strengthens the hypothesis that Saudi populations might carry a distinct risk allele in T2DM susceptibility gene TCF7L2. The present results confirm that rs12255372 and rs4506565 variants of TCF7L2 show an association, but not rs7903146, with T2DM for the Saudi population of the Eastern Province of Saudi Arabia.

Self-reported short sleep duration and insomnia symptoms as predictors of post-pregnancy weight change: Results from a cohort study

PubMed Central

Rognmo, Kamilla; Sivertsen, Børge; Eberhard-Gran, Malin

2016-01-01

This study aims to investigate whether change in sleep duration and insomnia symptoms in the postpartum period is related to change in body mass index from before to 2 years after pregnancy. This study is based on self-report data from a Norwegian cohort, the AHUS Birth Cohort Study. Data were collected at 8 weeks (T1) and 2 years (T2) postpartum. Data from 812 women were analyzed. The results showed that only women with symptoms of insomnia at both T1 and T2 (persistent symptoms) had a greater increase in body mass index compared to women with no insomnia symptoms at T1 or T2.The results indicate that persistent insomnia symptoms are related to a greater increase in body mass index. PMID:27634975

High Spatial Resolution and Temporally Resolved T2 * Mapping of Normal Human Myocardium at 7.0 Tesla: An Ultrahigh Field Magnetic Resonance Feasibility Study

PubMed Central

Hezel, Fabian; Thalhammer, Christof; Waiczies, Sonia; Schulz-Menger, Jeanette; Niendorf, Thoralf

2012-01-01

Myocardial tissue characterization using T2 * relaxation mapping techniques is an emerging application of (pre)clinical cardiovascular magnetic resonance imaging. The increase in microscopic susceptibility at higher magnetic field strengths renders myocardial T2 * mapping at ultrahigh magnetic fields conceptually appealing. This work demonstrates the feasibility of myocardial T2 * imaging at 7.0 T and examines the applicability of temporally-resolved and high spatial resolution myocardial T2 * mapping. In phantom experiments single cardiac phase and dynamic (CINE) gradient echo imaging techniques provided similar T2 * maps. In vivo studies showed that the peak-to-peak B0 difference following volume selective shimming was reduced to approximately 80 Hz for the four chamber view and mid-ventricular short axis view of the heart and to 65 Hz for the left ventricle. No severe susceptibility artifacts were detected in the septum and in the lateral wall for T2 * weighting ranging from TE = 2.04 ms to TE = 10.2 ms. For TE >7 ms, a susceptibility weighting induced signal void was observed within the anterior and inferior myocardial segments. The longest T2 * values were found for anterior (T2 * = 14.0 ms), anteroseptal (T2 * = 17.2 ms) and inferoseptal (T2 * = 16.5 ms) myocardial segments. Shorter T2 * values were observed for inferior (T2 * = 10.6 ms) and inferolateral (T2 * = 11.4 ms) segments. A significant difference (p = 0.002) in T2 * values was observed between end-diastole and end-systole with T2 * changes of up to approximately 27% over the cardiac cycle which were pronounced in the septum. To conclude, these results underscore the challenges of myocardial T2 * mapping at 7.0 T but demonstrate that these issues can be offset by using tailored shimming techniques and dedicated acquisition schemes. PMID:23251708

Dextromethorphan mediated bitter taste receptor activation in the pulmonary circuit causes vasoconstriction.

PubMed

Upadhyaya, Jasbir D; Singh, Nisha; Sikarwar, Anurag S; Chakraborty, Raja; Pydi, Sai P; Bhullar, Rajinder P; Dakshinamurti, Shyamala; Chelikani, Prashen

2014-01-01

Activation of bitter taste receptors (T2Rs) in human airway smooth muscle cells leads to muscle relaxation and bronchodilation. This finding led to our hypothesis that T2Rs are expressed in human pulmonary artery smooth muscle cells and might be involved in regulating the vascular tone. RT-PCR was performed to reveal the expression of T2Rs in human pulmonary artery smooth muscle cells. Of the 25 T2Rs, 21 were expressed in these cells. Functional characterization was done by calcium imaging after stimulating the cells with different bitter agonists. Increased calcium responses were observed with most of the agonists, the largest increase seen for dextromethorphan. Previously in site-directed mutational studies, we have characterized the response of T2R1 to dextromethorphan, therefore, T2R1 was selected for further analysis in this study. Knockdown with T2R1 specific shRNA decreased mRNA levels, protein levels and dextromethorphan-induced calcium responses in pulmonary artery smooth muscle cells by up to 50%. To analyze if T2Rs are involved in regulating the pulmonary vascular tone, ex vivo studies using pulmonary arterial and airway rings were pursued. Myographic studies using porcine pulmonary arterial and airway rings showed that stimulation with dextromethorphan led to contraction of the pulmonary arterial and relaxation of the airway rings. This study shows that dextromethorphan, acting through T2R1, causes vasoconstrictor responses in the pulmonary circuit and relaxation in the airways.

Type 2 Diabetes Susceptibility in the Greek-Cypriot Population: Replication of Associations with TCF7L2, FTO, HHEX, SLC30A8 and IGF2BP2 Polymorphisms

PubMed Central

Votsi, Christina; Toufexis, Costas; Michailidou, Kyriaki; Antoniades, Athos; Skordis, Nicos; Karaolis, Minas; Pattichis, Constantinos S.; Christodoulou, Kyproula

2017-01-01

Type 2 diabetes (T2D) has been the subject of numerous genetic studies in recent years which revealed associations of the disease with a large number of susceptibility loci. We hereby initiate the evaluation of T2D susceptibility loci in the Greek-Cypriot population by performing a replication case-control study. One thousand and eighteen individuals (528 T2D patients, 490 controls) were genotyped at 21 T2D susceptibility loci, using the allelic discrimination method. Statistically significant associations of T2D with five of the tested single nucleotide polymorphisms (SNPs) (TCF7L2 rs7901695, FTO rs8050136, HHEX rs5015480, SLC30A8 rs13266634 and IGF2BP2 rs4402960) were observed in this study population. Furthermore, 14 of the tested SNPs had odds ratios (ORs) in the same direction as the previously published studies, suggesting that these variants can potentially be used in the Greek-Cypriot population for predictive testing of T2D. In conclusion, our findings expand the genetic assessment of T2D susceptibility loci and reconfirm five of the worldwide established loci in a distinct, relatively small, newly investigated population. PMID:28067832

Utility of diffusion-weighted MR imaging in the diagnosis of placenta accreta spectrum abnormality.

PubMed

Sannananja, Bhagya; Ellermeier, Anna; Hippe, Daniel S; Winter, Thomas C; Kang, Stella K; Lee, Susanna I; Kilgore, Mark R; Dighe, Manjiri K

2018-04-17

The aim of this study was to evaluate the utility of added DWI sequences as an adjunct to traditional MR imaging in the evaluation of abnormal placentation in patients with suspicion for placenta accreta spectrum abnormality or morbidly adherent placenta (MAP). The study was approved by local ethics committee. The subjects included pregnant women with prenatal MRI performed between July 2013 to July 2015. All imaging was performed on a Philips 1.5T MR scanner using pelvic phased-array coil. Only T2-weighted and diffusion-weighted imaging (DWI) series were compiled for review. Two randomized imaging sets were created: set 1 included T2-weighted series only (T2W); set 2 included T2W with DWI series together (T2W + DWI). Three radiologists, blinded to history and pathology, reviewed the imaging, with 2 weeks of time between the two image sets. Sensitivity, specificity, and overall accuracy for MAP were calculated and compared between T2W only and T2W + DWI reads. Associations between imaging findings and invasion on pathology were tested using the Chi-squared test. Confidence scores, inter-reader agreement, and systematic differences were documented. A total of 17 pregnant women were included in the study. 8 cases were pathologically diagnosed with MAP. There were no significant differences in the diagnostic accuracy between T2W and T2W + DWI in the diagnosis of MAP in terms of overall accuracy (62.7% for T2W vs. 68.6% for T2W + DWI, p = 0.68), sensitivity (70.8% for T2W vs. 95.8% for T2W + DWI, p = 0.12), and specificity (55.6% for T2W vs. 44.4% for T2W + DWI, p = 0.49). There was no significant difference in the diagnostic confidence between the review of T2W images alone and the T2W + DWI review (mean 7.3 ± 1.8 for T2W vs. 7.5 ± 1.8 for T2W + DWI, p = 0.37). With the current imaging technique, addition of DWI sequence to the traditional T2W images cannot be shown to significantly increase the accuracy or reader confidence for diagnosis of placenta accreta spectrum abnormality. However, DWI does improve identification of abnormalities in the placental-myometrial interface.

Physiological Changes Following Competition in Male and Female Physique Athletes: A Pilot Study.

PubMed

Trexler, Eric T; Hirsch, Katie R; Campbell, Bill I; Smith-Ryan, Abbie E

2017-10-01

The purpose of the current study was to evaluate changes in body composition, metabolic rate, and hormones during postcompetition recovery. Data were collected from natural physique athletes (7 male/8 female) within one week before (T1) competition, within one week after (T2), and 4-6 weeks after (T3) competition. Measures included body composition (fat mass [FM] and lean mass [LM] from ultrasongraphy), resting metabolic rate (RMR; indirect calorimetry), and salivary leptin, testosterone, cortisol, ghrelin, and insulin. Total body water (TBW; bioelectrical impedance spectroscopy) was measured at T1 and T2 in a subsample (n = 8) of athletes. Significant (p < .05) changes were observed for weight (T1 = 65.4 ± 12.2 kg, T2 = 67.4 ± 12.6, T3 = 69.3 ± 13.4; T3 > T2 > T1), LM (T1 = 57.6 ± 13.9 kg, T2 = 59.4 ± 14.2, T3 = 59.3 ± 14.2; T2 and T3 > T1), and FM (T1 = 7.7 ± 4.4 kg, T2 = 8.0 ± 4.4, T3 = 10.0 ± 6.2; T3 > T1 and T2). TBW increased from T1 to T2 (Δ=1.9 ± 1.3 L, p < .01). RMR increased from baseline (1612 ± 266 kcal/day; 92.0% of predicted) to T2 (1881 ± 329, 105.3%; p < .01) and T3 (1778 ± 257, 99.6%; p < .001). Cortisol was higher (p < .05) at T2 (0.41 ± 0.31 μg/dL) than T1 (0.34 ± 0.31) and T3 (0.35 ± 0.27). Male testosterone at T3 (186.6 ± 41.3 pg/mL) was greater than T2 (148.0 ± 44.6, p = .04). RMR changes were associated (p ≤ .05) with change in body fat percent (ΔBF%; r = .59) and T3 protein intake (r= .60); male testosterone changes were inversely associated (p≤ .05) with ΔBF%, ΔFM, and Δweight (r=-0.81--0.88). TBW increased within days of competition. Precompetition RMR suppression appeared to be variable and markedly reversed by overfeeding, and reverted toward normal levels following competition. RMR and male testosterone increased while FM was preferentially gained 4-6 weeks postcompetition.

T2 mapping provides multiple approaches to characterize muscle involvement in neuromuscular diseases: a cross-sectional study of lower leg muscles in 5–15 year old boys with Duchenne Muscular Dystrophy

PubMed Central

Arpan, Ishu; Forbes, Sean C; Lott, Donovan J; Senesac, Claudia R; Daniels, Michael J; Triplett, William T; Deol, Jasjit K; Sweeney, H Lee; Walter, Glenn A; Vandenborne, Krista

2012-01-01

Purpose Skeletal muscles of children with Duchenne muscular dystrophy (DMD) have enhanced susceptibility to damage and progressive lipid infiltration, which contribute to an increase in magnetic resonance proton transverse relaxation time (T2). Therefore, examining T2 changes in individual muscles may be useful for monitoring disease progression in DMD. In this study we utilized mean T2, percent elevated pixels, and T2 heterogeneity to assess changes in composition of dystrophic muscles. In addition, we used fat saturation (fatsat) to distinguish T2 changes due to edema and inflammation from fat infiltration in muscles. Methods Thirty subjects with DMD and 15 age-matched controls underwent T2-weighted imaging of their lower leg using 3-T MR system. T2 maps were developed and four lower leg muscles were manually traced (soleus, medial gastrocnemius, peroneal and tibialis anterior). Mean T2 of the traced regions of interest (ROI), width of T2 histograms, and percent-elevated pixels were calculated. Results We found that even in young children with DMD, muscles had elevated mean T2, were more heterogeneous, and had a greater percent-elevated pixels in the lower leg muscles than controls. T2 measures decreased with fat saturation, but were still higher (p<0.05) in dystrophic muscles than controls. Further, T2 measures showed positive correlations with timed functional tests (r=0.23–0.79). Conclusion The elevated T2 measures with and without fat saturation in all ages of DMD examined (5–15 years) compared to unaffected controls indicate that the dystrophic muscles have increased regions of damage, edema, and fat infiltration. This study shows that T2 mapping provides multiple approaches that can be effectively utilized to characterize muscle tissue in children with DMD even in the early stages of the disease. Therefore, T2 mapping may prove clinically useful in monitoring muscle changes due to disease process or therapeutic interventions in DMD. PMID:23044995

Smoking and the risk of type 2 diabetes in Japan: A systematic review and meta-analysis.

PubMed

Akter, Shamima; Goto, Atsushi; Mizoue, Tetsuya

2017-12-01

Cigarette smoking is the leading avoidable cause of disease burden. Observational studies have suggested an association between smoking and risk of type 2 diabetes mellitus (T2DM). We conducted a meta-analysis of prospective observational studies to investigate the association of smoking status, smoking intensity, and smoking cessation with the risk of T2DM in Japan, where the prevalence of smoking has been decreasing but remains high. We systematically searched MEDLINE and the Ichushi database to December 2015 and identified 22 eligible articles, representing 343,573 subjects and 16,383 patients with T2DM. We estimated pooled relative risks (RRs) using a random-effects model and conducted subgroup analyses by participant and study characteristics. Compared with nonsmoking, the pooled RR of T2DM was 1.38 (95% confidence interval [CI], 1.28-1.49) for current smoking (19 studies) and 1.19 (95% CI, 1.09-1.31) for former smoking (15 studies). These associations persisted in all subgroup and sensitivity analyses. We found a linear dose-response relationship between cigarette consumption and T2DM risk; the risk of T2DM increased by 16% for each increment of 10 cigarettes smoked per day. The risk of T2DM remained high among those who quit during the preceding 5 years but decreased steadily with increasing duration of cessation, reaching a risk level comparable to that of never smokers after 10 years of smoking cessation. We estimated that 18.8% of T2DM cases in men and 5.4% of T2DM cases in women were attributable to smoking. The present findings suggest that cigarette smoking is associated with an increased risk of T2DM, so tobacco control programs to reduce smoking could have a substantial effect to decrease the burden of T2DM in Japan. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Metformin inhibits goitrogenous effects of type 2 diabetes.

PubMed

Ittermann, Till; Markus, Marcello R P; Schipf, Sabine; Derwahl, Michael; Meisinger, Christa; Völzke, Henry

2013-07-01

Data on the association between type 2 diabetes mellitus (T2DM) and thyroid volume are sparse. An experimental study demonstrated an inhibitory effect of metformin on the growth of human thyroid cells. So far no study on humans has investigated potentially modulating effects of metformin on the association between T2DM and thyroid volume. Therefore, we investigated these effects in a population-based cohort study. We used data from the Study of Health in Pomerania and included 2570 individuals for cross-sectional and 1088 individuals for longitudinal analyses. T2DM was defined by physician-diagnosed self-report or intake of antidiabetic medication. In the cross-sectional data, females with T2DM treated with antidiabetic medication other than metformin had a larger thyroid volume (β=4.69; 95% CI 1.87 to 7.50) and a higher odds ratio (OR) for goiter (OR=1.71; 95% CI 1.05 to 2.79) than females without T2DM, whereas in males, no such association was detected. In females or males treated with metformin, T2DM was not associated with thyroid volume or goiter. In longitudinal analyses, incident T2DM not treated with metformin was significantly associated with a higher risk for incident goiter in the total population (incidence rate ratio (IRR)=1.70; 95% CI 1.10 to 2.91). Individuals with T2DM having changed from metformin to other antidiabetic agents during follow-up also had a higher risk for incident goiter than individuals without T2DM (IRR=2.71; 95% CI 1.74 to 4.20). We demonstrate an inhibitory effect of metformin on prevalent and incident goiter. Anti-goitrogenous effects of metformin add to the general benefits of metformin treatment of T2DM.

Coffee and caffeine intake and incidence of type 2 diabetes mellitus: a meta-analysis of prospective studies.

PubMed

Jiang, Xiubo; Zhang, Dongfeng; Jiang, Wenjie

2014-02-01

Coffee and caffeine have been linked to type 2 diabetes mellitus (T2DM). A dose-response meta-analysis of prospective studies was conducted to assess the association between coffee and caffeine intake and T2DM incidence. Pertinent studies were identified by a search of PubMed and EMBASE. The fixed- or random-effect pooled measure was selected based on between-study heterogeneity. Dose-response relationship was assessed by restricted cubic spline. Compared with the lowest level, the pooled relative risk (95 % CI) of T2DM was 0.71 (0.67-0.76) for the highest level of coffee intake (26 articles involving 50,595 T2DM cases and 1,096,647 participants), 0.79 (0.69-0.91) for the highest level of decaffeinated coffee intake (10 articles involving 29,165 T2DM cases and 491,485 participants) and 0.70 (0.65-0.75) for the highest level of caffeine intake (6 articles involving 9,302 T2DM cases and 321,960 participants). The association of coffee, decaffeinated coffee and caffeine intake with T2DM incidence was stronger for women than that for men. A stronger association of coffee intake with T2DM incidence was found for non-smokers and subjects with body mass index <25 kg/m(2). Dose-response analysis suggested that incidence of T2DM decreased by 12 % [0.88 (0.86-0.90)] for every 2 cups/day increment in coffee intake, 11 % [0.89 (0.82-0.98)] for every 2 cups/day increment in decaffeinated coffee intake and 14 % [0.86 (0.82-0.91)] for every 200 mg/day increment in caffeine intake. Coffee and caffeine intake might significantly reduce the incidence of T2DM.

Myocardial 2D strain echocardiography and cardiac biomarkers in children during and shortly after anthracycline therapy for acute lymphoblastic leukaemia (ALL): a prospective study.

PubMed

Mavinkurve-Groothuis, Annelies M C; Marcus, Karen A; Pourier, Milanthy; Loonen, Jacqueline; Feuth, Ton; Hoogerbrugge, Peter M; de Korte, Chris L; Kapusta, Livia

2013-06-01

The aim of this study was to investigate myocardial 2D strain echocardiography and cardiac biomarkers in the assessment of cardiac function in children with acute lymphoblastic leukaemia (ALL) during and shortly after treatment with anthracyclines. Cardiac function of 60 children with ALL was prospectively studied with measurements of cardiac troponin T (cTnT) and N-terminal-pro-brain natriuretic peptide (NT-pro-BNP) and conventional and myocardial 2D strain echocardiography before start (T = 0), after 3 months (T = 1), and after 1 year (T = 2), and were compared with 60 healthy age-matched controls. None of the patients showed clinical signs of cardiac failure or abnormal fractional shortening. Cardiac function decreased significantly during treatment and was significantly decreased compared with normal controls. Cardiac troponin T levels were abnormal in 11% of the patients at T = 1 and were significantly related to increased time to global peak systolic longitudinal strain at T = 2 (P = 0.003). N-terminal-pro-brain natriuretic peptide levels were abnormal in 13% of patients at T = 1 and in 20% at T = 2, absolute values increased throughout treatment in 59%. Predictors for abnormal NT-pro-BNP at T = 2 were abnormal NT-pro-BNP at T = 0 and T = 1, for abnormal myocardial 2D strain parameters at T = 2 cumulative anthracycline dose and z-score of the diastolic left ventricular internal diameter at baseline. Children with newly diagnosed ALL showed decline of systolic and diastolic function during treatment with anthracyclines using cardiac biomarkers and myocardial 2D strain echocardiography. N-terminal-pro-brain natriuretic peptide levels were not related to echocardiographic strain parameters and cTnT was not a predictor for abnormal strain at T = 2.Therefore, the combination of cardiac biomarkers and myocardial 2D strain echocardiography is important in the assessment of cardiac function of children with ALL treated with anthracyclines.

Evaluation of T1/T2 ratios in a pilot study as a potential biomarker of biopsy: proven benign and malignant breast lesions in correlation with histopathological disease stage.

PubMed

Malikova, Marina A; Tkacz, Jaroslaw N; Slanetz, Priscilla J; Guo, Chao-Yu; Aakil, Adam; Jara, Hernan

2017-08-01

Early breast cancer detection is important for intervention and prognosis. Advances in treatment and outcome require diagnostic tools with highly positive predictive value. To study the potential role of quantitative MRI (qMRI) using T1/T2 ratios to differentiate benign from malignant breast lesions. A cross-sectional study of 69 women with 69 known or suspicious breast lesions were scanned with mixed-turbo spin echo pulse sequence. Patients were grouped according to histopathological assessment of disease stage: untreated malignant tumor, treated malignancy and benign disease. Elevated T1/T2 means were observed for biopsy-proven malignant lesions and for malignant lesions treated prior to qMRI with chemotherapy and/or radiation, as compared with benign lesions. The qMRI-obtained T1/T2 ratios correlated with histopathology. Analysis revealed correlation between elevated T1/T2 ratio and disease stage. This could provide valuable complementary information on tissue properties as an additional diagnostic tool.

Dose-Response Relationship between Dietary Magnesium Intake and Risk of Type 2 Diabetes Mellitus: A Systematic Review and Meta-Regression Analysis of Prospective Cohort Studies

PubMed Central

Fang, Xin; Han, Hedong; Li, Mei; Liang, Chun; Fan, Zhongjie; Aaseth, Jan; He, Jia; Montgomery, Scott; Cao, Yang

2016-01-01

The epidemiological evidence for a dose-response relationship between magnesium intake and risk of type 2 diabetes mellitus (T2D) is sparse. The aim of the study was to summarize the evidence for the association of dietary magnesium intake with risk of T2D and evaluate the dose-response relationship. We conducted a systematic review and meta-analysis of prospective cohort studies that reported dietary magnesium intake and risk of incident T2D. We identified relevant studies by searching major scientific literature databases and grey literature resources from their inception to February 2016. We included cohort studies that provided risk ratios, i.e., relative risks (RRs), odds ratios (ORs) or hazard ratios (HRs), for T2D. Linear dose-response relationships were assessed using random-effects meta-regression. Potential nonlinear associations were evaluated using restricted cubic splines. A total of 25 studies met the eligibility criteria. These studies comprised 637,922 individuals including 26,828 with a T2D diagnosis. Compared with the lowest magnesium consumption group in the population, the risk of T2D was reduced by 17% across all the studies; 19% in women and 16% in men. A statistically significant linear dose-response relationship was found between incremental magnesium intake and T2D risk. After adjusting for age and body mass index, the risk of T2D incidence was reduced by 8%–13% for per 100 mg/day increment in dietary magnesium intake. There was no evidence to support a nonlinear dose-response relationship between dietary magnesium intake and T2D risk. The combined data supports a role for magnesium in reducing risk of T2D, with a statistically significant linear dose-response pattern within the reference dose range of dietary intake among Asian and US populations. The evidence from Europe and black people is limited and more prospective studies are needed for the two subgroups. PMID:27869762

Mechanisms of behavioural maintenance: Long-term effects of theory-based interventions to promote safe water consumption.

PubMed

Inauen, Jennifer; Mosler, Hans-Joachim

2016-01-01

Theory-based interventions can enhance people's safe water consumption, but the sustainability of these interventions and the mechanisms of maintenance remain unclear. We investigated these questions based on an extended theory of planned behaviour. Seven hundred and ten (445 analysed) randomly selected households participated in two cluster-randomised controlled trials in Bangladesh. Study 1 promoted switching to neighbours' arsenic-safe wells, and Study 2 promoted switching to arsenic-safe deep wells. Both studies included two intervention phases. Structured interviews were conducted at baseline (T1), and at 1-month (T2), 2-month (T3) and 9-month (T4) follow-ups. In intervention phase 1 (between T1 and T2), commitment-based behaviour change techniques--reminders, implementation intentions and public commitment--were combined with information and compared to an information-only control group. In phase 2 (between T2 and T3), half of each phase 1 intervention group was randomly assigned to receive either commitment-based techniques once more or coping planning with reminders and information. Initial well-switching rates of up to 60% significantly declined by T4: 38.3% of T2 safe water users stopped consuming arsenic-safe water. The decline depended on the intervention. Perceived behavioural control, intentions, commitment strength and coping planning were associated with maintenance. In line with previous studies, the results indicate that commitment and reminders engender long-term behavioural change.

Recreational alcohol use induces changes in the concentrations of choline-containing compounds and total creatine in the brain: a (1)H MRS study of healthy subjects.

PubMed

Tunc-Skarka, Nuran; Weber-Fahr, Wolfgang; Ende, Gabriele

2015-10-01

It has previously been reported that even social alcohol consumption affects the magnetic resonance spectroscopy (MRS) signals of choline-containing compounds (tCho). The purpose of this study was to investigate whether the consumption of alcohol affects the concentrations of the metabolites tCho, N-acetylaspartate, creatine, or myo-inositol and/or their T 2 relaxation times. (1)H MR spectra were obtained at 3 T from a frontal white matter voxel of 25 healthy subjects with social alcohol consumption (between 0 and 25.9 g/day). Absolute brain metabolite concentrations and T 2 relaxation times of metabolites were examined via MRS measurements at different echo times. Metabolite concentrations and their T 2 relaxation times were correlated with subjects' alcohol consumption, controlling for age. We observed positive correlations of absolute tCho and phosphocreatine and creatine (tCr) concentrations with alcohol consumption but no correlation between any metabolite T 2 relaxation time and alcohol consumption. This study shows that even social alcohol consumption affects the concentrations of tCho and tCr in cerebral white matter. Future studies assessing brain tCho and tCr levels should control for the confounding factor alcohol consumption.

Bi-exponential T2 analysis of healthy and diseased Achilles tendons: an in vivo preliminary magnetic resonance study and correlation with clinical score.

PubMed

Juras, Vladimir; Apprich, Sebastian; Szomolanyi, Pavol; Bieri, Oliver; Deligianni, Xeni; Trattnig, Siegfried

2013-10-01

To compare mono- and bi-exponential T2 analysis in healthy and degenerated Achilles tendons using a recently introduced magnetic resonance variable-echo-time sequence (vTE) for T2 mapping. Ten volunteers and ten patients were included in the study. A variable-echo-time sequence was used with 20 echo times. Images were post-processed with both techniques, mono- and bi-exponential [T2 m, short T2 component (T2 s) and long T2 component (T2 l)]. The number of mono- and bi-exponentially decaying pixels in each region of interest was expressed as a ratio (B/M). Patients were clinically assessed with the Achilles Tendon Rupture Score (ATRS), and these values were correlated with the T2 values. The means for both T2 m and T2 s were statistically significantly different between patients and volunteers; however, for T2 s, the P value was lower. In patients, the Pearson correlation coefficient between ATRS and T2 s was -0.816 (P = 0.007). The proposed variable-echo-time sequence can be successfully used as an alternative method to UTE sequences with some added benefits, such as a short imaging time along with relatively high resolution and minimised blurring artefacts, and minimised susceptibility artefacts and chemical shift artefacts. Bi-exponential T2 calculation is superior to mono-exponential in terms of statistical significance for the diagnosis of Achilles tendinopathy. • Magnetic resonance imaging offers new insight into healthy and diseased Achilles tendons • Bi-exponential T2 calculation in Achilles tendons is more beneficial than mono-exponential • A short T2 component correlates strongly with clinical score • Variable echo time sequences successfully used instead of ultrashort echo time sequences.

Identification of functional bitter taste receptors and their antagonist in chickens.

PubMed

Dey, Bapon; Kawabata, Fuminori; Kawabata, Yuko; Yoshida, Yuta; Nishimura, Shotaro; Tabata, Shoji

2017-01-22

Elucidation of the taste sense of chickens is important not only for the development of chicken feedstuffs for the chicken industry but also to help clarify the evolution of the taste sense among animals. There are three putative chicken bitter taste receptors, chicken T2R1 (cT2R1), cT2R2 and cT2R7, which were identified using genome information and cell-based assays. Previously, we have shown that cT2R1 is a functional bitter taste receptor through both cell-based assays and behavioral tests. In this study, therefore, we focused on the sensitivities of the other two bitter receptors, cT2R2 and cT2R7, by using their agonists in behavioral tests. We tested three agonists of cT2R2 and three agonists of cT2R7. In a 10-min drinking study, the intakes of cT2R2 agonist solutions were not different from that of water. On the other hand, the intakes of cT2R7 agonist solutions were significantly lower compared to water. In addition, we constructed cT2R1-and cT2R7-expressing cells in order to search for an antagonist for these functional bitter taste receptors. By using Ca 2+ imaging methods, we found that 6-methoxyflavanone (6-meth) can inhibit the activities of both cT2R1 and cT2R7. Moreover, 6-meth also inhibited the reduction of the intake of bitter solutions containing cT2R1 or cT2R7 agonists in behavioral tests. Taken together, these results suggested that cT2R7 is a functional bitter taste receptor like cT2R1, but that cT2R2 is not, and that 6-meth is an antagonist for these two functional chicken bitter taste receptors. This is the first identification of an antagonist of chicken bitter receptors. Copyright © 2016 Elsevier Inc. All rights reserved.

A Virtual Water Maze Revisited: Two-Year Changes in Navigation Performance and their Neural Correlates in Healthy Adults

PubMed Central

Daugherty, Ana M.; Raz, Naftali

2016-01-01

Age-related declines in spatial navigation are associated with deficits in procedural and episodic memory and deterioration of their neural substrates. For the lack of longitudinal evidence, the pace and magnitude of these declines and their neural mediators remain unclear. Here we examined virtual navigation in healthy adults (N=213, age 18–77 years) tested twice, two years apart, with complementary indices of navigation performance (path length and complexity) measured over six learning trials at each occasion. Slopes of skill acquisition curves and longitudinal change therein were estimated in structural equation modeling, together with change in regional brain volumes and iron content (R2* relaxometry). Although performance on the first trial did not differ between occasions separated by two years, the slope of path length improvement over trials was shallower and end-of-session performance worse at follow-up. Advanced age, higher pulse pressure, smaller cerebellar and caudate volumes, and greater caudate iron content were associated with longer search paths, i.e. poorer navigation performance. In contrast, path complexity diminished faster over trials at follow-up, albeit less so in older adults. Improvement in path complexity after two years was predicted by lower baseline hippocampal iron content and larger parahippocampal volume. Thus, navigation path length behaves as an index of perceptual-motor skill that is vulnerable to age-related decline, whereas path complexity may reflect cognitive mapping in episodic memory that improves with repeated testing, although not enough to overcome age-related deficits. PMID:27659539

A virtual water maze revisited: Two-year changes in navigation performance and their neural correlates in healthy adults.

PubMed

Daugherty, Ana M; Raz, Naftali

2017-02-01

Age-related declines in spatial navigation are associated with deficits in procedural and episodic memory and deterioration of their neural substrates. For the lack of longitudinal evidence, the pace and magnitude of these declines and their neural mediators remain unclear. Here we examined virtual navigation in healthy adults (N=213, age 18-77 years) tested twice, two years apart, with complementary indices of navigation performance (path length and complexity) measured over six learning trials at each occasion. Slopes of skill acquisition curves and longitudinal change therein were estimated in structural equation modeling, together with change in regional brain volumes and iron content (R2* relaxometry). Although performance on the first trial did not differ between occasions separated by two years, the slope of path length improvement over trials was shallower and end-of-session performance worse at follow-up. Advanced age, higher pulse pressure, smaller cerebellar and caudate volumes, and greater caudate iron content were associated with longer search paths, i.e. poorer navigation performance. In contrast, path complexity diminished faster over trials at follow-up, albeit less so in older adults. Improvement in path complexity after two years was predicted by lower baseline hippocampal iron content and larger parahippocampal volume. Thus, navigation path length behaves as an index of perceptual-motor skill that is vulnerable to age-related decline, whereas path complexity may reflect cognitive mapping in episodic memory that improves with repeated testing, although not enough to overcome age-related deficits. Copyright © 2016 Elsevier Inc. All rights reserved.

Chondromalacia patellae: an in vitro study. Comparison of MR criteria with histologic and macroscopic findings.

PubMed

van Leersum, M; Schweitzer, M E; Gannon, F; Finkel, G; Vinitski, S; Mitchell, D G

1996-11-01

To develop MR criteria for grades of chondromalacia patellae and to assess the accuracy of these grades. Fat-suppressed T2-weighted double-echo, fat-suppressed T2-weighted fast spin echo, fat-suppressed T1-weighted, and gradient echo sequences were performed at 1.5 T for the evaluation of chondromalacia. A total of 1000 MR, 200 histologic, and 200 surface locations were graded for chondromalacia and statistically compared. Compared with gross inspection as well as with histology the most accurate sequences were fat-suppressed T2-weighted conventional spin echo and fat suppressed T2-weighted fast spin echo, although the T1-weighted and proton density images also correlated well. The most accurate MR criteria applied to the severe grades of chondromalacia, with less accurate results for lesser grades. This study demonstrates that fat-suppressed routine T2-weighted and fast spin echo T2-weighted sequences seem to be more accurate than proton density, T1-weighted, and gradient echo sequences in grading chondromalacia. Good histologic and macroscopic correlation was seen in more severe grades of chondromalacia, but problems remain for the early grades in all sequences studied.

Mendelian Randomization Study of B-Type Natriuretic Peptide and Type 2 Diabetes: Evidence of Causal Association from Population Studies

PubMed Central

Pfister, Roman; Sharp, Stephen; Luben, Robert; Welsh, Paul; Barroso, Inês; Salomaa, Veikko; Meirhaeghe, Aline; Khaw, Kay-Tee; Sattar, Naveed; Langenberg, Claudia; Wareham, Nicholas J.

2011-01-01

Background Genetic and epidemiological evidence suggests an inverse association between B-type natriuretic peptide (BNP) levels in blood and risk of type 2 diabetes (T2D), but the prospective association of BNP with T2D is uncertain, and it is unclear whether the association is confounded. Methods and Findings We analysed the association between levels of the N-terminal fragment of pro-BNP (NT-pro-BNP) in blood and risk of incident T2D in a prospective case-cohort study and genotyped the variant rs198389 within the BNP locus in three T2D case-control studies. We combined our results with existing data in a meta-analysis of 11 case-control studies. Using a Mendelian randomization approach, we compared the observed association between rs198389 and T2D to that expected from the NT-pro-BNP level to T2D association and the NT-pro-BNP difference per C allele of rs198389. In participants of our case-cohort study who were free of T2D and cardiovascular disease at baseline, we observed a 21% (95% CI 3%–36%) decreased risk of incident T2D per one standard deviation (SD) higher log-transformed NT-pro-BNP levels in analysis adjusted for age, sex, body mass index, systolic blood pressure, smoking, family history of T2D, history of hypertension, and levels of triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. The association between rs198389 and T2D observed in case-control studies (odds ratio = 0.94 per C allele, 95% CI 0.91–0.97) was similar to that expected (0.96, 0.93–0.98) based on the pooled estimate for the log-NT-pro-BNP level to T2D association derived from a meta-analysis of our study and published data (hazard ratio = 0.82 per SD, 0.74–0.90) and the difference in NT-pro-BNP levels (0.22 SD, 0.15–0.29) per C allele of rs198389. No significant associations were observed between the rs198389 genotype and potential confounders. Conclusions Our results provide evidence for a potential causal role of the BNP system in the aetiology of T2D. Further studies are needed to investigate the mechanisms underlying this association and possibilities for preventive interventions. Please see later in the article for the Editors' Summary PMID:22039354

Genome-wide association study in people of South Asian ancestry identifies six novel susceptibility loci for type 2 diabetes

PubMed Central

Kooner, Jaspal S; Saleheen, Danish; Sim, Xueling; Sehmi, Joban; Zhang, Weihua; Frossard, Philippe; Been, Latonya F; Chia, Kee-Seng; Dimas, Antigone S; Hassanali, Neelam; Jafar, Tazeen; Jowett, Jeremy BM; Li, Xinzhing; Radha, Venkatesan; Rees, Simon D; Takeuchi, Fumihiko; Young, Robin; Aung, Tin; Basit, Abdul; Chidambaram, Manickam; Das, Debashish; Grunberg, Elin; Hedman, Åsa K; Hydrie, Zafar I; Islam, Muhammed; Khor, Chiea-Chuen; Kowlessur, Sudhir; Kristensen, Malene M; Liju, Samuel; Lim, Wei-Yen; Matthews, David R; Liu, Jianjun; Morris, Andrew P; Nica, Alexandra C; Pinidiyapathirage, Janani M; Prokopenko, Inga; Rasheed, Asif; Samuel, Maria; Shah, Nabi; Shera, A Samad; Small, Kerrin S; Suo, Chen; Wickremasinghe, Ananda R; Wong, Tien Yin; Yang, Mingyu; Zhang, Fan; Abecasis, Goncalo R; Barnett, Anthony H; Caulfield, Mark; Deloukas, Panos; Frayling, Tim; Froguel, Philippe; Kato, Norihiro; Katulanda, Prasad; Kelly, M Ann; Liang, Junbin; Mohan, Viswanathan; Sanghera, Dharambir K; Scott, James; Seielstad, Mark; Zimmet, Paul Z; Elliott, Paul; Teo, Yik Ying; McCarthy, Mark I; Danesh, John; Tai, E Shyong; Chambers, John C

2013-01-01

We carried out a genome wide association study of type-2 diabetes (T2D) amongst 20,119 people of South Asian ancestry (5,561 with T2D); we identified 20 independent SNPs associated with T2D at P<10−4 for testing amongst a further 38,568 South Asians (13,170 with T2D). In combined analysis, common genetic variants at six novel loci (GRB14, ST6GAL1, VPS26A, HMG20A, AP3S2 and HNF4A) were associated with T2D (P=4.1×10−8 to P=1.9×10−11); SNPs at GRB14 were also associated with insulin sensitivity, and at ST6GAL1 and HNF4A with pancreatic beta-cell function respectively. Our findings provide additional insight into mechanisms underlying T2D, and demonstrate the potential for new discovery from genetic association studies in South Asians who have increased susceptibility to T2D. PMID:21874001

Association between urbanisation and type 2 diabetes: an ecological study.

PubMed

Gassasse, Zakariah; Smith, Dianna; Finer, Sarah; Gallo, Valentina

2017-01-01

Previous studies have explored the effect of urbanisation on the prevalence of type 2 diabetes (T2D) at regional/national level. The aim of this study is to investigate the association between urbanisation and T2D at country level, worldwide, and to explore the role of intermediate variables (physical inactivity, sugar consumption and obesity). The potential effect modification of gross domestic product (GDP) was also assessed. Data for 207 countries were collected from accessible datasets. Direct acyclic graphs were used to describe the association between urbanisation, T2D and their intermediate variables (physical inactivity, sugar consumption and obesity). Urbanisation was measured as urban percentage (UP) and as agglomeration index (AI). Crude and multivariate linear regression analyses were conducted to explore selected associations. The interaction between urbanisation and T2D across levels of GDP per capita was investigated. The association between urbanisation and T2D diverged by exposure: AI was positively associated, while UP negatively associated with T2D prevalence. Physical inactivity and obesity were statistically significantly associated with increased prevalence of T2D. In middle-income countries (MIC) UP, AI and GDP were significantly associated with T2D prevalence, while in high-income countries (HIC), physical inactivity and obesity were the main determinant of T2D prevalence. The type of urban growth, not urbanisation per se, predicted T2D prevalence at country level. In MIC, population density and GDP were the main determinant of diabetes, while in HIC. these were physical inactivity and obesity. Globalisation is playing an important role in the rise of T2D worldwide.

Differences in hypothalamic type 2 deiodinase ubiquitination explain localized sensitivity to thyroxine

PubMed Central

Werneck de Castro, Joao Pedro; Fonseca, Tatiana L.; Ueta, Cintia B.; McAninch, Elizabeth A.; Abdalla, Sherine; Wittmann, Gabor; Lechan, Ronald M.; Gereben, Balazs; Bianco, Antonio C.

2015-01-01

The current treatment for patients with hypothyroidism is levothyroxine (L-T4) along with normalization of serum thyroid-stimulating hormone (TSH). However, normalization of serum TSH with L-T4 monotherapy results in relatively low serum 3,5,3′-triiodothyronine (T3) and high serum thyroxine/T3 (T4/T3) ratio. In the hypothalamus-pituitary dyad as well as the rest of the brain, the majority of T3 present is generated locally by T4 deiodination via the type 2 deiodinase (D2); this pathway is self-limited by ubiquitination of D2 by the ubiquitin ligase WSB-1. Here, we determined that tissue-specific differences in D2 ubiquitination account for the high T4/T3 serum ratio in adult thyroidectomized (Tx) rats chronically implanted with subcutaneous L-T4 pellets. While L-T4 administration decreased whole-body D2-dependent T4 conversion to T3, D2 activity in the hypothalamus was only minimally affected by L-T4. In vivo studies in mice harboring an astrocyte-specific Wsb1 deletion as well as in vitro analysis of D2 ubiquitination driven by different tissue extracts indicated that D2 ubiquitination in the hypothalamus is relatively less. As a result, in contrast to other D2-expressing tissues, the hypothalamus is wired to have increased sensitivity to T4. These studies reveal that tissue-specific differences in D2 ubiquitination are an inherent property of the TRH/TSH feedback mechanism and indicate that only constant delivery of L-T4 and L-T3 fully normalizes T3-dependent metabolic markers and gene expression profiles in Tx rats. PMID:25555216

Use of conventional tomography to evaluate changes in the nasal cavity with rapid palatal expansion.

PubMed

Palaisa, Jacqueline; Ngan, Peter; Martin, Chris; Razmus, Thomas

2007-10-01

The relationship between nasal airway resistance and the use of rapid palatal expansion appliances remains controversial. The purpose of this study was to use conventional tomography to determine the anatomical changes in the nasal cavity after maxillary expansion. Nineteen patients (aged 8-15 years) were included in the study. Tomograms were taken before expansion (T1), immediately after expansion (T2), and 3 months after expansion (T3). Areas for the left and right anterior, middle, and posterior nasal cavity and total volume were calculated by using the computer software, AutoCAD LT 2005. Data were analyzed with paired t tests. Significant increases in area were found in the anterior nasal cavity from T1 to T2 (0.85 +/- 1.19 cm2, 11.7% increase), T2 to T3 (1.18 +/- 1.2 cm2, 22.2% increase), and T1 to T3 (2.6 +/- 1.7 cm2, 35.7% increase) (P <.05). Similar increases were found in the middle and posterior nasal cavity. Significant increases in volume were found from T1 to T2 (2.1 +/- 2.7 cm3, 10.7% increase), T2 to T3 (4.9 +/- 2.3 cm3, 22.6% increase), and T1 to T3 (6.99 +/- 2.45 cm3, 27.8% increase). No significant differences were found in the area or the volume of the left and right sides of the nasal cavity. Individual variations in response to maxillary expansion were large for most of the parameters tested. These data suggest that rapid palatal expansion is usually accompanied by increases in area and volume of the nasal cavity, and these changes remain stable 3 months after maxillary expansion.

Myocardial effective transverse relaxation time T2* Correlates with left ventricular wall thickness: A 7.0 T MRI study.

PubMed

Huelnhagen, Till; Hezel, Fabian; Serradas Duarte, Teresa; Pohlmann, Andreas; Oezerdem, Celal; Flemming, Bert; Seeliger, Erdmann; Prothmann, Marcel; Schulz-Menger, Jeanette; Niendorf, Thoralf

2017-06-01

Myocardial effective relaxation time T2* is commonly regarded as a surrogate for myocardial tissue oxygenation. However, it is legitimate to assume that there are multiple factors that influence T2*. To this end, this study investigates the relationship between T2* and cardiac macromorphology given by left ventricular (LV) wall thickness and left ventricular radius, and provides interpretation of the results in the physiological context. High spatio-temporally resolved myocardial CINE T2* mapping was performed in 10 healthy volunteers using a 7.0 Tesla (T) full-body MRI system. Ventricular septal wall thickness, left ventricular inner radius, and T2* were analyzed. Macroscopic magnetic field changes were elucidated using cardiac phase-resolved magnetic field maps. Ventricular septal T2* changes periodically over the cardiac cycle, increasing in systole and decreasing in diastole. Ventricular septal wall thickness and T2* showed a significant positive correlation, whereas the inner LV radius and T2* were negatively correlated. The effect of macroscopic magnetic field gradients on T2* can be considered minor in the ventricular septum. Our findings suggest that myocardial T2* is related to tissue blood volume fraction. Temporally resolved T2* mapping could be beneficial for myocardial tissue characterization and for understanding cardiac (patho)physiology in vivo. Magn Reson Med 77:2381-2389, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Interaction between CYP1A2-T2467DELT polymorphism and smoking in adenocarcinoma and squamous cell carcinoma of the lung.

PubMed

Pavanello, Sofia; B'chir, Fatma; Pulliero, Alessandra; Saguem, Saâd; Ben Fraj, Radhia; El Aziz Hayouni, Abed; Clonfero, Erminio; Mastrangelo, Giuseppe

2007-09-01

This study aimed to identify new genetic characteristics contributing to individual susceptibility to smoke-induced lung cancer. Despite functional evidence of a possible role of cytochrome P450 1A2 (CYP1A2) in lung cancer susceptibility, no studies have evaluated the influence of CYP1A2 genotypes on lung cancer risk. We investigated the interaction between CYP1A2-T2467delT (allele*1D) polymorphism and smoking in Tunisian lung cancer cases (n=101 male smokers) separately for the histological types squamous cell carcinoma (SCC) (n=60) and adenocarcinoma (n=41), and in controls (n=98 male smokers) using a case-only study design. A significant interaction between CYP1A2-T/delT or delT/delT genotypes and tobacco consumption (pack-years) adjusted for age was evident (OR (95% CI) 7.78 (1.52-42.8)) in the SCC cases who smoked relatively less (< or =33 pack-years, I quartile value), but not in adenocarcinoma and controls. Our results suggest that CYP1A2-T2467delT polymorphism has an important role in lung carcinogenesis, especially SCC, among smokers.

Does scapula stabilizing t-shirt help over-head athletes in shoulder discomfort? A randomized control study.

PubMed

Pellegrini, Andrea; Pogliacomi, Francesco; Costantino, Cosimo; Desimoni, Stefano; Giovanelli, Margherita; Golz, Andrew; Tonino, Pietro; Ceccarelli, Francesco

2016-04-15

Scapular dyskinesis in pitchers can potentially lead to impairments in the optimal performance of muscles of the shoulder complex. The purpose of this prospective study was to evaluate whether the use of a scapula stabilizing t-shirt can decrease stress and discomfort in over-head baseball pitchers. Thirty-two semi-professional baseball pitchers were divided into 2 groups. Group A dressed the scapula stabilizing t-shirt during the weekly practice while group B (control group) continued to follow their training program without the t-shirt. All pitchers underwent a clinical examination at the beginning of the study (T0), 4 weeks (T1) and 8 weeks after (T2). Data collected showed a better clinical outcome at T1 which increased in T2 for pitchers in Group A, while in Group B athletes these positive results were not observed. This study underlines that scapula-stabilizing t-shirt can have positive effects on shoulder discomfort in over-head athletes.

Treatment outcomes in 3 modes of orthodontic practice.

PubMed

Poulton, Donald R; Baumrind, Sheldon; Vlaskalic, Vicki

2002-02-01

This study examined differences in pretreatment severity and treatment outcome among orthodontic patients treated in 3 different practice-management modes. Samples of pretreatment (T1) and end of treatment (T2) study casts were selected from traditional private practices (TPP, 3 offices, 81 cases), a dental corporation (COMP, 2 offices, 53 cases), and a dental management service organization (DMSO, 1 office, 36 cases). Orthodontic specialists had treated all patients. Cases were initially selected on a consecutive start basis. From each practice, the first 30 cases satisfying the study criteria were included in the sample. The T1 and T2 study casts were evaluated with the PAR and HLD indexes. The PAR and HLD indexes showed a high level of agreement on T1 cast scores but not on the T2 casts. Mean T1 scores were highest in the COMP cases, followed by the DMSO and the TPP cases. T2 scores were lowest in the TPP cases, followed by the DMSO and the COMP cases. The percentage of PAR score reduction showed that, in all 3 modes, patients were treated to a high standard.

Effect of Definition on Incidence and Prognosis of Type 2 Myocardial Infarction.

PubMed

Nestelberger, Thomas; Boeddinghaus, Jasper; Badertscher, Patrick; Twerenbold, Raphael; Wildi, Karin; Breitenbücher, Dominik; Sabti, Zaid; Puelacher, Christian; Rubini Giménez, Maria; Kozhuharov, Nikola; Strebel, Ivo; Sazgary, Lorraine; Schneider, Deborah; Jann, Janina; du Fay de Lavallaz, Jeanne; Miró, Òscar; Martin-Sanchez, F Javier; Morawiec, Beata; Kawecki, Damian; Muzyk, Piotr; Keller, Dagmar I; Geigy, Nicolas; Osswald, Stefan; Reichlin, Tobias; Mueller, Christian

2017-09-26

Uncertainties regarding the most appropriate definition and treatment of type 2 myocardial infarction (T2MI) due to supply-demand mismatch have contributed to inconsistent adoption in clinical practice. This study sought a better understanding of the effect of the definition of T2MI on its incidence, treatment, and event-related mortality, thereby addressing an important unmet clinical need. The final diagnosis was adjudicated in patients presenting with symptoms suggestive of myocardial infarction by 2 independent cardiologists by 2 methods: 1 method required the presence of coronary artery disease, a common interpretation of the 2007 universal definition (T2MI 2007 ); and 1 method did not require coronary artery disease, the 2012 universal definition (T2MI 2012 ). Overall, 4,015 consecutive patients were adjudicated. The incidence of T2MI based on the T2MI 2007 definition was 2.8% (n = 112). The application of the more liberal T2MI 2012 definition resulted in an increase of T2MI incidence of 6% (n = 240), a relative increase of 114% (128 reclassified patients, defined as T2MI 2012reclassified ). Among T2MI 2007 , 6.3% of patients received coronary revascularization, 22% dual-antiplatelet therapy, and 71% high-dose statin therapy versus 0.8%, 1.6%, and 31% among T2MI 2012reclassified patients, respectively (all p < 0.01). Cardiovascular mortality at 90 days was 0% among T2MI 2012reclassified , which was similar to patients with noncardiac causes of chest discomfort (0.2%), and lower than T2MI 2007 (3.6%) and type 1 myocardial infarction (T1MI) (4.8%) (T2MI 2012reclassified vs. T2MI 2007 and T1MI: p = 0.03 and 0.01, respectively). T2MI 2012reclassified has a substantially lower event-related mortality rate compared with T2MI 2007 and T1MI. (Advantageous Predictors of Acute Coronary Syndromes Evaluation [APACE] Study; NCT00470587). Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Association between IGF2BP2 Polymorphisms and Type 2 Diabetes Mellitus: A Case–Control Study and Meta-Analysis

PubMed Central

Rao, Ping; Wang, Hao; Fang, Honghong; Gao, Qing; Zhang, Jie; Song, Manshu; Zhou, Yong; Wang, Youxin; Wang, Wei

2016-01-01

Background: Genome-wide association studies (GWAS) found that IGF2BP2 rs4402960 and rs1470579 polymorphisms were associated with type 2 diabetes mellitus (T2DM) risk. Many studies have replicated this association, but yielded inconsistent results. Materials and Methods: A case-control study consisting of 461 T2DM patients and 434 health controls was conducted to detect the genetic susceptibility of IGF2BP2 in a northern Han Chinese population. A meta-analysis was to evaluate the association more precisely in Asians. Results: In the case-control study, the carriers of TT genotype at rs4402960 had a higher T2DM risk than the G carriers (TG + GG) (adjusted odd ratio (AOR) = 1.962, 95% confidence interval (95% CI) = 1.065–3.612, p = 0.031]; CC carriers at rs1470579 were more susceptible to T2DM than A carriers (CA + AA) (AOR = 2.014, 95% CI = 1.114–3.642, p = 0.021). The meta-analysis containing 36 studies demonstrated that the two polymorphisms were associated with T2DM under the allele comparison, genetic models of dominant and recessive in Asians (p < 0.05). The rs4402960 polymorphisms were significantly associated with the T2DM risk after stratification by diagnostic criterion, size of sample and average age and BMI of cases, while there’re no consistent results for rs1470579. Conclusions: Our data suggests that IGF2BP2 polymorphisms are associated with T2DM in Asian populations. PMID:27294943

Effect of dietary supplementation of sea buckthorn and giloe leaf meal on the body weight gain, feed conversion ratio, biochemical attributes, and meat composition of turkey poults

PubMed Central

Sharma, Aditya; Shukla, Pankaj Kumar; Bhattacharyya, Amitav; Kumar, Upendra; Roy, Debashis; Yadav, Brijesh; Prakash, Atul

2018-01-01

Aim: In the recent past, few studies have been carried out about sea buckthorn (SBT) and giloe in chicken as a part of the quest for suitable alternatives to antibiotics. However, studies in turkeys are lacking. Hence, the present study was conducted to evaluate the effects of SBT and giloe leaf meal by dietary feed supplementation in turkey poults. Materials and Methods: A total of 1-day-old turkey poults (n=84) of small white variety were distributed into four dietary treatments having three replicates each with seven birds. The study was conducted in turkey poults during 0-8 weeks of age. During the experiment, the poults were fed basal ration (28% crude protein [CP], 2800 Kcal/kg ME) T1, T2-basal ration was supplemented with SBT leaf meal powder at 0.5%, T3-basal ration was supplemented with giloe leaf meal powder at 0.5%, and T4-basal ration was fed along with supplementation of both SBT at 0.5% and giloe leaf meal powder at 0.5%. Results: T2 turkey poults had a significantly higher (p<0.01) body weight gain than T3 and T4 at 7th week of age. Weekly body weight gain was significantly higher (p<0.05) in T2 than T3 during 5th-8th week and 0-8th week of the growth phase. Feed conversion ratio (FCR) was significantly better (p<0.01) in T2 than other treatment groups during 4th-8th week phase of growth (2.09 vs. 2.36, 2.29 and 2.31). Further, FCR was significantly better (p<0.01) in T2 group as compared to other treatment groups during 0-8th week of growth phase (1.95 vs. 2.21, 2.21 and 2.12). Plasma uric acid was found significantly increased (p<0.05) in T1 than T3 and T4, and alkaline phosphatase value was significantly higher (p<0.05) in T1 and T3 than T2. Zinc content of breast (pectoralis major) muscles was significantly higher (p<0.05) in T2 and T4 as compared to T1, while ether extract (EE) in thigh (ilio tibialis) muscles was significantly higher (p<0.05) in T2 as compared to the other treatment groups. Conclusion: It may be concluded that supplementation of SBT leaf meal at 0.5% may improve production performance of turkey poults. Supplementation of 0.5% SBT leaf meal may result in higher levels of zinc and EE in the breast and thigh cuts of turkey poults. PMID:29479163

Effect of dietary supplementation of sea buckthorn and giloe leaf meal on the body weight gain, feed conversion ratio, biochemical attributes, and meat composition of turkey poults.

PubMed

Sharma, Aditya; Shukla, Pankaj Kumar; Bhattacharyya, Amitav; Kumar, Upendra; Roy, Debashis; Yadav, Brijesh; Prakash, Atul

2018-01-01

In the recent past, few studies have been carried out about sea buckthorn (SBT) and giloe in chicken as a part of the quest for suitable alternatives to antibiotics. However, studies in turkeys are lacking. Hence, the present study was conducted to evaluate the effects of SBT and giloe leaf meal by dietary feed supplementation in turkey poults. A total of 1-day-old turkey poults (n=84) of small white variety were distributed into four dietary treatments having three replicates each with seven birds. The study was conducted in turkey poults during 0-8 weeks of age. During the experiment, the poults were fed basal ration (28% crude protein [CP], 2800 Kcal/kg ME) T1, T2-basal ration was supplemented with SBT leaf meal powder at 0.5%, T3-basal ration was supplemented with giloe leaf meal powder at 0.5%, and T4-basal ration was fed along with supplementation of both SBT at 0.5% and giloe leaf meal powder at 0.5%. T2 turkey poults had a significantly higher (p<0.01) body weight gain than T3 and T4 at 7 th week of age. Weekly body weight gain was significantly higher (p<0.05) in T2 than T3 during 5 th -8 th week and 0-8 th week of the growth phase. Feed conversion ratio (FCR) was significantly better (p<0.01) in T2 than other treatment groups during 4 th -8 th week phase of growth (2.09 vs. 2.36, 2.29 and 2.31). Further, FCR was significantly better (p<0.01) in T2 group as compared to other treatment groups during 0-8 th week of growth phase (1.95 vs. 2.21, 2.21 and 2.12). Plasma uric acid was found significantly increased (p<0.05) in T1 than T3 and T4, and alkaline phosphatase value was significantly higher (p<0.05) in T1 and T3 than T2. Zinc content of breast (pectoralis major) muscles was significantly higher (p<0.05) in T2 and T4 as compared to T1, while ether extract (EE) in thigh (ilio tibialis) muscles was significantly higher (p<0.05) in T2 as compared to the other treatment groups. It may be concluded that supplementation of SBT leaf meal at 0.5% may improve production performance of turkey poults. Supplementation of 0.5% SBT leaf meal may result in higher levels of zinc and EE in the breast and thigh cuts of turkey poults.

Development of mRuby2-Transfected C3H10T1/2 Fibroblasts for Musculoskeletal Tissue Engineering

PubMed Central

Yang, Yunzhi Peter

2015-01-01

Mouse C3H10T1/2 fibroblasts are multipotent, mesenchymal stem cell (MSC)-like progenitor cells that are widely used in musculoskeletal research. In this study, we have established a clonal population of C3H10T1/2 cells stably-transfected with mRuby2, an orange-red fluorescence reporter gene. Flow cytometry analysis and fluorescence imaging confirmed successful transfection of these cells. Cell counting studies showed that untransfected C3H10T1/2 cells and mRuby2-transfected C3H10T1/2 cells proliferated at similar rates. Adipogenic differentiation experiments demonstrated that untransfected C3H10T1/2 cells and mRuby2-transfected C3H10T1/2 cells stained positive for Oil Red O and showed increased expression of adipogenic genes including adiponectin and lipoprotein lipase. Chondrogenic differentiation experiments demonstrated that untransfected C3H10T1/2 cells and mRuby2-transfected C3H10T1/2 cells stained positive for Alcian Blue and showed increased expression of chondrogenic genes including aggrecan. Osteogenic differentiation experiments demonstrated that untransfected C3H10T1/2 cells and mRuby2-transfected C3H10T1/2 cells stained positive for alkaline phosphatase (ALP) as well as Alizarin Red and showed increased expression of osteogenic genes including alp, ocn and osf-1. When seeded on calcium phosphate-based ceramic scaffolds, mRuby2-transfected C3H10T1/2 cells maintained even fluorescence labeling and osteogenic differentiation. In summary, mRuby2-transfected C3H10T1/2 cells exhibit mRuby2 fluorescence and showed little-to-no difference in terms of cell proliferation and differentiation as untransfected C3H10T1/2 cells. These cells will be available from American Type Culture Collection (ATCC; CRL-3268™) and may be a valuable tool for preclinical studies. PMID:26407291

Development of mRuby2-Transfected C3H10T1/2 Fibroblasts for Musculoskeletal Tissue Engineering.

PubMed

Ker, Dai Fei Elmer; Sharma, Rashmi; Wang, Evelyna Tsi Hsin; Yang, Yunzhi Peter

2015-01-01

Mouse C3H10T1/2 fibroblasts are multipotent, mesenchymal stem cell (MSC)-like progenitor cells that are widely used in musculoskeletal research. In this study, we have established a clonal population of C3H10T1/2 cells stably-transfected with mRuby2, an orange-red fluorescence reporter gene. Flow cytometry analysis and fluorescence imaging confirmed successful transfection of these cells. Cell counting studies showed that untransfected C3H10T1/2 cells and mRuby2-transfected C3H10T1/2 cells proliferated at similar rates. Adipogenic differentiation experiments demonstrated that untransfected C3H10T1/2 cells and mRuby2-transfected C3H10T1/2 cells stained positive for Oil Red O and showed increased expression of adipogenic genes including adiponectin and lipoprotein lipase. Chondrogenic differentiation experiments demonstrated that untransfected C3H10T1/2 cells and mRuby2-transfected C3H10T1/2 cells stained positive for Alcian Blue and showed increased expression of chondrogenic genes including aggrecan. Osteogenic differentiation experiments demonstrated that untransfected C3H10T1/2 cells and mRuby2-transfected C3H10T1/2 cells stained positive for alkaline phosphatase (ALP) as well as Alizarin Red and showed increased expression of osteogenic genes including alp, ocn and osf-1. When seeded on calcium phosphate-based ceramic scaffolds, mRuby2-transfected C3H10T1/2 cells maintained even fluorescence labeling and osteogenic differentiation. In summary, mRuby2-transfected C3H10T1/2 cells exhibit mRuby2 fluorescence and showed little-to-no difference in terms of cell proliferation and differentiation as untransfected C3H10T1/2 cells. These cells will be available from American Type Culture Collection (ATCC; CRL-3268™) and may be a valuable tool for preclinical studies.

The prevalence of mild cognitive impairment with type 2 diabetes mellitus among elderly people in China: A cross-sectional study.

PubMed

Gao, Yuxia; Xiao, Yanyu; Miao, Rujuan; Zhao, Jiangang; Cui, Mingfei; Huang, Guowei; Fei, Ma

2016-01-01

In absence of curative treatments for dementia with type 2 diabetes mellitus (T2DM), mild cognitive impairment (MCI) in T2DM, the preclinical transitional states of dementia with T2DM has attracted dramatic attention. Our study was to estimate the prevalence and distribution of MCI in T2DM subjects from China, and identify influencing factors of subjects in MCI with T2DM. In the present study, we performed cluster random sampling of 8213 people aged 65 years and older in Tianjin, a metropolitan city, located in northern China. All participants were interviewed and screened for T2DM. 1109 subjects with T2DM were initially screened with American Diabetes Association criteria for diagnosis of diabetes mellitus and were diagnosed with MCI and dementia according to the criteria of DSM-IIIR. The prevalence of MCI and dementia in subjects with T2DM were compared with that in ordinary subjects. Logistic regression analyses were performed to evaluate risk of MCI with T2DM. Among all 8213 subjects, overall MCI and dementia with T2DM prevalence were 13.5% and 2.34%, respectively. Compared with ordinary subjects, the prevalence of MCI in the present study was more frequent than the prevalence of MCI for the general population in almost each age group. In the univariate analyses, among all diabetic subjects, compared with cognitive intactly subjects, MCI subjects had significantly higher levels of age, current smoking, mean waist circumference, duration from onset of diabetes, insulin intake, systolic BP, fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c) and immunoreactive insulin (IRI). In multivariate logistic regression analyses, variables including current smoking, duration from onset of diabetes, FPG, HbA1c and IRI were significantly associated with increased risk for MCI with T2DM, the ORs were 1.36,1.33,1.17,1.25 and 1.33, respectively (all P<0.05). The present study confirms the high prevalence of MCI with T2DM among the elderly population of China. T2DM is related to a higher risk of MCI in a population with a high prevalence of this disorder and may aggravate the clinical picture as a concomitant factor. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Meal-induced platelet activation in diabetes mellitus type 1 or type 2 is related to postprandial insulin rather than glucose levels.

PubMed

Spectre, Galia; Stålesen, Ragnhild; Östenson, Claes-Göran; Hjemdahl, Paul

2016-05-01

Postprandial platelet activation was related to postprandial insulin rather than glucose levels in a previous meal insulin study in type 2 diabetes mellitus (T2DM). We therefore compared postprandial platelet activation in type 1 (T1DM) patients without insulin secretion and T2DM patients with high postprandial insulin levels. Patients with T1DM (n=11) and T2DM (n=12) were studied before and 90min after a standardized meal without premeal insulin. Five T1DM patients volunteered for a restudy with their regular premeal insulin. Platelet activation was assessed by flow cytometry, with and without the thromboxane analogue U46619 or ADP, and by whole blood aggregometry (Multiplate®). Effects of insulin (100μU/mL) in vitro were also studied. Before the meal, glucose, insulin and platelet activation markers other than platelet-leukocyte aggregates (PLAs) were similar in T1DM and T2DM; PLAs were higher in T1DM. Postprandial glucose levels increased more markedly in T1DM (to 22.1±1.4 vs. 11.2±0.6mmol/L) while insulin levels increased only in T2DM (from 24.4±4.4 to 68.8±12.3μU/mL). Platelet P-selectin expression, fibrinogen binding and PLA formation stimulated by U46619 were markedly enhanced (approximately doubled) and whole blood aggregation stimulated by U46619 was increased (p<0.05 for all) after the meal in T2DM patients but not in T1DM patients. The pilot study with premeal insulin in T1DM patients showed postprandial platelet activation when postprandial insulin levels increased. In vitro insulin mildly activated platelets in both groups. Postprandial platelet activation via the thromboxane pathway is related to postprandial hyperinsulinemia and not to postprandial hyperglycaemia in patients with diabetes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Longitudinal study of surrogate aging measures during human immunodeficiency virus seroconversion.

PubMed

Leung, Janice M; Fishbane, Nick; Jones, Meaghan; Morin, Alexander; Xu, Stella; Liu, Joseph Cy; MacIsaac, Julie; Milloy, M-J; Hayashi, Kanna; Montaner, Julio; Horvath, Steve; Kobor, Michael; Sin, Don D; Harrigan, P Richard; Man, S F Paul

2017-02-23

Persons living with human immunodeficiency virus (HIV) harbor an increased risk of age-related conditions. We measured changes in telomere length and DNA methylation in the peripheral blood of 31 intravenous drug users, who were followed longitudinally with blood samples pre-HIV (T1), immediately post-HIV (T2; 1.9±1 year from T1), and at a later follow-up time (T3; 2.2±1 year from T2). Absolute telomere length measurements were performed using polymerase chain reaction methods. Methylation profiles were obtained using the Illumina Human Methylation450 platform. Methylation aging was assessed using the Horvath method. Telomere length significantly decreased between T1 and T2 (227±46 at T1 vs. 201±48 kbp/genome at T2, p=0.045), while no differences were observed between T2 and T3 (201±48 at T2 vs. 186±27 kbp/genome at T3, p=0.244). Methylation aging as measured by the age acceleration residual increased over the time course of HIV infection (p=0.035). CpG sites corresponding to PCBP2 and CSRNP1 were differentially methylated between T1 and T2 at a q-value <0.05. Telomere shortening and methylation changes can therefore be observed in the short-term period immediately following HIV seroconversion. Further studies to confirm these results in larger sample sizes and to compare these results to non-HIV and non-injection drug users are warranted.

T1- or T2-weighted magnetic resonance imaging: what is the best choice to evaluate atrophy of the hippocampus?

PubMed

Fischbach-Boulanger, C; Fitsiori, A; Noblet, V; Baloglu, S; Oesterle, H; Draghici, S; Philippi, N; Duron, E; Hanon, O; Dietemann, J-L; Blanc, F; Kremer, S

2018-05-01

Magnetic resonance imaging is part of the diagnostic criteria for Alzheimer's disease (AD) through the evaluation of hippocampal atrophy. The objective of this study was to evaluate which sequence of T1-weighted (T1WI) and T2-weighted (T2WI) imaging allowed the best visual evaluation of hippocampal atrophy. Visual qualitative ratings of the hippocampus of 100 patients with mild cognitive impairment (MCI) and 50 patients with AD were made independently by four operators according to the medial temporal lobe atrophy score based either on T1WI or T2WI. These two evaluations were compared in terms of interobserver reproducibility, concordance with a quantitative volumetric measure, discrimination power between AD and MCI groups, and correlation with several neuropsychological tests. The medial temporal lobe atrophy score evaluated on either T1WI or T2WI exhibited similar interobserver variability and accordance with quantitative volumetric evaluation. However, the visual evaluation on T2WI seemed to provide better discrimination power between AD and MCI groups for both left (T1WI, P = 0.0001; T2WI, P = 7.072 × 10 -5 ) and right (T1WI, P = 0.008; T2WI, P = 0.001) hippocampus, and a higher overall correlation with neuropsychological tests. The present study suggests that T2WI provides a more adequate visual rating of hippocampal atrophy. © 2018 EAN.

A Predictive Metabolic Signature for the Transition From Gestational Diabetes Mellitus to Type 2 Diabetes.

PubMed

Allalou, Amina; Nalla, Amarnadh; Prentice, Kacey J; Liu, Ying; Zhang, Ming; Dai, Feihan F; Ning, Xian; Osborne, Lucy R; Cox, Brian J; Gunderson, Erica P; Wheeler, Michael B

2016-09-01

Gestational diabetes mellitus (GDM) affects 3-14% of pregnancies, with 20-50% of these women progressing to type 2 diabetes (T2D) within 5 years. This study sought to develop a metabolomics signature to predict the transition from GDM to T2D. A prospective cohort of 1,035 women with GDM pregnancy were enrolled at 6-9 weeks postpartum (baseline) and were screened for T2D annually for 2 years. Of 1,010 women without T2D at baseline, 113 progressed to T2D within 2 years. T2D developed in another 17 women between 2 and 4 years. A nested case-control design used 122 incident case patients matched to non-case patients by age, prepregnancy BMI, and race/ethnicity. We conducted metabolomics with baseline fasting plasma and identified 21 metabolites that significantly differed by incident T2D status. Machine learning optimization resulted in a decision tree modeling that predicted T2D incidence with a discriminative power of 83.0% in the training set and 76.9% in an independent testing set, which is far superior to measuring fasting plasma glucose levels alone. The American Diabetes Association recommends T2D screening in the early postpartum period via oral glucose tolerance testing after GDM, which is a time-consuming and inconvenient procedure. Our metabolomics signature predicted T2D incidence from a single fasting blood sample. This study represents the first metabolomics study of the transition from GDM to T2D validated in an independent testing set, facilitating early interventions. © 2016 by the American Diabetes Association.

A Predictive Metabolic Signature for the Transition From Gestational Diabetes Mellitus to Type 2 Diabetes

PubMed Central

Allalou, Amina; Nalla, Amarnadh; Prentice, Kacey J.; Liu, Ying; Zhang, Ming; Dai, Feihan F.; Ning, Xian; Osborne, Lucy R.; Cox, Brian J.

2016-01-01

Gestational diabetes mellitus (GDM) affects 3–14% of pregnancies, with 20–50% of these women progressing to type 2 diabetes (T2D) within 5 years. This study sought to develop a metabolomics signature to predict the transition from GDM to T2D. A prospective cohort of 1,035 women with GDM pregnancy were enrolled at 6–9 weeks postpartum (baseline) and were screened for T2D annually for 2 years. Of 1,010 women without T2D at baseline, 113 progressed to T2D within 2 years. T2D developed in another 17 women between 2 and 4 years. A nested case-control design used 122 incident case patients matched to non–case patients by age, prepregnancy BMI, and race/ethnicity. We conducted metabolomics with baseline fasting plasma and identified 21 metabolites that significantly differed by incident T2D status. Machine learning optimization resulted in a decision tree modeling that predicted T2D incidence with a discriminative power of 83.0% in the training set and 76.9% in an independent testing set, which is far superior to measuring fasting plasma glucose levels alone. The American Diabetes Association recommends T2D screening in the early postpartum period via oral glucose tolerance testing after GDM, which is a time-consuming and inconvenient procedure. Our metabolomics signature predicted T2D incidence from a single fasting blood sample. This study represents the first metabolomics study of the transition from GDM to T2D validated in an independent testing set, facilitating early interventions. PMID:27338739

Multivariate combination of magnetization transfer, T2* and B0 orientation to study the myelo-architecture of the in vivo human cortex

PubMed Central

Mangeat, G.; Govindarajan, S. T.; Mainero, C.; Cohen-Adad, J.

2015-01-01

Recently, T2* imaging at 7 tesla (T) MRI was shown to reveal microstructural features of the cortical myeloarchitecture thanks to an increase in contrast-to-noise ratio. However, several confounds hamper the specificity of T2* measures (iron content, blood vessels, tissues orientation). Another metric, magnetization transfer ratio (MTR), is known to also be sensitive to myelin content and thus would be an excellent complementary measure because its underlying contrast mechanisms are different than that from T2*. The goal of this study was thus to combine MTR and T2* using multivariate statistics in order to gain insights into cortical myelin content. Seven healthy subjects were scanned at 7T and 3T to obtain T2* and MTR data, respectively. A multivariate myelin estimation model (MMEM) was developed, and consists in (i) normalizing T2* and MTR values and (ii) extracting their shared information using independent component analysis (ICA). B0 orientation dependence and cortical thickness were also computed and included in the model. Results showed high correlation between MTR and T2* in the whole cortex (r=0.76, p<10−16), suggesting that both metrics are partly driven by a common source of contrast, here assumed to be the myelin. Average MTR and T2* were respectively 31.0 +/− 0.3% and 32.1 +/− 1.4 ms. Results of the MMEM spatial distribution showed similar trends to that from histological work stained for myelin (r=0.77, p<0.01). Significant right-left differences were detected in the primary motor cortex (p<0.05), the posterior cingulate cortex (p<0.05) and the visual cortex (p<0.05). This study demonstrates that MTR and T2* are highly correlated in the cortex. The combination of MTR, T2*, CT and B0 orientation may be a useful means to study cortical myeloarchitecture with more specificity than using any of the individual methods. The MMEM framework is extendable to other contrasts such as T1 and diffusion MRI. PMID:26095090

Association study of SREBF-2 gene polymorphisms and the risk of type 2 diabetes in a sample of Iranian population.

PubMed

Galavi, Hamidreza; Noorzehi, Nafiseh; Saravani, Ramin; Sargazi, Saman; Mollashahee-Kohkan, Fatemeh; Shahraki, Hojat

2018-06-20

Type 2 diabetes mellitus (T2D) as an important metabolic disorder is accompanied by dysregulation in lipid metabolism. Sterol regulatory element-binding factor-2 (SREBF-2) gene has a substantive role in lipid metabolism. Recently published report indicated the overexpression of this gene in diabetic patients. So, in this preliminary study we evaluated the effects of three common single nucleotide polymorphisms (SNPs), rs1052717G/A, rs2267439C/T, and rs2267443G/A in risk of T2D in a sample of Iranian population. Present case-control study consists of 250 patients with endocrinologically approved T2D and 250 healthy controls. The variants genotyped by using tetra amplification refractory mutation system polymerase chain reaction (Tetra ARMS-PCR) method. The findings demonstrated that the rs2267439C/T polymorphism increased the risk of T2D in all measured inheritance models (Codominant1; p = 0.003, codominant2; p = 0.014, dominant; p < 0.0001, recessive; p = 0.037, over-dominant; p = 0.0025, and log-additive; p = 0.0048) while our results did not show statistically association between rs1052717G/A and rs2267443G/A SNPs and T2D development. The current investigation indicated that the rs2267439C/T polymorphism in the SREBF-2 gene increased the T2D susceptibility in an Iranian population. Further studies with different ethnicities and more extensive sample sizes are demanded to confirm our finding. Copyright © 2018 Elsevier B.V. All rights reserved.

The Association of Multiple Biomarkers of Iron Metabolism and Type 2 Diabetes - the EPIC-InterAct Study

PubMed Central

Podmore, Clara; Meidtner, Karina; Schulze, Matthias B; Scott, Robert A; Ramond, Anna; Butterworth, Adam S; Di Angelantonio, Emanuele; Danesh, John; Arriola, Larraitz; Barricarte, Aurelio; Boeing, Heiner; Clavel-Chapelon, Françoise; Cross, Amanda J; Dahm, Christina C; Fagherazzi, Guy; Franks, Paul W; Gavrila, Diana; Grioni, Sara; Gunter, Marc J; Gusto, Gaelle; Jakszyn, Paula; Katzke, Verena; Key, Timothy J; Kühn, Tilman; Mattiello, Amalia; Nilsson, Peter M; Olsen, Anja; Overvad, Kim; Palli, Domenico; Quirós, J. Ramón; Rolandsson, Olov; Sacerdote, Carlotta; Sánchez-Cantalejo, Emilio; Slimani, Nadia; Sluijs, Ivonne; Spijkerman, Annemieke MW; Tjonneland, Anne; Tumino, Rosario; van der A, Daphne L; van der Schouw, Yvonne T; Feskens, Edith JM; Forouhi, Nita G; Sharp, Stephen J; Riboli, Elio; Langenberg, Claudia; Wareham, Nicholas J

2016-01-01

Objective Observational studies show an association between ferritin and type 2 diabetes (T2D), suggesting a role of high iron stores for T2D development. However, ferritin is influenced by factors other than iron stores, which is less the case for other biomarkers of iron metabolism. We investigate associations of ferritin, transferrin saturation (TSAT), serum iron and transferrin with T2D incidence, to clarify the role of iron in the pathogenesis of T2D. Research and Design Methods The EPIC-InterAct study includes 12,403 incident T2D cases and a representative sub-cohort of 16,154 individuals from a European cohort with 3.99 million person-years of follow-up. We studied the prospective association of ferritin, TSAT, serum iron and transferrin with incident T2D in 11,052 cases and a random sub-cohort of 15,182 individuals and assessed whether these associations differed by subgroups of the population. Results Higher levels of ferritin and transferrin were associated with a higher risk of T2D [HR in men and women, respectively: 1.07 (95% CI: 1.01; 1.12) and 1.12 (1.05; 1.19) per 100 μg/L higher ferritin level; 1.11 (1.00; 1.24) and 1.22 (1.12; 1.33) per 0.5 g/L higher transferrin level] after adjustment for age, centre, BMI, physical activity, smoking status, education, hsCRP, ALT and GGT. Elevated TSAT (≥45% versus <45%) was associated with a lower risk of T2D in women [0.68 (0.54; 0.86)] but was not statistically significantly associated in men [0.90 (0.75; 1.08)]. Serum iron was not associated with T2D. The association of ferritin with T2D was stronger among leaner individuals (pinteraction<0.01). Conclusions The pattern of association of TSAT and transferrin with T2D suggests that the underlying relationship between iron stores and T2D is more complex than the simple link suggested by the association of ferritin with T2D. PMID:26861925

Concrete/mortar water phase transition studied by single-point MRI methods.

PubMed

Prado, P J; Balcom, B J; Beyea, S D; Armstrong, R L; Bremner, T W; Grattan-Bellew, P E

1998-01-01

A series of magnetic resonance imaging (MRI) water density and T2* profiles in hardened concrete and mortar samples has been obtained during freezing conditions (-50 degrees C < T < 11 degrees C). The single-point ramped imaging with T1 enhancement (SPRITE) sequence is optimal for this study given the characteristic short relaxation times of water in this porous media (T2* < 200 microseconds and T1 < 3.6 ms). The frozen and evaporable water distribution was quantified through a position based study of the profile magnitude. Submillimetric resolution of proton-density and T2*-relaxation parameters as a function of temperature has been achieved.

Measurement and Quantification of Heterogeneity, Flow, and Mass Transfer in Porous Media Using NMR Low-Field Techiques

NASA Astrophysics Data System (ADS)

Paciok, E.; Olaru, A. M.; Haber, A.; van Landeghem, M.; Haber-Pohlmeier, S.; Sucre, O. E.; Perlo, J.; Casanova, F.; Blümich, B.; RWTH Aachen Mobile Low-Field NMR

2011-12-01

Nuclear magnetic resonance (NMR) is renowned for its unique potential to both reveal and correlate spectroscopic, relaxometric, spatial and dynamic properties in a large variety of organic and inorganic systems. NMR has no restrictions regarding sample opacity and is an entirely non-invasive method, which makes it the ideal tool for the investigation of porous media. However, for years NMR research of soils was limited by the use of high-field NMR devices, which necessitated elaborate NMR experiments and were not applicable to bulky samples or on-site field measurements. The evolution of low-field NMR devices during the past 20 years has brought forth portable, small-scale NMR systems with open and closed magnet arrangements specialized to specific NMR applications. In combination with recent advances in 2D-NMR Laplace methodology [1], low-field NMR has opened up the possibility to study real-life microporous systems ranging from granular media to natural soils and oil well boreholes. Thus, information becomes available, which before has not been accessible with high-field NMR. In this work, we present our recent progress in mobile low-field NMR probe design for field measurements of natural soils: a slim-line logging tool, which can be rammed into the soil of interest on-site. The performance of the device is demonstrated in measurements of moisture profiles of model soils [2] and field measurements of relaxometric properties and moisture profiles of natural soils [3]. Moreover, an improved concept of the slim-line logging tool is shown, with a higher excitation volume and a better signal-to-noise due to an improved coil design. Furthermore, we present our recent results in 2D exchange relaxometry and simulation. These include relaxation-relaxation experiments on natural soils with varying degree of moisture saturation, where we could draw a connection between the relaxometric properties of the soil to its pore size-related diffusivity and to its clay content. Also models, simulations and possibilities are discussed to derive from the so obtained information a "characteristic pore shape" that can be used to characterize and to fingerprint natural soils. [1] L. Venkataramanan et al., IEEE Trans. Signal Process. 2002, 50, 1017-26. [2] O. Sucre et al., Open Magn. Reson. J. 2010, 3, 63-68. [3] B. Blümich et al., New J. Phys. 2011, 13, 015003.

[The helpers' stress: Effectiveness of a web-based intervention for professionals working with trauma survivors in reducing job burnout and improving work engagement].

PubMed

Rogala, Anna; Smoktunowicz, Ewelina; Żukowska, Katarzyna; Kowalska, Martyna; Cieślak, Roman

The study aimed at evaluating effectiveness of the web-based intervention, "The Helpers' Stress," in reducing job burnout and enhancing work engagement among professionals working with trauma survivors. Participants were randomly allocated to 1 of the 3 intervention modules: 1 - the self-efficacy enhancement (N = 87), 2 - the social support enhancement (N = 85), or to 3 - the educational module (comparison group, N = 81). Participants completed the online questionnaires before the intervention (T1), immediately after (T2), and 4 weeks after the intervention (T3). Due to high drop-out rate at T2 and T3 in social support enhancement module, we excluded from analysis participants assigned to this condition. Participants assigned to the self-efficacy enhancement module presented higher levels of self-efficacy (at T2 and T3), compared to those assigned to the educational module. Job burnout decreased significantly between T1 and T2, and between T2 and T3, and work engagement increased significantly between T1 and T2, and between T1 and T3, among participants assigned to both modules mentioned above. Self-efficacy (T2) mediated the relationship between the group assignment (educational module vs. self-efficacy enhancement module) and respectively job burnout (T3) or work engagement (T3). The results of our study highlight the role of self-efficacy in reducing job burnout and increasing work engagement. Med Pr 2016;67(2):223-237. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

Experiencing type 2 diabetes mellitus: qualitative analysis of adolescents' concept of illness, adjustment, and motivation to engage in self-care behaviors.

PubMed

Salamon, Katherine S; Brouwer, Amanda M; Fox, Michelle M; Olson, Kimberly A; Yelich-Koth, Sara L; Fleischman, Katie M; Hains, Anthony A; Davies, W Hobart; Kichler, Jessica C

2012-01-01

The purpose of this study was to explore the perspectives of adolescents diagnosed with type 2 diabetes mellitus (T2DM) in terms of how youths conceptualized the effect of T2DM on daily life, adjustment to the illness, and motivation related to diabetes self-care management. The aims of the study were to gather essential information in order to develop appropriate intervention techniques and inform future studies intended to understand the psychosocial experiences of youths with T2DM. Eight adolescents diagnosed with T2DM were recruited from an outpatient pediatric diabetes clinic at a Midwestern children's hospital. A qualitative interview was developed, which was scheduled to last about 30 to 45 minutes. Data were analyzed using the consensual qualitative research methodology, wherein qualitative coders developed core ideas and themes related to the adolescent experience of T2DM. Three main themes were identified, including how the youths conceptualized the impact of T2DM, adjustment to self-care, and motivation to perform self-care behaviors. Knowledge related to the cause of T2DM and adjustment to completing self-care behaviors was varied among youths. Few adolescents spoke about motivation sources, although when mentioned, it typically involved witnessing negative health consequences in family members or friends with T2DM. The data represent essential initial information related to youths with T2DM, which will help guide in developing future studies designed to understand the psychosocial experiences of youths with T2DM and appropriate intervention techniques. Future research that aims to increase internal and external motivation may be able to subsequently impact adherence to self-care behaviors.

A Scoping Review of Behavioral Economic Interventions for Prevention and Treatment of Type 2 Diabetes Mellitus.

PubMed

Kullgren, Jeffrey T; Hafez, Dina; Fedewa, Allison; Heisler, Michele

2017-09-01

The purpose of this paper was to review studies of behavioral economic interventions (financial incentives, choice architecture modifications, or commitment devices) to prevent type 2 diabetes mellitus (T2DM) among at-risk patients or improve self-management among patients with T2DM. We found 15 studies that used varied study designs and outcomes to test behavioral economic interventions in clinical, workplace, or health plan settings. Of four studies that focused on prevention of T2DM, two found that financial incentives increased weight loss and completion of a fasting blood glucose test, and two choice architecture modifications had mixed effects in encouraging completion of tests to screen for T2DM. Of 11 studies that focused on improving self-management of T2DM, four of six tests of financial incentives demonstrated increased engagement in recommended care processes or improved biometric measures, and three of five tests of choice architecture modifications found improvements in self-management behaviors. Though few studies have tested behavioral economic interventions for prevention or treatment of T2DM, those that have suggested such approaches have the potential to improve patient behaviors and such approaches should be tested more broadly.

A Scoping Review of Behavioral Economic Interventions for Prevention and Treatment of Type 2 Diabetes Mellitus

PubMed Central

Kullgren, Jeffrey T.; Hafez, Dina; Fedewa, Allison; Heisler, Michele

2017-01-01

Purpose of review To review studies of behavioral economic interventions (financial incentives, choice architecture modifications, or commitment devices) to prevent type 2 diabetes mellitus (T2DM) among at-risk patients or improve self-management among patients with T2DM. Recent findings We found 15 studies that used varied study designs and outcomes to test behavioral economic interventions in clinical, workplace, or health plan settings. Of four studies that focused on prevention of T2DM, two found that financial incentives increased weight loss and completion of a fasting blood glucose test, and two choice architecture modifications had mixed effects in encouraging completion of tests to screen for T2DM. Of 11 studies that focused on improving self-management of T2DM, four of six tests of financial incentives demonstrated increased engagement in recommended care processes or improved biometric measures, and three of five tests of choice architecture modifications found improvements in self-management behaviors. Summary Though few studies have tested behavioral economic interventions for prevention or treatment of T2DM, those that have suggest such approaches have potential to improve patient behaviors and should be tested more broadly. PMID:28755061

Comparative bioavailability of different formulations of levothyroxine and liothyronine in healthy volunteers.

PubMed

Leggio, G M; Incognito, T; Privitera, G; Marano, M R; Drago, F

2006-12-01

To evaluate the relative bioavailability of T4 sodium and liothyronine sodium (T3), administered in single doses as oral solution (drops) and tablet forms, according to two separate study protocols. Twenty-four healthy, male volunteers were included in both studies. Two test drugs containing T4 or T3 (T4-Ibsa and T3-Ibsa, respectively) were compared to two reference drugs, ie Eutirox 100 and Ti-tre tablets, respectively. A single oral dose of 100 microg (1 ml or 1 tablet) of T4 and 20 microg (1 ml or 1 tablet) of T3 were administered with an open, randomized, crossover design. T4 and T3 serum concentrations were determined by a validated immunoassay in electro-chemo-luminescence method. Study 1: after administration of T4-Ibsa oral solution, Cmax was 14.26+/-0.61 microg/dl, AUC0-t was 282.70 +/-14.29 microg/dl/h, Tmax was 2.71+/-0.25 h. After administration of Eutirox 100 tablets, Cmax was 14.34+/-0.59 microg/dl, AUC0-t was 279.42+/-9.59 microg/dl/h and Tmax was 2.65+/-0.23 h. The 90% confidence interval ratios between test/reference drugs were 1.01 for AUC0-t and 0.99 for Cmax. Study 2: after administration of T3-Ibsa oral solution, Cmax was 3.19+/-0.25 ng/ml, AUC0-t was 44.79+/-2.15 ng/ml/h and Tmax was 2.31+/-0.25 h. After administration of Ti-tre tablets, Cmax was 3.16+/-0.23 ng/ml, AUC0-t was 45.19+/-2.19 ng/ml/h and Tmax was 2.44+/-0.34 h. The 90% confidence interval ratios between test /reference drugs were 0.99 for AUC0-t and 1.01 for Cmax. The bioavailability of the two oral solutions (T4-Ibsa and T3-Ibsa oral solutions) and the corresponding tablet forms (Eutirox 100 and Ti-tre tablets) were confirmed and they can be considered bioequivalent and therapeutically interchangeable.

Heart rate variability in type 2 diabetes mellitus.

PubMed

Stuckey, Melanie I; Petrella, Robert J

2013-01-01

Heart rate variability (HRV) is a noninvasive measure of cardiac autonomic modulation. Time and frequency domain measures have primarily been examined in patients with type 2 diabetes mellitus (T2D). Not only do frequency domain HRV parameters tend to be reduced in T2D, but healthy individuals with low HRV are also more likely to develop T2D. Furthermore, patients with T2D with low HRV have an increased prevalence of complications and risk of mortality compared with those with normal autonomic function. These findings provide support for the use of HRV as a risk indicator in T2D. Exercise is considered an important component to T2D prevention and treatment strategies. To date, few studies have examined the changes in HRV with exercise in T2D. One study showed changes in resting HRV, two studies showed changes in HRV during or following acute stressors, and one study showed no changes in HRV but improvements in baroreflex sensitivity. The most pronounced changes in HRV were realized following the exercise intervention with the greatest frequency of supervised exercise sessions and with the greatest intensity and duration of exercise bouts. These findings suggest that exercise following current American College of Sports Medicine/American Diabetes Association guidelines may be important in the prevention and treatment of T2D to improve autonomic function and reduce the risk of complications and mortality.

Spectroscopic Studies of Perturbed T1 Cu Sites in the Multicopper Oxidases Saccharomyces Cerevisiae Fet3p And Rhus Vernicifera Laccase: Allosteric Coupling Between the T1 And Trinuclear Cu Sites

DOE Office of Scientific and Technical Information (OSTI.GOV)

Augustine, A.J.; Kragh, M.E.; Sarangi, R.

2009-04-30

The multicopper oxidases catalyze the 4e{sup -} reduction of O{sub 2} to H{sub 2}O coupled to the 1e{sup -} oxidation of 4 equiv of substrate. This activity requires four Cu atoms, including T1, T2, and coupled binuclear T3 sites. The T2 and T3 sites form a trinuclear cluster (TNC) where O{sub 2} is reduced. The T1 is coupled to the TNC through a T1-Cys-His-T3 electron transfer (ET) pathway. In this study the two T3 Cu coordinating His residues which lie in this pathway in Fet3 have been mutated, H483Q, H483C, H485Q, and H485C, to study how perturbation at the TNCmore » impacts the T1 Cu site. Spectroscopic methods, in particular resonance Raman (rR), show that the change from His to Gln to Cys increases the covalency of the T1 Cu?S Cys bond and decreases its redox potential. This study of T1?TNC interactions is then extended to Rhus vernicifera laccase where a number of well-defined species including the catalytically relevant native intermediate (NI) can be trapped for spectroscopic study. The T1 Cu?S covalency and potential do not change in these species relative to resting oxidized enzyme, but interestingly the differences in the structure of the TNC in these species do lead to changes in the T1 Cu rR spectrum. This helps to confirm that vibrations in the cysteine side chain of the T1 Cu site and the protein backbone couple to the Cu?S vibration. These changes in the side chain and backbone provide a possible mechanism for regulating intramolecular T1 to TNC ET in NI and partially reduced enzyme forms for efficient turnover.« less

High-resolution T2-weighted cervical cancer imaging: a feasibility study on ultra-high-field 7.0-T MRI with an endorectal monopole antenna.

PubMed

Hoogendam, Jacob P; Kalleveen, Irene M L; de Castro, Catalina S Arteaga; Raaijmakers, Alexander J E; Verheijen, René H M; van den Bosch, Maurice A A J; Klomp, Dennis W J; Zweemer, Ronald P; Veldhuis, Wouter B

2017-03-01

We studied the feasibility of high-resolution T 2 -weighted cervical cancer imaging on an ultra-high-field 7.0-T magnetic resonance imaging (MRI) system using an endorectal antenna of 4.7-mm thickness. A feasibility study on 20 stage IB1-IIB cervical cancer patients was conducted. All underwent pre-treatment 1.5-T MRI. At 7.0-T MRI, an external transmit/receive array with seven dipole antennae and a single endorectal monopole receive antenna were used. Discomfort levels were assessed. Following individualised phase-based B 1 + shimming, T 2 -weighted turbo spin echo sequences were completed. Patients had stage IB1 (n = 9), IB2 (n = 4), IIA1 (n = 1) or IIB (n = 6) cervical cancer. Discomfort (ten-point scale) was minimal at placement and removal of the endorectal antenna with a median score of 1 (range, 0-5) and 0 (range, 0-2) respectively. Its use did not result in adverse events or pre-term session discontinuation. To demonstrate feasibility, T 2 -weighted acquisitions from 7.0-T MRI are presented in comparison to 1.5-T MRI. Artefacts on 7.0-T MRI were due to motion, locally destructive B 1 interference, excessive B 1 under the external antennae and SENSE reconstruction. High-resolution T 2 -weighted 7.0-T MRI of stage IB1-IIB cervical cancer is feasible. The addition of an endorectal antenna is well tolerated by patients. • High resolution T 2 -weighted 7.0-T MRI of the inner female pelvis is challenging • We demonstrate a feasible approach for T 2 -weighted 7.0-T MRI of cervical cancer • An endorectal monopole receive antenna is well tolerated by participants • The endorectal antenna did not lead to adverse events or session discontinuation.

Lipid-Lowering Pharmaceutical Clofibrate Inhibits Human Sweet Taste

PubMed Central

Kochem, Matthew

2017-01-01

T1R2-T1R3 is a heteromeric receptor that binds sugars, high potency sweeteners, and sweet taste blockers. In rodents, T1R2-T1R3 is largely responsible for transducing sweet taste perception. T1R2-T1R3 is also expressed in non-taste tissues, and a growing body of evidence suggests that it helps regulate glucose and lipid metabolism. It was previously shown that clofibric acid, a blood lipid-lowering drug, binds T1R2-T1R3 and inhibits its activity in vitro. The purpose of this study was to determine whether clofibric acid inhibits sweetness perception in humans and is, therefore, a T1R2-T1R3 antagonist in vivo. Fourteen participants rated the sweetness intensity of 4 sweeteners (sucrose, sucralose, Na cyclamate, acesulfame K) across a broad range of concentrations. Each sweetener was prepared in solution neat and in mixture with either clofibric acid or lactisole. Clofibric acid inhibited sweetness of every sweetener. Consistent with competitive binding, inhibition by clofibric acid was diminished with increasing sweetener concentration. This study provides in vivo evidence that the lipid-lowering drug clofibric acid inhibits sweetness perception and is, therefore, a T1R carbohydrate receptor inhibitor. Our results are consistent with previous in vitro findings. Given that T1R2-T1R3 may in part regulate glucose and lipid metabolism, future studies should investigate the metabolic effects of T1R inhibition. PMID:27742692

Longitudinal association between television watching and computer use and risk markers in diabetes in the SEARCH for Diabetes in Youth Study

PubMed Central

Li, Chao; Beech, Bettina; Crume, Tessa; D’Agostino, Ralph B.; Dabelea, Dana; Kaar, Jill L; Liese, Angela D.; Mayer-Davis, Elizabeth J.; Pate, Russell; Pettitt, David J.; Taplin, Craig; Rodriguez, Beatriz; Merchant, Anwar T.

2014-01-01

Background The study provides evidence of the longitudinal association between screen time with hemoglobin A1c and cardiovascular risk markers among youth with type 1 (T1D) and type 2 diabetes (T2D) . Objective To examine the longitudinal relationship of screen time with HbA1c and serum lipids among youth with diabetes. Subjects Youth with T1D and T2D. Methods We followed up 1049 youth (≥10 yr. old) with recently diagnosed T1D and T2D participating in the SEARCH for Diabetes in Youth Study. Results Increased television watching on weekdays and during the week over time was associated with larger increases in HbA1c among youth with T1D and T2D (p-value<0.05). Among youth with T1D, significant longitudinal associations were observed between television watching and TG (p-value<0.05) (week days and whole week), and LDL-c (p-value<0.05) (whole week). For example, for youth who watched 1 hour of television per weekday at the outset and 3 hours per weekday 5 years later, the longitudinal model predicted greater absolute increases in HbA1c (2.19% for T1D and 2.16% for T2D); whereas for youth who watched television 3 hours per weekday at the outset and 1 hour per weekday 5 years later, the model predicted lesser absolute increases in HbA1c (2.08% for T1D and 1.06% for T2D). Conclusions Youth with T2D who increased their television watching over time vs those that decreased it had larger increases in HbA1c over 5 years. Youth with T1D who increased their television watching over time had increases in LDL-c, TG and to a lesser extent HbA1c . PMID:25041407

Alcohol and type 2 diabetes. A review.

PubMed

Pietraszek, A; Gregersen, S; Hermansen, K

2010-06-01

To describe a) the association between alcohol consumption and the risk of type 2 diabetes (T2D) and b) the impact of alcohol on the glycemic control with and without anti-diabetic drugs. We searched MEDLINE and the Cochrane Library data base with the key words "Diabetes Mellitus, type 2" and "Alcohol Drinking" in English-language studies in adults. For the first part of the review we selected meta-analyses, review articles and observational studies more recent than year 1990 including at least 1000 participants. For the second part of the review we included all articles more recent than year 1990. Most observational studies find a J-shaped association between alcohol intake and incidence of T2D. Interestingly, drinking pattern plays a role, i.e. binge drinking increases the risk of T2D. Opposing information exists about the influence of beverage type. In T2D the acute effects on plasma glucose, insulin, fatty acids and triglyceride vary, in part depending on concomitant intake of food. Acute alcohol intake does not induce hypoglycemia in diet treated T2D, but increases the risk of hypoglycemia in sulphonylurea treated patients. In most studies, long-term alcohol use is associated with improved glycemic control in T2D. Alcohol consumption reduces the incidence of T2D, however, binge drinking seems to increase the incidence. Acute intake of alcohol does not increase risk of hypoglycemia in diet treated subjects with T2D, only when sulphonylurea is co-administered. Long-term alcohol use seems to be associated with improved glycemic control in T2D probably due to improved insulin sensitivity.

Joint Effects of Known Type 2 Diabetes Susceptibility Loci in Genome-Wide Association Study of Singapore Chinese: The Singapore Chinese Health Study

PubMed Central

Chen, Zhanghua; Pereira, Mark A.; Seielstad, Mark; Koh, Woon-Puay; Tai, E. Shyong; Teo, Yik-Ying; Liu, Jianjun; Hsu, Chris; Wang, Renwei; Odegaard, Andrew O.; Thyagarajan, Bharat; Koratkar, Revati; Yuan, Jian-Min; Gross, Myron D.; Stram, Daniel O.

2014-01-01

Background Genome-wide association studies (GWAS) have identified genetic factors in type 2 diabetes (T2D), mostly among individuals of European ancestry. We tested whether previously identified T2D-associated single nucleotide polymorphisms (SNPs) replicate and whether SNPs in regions near known T2D SNPs were associated with T2D within the Singapore Chinese Health Study. Methods 2338 cases and 2339 T2D controls from the Singapore Chinese Health Study were genotyped for 507,509 SNPs. Imputation extended the genotyped SNPs to 7,514,461 with high estimated certainty (r2>0.8). Replication of known index SNP associations in T2D was attempted. Risk scores were computed as the sum of index risk alleles. SNPs in regions ±100 kb around each index were tested for associations with T2D in conditional fine-mapping analysis. Results Of 69 index SNPs, 20 were genotyped directly and genotypes at 35 others were well imputed. Among the 55 SNPs with data, disease associations were replicated (at p<0.05) for 15 SNPs, while 32 more were directionally consistent with previous reports. Risk score was a significant predictor with a 2.03 fold higher risk CI (1.69–2.44) of T2D comparing the highest to lowest quintile of risk allele burden (p = 5.72×10−14). Two improved SNPs around index rs10923931 and 5 new candidate SNPs around indices rs10965250 and rs1111875 passed simple Bonferroni corrections for significance in conditional analysis. Nonetheless, only a small fraction (2.3% on the disease liability scale) of T2D burden in Singapore is explained by these SNPs. Conclusions While diabetes risk in Singapore Chinese involves genetic variants, most disease risk remains unexplained. Further genetic work is ongoing in the Singapore Chinese population to identify unique common variants not already seen in earlier studies. However rapid increases in T2D risk have occurred in recent decades in this population, indicating that dynamic environmental influences and possibly gene by environment interactions complicate the genetic architecture of this disease. PMID:24520337

Joint effects of known type 2 diabetes susceptibility loci in genome-wide association study of Singapore Chinese: the Singapore Chinese health study.

PubMed

Chen, Zhanghua; Pereira, Mark A; Seielstad, Mark; Koh, Woon-Puay; Tai, E Shyong; Teo, Yik-Ying; Liu, Jianjun; Hsu, Chris; Wang, Renwei; Odegaard, Andrew O; Thyagarajan, Bharat; Koratkar, Revati; Yuan, Jian-Min; Gross, Myron D; Stram, Daniel O

2014-01-01

Genome-wide association studies (GWAS) have identified genetic factors in type 2 diabetes (T2D), mostly among individuals of European ancestry. We tested whether previously identified T2D-associated single nucleotide polymorphisms (SNPs) replicate and whether SNPs in regions near known T2D SNPs were associated with T2D within the Singapore Chinese Health Study. 2338 cases and 2339 T2D controls from the Singapore Chinese Health Study were genotyped for 507,509 SNPs. Imputation extended the genotyped SNPs to 7,514,461 with high estimated certainty (r(2)>0.8). Replication of known index SNP associations in T2D was attempted. Risk scores were computed as the sum of index risk alleles. SNPs in regions ± 100 kb around each index were tested for associations with T2D in conditional fine-mapping analysis. Of 69 index SNPs, 20 were genotyped directly and genotypes at 35 others were well imputed. Among the 55 SNPs with data, disease associations were replicated (at p<0.05) for 15 SNPs, while 32 more were directionally consistent with previous reports. Risk score was a significant predictor with a 2.03 fold higher risk CI (1.69-2.44) of T2D comparing the highest to lowest quintile of risk allele burden (p = 5.72 × 10(-14)). Two improved SNPs around index rs10923931 and 5 new candidate SNPs around indices rs10965250 and rs1111875 passed simple Bonferroni corrections for significance in conditional analysis. Nonetheless, only a small fraction (2.3% on the disease liability scale) of T2D burden in Singapore is explained by these SNPs. While diabetes risk in Singapore Chinese involves genetic variants, most disease risk remains unexplained. Further genetic work is ongoing in the Singapore Chinese population to identify unique common variants not already seen in earlier studies. However rapid increases in T2D risk have occurred in recent decades in this population, indicating that dynamic environmental influences and possibly gene by environment interactions complicate the genetic architecture of this disease.

Gene-Diet Interactions in Type 2 Diabetes: The Chicken and Egg Debate

PubMed Central

Ortega, Ángeles; Berná, Genoveva; Rojas, Anabel; Martín, Franz; Soria, Bernat

2017-01-01

Consistent evidence from both experimental and human studies indicates that Type 2 diabetes mellitus (T2DM) is a complex disease resulting from the interaction of genetic, epigenetic, environmental, and lifestyle factors. Nutrients and dietary patterns are important environmental factors to consider in the prevention, development and treatment of this disease. Nutritional genomics focuses on the interaction between bioactive food components and the genome and includes studies of nutrigenetics, nutrigenomics and epigenetic modifications caused by nutrients. There is evidence supporting the existence of nutrient-gene and T2DM interactions coming from animal studies and family-based intervention studies. Moreover, many case-control, cohort, cross-sectional cohort studies and clinical trials have identified relationships between individual genetic load, diet and T2DM. Some of these studies were on a large scale. In addition, studies with animal models and human observational studies, in different countries over periods of time, support a causative relationship between adverse nutritional conditions during in utero development, persistent epigenetic changes and T2DM. This review provides comprehensive information on the current state of nutrient-gene interactions and their role in T2DM pathogenesis, the relationship between individual genetic load and diet, and the importance of epigenetic factors in influencing gene expression and defining the individual risk of T2DM. PMID:28574454

Non-targeted metabolomic biomarkers and metabotypes of type 2 diabetes: A cross-sectional study of PREDIMED trial participants.

PubMed

Urpi-Sarda, M; Almanza-Aguilera, E; Llorach, R; Vázquez-Fresno, R; Estruch, R; Corella, D; Sorli, J V; Carmona, F; Sanchez-Pla, A; Salas-Salvadó, J; Andres-Lacueva, C

2018-02-20

To characterize the urinary metabolomic fingerprint and multi-metabolite signature associated with type 2 diabetes (T2D), and to classify the population into metabotypes related to T2D. A metabolomics analysis using the 1 H-NMR-based, non-targeted metabolomic approach was conducted to determine the urinary metabolomic fingerprint of T2D compared with non-T2D participants in the PREDIMED trial. The discriminant metabolite fingerprint was subjected to logistic regression analysis and ROC analyses to establish and to assess the multi-metabolite signature of T2D prevalence, respectively. Metabotypes associated with T2D were identified using the k-means algorithm. A total of 33 metabolites were significantly different (P<0.05) between T2D and non-T2D participants. The multi-metabolite signature of T2D comprised high levels of methylsuccinate, alanine, dimethylglycine and guanidoacetate, and reduced levels of glutamine, methylguanidine, 3-hydroxymandelate and hippurate, and had a 96.4% AUC, which was higher than the metabolites on their own and glucose. Amino-acid and carbohydrate metabolism were the main metabolic alterations in T2D, and various metabotypes were identified in the studied population. Among T2D participants, those with a metabotype of higher levels of phenylalanine, phenylacetylglutamine, p-cresol and acetoacetate had significantly higher levels of plasma glucose. The multi-metabolite signature of T2D highlights the altered metabolic fingerprint associated mainly with amino-acid, carbohydrate and microbiota metabolism. Metabotypes identified in this patient population could be related to higher risk of long-term cardiovascular events and therefore require further studies. Metabolomics is a useful tool for elucidating the metabolic complexity and interindividual variation in T2D towards the development of stratified precision nutrition and medicine. Trial registration at www.controlled-trials.com: ISRCTN35739639. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Tuning the relaxation rates of dual-mode T1/T2 nanoparticle contrast agents: a study into the ideal system

NASA Astrophysics Data System (ADS)

Keasberry, Natasha A.; Bañobre-López, Manuel; Wood, Christopher; Stasiuk, Graeme. J.; Gallo, Juan; Long, Nicholas. J.

2015-09-01

Magnetic resonance imaging (MRI) is an excellent imaging modality. However the low sensitivity of the technique poses a challenge to achieving an accurate image of function at the molecular level. To overcome this, contrast agents are used; typically gadolinium based agents for T1 weighted imaging, or iron oxide based agents for T2 imaging. Traditionally, only one imaging mode is used per diagnosis although several physiological situations are known to interfere with the signal induced by the contrast agents in each individual imaging mode acquisition. Recently, the combination of both T1 and T2 imaging capabilities into a single platform has emerged as a tool to reduce uncertainties in MR image analysis. To date, contradicting reports on the effect on the contrast of the coupling of a T1 and T2 agent have hampered the application of these specialised probes. Herein, we present a systematic experimental study on a range of gadolinium-labelled magnetite nanoparticles envisioned to bring some light into the mechanism of interaction between T1 and T2 components, and advance towards the design of efficient (dual) T1 and T2 MRI probes. Unexpected behaviours observed in some of the constructs will be discussed. In this study, we demonstrate that the relaxivity of such multimodal probes can be rationally tuned to obtain unmatched potentials in MR imaging, exemplified by preparation of the magnetite-based nanoparticle with the highest T2 relaxivity described to date.Magnetic resonance imaging (MRI) is an excellent imaging modality. However the low sensitivity of the technique poses a challenge to achieving an accurate image of function at the molecular level. To overcome this, contrast agents are used; typically gadolinium based agents for T1 weighted imaging, or iron oxide based agents for T2 imaging. Traditionally, only one imaging mode is used per diagnosis although several physiological situations are known to interfere with the signal induced by the contrast agents in each individual imaging mode acquisition. Recently, the combination of both T1 and T2 imaging capabilities into a single platform has emerged as a tool to reduce uncertainties in MR image analysis. To date, contradicting reports on the effect on the contrast of the coupling of a T1 and T2 agent have hampered the application of these specialised probes. Herein, we present a systematic experimental study on a range of gadolinium-labelled magnetite nanoparticles envisioned to bring some light into the mechanism of interaction between T1 and T2 components, and advance towards the design of efficient (dual) T1 and T2 MRI probes. Unexpected behaviours observed in some of the constructs will be discussed. In this study, we demonstrate that the relaxivity of such multimodal probes can be rationally tuned to obtain unmatched potentials in MR imaging, exemplified by preparation of the magnetite-based nanoparticle with the highest T2 relaxivity described to date. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr04400f

The attentional blink is not affected by backward masking of T2, T2-mask SOA, or level of T2 impoverishment.

PubMed

Jannati, Ali; Spalek, Thomas M; Lagroix, Hayley E P; Di Lollo, Vincent

2012-02-01

Identification of the second of two targets (T2) is impaired when presented shortly after the first (T1). This attentional blink (AB) is thought to arise from a delay in T2 processing during which T2 is vulnerable to masking. Conventional studies have measured T2 accuracy which is constrained by the 100% ceiling. We avoided this problem by using a dynamic threshold-tracking procedure that is inherently free from ceiling constraints. In two experiments we examined how AB magnitude is affected by three masking-related factors: (a) presence/absence of T2 mask, (b) T2-mask stimulus onset asynchrony (SOA), and (c) level of T2 impoverishment (signal-to-noise ratio [SNR]). In Experiment 1, overall accuracy decreased with T2-mask SOA. The magnitude of the AB, however, was invariant with SOA and with mask presence/absence. Experiment 2 further showed that the AB was invariant with T2 SNR. The relationship among mask presence/absence, SOA, and T2 SNR and the AB is encompassed in a qualitative model.

Quantitative analysis of changes in salivary mutans streptococci after orthodontic treatment.

PubMed

Jung, Woo-Sun; Kim, Ho; Park, So-Yoon; Cho, Eun-Jung; Ahn, Sug-Joon

2014-05-01

The purpose of this study was to analyze the initial changes in salivary mutans streptococci levels after orthodontic treatment with fixed appliances. Our subjects consisted of 58 adults. Whole saliva and simplified oral hygiene index values were obtained at 4 time points: at debonding (T1), 1 week after debonding (T2), 5 weeks after debonding (T3), and 13 weeks after debonding (T4). Repeated measures analysis of variance was used to determine the time-related differences in salivary bacterial levels and the simplified oral hygiene index values among the 4 time points after quantifying the salivary levels of Streptococcus mutans, Streptococcus sobrinus, and total bacteria with real-time polymerase chain reaction. Simplified oral hygiene index values and total bacteria significantly decreased, but salivary mutans streptococci levels significantly increased after orthodontic treatment. The amounts of total bacteria in saliva significantly decreased at T3 (T1, T2 > T3, T4), and the simplified oral hygiene index values decreased at T2 (T1 > T2, T3, T4). However, salivary S mutans and S sobrinus significantly increased at T3 and T4, respectively (T1, T2 < T3 < T4). Furthermore, the proportion of mutans streptococci to total bacteria significantly increased at T4 (T1, T2, T3 < T4). This study suggests that careful hygienic procedures are needed to reduce the risk for dental caries after orthodontic treatment, despite overall improved oral hygiene status. Copyright © 2014 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

Fast magnetic resonance fingerprinting for dynamic contrast-enhanced studies in mice.

PubMed

Gu, Yuning; Wang, Charlie Y; Anderson, Christian E; Liu, Yuchi; Hu, He; Johansen, Mette L; Ma, Dan; Jiang, Yun; Ramos-Estebanez, Ciro; Brady-Kalnay, Susann; Griswold, Mark A; Flask, Chris A; Yu, Xin

2018-05-09

The goal of this study was to develop a fast MR fingerprinting (MRF) method for simultaneous T 1 and T 2 mapping in DCE-MRI studies in mice. The MRF sequences based on balanced SSFP and fast imaging with steady-state precession were implemented and evaluated on a 7T preclinical scanner. The readout used a zeroth-moment-compensated variable-density spiral trajectory that fully sampled the entire k-space and the inner 10 × 10 k-space with 48 and 4 interleaves, respectively. In vitro and in vivo studies of mouse brain were performed to evaluate the accuracy of MRF measurements with both fully sampled and undersampled data. The application of MRF to dynamic T 1 and T 2 mapping in DCE-MRI studies were demonstrated in a mouse model of heterotopic glioblastoma using gadolinium-based and dysprosium-based contrast agents. The T 1 and T 2 measurements in phantom showed strong agreement between the MRF and the conventional methods. The MRF with spiral encoding allowed up to 8-fold undersampling without loss of measurement accuracy. This enabled simultaneous T 1 and T 2 mapping with 2-minute temporal resolution in DCE-MRI studies. Magnetic resonance fingerprinting provides the opportunity for dynamic quantification of contrast agent distribution in preclinical tumor models on high-field MRI scanners. © 2018 International Society for Magnetic Resonance in Medicine.

Is the Susceptibility Vessel Sign on 3-Tesla Magnetic Resonance T2*-Weighted Imaging a Useful Tool to Predict Recanalization in Intravenous Tissue Plasminogen Activator?

PubMed

Yamamoto, N; Satomi, J; Harada, M; Izumi, Y; Nagahiro, S; Kaji, R

2016-09-01

The aim of this study was to investigate the independent factors associated with the absence of recanalization approximately 24 h after intravenous administration of tissue-type plasminogen activator (IV TPA). The previous studies have been conducted using 1.5-Tesla (T) magnetic resonance imaging (MRI). We studied whether the characteristics of 3-T MRI findings were useful to predict outcome and recanalization after IV tPA. Patients with internal carotid artery (ICA) or middle cerebral artery (MCA) (horizontal portion, M1; Sylvian portion, M2) occlusion and treated by IV tPA were enrolled. We studied whether the presence of susceptibility vessel sign (SVS) at M1 and low clot burden score on T2*-weighted imaging (T2*-CBS) on 3-T MRI were associated with the absence of recanalization. A total of 49 patients were enrolled (27 men; mean age, 73.9 years). MR angiography obtained approximately 24 h after IV tPA revealed recanalization in 21 (42.9 %) patients. Independent factors associated with the absence of recanalization included ICA or proximal M1 occlusion (odds ratio, 69.6; 95 % confidence interval, 5.05-958.8, p = 0.002). In this study, an independent factor associated with the absence of recanalization may be proximal occlusion of the cerebral arteries rather than SVS in the MCA or low T2*-CBS on 3-T MRI.

Magnetic resonance measurement of muscle T2, fat-corrected T2 and fat fraction in the assessment of idiopathic inflammatory myopathies

PubMed Central

Yao, Lawrence; Yip, Adrienne L.; Shrader, Joseph A.; Mesdaghinia, Sepehr; Volochayev, Rita; Jansen, Anna V.; Miller, Frederick W.

2016-01-01

Objective. This study examines the utility of MRI, including T2 maps and T2 maps corrected for muscle fat content, in evaluating patients with idiopathic inflammatory myopathy. Methods. A total of 44 patients with idiopathic inflammatory myopathy, 18 of whom were evaluated after treatment with rituximab, underwent MRI of the thighs and detailed clinical assessment. T2, fat fraction (FF) and fat corrected T2 (fc-T2) maps were generated from standardized MRI scans, and compared with semi-quantitative scoring of short tau inversion recovery (STIR) and T1-weighted sequences, as well as various myositis disease metrics, including the Physician Global Activity, the modified Childhood Myositis Assessment Scale and the muscle domain of the Myositis Disease Activity Assessment Tool-muscle (MDAAT-muscle). Results. Mean T2 and mean fc-T2 correlated similarly with STIR scores (Spearman rs = 0.64 and 0.64, P < 0.01), while mean FF correlated with T1 damage scores (rs = 0.69, P < 0.001). Baseline T2, fc-T2 and STIR scores correlated significantly with the Physician Global Activity, modified Childhood Myositis Assessment Scale and MDAAT-muscle (rs range = 0.41–0.74, P < 0.01). The response of MRI measures to rituximab was variable, and did not significantly agree with a standardized clinical definition of improvement. Standardized response means for the MRI measures were similar. Conclusion. Muscle T2, fc-T2 and FF measurements exhibit content validity with reference to semi-quantitative scoring of STIR and T1 MRI, and also exhibit construct validity with reference to several myositis activity and damage measures. T2 was as responsive as fc-T2 and STIR scoring, although progression of muscle damage was negligible during the study. PMID:26412808

Evaluation of the relationship between T1ρ and T2 values and patella cartilage degeneration in patients of the same age group.

PubMed

Nishioka, Hiroaki; Hirose, Jun; Okamoto, Nobukazu; Okada, Tatsuya; Oka, Kiyoshi; Taniwaki, Takuya; Nakamura, Eiichi; Yamashita, Yasuyuki; Mizuta, Hiroshi

2015-03-01

The aim of this study was to investigate the association between the T1ρ and T2 values and the progression of cartilage degeneration in patients of the same age group. Sagittal T1ρ and T2 mapping and three-dimensional (3D) gradient-echo images were obtained from 78 subjects with medial knee osteoarthritis (OA). The degree of patella cartilage degeneration was classified into four groups using MRI-based grading: apparently normal cartilage, mild OA, moderate OA, and severe OA group. We measured the T1ρ and T2 values (ms) in the regions of interest set on the full-thickness patella cartilage. Then, we analyzed the relationship between the T1ρ and T2 values and the degree of patella cartilage degeneration. There were no significant differences in age among the four groups. Both the T1ρ and T2 values showed a positive correlation with the degree of OA progression (ρ=0.737 and ρ=0.632, respectively). By comparison between the apparently normal cartilage and the mild OA groups, there were significant differences in the T1ρ mapping, but not in the T2 mapping. Our study confirmed that T1ρ and T2 mapping can quantitatively evaluate the degree of patella cartilage degeneration in patients within the same age group. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Genetic Predisposition to Central Obesity and Risk of Type 2 Diabetes: Two Independent Cohort Studies

PubMed Central

Huang, Tao; Qi, Qibin; Zheng, Yan; Ley, Sylvia H.; Manson, JoAnn E.; Hu, Frank B.

2015-01-01

OBJECTIVE Abdominal obesity is a major risk factor for type 2 diabetes (T2D). We aimed to examine the association between the genetic predisposition to central obesity, assessed by the waist-to-hip ratio (WHR) genetic score, and T2D risk. RESEARCH DESIGN AND METHODS The current study included 2,591 participants with T2D and 3,052 participants without T2D of European ancestry from the Nurses’ Health Study (NHS) and the Health Professionals Follow-up Study (HPFS). Genetic predisposition to central obesity was estimated using a genetic score based on 14 established loci for the WHR. RESULTS We found that the central obesity genetic score was linearly related to higher T2D risk. Results were similar in the NHS (women) and HPFS (men). In combined results, each point of the central obesity genetic score was associated with an odds ratio (OR) of 1.04 (95% CI 1.01–1.07) for developing T2D, and the OR was 1.24 (1.03–1.45) when comparing extreme quartiles of the genetic score after multivariate adjustment. CONCLUSIONS The data indicate that genetic predisposition to central obesity is associated with higher T2D risk. This association is mediated by central obesity. PMID:25852209

Type 2 Diabetes Risk Allele Loci in the Qatari Population

PubMed Central

Abi Khalil, Charbel; Fakhro, Khalid A.; Robay, Amal; Ramstetter, Monica D.; Al-Azwani, Iman K.; Malek, Joel A.; Zirie, Mahmoud; Jayyousi, Amin; Badii, Ramin; Al-Nabet Al-Marri, Ajayeb; Chiuchiolo, Maria J.; Al-Shakaki, Alya; Chidiac, Omar; Gharbiah, Maey; Bener, Abdulbari; Stadler, Dora; Hackett, Neil R.; Mezey, Jason G.; Crystal, Ronald G.

2016-01-01

Background The prevalence of type 2 diabetes (T2D) is increasing in the Middle East. However, the genetic risk factors for T2D in the Middle Eastern populations are not known, as the majority of studies of genetic risk for T2D are in Europeans and Asians. Methods All subjects were ≥3 generation Qataris. Cases with T2D (n = 1,124) and controls (n = 590) were randomly recruited and assigned to the 3 known Qatari genetic subpopulations [Bedouin (Q1), Persian/South Asian (Q2) and African (Q3)]. Subjects underwent genotyping for 37 single nucleotide polymorphisms (SNPs) in 29 genes known to be associated with T2D in Europeans and/or Asian populations, and an additional 27 tag SNPs related to these susceptibility loci. Pre-study power analysis suggested that with the known incidence of T2D in adult Qataris (22%), the study population size would be sufficient to detect significant differences if the SNPs were risk factors among Qataris, assuming that the odds ratio (OR) for T2D SNPs in Qatari’s is greater than or equal to the SNP with highest known OR in other populations. Results Haplotype analysis demonstrated that Qatari haplotypes in the region of known T2D risk alleles in Q1 and Q2 genetic subpopulations were similar to European haplotypes. After Benjamini-Hochberg adjustment for multiple testing, only two SNPs (rs7903146 and rs4506565), both associated with transcription factor 7-like 2 (TCF7L2), achieved statistical significance in the whole study population. When T2D subjects and control subjects were assigned to the known 3 Qatari subpopulations, and analyzed individually and with the Q1 and Q2 genetic subpopulations combined, one of these SNPs (rs4506565) was also significant in the admixed group. No other SNPs associated with T2D in all Qataris or individual genetic subpopulations. Conclusions With the caveats of the power analysis, the European/Asian T2D SNPs do not contribute significantly to the high prevalence of T2D in the Qatari population, suggesting that the genetic risks for T2D are likely different in Qataris compared to Europeans and Asians. PMID:27383215

Sinonasal solitary chemosensory cells "taste" the upper respiratory environment to regulate innate immunity.

PubMed

Lee, Robert J; Cohen, Noam A

2014-01-01

It is not fully understood how sinonasal epithelial cells detect the presence of pathogens and activate innate defense responses necessary for protecting the upper airway from infection. One mechanism is through bitter taste receptors (T2Rs), which are expressed in the sinonasal cavity. One T2R isoform, T2R38, is expressed in ciliated cells and detects quorum-sensing molecules from gram-negative bacteria, activating antimicrobial nitric oxide production. More recent studies have examined the role of T2Rs expressed in a sinonasal cell type that has only recently been identified in humans, the solitary chemosensory cell (SCC). We sought to provide an overview of SCCs and taste receptor function in human sinonasal defense as well as implications for chronic rhinosinusitis (CRS). A literature review of the current knowledge of SCCs and taste receptors in sinonasal physiology and CRS was conducted. Human sinonasal SCCs express both bitter T2R and sweet T1R2/3 receptors. Activation of SCC T2Rs activates a calcium signal that propagates to the surrounding epithelial cells and causes secretion of antimicrobial peptides. T1R2/3 sweet receptor activation by physiological airway surface liquid (ASL) glucose concentrations attenuates the T2R response, likely as a mechanism to prevent full activation of the T2R pathway except during times of infection, when pathogens may consume ASL glucose and reduce its concentration. SCCs appear to be important mediators of upper airway innate immunity, as the SCC T2Rs regulate antimicrobial peptide secretion, but further study is needed to determine the specific T2R isoforms involved as well as whether polymorphisms in these isoforms affect susceptibility to infection or patient outcomes in CRS. The inhibitory role of T1R2/3 sweet receptor suggests that T1R2/3 blockers may have therapeutic potential in some CRS patients, particularly those with diabetes mellitus. However, further clinical study of the relationship between infection and T1R2/3 genotype is required.

A longitudinal study on psychosocial causes and consequences of Internet gaming disorder in adolescence.

PubMed

Wartberg, Lutz; Kriston, Levente; Zieglmeier, Matthias; Lincoln, Tania; Kammerl, Rudolf

2018-04-06

In 2013, Internet gaming disorder (IGD) was incorporated in the current version of the DSM-5. IGD refers to a problematic use of video games. Longitudinal studies on the etiology of IGD are lacking. Furthermore, it is currently unclear to which extent associated psychopathological problems are causes or consequences of IGD. In the present survey, longitudinal associations between IGD and adolescent and parental mental health were investigated for the first time, as well as the temporal stability of IGD. In a cross-lagged panel design study, family dyads (adolescent with a parent each) were examined in 2016 (t1) and again 1 year later (2017, t2). Overall, 1095 family dyads were assessed at t1 and 985 dyads were re-assessed at t2 with standardized measures of IGD and several aspects of adolescent and parental mental health. Data were analyzed with structural equation modeling (SEM). Male gender, a higher level of hyperactivity/inattention, self-esteem problems and IGD at t1 were predictors of IGD at t2. IGD at t1 was a predictor for adolescent emotional distress at t2. Overall, 357 out of the 985 adolescents received a diagnosis of IGD at t1 or t2: 142 (14.4%) at t1 and t2, 100 (10.2%) only at t1, and 115 (11.7%) only at t2. Hyperactivity/inattention and self-esteem problems seem to be important for the development of IGD. We found first empirical evidence that IGD could prospectively contribute to a deterioration of adolescent mental health. Only a subgroup of affected adolescents showed IGD consistently over 1 year.

Differential localization of vesicular glutamate transporters and peptides in corneal afferents to trigeminal nucleus caudalis.

PubMed

Hegarty, Deborah M; Tonsfeldt, Karen; Hermes, Sam M; Helfand, Helen; Aicher, Sue A

2010-09-01

Trigeminal afferents convey nociceptive information from the corneal surface of the eye to the trigeminal subnucleus caudalis (Vc). Trigeminal afferents, like other nociceptors, are thought to use glutamate and neuropeptides as neurotransmitters. The current studies examined whether corneal afferents contain both neuropeptides and vesicular glutamate transporters. Corneal afferents to the Vc were identified by using cholera toxin B (CTb). Corneal afferents project in two clusters to the rostral and caudal borders of the Vc, regions that contain functionally distinct nociceptive neurons. Thus, corneal afferents projecting to these two regions were examined separately. Dual immunocytochemical studies combined CTb with either calcitonin gene-related peptide (CGRP), substance P (SP), vesicular glutamate transporter 1 (VGluT1), or VGluT2. Corneal afferents were more likely to contain CGRP than SP, and corneal afferents projecting to the rostral region were more likely to contain CGRP than afferents projecting caudally. Overall, corneal afferents were equally likely to contain VGluT1 or VGluT2. Together, 61% of corneal afferents contained either VGluT1 or VGluT2, suggesting that some afferents lack a VGluT. Caudal corneal afferents were more likely to contain VGluT2 than VGluT1, whereas rostral corneal afferents were more likely to contain VGluT1 than VGluT2. Triple-labeling studies combining CTb, CGRP, and VGluT2 showed that very few corneal afferents contain both CGRP and VGluT2, caudally (1%) and rostrally (2%). These results suggest that most corneal afferents contain a peptide or a VGluT, but rarely both. Our results are consistent with a growing literature suggesting that glutamatergic and peptidergic sensory afferents may be distinct populations.

Dental arch changes in postretention in Class II division 1 extraction cases.

PubMed

Anuwongnukroh, Niwat; Dechkunakorn, Surachai; Kunakornporamut, Kannida; Tua-Ngam, Peerapong

2017-06-01

The purpose of this study is to evaluate the postretention stability of the dental arches in Class II division 1 patients treated with four bicuspid extractions and the edgewise technique. A digital caliper was used to analyze the dental casts from 29 Class II division 1 malocclusion patients with skeletal type II (14 males, 15 females; ages ranging from 10.2-18.0 years), treated with four bicuspid extractions and the edgewise technique. Intercanine width, intermolar width, arch length, irregularity index, overjet and overbite were evaluated at three times: pretreatment (T1), posttreatment (T2) and postretention (T3) (mean: 4.15 years). Student's t-tests were used to compare the pretreatment-posttreatment, posttreatment-postretention and pretreatment-postretention. Significance was determined at P<0.05. The results of the study are listed as: (1) The upper and lower intercanine widths significantly increased (P<0.05) between T1-T2 and decreased between T2-T3. However, no significant changes were observed between T1-T3; (2) The upper and lower intermolar widths significantly decreased (P<0.05) between T1-T2, between T2-T3 and between T1-T3, except for the upper intermolar width between T2-T3 which showed no significant change; (3) The upper and lower arch lengths significantly decreased (P<0.05) at posttreatment and postretention due to the closure of extraction spaces. Both the upper and lower arch lengths significantly decreased between T1-T2, T2-T3, and T1-T3, except for the upper arch length between T2-T3, which showed no significant change; (4) The irregularity index was significantly improved after treatment. However, there was a slight increase in incisor irregularity at postretention. At postretention, 75.86% of the patients had mild crowding, 20.68% had moderate crowding, 3.48% had severe crowding; (5) The overjet and overbite significantly decreased (P<0.05) between T1-T2 and increased between T2-T3. The changes in the dental arches were small at postretention with a tendency to return towards their original position. The overall stability of Class II division 1 extraction cases is relatively good. Copyright © 2017 CEO. Published by Elsevier Masson SAS. All rights reserved.

Does elimination of planned postoperative radiation to the primary bed in p16-positive, transorally-resected oropharyngeal carcinoma associate with poorer outcomes?

PubMed

Sinha, Parul; Pipkorn, Patrik; Thorstad, Wade L; Gay, Hiram A; Haughey, Bruce H

2016-10-01

The purpose of our study is to compare oncologic and functional outcomes of p16-positive oropharyngeal squamous cell carcinoma (OPSCC) patients, in the presence and absence of planned radiation to the primary bed following transoral surgery (TOS), stratified by T-classification. Retrospective cohort study of 261, T1-T4, consecutively TOS-treated OPSCC patients. At a median follow-up of 61months, local recurrence (LR) occurred in 6 (2.3%)patients (3 each in T1-T2 and T3-T4 groups), of which 5 had tumors in the tongue base and one in the tonsil. Of patients not receiving planned primary bed radiation, LR occurred in 3% of T1-T2s versus 17% of T3-T4s. In patients with T1-T2 tumors, Absolute Risk Reduction of LR with primary bed radiation was 3.26% (95% CI: -0.37%, 7%); Number Needed to Treat to prevent one LR was 31 (95% CI: 14.5, 271). Absolute Risk Increase for gastrostomy-tube with primary bed radiation was 34.4% (95% CI: 24%, 45%); Number Needed to Harm was 3 (95% CI: 2.2, 4.2), i.e., for every three patients with T1-T2 tumors receiving primary bed radiation, one had a gastrostomy-tube. Elimination of primary bed radiation in margin-negative resected, T1-T2 p16-positive OPSCC was not associated with significant compromise of local control, and correlated with superior swallowing preservation, assessed using gastrostomy rate as a surrogate. Lack of primary bed radiation in T3-T4 tumors associated with significantly increased LR rates. Copyright © 2016 Elsevier Ltd. All rights reserved.

Thyroid Signaling, Insulin Resistance, and 2 Diabetes Mellitus: A Mendelian Randomization Study.

PubMed

Bos, Maxime M; Smit, Roelof A J; Trompet, Stella; van Heemst, Diana; Noordam, Raymond

2017-06-01

Increasing evidence suggests an association between thyroid-stimulating hormone (TSH), free thyroxine (fT4), and deiodinases with insulin resistance and type 2 diabetes mellitus (T2D). We examined whether TSH and fT4 levels and deiodinases are causally associated with insulin resistance and T2D, using Mendelian randomization. We selected 20 genetic variants for TSH level and four for fT4 level (identified in a genome-wide association study (GWAS) meta-analysis of European-ancestry cohorts) as instrumental variables for TSH and fT4 levels, respectively. We used summary data from GWASs on the outcomes T2D [Diabetes, Genetics Replication and Meta-analysis (DIAGRAM), n = 12,171 cases and n = 56,862 control subjects] and glycemic traits in patients without diabetes [Meta-Analyses of Glucose and Insulin-Related Traits Consortium (MAGIC), n = 46,186 for fasting glucose and insulin and n = 46,368 for hemoglobin A1c]. To examine whether the associations between TSH/fT4 levels and the study outcomes were causal, we combined the effects of the genetic instruments. Furthermore, we examined the associations among 16 variants in DIO1, DIO2, DIO3, and T2D and glycemic traits. We found no evidence for an association between the combined genetic instrumental variables for TSH and fT4 and the study outcomes. For example, we did not observe a genetically determined association between high TSH level and T2D (odds ratio, 0.91 per standard deviation TSH increase; 95% confidence interval, 0.78 to 1.07). Selected genetic variants in DIO1 (e.g., rs7527713) were associated with measures of insulin resistance. We found no evidence for a causal association between circulatory levels of TSH and fT4 with insulin resistance and T2D, but we found suggestive evidence that DIO1 affects glucose metabolism. Copyright © 2017 by the Endocrine Society

Can T1 w/T2 w ratio be used as a myelin-specific measure in subcortical structures? Comparisons between FSE-based T1 w/T2 w ratios, GRASE-based T1 w/T2 w ratios and multi-echo GRASE-based myelin water fractions.

PubMed

Uddin, Md Nasir; Figley, Teresa D; Marrie, Ruth Ann; Figley, Chase R

2018-03-01

Given the growing popularity of T 1 -weighted/T 2 -weighted (T 1 w/T 2 w) ratio measurements, the objective of the current study was to evaluate the concordance between T 1 w/T 2 w ratios obtained using conventional fast spin echo (FSE) versus combined gradient and spin echo (GRASE) sequences for T 2 w image acquisition, and to compare the resulting T 1 w/T 2 w ratios with histologically validated myelin water fraction (MWF) measurements in several subcortical brain structures. In order to compare these measurements across a relatively wide range of myelin concentrations, whole-brain T 1 w magnetization prepared rapid acquisition gradient echo (MPRAGE), T 2 w FSE and three-dimensional multi-echo GRASE data were acquired from 10 participants with multiple sclerosis at 3 T. Then, after high-dimensional, non-linear warping, region of interest (ROI) analyses were performed to compare T 1 w/T 2 w ratios and MWF estimates (across participants and brain regions) in 11 bilateral white matter (WM) and four bilateral subcortical grey matter (SGM) structures extracted from the JHU_MNI_SS 'Eve' atlas. Although the GRASE sequence systematically underestimated T 1 w/T 2 w values compared to the FSE sequence (revealed by Bland-Altman and mountain plots), linear regressions across participants and ROIs revealed consistently high correlations between the two methods (r 2 = 0.62 for all ROIs, r 2 = 0.62 for WM structures and r 2 = 0.73 for SGM structures). However, correlations between either FSE-based or GRASE-based T 1 w/T 2 w ratios and MWFs were extremely low in WM structures (FSE-based, r 2 = 0.000020; GRASE-based, r 2 = 0.0014), low across all ROIs (FSE-based, r 2 = 0.053; GRASE-based, r 2 = 0.029) and moderate in SGM structures (FSE-based, r 2 = 0.20; GRASE-based, r 2 = 0.17). Overall, our findings indicated a high degree of correlation (but not equivalence) between FSE-based and GRASE-based T 1 w/T 2 w ratios, and low correlations between T 1 w/T 2 w ratios and MWFs. This suggests that the two T 1 w/T 2 w ratio approaches measure similar facets of subcortical tissue microstructure, whereas T 1 w/T 2 w ratios and MWFs appear to be sensitized to different microstructural properties. On this basis, we conclude that multi-echo GRASE sequences can be used in future studies to efficiently elucidate both general (T 1 w/T 2 w ratio) and myelin-specific (MWF) tissue characteristics. Copyright © 2018 John Wiley & Sons, Ltd.

Association between matrix metalloproteinase 2 (MMP2) promoter polymorphisms and the susceptibility to non-Hodgkin's lymphoma in Egyptians.

PubMed

Gouda, Heba Mahmoud; Khorshied, Mervat Mamdooh; El Sissy, Maha Hamdi; Shaheen, Iman Abdel Mohsen; Mohsen, Mohsen Mokhtar Abdel

2014-08-01

Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases capable of extracellular matrix degradation. MMP2 is the key molecule that control invasion, tumor growth, and metastasis, and has been associated with poor prognosis in several tumors. Several epidemiological studies have focused on the associations between MMP2 promoter polymorphisms and cancer susceptibility; however, little is known about their role in hematological malignancies. The present study aimed to investigate the association of MMP2 -735C/T and -1306C/T promoter polymorphisms with B-NHL susceptibility and their clinicopathological characteristics. The study included 100 B-NHL patients and 100 healthy controls. Genotyping of MMP2 -735C/T and MMP2 -1306C/T was done by polymerase chain reaction restricted fragment length polymorphism (PCR-RFLP) technique. MMP2 -735C/T heteromutant genotype (CT) was detected in 23 % of patients, and the homomutant genotype (TT) was detected in 7 % of patients. The polymorphic allele, T allele, was associated with susceptibility to B-NHL (OR = 2.8:95 %CI = 1.48-5.28). For MMP2 -1306C/T, the frequencies of the polymorphic variants were 5 % for the heteromutant genotype (CT) and 3 % for the homomutant genotype (TT). The polymorphic allele, T allele, conferred almost fourfold increased risk of B-NHL (OR = 3.8, 95 %CI = 1.05-13.9), and the risk elevated to be almost eight folds when confined to diffuse large B-cell lymphoma (DLBCL) (OR = 7.9, 95 %CI = 1.67-32.27). MMP2 -735C/T polymorphic genotypes were correlated with advanced clinical stages of the disease (stages III and IV). In conclusion, the study revealed that the variant alleles of MMP2 -735C/T and MMP2 -1306C/T can be considered as molecular risk factors for B-NHL among Egyptians.

Salivary inflammatory markers and microbiome in normoglycemic lean and obese children compared to obese children with type 2 diabetes.

PubMed

Janem, Waleed F; Scannapieco, Frank A; Sabharwal, Amarpeet; Tsompana, Maria; Berman, Harvey A; Haase, Elaine M; Miecznikowski, Jeffrey C; Mastrandrea, Lucy D

2017-01-01

There is emerging evidence linking diabetes with periodontal disease. Diabetes is a well-recognized risk factor for periodontal disease. Conversely, pro-inflammatory molecules released by periodontally-diseased tissues may enter the circulation to induce insulin resistance. While this association has been demonstrated in adults, there is little information regarding periodontal status in obese children with and without type 2 diabetes (T2D). We hypothesized that children with T2D have higher rates of gingivitis, elevated salivary inflammatory markers, and an altered salivary microbiome compared to children without T2D. Three pediatric cohorts ages 10-19 years were studied: lean (normal weight-C), obese (Ob), and obese with T2D (T2D). Each subject completed an oral health survey, received a clinical oral examination, and provided unstimulated saliva for measurement of inflammatory markers and microbiome analysis. The diabetes group was less likely to have had a dental visit within the last six months. Body mass index (BMI) Z-scores and waist circumference/height ratios were similar between Ob and T2D cohorts. The number of carious lesions and fillings were similar for all three groups. The gingival index was greater in the T2D group compared to the Ob and C groups. Although salivary microbial diversity was minimal between groups, a few differences in bacterial genus composition were noted. Obese children with T2D show a trend toward poorer oral health compared to normal weight and obese children without T2D. This study characterizes the salivary microbiome of children with and without obesity and T2D. This study supports a modest link between T2D and periodontal inflammation in the pediatric population.

Association between urbanisation and type 2 diabetes: an ecological study

PubMed Central

Gassasse, Zakariah; Smith, Dianna; Finer, Sarah

2017-01-01

Introduction Previous studies have explored the effect of urbanisation on the prevalence of type 2 diabetes (T2D) at regional/national level. The aim of this study is to investigate the association between urbanisation and T2D at country level, worldwide, and to explore the role of intermediate variables (physical inactivity, sugar consumption and obesity). The potential effect modification of gross domestic product (GDP) was also assessed. Methods Data for 207 countries were collected from accessible datasets. Direct acyclic graphs were used to describe the association between urbanisation, T2D and their intermediate variables (physical inactivity, sugar consumption and obesity). Urbanisation was measured as urban percentage (UP) and as agglomeration index (AI). Crude and multivariate linear regression analyses were conducted to explore selected associations. The interaction between urbanisation and T2D across levels of GDP per capita was investigated. Results The association between urbanisation and T2D diverged by exposure: AI was positively associated, while UP negatively associated with T2D prevalence. Physical inactivity and obesity were statistically significantly associated with increased prevalence of T2D. In middle-income countries (MIC) UP, AI and GDP were significantly associated with T2D prevalence, while in high-income countries (HIC), physical inactivity and obesity were the main determinant of T2D prevalence. Conclusions The type of urban growth, not urbanisation per se, predicted T2D prevalence at country level. In MIC, population density and GDP were the main determinant of diabetes, while in HIC. these were physical inactivity and obesity. Globalisation is playing an important role in the rise of T2D worldwide. PMID:29104770

Gender differences in the association of individual social class and neighbourhood unemployment rate with prevalent type 2 diabetes mellitus: a cross-sectional study from the DIAB-CORE consortium.

PubMed

Müller, Grit; Hartwig, Saskia; Greiser, Karin Halina; Moebus, Susanne; Pundt, Noreen; Schipf, Sabine; Völzke, Henry; Maier, Werner; Meisinger, Christa; Tamayo, Teresa; Rathmann, Wolfgang; Berger, Klaus

2013-06-21

To analyse gender differences in the relationship of individual social class, employment status and neighbourhood unemployment rate with present type 2 diabetes mellitus (T2DM). Five cross-sectional studies. Studies were conducted in five regions of Germany from 1997 to 2006. The sample consisted of 8871 individuals residing in 226 neighbourhoods from five urban regions. Prevalent T2DM. We found significant multiplicative interactions between gender and the individual variables--social class and employment status. Social class was statistically significantly associated with T2DM in men and women, whereby this association was stronger in women (lower vs higher social class: OR 2.68 (95% CIs 1.66 to 4.34)) than men (lower vs higher social class: OR 1.78 (95% CI 1.22 to 2.58)). Significant associations of employment status and T2DM were only found in women (unemployed vs employed: OR 1.73 (95% CI 1.02 to 2.92); retired vs employed: OR 1.77 (95% CI 1.10 to 2.84); others vs employed: OR 1.64 (95% CI 1.01 to 2.67)). Neighbourhood unemployment rate was associated with T2DM in men (high vs low tertile: OR 1.52 (95% CI 1.18 to 1.96)). Between-study and between-neighbourhood variations in T2DM prevalence were more pronounced in women. The considered covariates helped to explain statistically the variation in T2DM prevalence among men, but not among women. Social class was inversely associated with T2DM in both men and women, whereby the association was more pronounced in women. Employment status only affected T2DM in women. Neighbourhood unemployment rate is an important predictor of T2DM in men, but not in women.

Optimism in prolonged grief and depression following loss: A three-wave longitudinal study.

PubMed

Boelen, Paul A

2015-06-30

There is considerable evidence that optimism, the predisposition to have generalized favorable expectancies for the future, is associated with numerous desirable outcomes. Few studies have examined the association of optimism with emotional distress following the death of a loved one. Doing so is important, because optimism may be an important target for interventions for post-loss psychopathology. In the current study, we examined the degree to which optimism, assessed in the first year post-loss (Time 1, T1), was associated with symptom levels of prolonged grief and depression six months (Time 2, T2) and fifteen months (Time 3, T3) later, controlling for baseline symptoms and also taking into account positive automatic cognitions at T1. Findings showed that higher optimism at T1 was associated with lower concurrent prolonged grief and depression severity. Higher optimism at T1 was also inversely related with depression symptom severity at T2 and T3, but not prolonged grief severity at T2 and T3. Implications of these findings are discussed. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Investigating shared aetiology between type 2 diabetes and major depressive disorder in a population based cohort.

PubMed

Clarke, Toni-Kim; Obsteter, Jana; Hall, Lynsey S; Hayward, Caroline; Thomson, Pippa A; Smith, Blair H; Padmanabhan, Sandosh; Hocking, Lynne J; Deary, Ian J; Porteous, David J; McIntosh, Andrew M

2017-04-01

Type II diabetes (T2D) and major depressive disorder (MDD) are often co-morbid. The reasons for this co-morbidity are unclear. Some studies have highlighted the importance of environmental factors and a causal relationship between T2D and MDD has also been postulated. In the present study we set out to investigate the shared aetiology between T2D and MDD using Mendelian randomization in a population based sample, Generation Scotland: the Scottish Family Health Study (N = 21,516). Eleven SNPs found to be associated with T2D were tested for association with MDD and psychological distress (General Health Questionnaire scores). We also assessed causality and genetic overlap between T2D and MDD using polygenic risk scores (PRS) assembled from the largest available GWAS summary statistics to date. No single T2D risk SNP was associated with MDD in the MR analyses and we did not find consistent evidence of genetic overlap between MDD and T2D in the PRS analyses. Linkage disequilibrium score regression analyses supported these findings as no genetic correlation was observed between T2D and MDD (rG = 0.0278 (S.E. 0.11), P-value = 0.79). As suggested by previous studies, T2D and MDD covariance may be better explained by environmental factors. Future studies would benefit from analyses in larger cohorts where stratifying by sex and looking more closely at MDD cases demonstrating metabolic dysregulation is possible. © 2016 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc. © 2016 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc.

Raman spectroscopy studies of temperature induced phase transitions in [N(CH3)3H]CdCl3 and DFT (B3LYP) calculations

NASA Astrophysics Data System (ADS)

Kchaou, H.; Karoui, K.; Bulou, A.; Ben Rhaiem, A.

2017-04-01

[N(CH3)3H]CdCl3 between 295 and 433 K possesses four phases. Three phase transition at T1=416 K, T2=373 K and T3=330 K (on heating) and T1=410 K, T2=386 K and T3=322 K (on cooling) was determined by differential scanning calorimetry. Thermal hysteresis of these transitions ΔT1=6 K, ΔT2=13 K and ΔT3=8 K, indicating a first order character. The X-ray diffraction study at room temperature revealed an orthorhombic system with Pbnm space group. The vibrational characteristics have been measured at room temperature by infrared spectroscopy (400-3800 cm-1) and by polarized Raman spectroscopy (10-3800 cm-1) on microcrystals orientated with respect to the organic and inorganic sublattice. The structure of this compound was optimized by density functional theory (DFT) using B3LYP with LanL2DZ and LanL2MB basis sets. The temperature dependence of the Raman line shifts ν and the half-width Δν detect the phase transitions (T1, T2 and T3).

Replication of genome-wide association signals in Asian Indians with early-onset type 2 diabetes.

PubMed

Chidambaram, Manickam; Liju, Samuel; Saboo, Banshi; Sathyavani, Kumpatla; Viswanathan, Vijay; Pankratz, Nathan; Gross, Myron; Mohan, Viswanathan; Radha, Venkatesan

2016-12-01

To evaluate the association of 87 genetic variants previously associated with type 2 diabetes mellitus (T2DM) in genome-wide association studies of populations of European ancestry in an Asian Indian population with early-onset type 2 diabetes mellitus (EOT2DM). The study groups comprised of 877 type 2 diabetes individuals, 436 individuals with EOT2DM (age at diagnosis below 35 years), 441 individuals with older T2DM (diagnosis at 35 years or greater) and controls with normal glucose tolerance (NGT) (n = 400 younger than 35 years; n = 438 older than 35 years). The participants were genotyped for 87 SNPs from 44 genes and 27 intergenic loci. Associations were tested using logistic regression. All the variants in TCF7L2 and CDKN2A/2B showed study-wide significance (p < 1.4 × 10 -4 ) with T2DM, but only rs7903146, rs12243326, rs12255372 of TCF7L2 and rs7020996 of CDKN2A/2B showed study-wide significance (p < 1.4 × 10 -4 ) with EOT2DM in this population. In addition, an intergenic SNP on chromosome 1 (rs10493685) was also shown to be study-wide significant (p = 7.1 × 10 -6 ). Several additional SNPs previously associated with T2DM reached borderline significance in this study, but may have been limited by relatively low sample numbers. Various other SNPs of T2DM were not associated with EOT2DM. Some of the variants in TCF7L2 and CDKN2A/2B associated with T2DM are associated with EOT2DM as well. An intergenic SNP on chromosome 1p31 showed association only with early-onset T2DM in this Asian Indian population. The lack of association with many other SNPs of T2DM may be a reflection of the lack of power of the study, sample size, differences in the frequencies of genetic polymorphisms in different ethnic groups, effect sizes, as well as ancestral differences in pattern of LD between the genetic variants involved in early- and late-onset T2DM.

Isotropic three-dimensional T2 mapping of knee cartilage: Development and validation.

PubMed

Colotti, Roberto; Omoumi, Patrick; Bonanno, Gabriele; Ledoux, Jean-Baptiste; van Heeswijk, Ruud B

2018-02-01

1) To implement a higher-resolution isotropic 3D T 2 mapping technique that uses sequential T 2 -prepared segmented gradient-recalled echo (Iso3DGRE) images for knee cartilage evaluation, and 2) to validate it both in vitro and in vivo in healthy volunteers and patients with knee osteoarthritis. The Iso3DGRE sequence with an isotropic 0.6 mm spatial resolution was developed on a clinical 3T MR scanner. Numerical simulations were performed to optimize the pulse sequence parameters. A phantom study was performed to validate the T 2 estimation accuracy. The repeatability of the sequence was assessed in healthy volunteers (n = 7). T 2 values were compared with those from a clinical standard 2D multislice multiecho (MSME) T 2 mapping sequence in knees of healthy volunteers (n = 13) and in patients with knee osteoarthritis (OA, n = 5). The numerical simulations resulted in 100 excitations per segment and an optimal radiofrequency (RF) excitation angle of 15°. The phantom study demonstrated a good correlation of the technique with the reference standard (slope 0.9 ± 0.05, intercept 0.2 ± 1.7 msec, R 2 ≥ 0.99). Repeated measurements of cartilage T 2 values in healthy volunteers showed a coefficient of variation of 5.6%. Both Iso3DGRE and MSME techniques found significantly higher cartilage T 2 values (P < 0.03) in OA patients. Iso3DGRE precision was equal to that of the MSME T 2 mapping in healthy volunteers, and significantly higher in OA (P = 0.01). This study successfully demonstrated that high-resolution isotropic 3D T 2 mapping for knee cartilage characterization is feasible, accurate, repeatable, and precise. The technique allows for multiplanar reformatting and thus T 2 quantification in any plane of interest. 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:362-371. © 2017 International Society for Magnetic Resonance in Medicine.

Longitudinal evaluation of T1ρ and T2 spatial distribution in osteoarthritic and healthy medial knee cartilage.

PubMed

Schooler, J; Kumar, D; Nardo, L; McCulloch, C; Li, X; Link, T M; Majumdar, S

2014-01-01

To investigate longitudinal changes in laminar and spatial distribution of knee articular cartilage magnetic resonance imaging (MRI) T1ρ and T2 relaxation times, in individuals with and without medial compartment cartilage defects. All subjects (at baseline n = 88, >18 years old) underwent 3-Tesla knee MRI at baseline and annually thereafter for 3 years. The MR studies were evaluated for presence of cartilage defects (modified Whole-Organ Magnetic Resonance Imaging Scoring - mWORMS), and quantitative T1ρ and T2 relaxation time maps. Subjects were segregated into those with (mWORMS ≥2) and without (mWORMS ≤1) cartilage lesions at the medial tibia (MT) or medial femur (MF) at each time point. Laminar (bone and articular layer) and spatial (gray level co-occurrence matrix - GLCM) distribution of the T1ρ and T2 relaxation time maps were calculated. Linear regression models (cross-sectional) and Generalized Estimating Equations (GEEs) (longitudinal) were used. Global T1ρ, global T2 and articular layer T2 relaxation times at the MF, and global and articular layer T2 relaxation times at the MT, were higher in subjects with cartilage lesions compared to those without lesions. At the MT global T1ρ relaxation times were higher at each time point in subjects with lesions. MT T1ρ and T2 became progressively more heterogeneous than control compartments over the course of the study. Spatial distribution of T1ρ and T2 relaxation time maps in medial knee OA using GLCM technique may be a sensitive indicator of cartilage deterioration, in addition to whole-compartment relaxation time data. Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Trastuzumab Emtansine With or Without Pertuzumab Versus Trastuzumab Plus Taxane for Human Epidermal Growth Factor Receptor 2-Positive, Advanced Breast Cancer: Primary Results From the Phase III MARIANNE Study.

PubMed

Perez, Edith A; Barrios, Carlos; Eiermann, Wolfgang; Toi, Masakazu; Im, Young-Hyuck; Conte, Pierfranco; Martin, Miguel; Pienkowski, Tadeusz; Pivot, Xavier; Burris, Howard; Petersen, Jennifer A; Stanzel, Sven; Strasak, Alexander; Patre, Monika; Ellis, Paul

2017-01-10

Purpose Trastuzumab and pertuzumab are human epidermal growth factor receptor 2 (HER2) -targeted monoclonal antibodies, and trastuzumab emtansine (T-DM1) is an antibody-drug conjugate that combines the properties of trastuzumab with the cytotoxic activity of DM1. T-DM1 demonstrated encouraging efficacy and safety in a phase II study of patients with previously untreated HER2-positive metastatic breast cancer. Combination T-DM1 and pertuzumab showed synergistic activity in cell culture models and had an acceptable safety profile in a phase Ib and II study. Methods In the MARIANNE study, 1,095 patients with centrally assessed, HER2-positive, advanced breast cancer and no prior therapy for advanced disease were randomly assigned 1:1:1 to control (trastuzumab plus taxane), T-DM1 plus placebo, hereafter T-DM1, or T-DM1 plus pertuzumab at standard doses. Primary end point was progression-free survival (PFS), as assessed by independent review. Results T-DM1 and T-DM1 plus pertuzumab showed noninferior PFS compared with trastuzumab plus taxane (median PFS: 13.7 months with trastuzumab plus taxane, 14.1 months with T-DM1, and 15.2 months with T-DM1 plus pertuzumab). Neither experimental arm showed PFS superiority to trastuzumab plus taxane. Response rate was 67.9% in patients who were treated with trastuzumab plus taxane, 59.7% with T-DM1, and 64.2% with T-DM1 plus pertuzumab; median response duration was 12.5 months, 20.7 months, and 21.2 months, respectively. The incidence of grade ≥ 3 adverse events was numerically higher in the control arm (54.1%) versus the T-DM1 arm (45.4%) and T-DM1 plus pertuzumab arm (46.2%). Numerically fewer patients discontinued treatment because of adverse events in the T-DM1 arms, and health-related quality of life was maintained for longer in the T-DM1 arms. Conclusion T-DM1 showed noninferior, but not superior, efficacy and better tolerability than did taxane plus trastuzumab for first-line treatment of HER2-positive, advanced breast cancer.

Trastuzumab Emtansine With or Without Pertuzumab Versus Trastuzumab Plus Taxane for Human Epidermal Growth Factor Receptor 2–Positive, Advanced Breast Cancer: Primary Results From the Phase III MARIANNE Study

PubMed Central

Perez, Edith A.; Barrios, Carlos; Eiermann, Wolfgang; Toi, Masakazu; Im, Young-Hyuck; Conte, Pierfranco; Martin, Miguel; Pienkowski, Tadeusz; Pivot, Xavier; Burris, Howard; Petersen, Jennifer A.; Stanzel, Sven; Strasak, Alexander; Patre, Monika; Ellis, Paul

2017-01-01

Purpose Trastuzumab and pertuzumab are human epidermal growth factor receptor 2 (HER2) –targeted monoclonal antibodies, and trastuzumab emtansine (T-DM1) is an antibody–drug conjugate that combines the properties of trastuzumab with the cytotoxic activity of DM1. T-DM1 demonstrated encouraging efficacy and safety in a phase II study of patients with previously untreated HER2-positive metastatic breast cancer. Combination T-DM1 and pertuzumab showed synergistic activity in cell culture models and had an acceptable safety profile in a phase Ib and II study. Methods In the MARIANNE study, 1,095 patients with centrally assessed, HER2-positive, advanced breast cancer and no prior therapy for advanced disease were randomly assigned 1:1:1 to control (trastuzumab plus taxane), T-DM1 plus placebo, hereafter T-DM1, or T-DM1 plus pertuzumab at standard doses. Primary end point was progression-free survival (PFS), as assessed by independent review. Results T-DM1 and T-DM1 plus pertuzumab showed noninferior PFS compared with trastuzumab plus taxane (median PFS: 13.7 months with trastuzumab plus taxane, 14.1 months with T-DM1, and 15.2 months with T-DM1 plus pertuzumab). Neither experimental arm showed PFS superiority to trastuzumab plus taxane. Response rate was 67.9% in patients who were treated with trastuzumab plus taxane, 59.7% with T-DM1, and 64.2% with T-DM1 plus pertuzumab; median response duration was 12.5 months, 20.7 months, and 21.2 months, respectively. The incidence of grade ≥ 3 adverse events was numerically higher in the control arm (54.1%) versus the T-DM1 arm (45.4%) and T-DM1 plus pertuzumab arm (46.2%). Numerically fewer patients discontinued treatment because of adverse events in the T-DM1 arms, and health-related quality of life was maintained for longer in the T-DM1 arms. Conclusion T-DM1 showed noninferior, but not superior, efficacy and better tolerability than did taxane plus trastuzumab for first-line treatment of HER2-positive, advanced breast cancer. PMID:28056202

Three-dimensional T1 and T2* mapping of human lung parenchyma using interleaved saturation recovery with dual echo ultrashort echo time imaging (ITSR-DUTE).

PubMed

Gai, Neville D; Malayeri, Ashkan A; Bluemke, David A

2017-04-01

To develop and assess a new technique for three-dimensional (3D) full lung T1 and T2* mapping using a single free breathing scan during a clinically feasible time. A 3D stack of dual-echo ultrashort echo time (UTE) radial acquisition interleaved with and without a WET (water suppression enhanced through T1 effects) saturation pulse was used to map T1 and T2* simultaneously in a single scan. Correction for modulation due to multiple views per segment was derived. Bloch simulations were performed to study saturation pulse excitation profile on lung tissue. Optimization of the saturation delay time (for T1 mapping) and echo time (for T2* mapping) was performed. Monte Carlo simulation was done to predict accuracy and precision of the sequence with signal-to-noise ratio of in vivo images used in the simulation. A phantom study was carried out using the 3D interleaved saturation recovery with dual echo ultrashort echo time imaging (ITSR-DUTE) sequence and reference standard inversion recovery spin echo sequence (IR-SE) to compare accuracy of the sequence. Nine healthy volunteers were imaged and mean (SD) of T1 and T2* in lung parenchyma at 3T were estimated through manually assisted segmentation. 3D lung coverage with a resolution of 2.5 × 2.5 × 6 mm 3 was performed and nominal scan time was recorded for the scans. Repeatability was assessed in three of the volunteers. Regional differences in T1/T2* values were also assessed. The phantom study showed accuracy of T1 values to be within 2.3% of values obtained from IR-SE. Mean T1 value in lung parenchyma was 1002 ± 82 ms while T2* was 0.85 ± 0.1 ms. Scan time was ∼10 min for volunteer scans. Mean coefficient of variation (CV) across slices was 0.057 and 0.09, respectively. Regional variation along the gravitational direction and between right and left lung were not significant (P = 0.25 and P = 0.06, respectively) for T1. T2* showed significant variation (P = 0.03) along the gravitational direction. Repeatability for three volunteers was within 0.7% for T1 and 1.9% for T2*. 3D T1 and T2* maps of the entire lung can be obtained in a single scan of ∼10 min with a resolution of 2.5 × 2.5 × 6 mm 3 . 2 J. Magn. Reson. Imaging 2017;45:1097-1104. 2016 International Society for Magnetic Resonance in Medicine.

Polymorphism of the Transcription Factor 7-Like 2 Gene (TCF7L2) Interacts with Obesity on Type-2 Diabetes in the PREDIMED Study Emphasizing the Heterogeneity of Genetic Variants in Type-2 Diabetes Risk Prediction: Time for Obesity-Specific Genetic Risk Scores.

PubMed

Corella, Dolores; Coltell, Oscar; Sorlí, Jose V; Estruch, Ramón; Quiles, Laura; Martínez-González, Miguel Ángel; Salas-Salvadó, Jordi; Castañer, Olga; Arós, Fernando; Ortega-Calvo, Manuel; Serra-Majem, Lluís; Gómez-Gracia, Enrique; Portolés, Olga; Fiol, Miquel; Díez Espino, Javier; Basora, Josep; Fitó, Montserrat; Ros, Emilio; Ordovás, José M

2016-12-06

Nutrigenetic studies analyzing gene-diet interactions of the TCF7L2-rs7903146 C > T polymorphism on type-2 diabetes (T2D) have shown controversial results. A reason contributing to this may be the additional modulation by obesity. Moreover, TCF7L2-rs7903146 is one of the most influential variants in T2D-genetic risk scores (GRS). Therefore, to increase the predictive value (PV) of GRS it is necessary to first see whether the included polymorphisms have heterogeneous effects. We comprehensively investigated gene-obesity interactions between the TCF7L2-rs7903146 C > T polymorphism on T2D (prevalence and incidence) and analyzed other T2D-polymorphisms in a sub-sample. We studied 7018 PREDIMED participants at baseline and longitudinally (8.7 years maximum follow-up). Obesity significantly interacted with the TCF7L2-rs7903146 on T2D prevalence, associations being greater in non-obese subjects. Accordingly, we prospectively observed in non-T2D subjects ( n = 3607) that its association with T2D incidence was stronger in non-obese (HR: 1.81; 95% CI: 1.13-2.92, p = 0.013 for TT versus CC) than in obese subjects (HR: 1.01; 95% CI: 0.61-1.66; p = 0.979; p -interaction = 0.048). Accordingly, TCF7L2-PV was higher in non-obese subjects. Additionally, we created obesity-specific GRS with ten T2D-polymorphisms and demonstrated for the first time their higher strata-specific PV. In conclusion, we provide strong evidence supporting the need for considering obesity when analyzing the TCF7L2 effects and propose the use of obesity-specific GRS for T2D.

Serum cystatin C in youth with diabetes: The SEARCH for diabetes in youth study.

PubMed

Kanakatti Shankar, Roopa; Dolan, Lawrence M; Isom, Scott; Saydah, Sharon; Maahs, David M; Dabelea, Dana; Reynolds, Kristi; Hirsch, Irl B; Rodriguez, Beatriz L; Mayer-Davis, Elizabeth J; Marcovina, Santica; D'Agostino, Ralph; Mauer, Michael; Mottl, Amy K

2017-08-01

We compared cystatin C in youth with versus without diabetes and determined factors associated with cystatin C in youth with type 1 diabetes (T1D) and type 2 diabetes (T2D). Youth (ages 12-19years) without diabetes (N=544) were ascertained from the NHANES Study 2000-2002 and those with T1D (N=977) and T2D (N=168) from the SEARCH for Diabetes in Youth Study. Adjusted means of cystatin C concentrations were compared amongst the 3 groups. Next, we performed multivariable analyses within the T1D and T2D SEARCH samples to determine the association between cystatin C and race, sex, age, diabetes duration, HbA1c, fasting glucose, and BMI. Adjusted cystatin C concentrations were statistically higher in NHANES (0.85mg/L) than in either the T1D (0.75mg/L) or T2D (0.70mg/L) SEARCH groups (P<0.0001). Fasting glucose was inversely related to cystatin C only in T1D (P<0.001) and BMI positively associated only in T2D (P<0.01) while HbA1c was inversely associated in both groups. Cystatin C concentrations are statistically higher in youth without diabetes compared to T1D or T2D, however the clinical relevance of this difference is quite small, especially in T1D. In youth with diabetes, cystatin C varies with BMI and acute and chronic glycemic control, however their effects may be different according to diabetes type. Copyright © 2017 Elsevier B.V. All rights reserved.

Educational level and family structure influence the dietary changes after the diagnosis of type 2 diabetes: evidence from the E3N study.

PubMed

Mancini, Francesca Romana; Affret, Aurelie; Dow, Courtney; Balkau, Beverley; Bihan, Hélène; Clavel-Chapelon, Françoise; Boutron-Ruault, Marie-Christine; Bonnet, Fabrice; Fagherazzi, Guy

2017-08-01

Type 2 diabetes (T2D) has no cure but can be controlled by medication, diet, and lifestyle changes. It has been suggested that diabetes dietary self-management is more difficult for people with socioeconomic difficulties. The objective of our study was to test the hypothesis that socioeconomic factors impact the change of diet after T2D diagnosis. The 57 304 French women included in the present study answered food frequency questionnaires in 1993 and 2005 and questionnaires on socioeconomic factors, and were free from T2D in 1993. Between 1993 and 2005, 1249 women developed T2D. Linear regression models evaluated whether having T2D diagnosed had an impact on energy and nutrient intakes and whether socioeconomic factors were implicated. T2D was associated with a reduction of energy (β=-312.54 kJ/d, P<.001), carbohydrate (β=-9.29 g/d, P<.001), lipid (β=-2.01g/d, P<.001), and alcohol (β=-2.74g/d, P=.002) intakes, whereas there was no association with changes in protein or fiber intakes. The main socioeconomic factors that had an impact on dietary change were the level of education of T2D patients and whether or not they had a family (having a partner and/or children). The present study provides evidence that socioeconomic factors impact the way people with T2D change their dietary habits after diagnosis. Furthermore, the family plays a crucial role in dietary self-management, probably encouraging T2D patients to follow dietary recommendations. Copyright © 2017 Elsevier Inc. All rights reserved.

Role of T1 mapping as a complementary tool to T2* for non-invasive cardiac iron overload assessment.

PubMed

Torlasco, Camilla; Cassinerio, Elena; Roghi, Alberto; Faini, Andrea; Capecchi, Marco; Abdel-Gadir, Amna; Giannattasio, Cristina; Parati, Gianfranco; Moon, James C; Cappellini, Maria D; Pedrotti, Patrizia

2018-01-01

Iron overload-related heart failure is the principal cause of death in transfusion dependent patients, including those with Thalassemia Major. Linking cardiac siderosis measured by T2* to therapy improves outcomes. T1 mapping can also measure iron; preliminary data suggests it may have higher sensitivity for iron, particularly for early overload (the conventional cut-point for no iron by T2* is 20ms, but this is believed insensitive). We compared T1 mapping to T2* in cardiac iron overload. In a prospectively large single centre study of 138 Thalassemia Major patients and 32 healthy controls, we compared T1 mapping to dark blood and bright blood T2* acquired at 1.5T. Linear regression analysis was used to assess the association of T2* and T1. A "moving window" approach was taken to understand the strength of the association at different levels of iron overload. The relationship between T2* (here dark blood) and T1 is described by a log-log linear regression, which can be split in three different slopes: 1) T2* low, <20ms, r2 = 0.92; 2) T2* = 20-30ms, r2 = 0.48; 3) T2*>30ms, weak relationship. All subjects with T2*<20ms had low T1; among those with T2*>20ms, 38% had low T1 with most of the subjects in the T2* range 20-30ms having a low T1. In established cardiac iron overload, T1 and T2* are concordant. However, in the 20-30ms T2* range, T1 mapping appears to detect iron. These data support previous suggestions that T1 detects missed iron in 1 out of 3 subjects with normal T2*, and that T1 mapping is complementary to T2*. The clinical significance of a low T1 with normal T2* should be further investigated.

Association between alcohol consumption and the risk of incident type 2 diabetes: a systematic review and dose-response meta-analysis.

PubMed

Li, Xiao-Hua; Yu, Fei-Fei; Zhou, Yu-Hao; He, Jia

2016-03-01

Previous cohort studies have shown that moderate alcohol consumption was associated with a lower risk of type 2 diabetes (T2D). However, whether these associations differ according to the characteristics of patients with T2D remains controversial. The purpose of this study was to explore and summarize the evidence on the strength of the association between alcohol consumption and the subsequent risk of T2D by using a dose-response meta-analytic approach. We identified potential studies by searching the PubMed, Embase, and Cochrane Library databases up to 24 March 2015. Prospective observational studies that evaluated the relation between alcohol consumption and the risk of T2D and reported its effect estimates with 95% CIs were included. Analyses were based on 706,716 individuals (275,711 men and 431,005 women) from 26 studies with 31,621 T2D cases. We detected a nonlinear relation between alcohol consumption and the risk of T2D, which was identified in all cohorts (P-trend < 0.001, P-nonlinearity < 0.001), in men (P-trend < 0.001, P-nonlinearity < 0.001), and in women (P-trend < 0.001, P-nonlinearity < 0.001). Compared with the minimal category of alcohol consumption, light (RR: 0.83; 95% CI: 0.73, 0.95; P = 0.005) and moderate (RR: 0.74; 95% CI: 0.67, 0.82; P < 0.001) alcohol consumption was associated with a lower risk of T2D. However, heavy alcohol consumption had little or no effect on subsequent T2D risk. Furthermore, the summary RR ratio (RRR; male to female) of the comparison between moderate alcohol consumption and the minimal alcohol categories for T2D was significantly higher, and the pooled RRR (current smoker to never smoker) of light alcohol consumption was significantly reduced. Light and moderate alcohol consumption was associated with a lower risk of T2D, whereas heavy alcohol consumption was not related to the risk of T2D. © 2016 American Society for Nutrition.

NMR signal analysis to characterize solid, aqueous, and lipid phases in baked cakes.

PubMed

Le Grand, F; Cambert, M; Mariette, F

2007-12-26

Proton mobility was studied in molecular fractions of some model systems and of cake using a 1H nuclear magnetic resonance (NMR) relaxation technique. For cake, five spin-spin relaxation times (T2) were obtained from transverse relaxation curves: T2 (1) approximately 20 micros, T2 (2) approximately 0.2 ms, T2 (3) approximately 3 ms, T2 (4) approximately 50 ms, and T2 (2) approximately 165 ms. The faster component was attributed to the solid phase, components 2 and 3 were associated with the aqueous phase, and the two slowest components were linked to the lipid phase. After cooking, the crust contained more fat but less water than the center part of the cake. The amount of gelatinized starch was lower in the crust, and water was more mobile due to less interaction with macromolecules. This preliminary study revealed different effects of storage on the center and crust.

Paradoxical Lower Serum Triglyceride Levels and Higher Type 2 Diabetes Mellitus Susceptibility in Obese Individuals with the PNPLA3 148M Variant

PubMed Central

Pirazzi, Carlo; Burza, Maria Antonella; Adiels, Martin; Burch, Lindsay; Donnelly, Louise A.; Colhoun, Helen; Doney, Alexander S.; Dillon, John F.; Pearson, Ewan R.; McCarthy, Mark; Hattersley, Andrew T.; Frayling, Tim; Morris, Andrew D.; Peltonen, Markku; Svensson, Per-Arne; Jacobson, Peter; Borén, Jan; Sjöström, Lars; Carlsson, Lena M. S.; Romeo, Stefano

2012-01-01

Background Obesity is highly associated with elevated serum triglycerides, hepatic steatosis and type 2 diabetes (T2D). The I148M (rs738409) genetic variant of patatin-like phospholipase domain-containing 3 gene (PNPLA3) is known to modulate hepatic triglyceride accumulation, leading to steatosis. No association between PNPLA3 I148M genotype and T2D in Europeans has been reported. Aim of this study is to examine the relationship between PNPLA3 I148M genotypes and serum triglycerides, insulin resistance and T2D susceptibility by testing a gene-environment interaction model with severe obesity. Methods and Findings PNPLA3 I148M was genotyped in a large obese cohort, the SOS study (n = 3,473) and in the Go-DARTS (n = 15,448), a T2D case-control study. Metabolic parameters were examined across the PNPLA3 I148M genotypes in participants of the SOS study at baseline and at 2- and 10-year follow up after bariatric surgery or conventional therapy. The associations with metabolic parameters were validated in the Go-DARTS study. Serum triglycerides were found to be lower in the PNPLA3 148M carriers from the SOS study at baseline and from the Go-DARTS T2D cohort. An increased risk for T2D conferred by the 148M allele was found in the SOS study (O.R. 1.09, 95% C.I. 1.01-1.39, P = 0.040) and in severely obese individuals in the Go-DARTS study (O.R. 1.37, 95% C.I. 1.13-1.66, P = 0.001). The 148M allele was no longer associated with insulin resistance or T2D after bariatric surgery in the SOS study and no association with the 148M allele was observed in the less obese (BMI<35) individuals in the Go-DARTS study (P for interaction  = 0.002). This provides evidence for the obesity interaction with I48M allele and T2D risk in a large-scale cross-sectional and a prospective interventional study. Conclusions Severely obese individuals carrying the PNPLA3 148M allele have lower serum triglyceride levels, are more insulin resistant and more susceptible to T2D. This study supports the hypothesis that obesity-driven hepatic lipid accumulation may contribute to T2D susceptibility. PMID:22724004

Vesicular glutamate transporters, VGluT1 and VGluT2, in the trigeminal ganglion neurons of the rat, with special reference to coexpression.

PubMed

Li, Jin-Lian; Xiong, Kang-Hui; Dong, Yu-Lin; Fujiyama, Fumino; Kaneko, Takeshi; Mizuno, Noboru

2003-08-18

Vesicular glutamate transporters are responsible for glutamate transport into synaptic vesicles. In the present study, we examined immunohistochemically the expression of vesicular glutamate transporters, VGluT1 and VGluT2, in trigeminal ganglion neurons of the rat. Immunohistochemistry for VGluT1 and VGluT2 indicated that more than 80% of trigeminal ganglion neurons express VGluT1 and/or VGluT2 in their cell bodies. It also indicated that large and small trigeminal ganglion neurons express VGluT2 more frequently than VGluT1. Dual immunofluorescence histochemistry for VGluT1 and VGluT2 indicated that trigeminal ganglion neurons express VGluT2 more frequently than VGluT1 and that more than 80% of VGluT-expressing trigeminal ganglion neurons express VGluT1 and VGluT2. Many axon terminals in the superficial layers of the medullary dorsal horn also showed VGluT1 and VGluT2 immunoreactivities. Some of these axon terminals were confirmed to form the central core of the synaptic glomerulus. These results indicated that VGluT1 and VGluT2 are coexpressed in the cell bodies and axon terminals in most trigeminal ganglion neurons. Copyright 2003 Wiley-Liss, Inc.

Tetrahedral silsesquioxane-C2H2Ti complex for hydrogen storage

NASA Astrophysics Data System (ADS)

Konda, Ravinder; Tavhare, Priyanka; Ingale, Nilesh; Chaudhari, Ajay

2018-04-01

The interaction of molecular hydrogen with tetrahedral silsesquioxane (T4)-C2H2Ti complex has been studied using Density Functional Theory with M06-2X functional and MP2 method with 6-311++G** basis set. T4-C2H2Ti complex can absorb maximum five hydrogen molecules with the gravimetric hydrogen storage capacity of 3.4 wt %. Adsorption energy calculations show that H2 adsorption on T4-C2H2Ti complex is favorable at room temperature by both the methods. We have studied the effect of temperature and pressure on Gibbs free energy corrected adsorption energies. Molecular dynamics simulations for H2 adsorbed T4-C2H2Ti complex have also been performed at 300K and show that loosely bonded H2 molecule flies away within 1fs. Various interaction energies within the complex are studied. Stability of a complex is predicted by means of a gap between Highest Occupied Molecular Orbital (HUMO) and Lowest Unoccupied Molecular Orbital (LUMO). The H2 desorption temperature for T4-C2H2Ti complex is calculated with Van't Hoff equation and it is found to be 229K.

Multiple positive solutions to nonlinear boundary value problems of a system for fractional differential equations.

PubMed

Zhai, Chengbo; Hao, Mengru

2014-01-01

By using Krasnoselskii's fixed point theorem, we study the existence of at least one or two positive solutions to a system of fractional boundary value problems given by -D(0+)(ν1)y1(t) = λ1a1(t)f(y1(t), y2(t)), - D(0+)(ν2)y2(t) = λ2a2(t)g(y1(t), y2(t)), where D(0+)(ν) is the standard Riemann-Liouville fractional derivative, ν1, ν2 ∈ (n - 1, n] for n > 3 and n ∈ N, subject to the boundary conditions y1((i))(0) = 0 = y ((i))(0), for 0 ≤ i ≤ n - 2, and [D(0+)(α)y1(t)] t=1 = 0 = [D(0+ (α)y2(t)] t=1, for 1 ≤ α ≤ n - 2, or y1((i))(0) = 0 = y ((i))(0), for 0 ≤ i ≤ n - 2, and [D(0+)(α)y1(t)] t=1 = ϕ1(y1), [D(0+)(α)y2(t)] t=1 = ϕ2(y2), for 1 ≤ α ≤ n - 2, ϕ1, ϕ2 ∈ C([0,1], R). Our results are new and complement previously known results. As an application, we also give an example to demonstrate our result.

Initial size of unilateral pleural effusion determines impact of thoracocentesis on oxygenation.

PubMed

Michaelides, Stylianos A; Bablekos, George D; Analitis, Antonis; Michailidis, Avgerinos-Romanos; Charalabopoulos, Konstantinos A; Koulouris, Nikolaos

2017-11-01

There have been contradicting reports in the literature regarding the impact of pleural fluid aspiration on patients' oxygenation. The aim of this study was to assess the role of the initial size of effusion on post-drainage oxygenation. We studied 122 patients, aged (mean±SD) 61.2±16.8 years, with unilateral pleural effusion and no remarkable parenchymal lesion, by determining PaO 2 , PaCO 2 and [A-a] PaO 2 just before thoracocentesis (T1), 30 min after its completion (T2) and 48 hours after the procedure (T3). Patients were divided into group A (75 patients) with small and moderate sized effusions and group B (47 patients) with large and massive effusions. The position of the meniscus line on the posteroanterior film, being arbitrarily set at just above the upper costal margin of the sixth anterior rib, was used to divide the two groups. Patients were studied at rest, breathing room air in the sitting position. Repeated measures ANOVA (related samples) and the Friedman test when the normality assumption was violated were used. In group A, at T3, PaO 2 (mm Hg) showed a statistically significant increase versus T1 (p<0.001) and T2 (p=0.002), while [A-a] PaO 2 displayed a statistically significant decrease compared with T1 (p<0.001) and T2 (p=0.001). In group B, at T2, PaO 2 presented significant decrease versus T1 (p<0.001) and T3 (p<0.001), while [A-a] PO 2 was found to be significantly increased compared with both T1 and T3 (p<0.001). Patients with smaller effusions showed a small improvement in their oxygenation 48 hours post-thoracocentesis (T3). Patients with larger effusions exhibited a transient reduction in their oxygenation immediately after fluid removal (T2). © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Testosterone Therapy and Glucose Homeostasis in Men with Testosterone Deficiency (Hypogonadism).

PubMed

Saad, Farid

2017-01-01

Since the early 1990s, it has been recognized that testosterone (T) levels are lower in men with type 2 diabetes mellitus (T2DM) compared with nondiabetic men (controls). Hypogonadism has been reported in approximately 50% of men with T2DM with robust correlations with measures of obesity, such as waist circumference and body mass index (BMI). In longitudinal studies, hypogonadism has been identified as a predictor of incident T2DM. Experimental withdrawal of T led to acute decreased insulin sensitivity, which can be reversed by normalization of T concentrations. Androgen deprivation therapy, commonly used in men with advanced prostate cancer, increases the risk of incident T2DM significantly.While short-term studies of T therapy in hypogonadal men with T2DM show only minor effects, long-term administration of T leads to meaningful and sustained improvements of glycemic control with parallel reductions in body weight and waist circumference. The more insulin-resistant and obese a patient is at the time of initiation of T therapy, the more improvements are noted. The observed effects are likely mediated by the increase in lean body mass invariably achieved by T therapy, as well as the improvement in energy and motivation, referred to as the psychotropic effects of T. As recommended by various guidelines, measuring T levels and, if indicated, restoring men's T levels into the normal physiological range can have a substantial impact on ameliorating T2DM in hypogonadal men.

The association of polymorphisms in the type 1 and 2 deiodinase genes with circulating thyroid hormone parameters and atrophy of the medial temporal lobe.

PubMed

de Jong, Frank Jan; Peeters, Robin P; den Heijer, Tom; van der Deure, Wendy M; Hofman, Albert; Uitterlinden, André G; Visser, Theo J; Breteler, Monique M B

2007-02-01

Thyroid function has been related to Alzheimer disease (AD) and neuroimaging markers thereof. Whether thyroid dysfunction contributes to or results from developing AD remains unclear. Variations in the deiodinase type 1 (DIO1) and type 2 (DIO2) genes that potentially alter thyroid hormone bioactivity may help in elucidating the role of thyroid function in AD. We investigated the association of recently identified polymorphisms in the DIO1 (D1a-C/T, D1b-A/G) and DIO2 (D2-ORFa-Gly3Asp, D2-Thr92Ala) genes with circulating thyroid parameters and early neuroimaging markers of AD. The Rotterdam Scan Study is a population-based cohort study among 1,077 elderly individuals aged 60-90 yr. DIO1 and DIO2 polymorphisms and serum TSH, free T4, T3, and reverse T3 (rT3) levels were determined in 995 nondemented elderly, including 473 persons with assessments of hippocampal and amygdalar volume on brain magnetic resonance imaging. Carriers of the D1a-T allele had higher serum free T4 and rT3, lower T3, and lower T3/rT3. The D1b-G allele was associated with higher serum T3 and T3/rT3. The DIO2 variants were not associated with serum thyroid parameters. No associations were found with hippocampal or amygdalar volume. This is the first study to report an association of D1a-C/T and D1b-A/G polymorphisms with iodothyronine levels in the elderly. Polymorphisms in the DIO1 and DIO2 genes are not associated with early magnetic resonance imaging markers of AD. This suggests that the previously reported association between iodothyronine levels and brain atrophy reflects comorbidity or nonthyroidal illness rather than thyroid hormones being involved in developing AD.

Type 2 diabetes mellitus and risk of colorectal adenoma: a meta-analysis of observational studies.

PubMed

Yu, Feifei; Guo, Yibin; Wang, Hao; Feng, Jian; Jin, Zhichao; Chen, Qi; Liu, Yu; He, Jia

2016-08-17

To summarize the relationship between type 2 diabetes mellitus (T2DM) and risk of colorectal adenomas (CRA), we performed a meta-analysis of observational studies. To find studies, we searched PubMed, Embase, the Cochrane Library, Web of Science and conference abstracts and related publications for American Society of Clinical Oncology and the European Society of Medical Oncology. Studies that reported relative risks (RRs) or odds ratios (ORs) with 95 % confidence intervals (CIs) for the association between T2DM and risk of CRA were included. The meta-analysis assessed the relationships between T2DM and risk of CRA. Sensitivity analyses were performed in two ways: (1) by omitting each study iteratively and (2) by keeping high-quality studies only. Publication bias was detected by Egger's and Begg's tests and corrected using the trim and fill method. This meta-analysis included 17 studies with 28,999 participants and 6798 CRA cases. We found that T2DM was a risk factor for CRA (RR: 1.52; 95 % CI: 1.29-1.80), and also for the advanced adenoma (RR: 1.41; 95 % CI: 1.06-1.87). Patients with existing T2DM (RR: 1.56; 95 % CI: 1.16-2.08) or newly diagnosed T2DM (RR: 1.51; 95 % CI: 1.16-1.97) have a risk of CRA. Similar significant results were found in retrospective studies (RR: 1.57; 95 % CI: 1.30-1.89) and population based cross-sectional studies (RR: 1.46; 95 % CI: 1.21-1.89), but not in prospective studies (RR: 1.27; 95 % CI: 0.77-2.10). Our results suggested that T2DM plays a risk role in the risk of developing CRA. Consequently, medical workers should increase the rate of CRA screening for T2DM patients so that they can benefit from behavioural interventions that can help prevent the development of colorectal cancer. Additional, large prospective cohort studies are needed to make a more convincing case for these associations.

Risk factors at medical school for later severe depression: a 15-year longitudinal, nationwide study (NORDOC).

PubMed

Støen Grotmol, Kjersti; Gude, Tore; Moum, Torbjørn; Vaglum, Per; Tyssen, Reidar

2013-03-20

Doctors have an increased risk of suicide, and depressive symptoms are prominent among young doctors. We lack prospective studies that identify risk factors to be targeted in medical schools. From 1993 to 2008, graduating medical students (n=631) from all four Norwegian universities participated in the Longitudinal Study of Norwegian Medical Students and Doctors (NORDOC). After their graduating term (T1), they were followed up 1 (T2), 4 (T3), 10 (T4), and 15 (T5) years later with postal surveys. Severe depressive symptoms were measured by the General Health Questionnaire-28 (T1, T2, T3, T4, and T5) and analyzed by generalized estimating equations. At T1 and T5, 13.7% and 7.2%, respectively, of the doctors reported severe depressive symptoms; a significant reduction over time (p=0.001) in both genders (response rates 56-83%). Independent risk factors for future depressive symptoms were: young age (odds ratio [OR] 1.1, 95% confidence interval [CI] 1.04-1.2, p=0.003); high neuroticism (OR 3.4, 95% CI 1.5-7.6, p=0.003); high reality weakness (OR 2.3, 95% CI 1.2-4.2, p=0.008); and severe depressive symptoms at T1 (OR 3.6, 95% CI 2.1-6.1, p<0.001). Selection bias and concurrent life and work stress may have influenced the results. In addition to low age, high neuroticism yielded a threefold increased risk over the 15-year follow-up, whereas high reality weakness, which is linked to personality pathology, doubled the risk. These factors are clinically relevant for identification of students at risk. Copyright © 2012 Elsevier B.V. All rights reserved.

Emotion Regulation Mediates the Association Between ADHD and Depressive Symptoms in a Community Sample of Youth

PubMed Central

Seymour, Karen E.; Chronis-Tuscano, Andrea; Iwamoto, Derek K.; Kurdziel, Gretchen; MacPherson, Laura

2014-01-01

The purpose of this study was to examine the longitudinal relationship between attention-deficit/ hyperactivity disorder (ADHD) symptoms, emotion regulation (ER) ability, and depressive symptoms within a diverse community sample of 277 youth, ages 9–12 (56 % male). Participants were drawn from a larger study examining adolescent risk behaviors, and completed annual assessments over 3 years. Youth ADHD symptoms were assessed at Time 1 (T1) using the parent-reported Disruptive Behavior Disorders Rating Scale, ER was assessed with the parent-reported Emotion Regulation Checklist at Time 2 (T2), and youth depressive symptoms were assessed using the self-reported Revised Child Anxiety and Depression Scales at Time 3 (T3). Analyses examined T2 ER as a mediator between T1 ADHD symptoms (including the unique contributions of inattentive [IA] versus hyperactive/impulsive [HI] symptoms) and T3 depressive symptoms. Structural equation modeling (SEM) indicated the path model specified provided an excellent fit to the data. Tests of indirect effects suggested that T2 ER appears to be a significant mechanism that underlies the relationship between T1 ADHD and T3 depression, even when accounting for T1 oppositional defiant and depressive symptoms. Furthermore, while both T1 IA and HI symptoms had significant indirect effects on T3 depression through the mechanism T2 ER, HI proved a more robust predictor of T2 ER than IA. Results of this prospective study support cross-sectional findings pointing to ER as a potential mechanism linking ADHD and depressive symptoms in youth. Clinical implications and future directions are discussed. PMID:24221724

T2* Mapping Provides Information That Is Statistically Comparable to an Arthroscopic Evaluation of Acetabular Cartilage.

PubMed

Morgan, Patrick; Nissi, Mikko J; Hughes, John; Mortazavi, Shabnam; Ellerman, Jutta

2017-07-01

Objectives The purpose of this study was to validate T2* mapping as an objective, noninvasive method for the prediction of acetabular cartilage damage. Methods This is the second step in the validation of T2*. In a previous study, we established a quantitative predictive model for identifying and grading acetabular cartilage damage. In this study, the model was applied to a second cohort of 27 consecutive hips to validate the model. A clinical 3.0-T imaging protocol with T2* mapping was used. Acetabular regions of interest (ROI) were identified on magnetic resonance and graded using the previously established model. Each ROI was then graded in a blinded fashion by arthroscopy. Accurate surgical location of ROIs was facilitated with a 2-dimensional map projection of the acetabulum. A total of 459 ROIs were studied. Results When T2* mapping and arthroscopic assessment were compared, 82% of ROIs were within 1 Beck group (of a total 6 possible) and 32% of ROIs were classified identically. Disease prediction based on receiver operating characteristic curve analysis demonstrated a sensitivity of 0.713 and a specificity of 0.804. Model stability evaluation required no significant changes to the predictive model produced in the initial study. Conclusions These results validate that T2* mapping provides statistically comparable information regarding acetabular cartilage when compared to arthroscopy. In contrast to arthroscopy, T2* mapping is quantitative, noninvasive, and can be used in follow-up. Unlike research quantitative magnetic resonance protocols, T2* takes little time and does not require a contrast agent. This may facilitate its use in the clinical sphere.

First-principles study on structural, thermal, mechanical and dynamic stability of T'-MoS2.

PubMed

Liu, Y C; Wang, V; Xia, M G; Zhang, S L

2017-03-08

Using first-principles density functional theory calculations, we investigate the structure, stability, optical modes and electronic band gap of a distorted tetragonal MoS 2 monolayer (T'-MoS 2 ). Our simulated scanning tunnel microscopy (STM) images of T'-MoS 2 are dramatically similar to those STM images which were identified as K x (H 2 O) y MoS 2 from a previous experimental study. This similarity suggests that T'-MoS 2 might have already been experimentally observed, but due to being unexpected was misidentified. Furthermore, we verify the stability of T'-MoS 2 from the thermal, mechanical and dynamic aspects, by ab initio molecular dynamics simulation, elastic constants evaluation and phonon band structure calculation based on density functional perturbation theory, respectively. In addition, we calculate the eigenfrequencies and eigenvectors of the optical modes of T'-MoS 2 at [Formula: see text] point and distinguish their Raman and infrared activity by pointing out their irreducible representations using group theory. At the same time, we compare the Raman modes of T'-MoS 2 with those of H-MoS 2 and T-MoS 2 . Our results provide useful guidance for further experimental identification and characterization of T'-MoS 2 .

Characteristics of Type 2 Diabetes with Ketosis in Baoshan, Yunnan of China

PubMed Central

Du, Shichun; Yang, Xia; Shi, Degang; Su, Qing

2016-01-01

Objectives. The study provided data to demonstrate the characteristics of type 2 diabetes (T2D) with ketosis in rural parts of south-west border of China in order to help health professionals with optimizing diabetic care. Methods. All hospitalized adult diabetic patients consecutively between January 2011 and July 2015 in Baoshan People's Hospital, Yunnan province of China, were evaluated. T2D with ketosis, ordinary T2D (without ketosis), and type 1 diabetes (T1D) patients were analyzed according to the clinical and biochemical parameters and chronic complications in these subjects. Results. The prevalence of T2D with ketosis was 12% in the whole study subjects. Overweight and obese patients were predominant (49.1%) in T2D patients with ketosis. The mean HbA1c (13.3 ± 3.1%, P = 0.01), fasting plasma glucose (16.9 ± 6 mmol/L, P < 0.0001), and plasma triglyceride (4.0 ± 4.0 mmol/L, P < 0.0001) in T2D patients with ketosis were significantly higher than ordinary T2D patients without ketosis. Infections were the most common inducements in T2D patients with ketosis. Chronic complications including peripheral neuropathy (34.9%), retinopathy (12.7%), diabetic foot (18.1%), and persistent microalbuminuria (11.7%) were common in T2D patients with ketosis. Conclusions. This study indicated the poor glycemic control in diabetic patients in rural areas of south-west part of China. More efforts were urgently required to popularize public health education and improve medical quality in diabetic treatment in these regions. PMID:26881259

Characteristics of Type 2 Diabetes with Ketosis in Baoshan, Yunnan of China.

PubMed

Du, Shichun; Yang, Xia; Shi, Degang; Su, Qing

2016-01-01

The study provided data to demonstrate the characteristics of type 2 diabetes (T2D) with ketosis in rural parts of south-west border of China in order to help health professionals with optimizing diabetic care. All hospitalized adult diabetic patients consecutively between January 2011 and July 2015 in Baoshan People's Hospital, Yunnan province of China, were evaluated. T2D with ketosis, ordinary T2D (without ketosis), and type 1 diabetes (T1D) patients were analyzed according to the clinical and biochemical parameters and chronic complications in these subjects. The prevalence of T2D with ketosis was 12% in the whole study subjects. Overweight and obese patients were predominant (49.1%) in T2D patients with ketosis. The mean HbA1c (13.3 ± 3.1%, P = 0.01), fasting plasma glucose (16.9 ± 6 mmol/L, P < 0.0001), and plasma triglyceride (4.0 ± 4.0 mmol/L, P < 0.0001) in T2D patients with ketosis were significantly higher than ordinary T2D patients without ketosis. Infections were the most common inducements in T2D patients with ketosis. Chronic complications including peripheral neuropathy (34.9%), retinopathy (12.7%), diabetic foot (18.1%), and persistent microalbuminuria (11.7%) were common in T2D patients with ketosis. . This study indicated the poor glycemic control in diabetic patients in rural areas of south-west part of China. More efforts were urgently required to popularize public health education and improve medical quality in diabetic treatment in these regions.

Testing covariates of Type 2 diabetes-cognition associations in older adults: moderating or mediating effects?

PubMed

McFall, G Peggy; Geall, Bonnie P; Fischer, Ashley L; Dolcos, Sanda; Dixon, Roger A

2010-09-01

The general goal of this study was to advance our understanding of Type 2 diabetes (T2D)-cognition relationships in older adults by linking and testing comprehensive sets of potential moderators, potential mediators, and multiple cognitive outcomes. We identified in the literature 13 health-related (but T2D-distal) potential covariates, representing four informal domains (i.e., biological vitality, personal affect, subjective health, lifestyle activities). Cross-sectional data from the Victoria Longitudinal Study (age range = 53-90 years; n = 41 T2D and n = 458 control participants) were used. We first examined whether any of the 13 potential covariates influenced T2D-cognition associations, as measured by a comprehensive neuropsychological battery (15 measures). Next, using standard regression-based moderator and mediator analyses, we systematically tested whether the identified covariates would significantly alter observed T2D-cognition relationships. Six potential covariates were found to be sensitive to T2D associations with performance on seven cognitive measures. Three factors (systolic blood pressure, gait-balance composite, subjective health) were significant mediators. Each mediated multiple cognitive outcomes, especially measures of neurocognitive speed, executive functioning, and episodic memory. Our findings offer a relatively comprehensive perspective of T2D-related cognitive deficits, comorbidities, and modulating influences. The implications for future research reach across several fields of study and application. These include (1) neuropsychological research on neural and biological bases of T2D-related cognitive decline, (2) clinical research on intervention and treatment strategies, and (3) larger-scale longitudinal studies examining the potential multilateral and dynamic relationships among T2D status, related comorbidities, and cognitive outcomes. Copyright 2010 APA, all rights reserved.

A computerized photographic method to evaluate changes in head posture and scapular position following rapid palatal expansion: a pilot study.

PubMed

Cerruto, Carmen; Di Vece, Luca; Doldo, Tiziana; Giovannetti, Agostino; Polimeni, Antonella; Goracci, Cecilia

2012-01-01

To assess the applicability of a computerized method to measure on digital photographs the changes in head and scapular posture following rapid palatal expansion (RPE) treatment. Randomized controlled trial. Twenty-three children (age 9.2 +/- 70.88 years) diagnosed with maxillary constriction were randomly divided into two groups: 1. Study group (n = 12): patients receiving RPE treatment; 2. Untreated controls (n = 11). Postural measurements were taken on frontal, lateral, and dorsal views of each subject. In the study group measurements were taken at T0 (the day orthodontic records were taken), T1 (end of RPE active phase), and T2 (RPE removal). In controls the same observations were conducted at T0 and T1(98.18 +/- 36.01 days after T0). Measurements were statistically analyzed (Intraclass Correlation Coefficient, t-tests, Signed Rank test, One-Way Repeated Measures Analysis of Variance, Tukey test; p < 0.05). In the study group a significant reduction in forward head posture (FHP) occurred between T0 and T1. Forward shoulder posture (FSP) decreased significantly between T1 and T2. At T1 treated patients exhibited significantly lower values of the measurements indicating FHP and FSP than controls. Changes in head and scapular posture following RPE treatment can be documented with computerized measurements on digital photographs.

Silica-Immobilized Enzyme Reactors; Application to Cholinesterase-Inhibition Studies

DTIC Science & Technology

2006-03-01

a i a i e v b c a m p l 1 d Journal of Chromatography B, 843 (2006) 310–316 Silica-immobilized enzyme reactors; application to...however, have specific omat d t t i w i h c u C p R n t o t fl p f o l p d v t o s fl t t c t a b f c i h a t s m i b 2 2 ≈ c s 0 c A R I H l 2 b p a y ε c...b r T p d ( m 2 w

Vitamin D receptor gene polymorphisms among Emirati patients with type 2 diabetes mellitus.

PubMed

Safar, Habiba Al; Chehadeh, Sarah El Hajj; Abdel-Wareth, Laila; Haq, Afrozul; Jelinek, Herbert F; ElGhazali, Gehad; Anouti, Fatme Al

2018-01-01

At a prevalence rate close to 19.5%, the UAE has one of the highest rates of Type 2 Diabetes Mellitus (T2DM) in the world. Genome wide association studies (GWAS) have led to the identification of several genetic variants that are associated with T2DM. Recently, genes involved in vitamin D metabolism have gained interest because of the association between vitamin D deficiency (VDD) and increased risk for T2DM. Among these, the Vitamin D receptor (VDR) gene is a good candidate for T2DM susceptibility. The aim of this study was to investigate the association between VDR polymorphisms and T2DM among a representative sample of the Emirati population. In this cross sectional study, two hundred and sixty four patients with T2DM and ninety-one healthy controls were enrolled. The study population was genotyped for the three VDR gene mutations, TaqI (rs731236), FokI (rs2228570) and BsmI (rs1544410). VDR alleles and haplotypes were compared between patients and their healthy controls. The mean age of the T2DM cohort was 60±11.59years and 48.21±12.17years for the healthy controls. The G-allele and GG genotype of rs2228570 and T-allele and TT genotype of rs1544410 SNPs were associated with T2DM. In regards to T2DM-related metabolic complications, the AG and GG genotypes of rs731236 were significantly associated with higher total cholesterol (p=0.011) and LDL-cholesterol (p=0.009) levels in the patients with T2DM. In contrast, the CT genotype of rs1544410 was significantly associated with lower BMI (p=0.031) and the TT genotype was associated with lower LDL-cholesterol level (p=0.007). The frequency of AAT and GGC haplotypes was also different between groups (p=0.014; p=0.032, respectively), implying that these haplotypes of the VDR gene are associated with the susceptibility to T2DM in the Emirati population. To conclude, an association between SNPs in the VDR gene (except for rs731236) and T2DM per se was demonstrated. The rs731236 variant was shown to be associated with high cholesterol and LDL-cholesterol levels in T2DM patients, while rs1544410 was associated with lower BMI and lower LDL cholesterol levels. Our results imply that alleles and haploypes of the VDR gene are associated with the susceptibility to T2DM in the Emirati population. Copyright © 2017 Elsevier Ltd. All rights reserved.

Diagnosis of rotator cuff tears using 3-Tesla MRI versus 3-Tesla MRA: a systematic review and meta-analysis.

PubMed

McGarvey, Ciaran; Harb, Ziad; Smith, Christian; Houghton, Russell; Corbett, Steven; Ajuied, Adil

2016-02-01

To compare the diagnostic accuracy of magnetic resonance imaging (MRI), 2-dimensional magnetic resonance arthrogram (MRA) and 3-dimensional isotropic MRA in the diagnosis of rotator cuff tears when performed exclusively at 3-T. A systematic review was undertaken of the Cochrane, MEDLINE and PubMed databases in accordance with the PRISMA guidelines. Studies comparing 3-T MRI or 3-T MRA (index tests) to arthroscopic surgical findings (reference test) were included. Methodological appraisal was performed using QUADAS 2. Pooled sensitivity and specificity were calculated and summary receiver-operating curves generated. Kappa coefficients quantified inter-observer reliability. Fourteen studies comprising 1332 patients were identified for inclusion. Twelve studies were retrospective and there were concerns regarding index test bias and applicability in nine and six studies respectively. Reference test bias was a concern in all studies. Both 3-T MRI and 3-T MRA showed similar excellent diagnostic accuracy for full-thickness supraspinatus tears. Concerning partial-thickness supraspinatus tears, 3-T 2D MRA was significantly more sensitive (86.6 vs. 80.5 %, p = 0.014) but significantly less specific (95.2 vs. 100 %, p < 0.001). There was a trend towards greater accuracy in the diagnosis of subscapularis tears with 3-T MRA. Three-Tesla 3D isotropic MRA showed similar accuracy to 3-T conventional 2D MRA. Three-Tesla MRI appeared equivalent to 3-T MRA in the diagnosis of full- and partial-thickness tears, although there was a trend towards greater accuracy in the diagnosis of subscapularis tears with 3-T MRA. Three-Tesla 3D isotropic MRA appears equivalent to 3-T 2D MRA for all types of tears.

Trait Anger But Not Anxiety Predicts Incident Type 2 Diabetes: The Multi-Ethnic Study of Atherosclerosis (MESA)

PubMed Central

Abraham, Sherley; Shah, Nina G.; Roux, Ana Diez; Hill-Briggs, Felicia; Seeman, Teresa; Szklo, Moyses; Schreiner, Pamela J.; Golden, Sherita Hill

2015-01-01

Objective Prior studies have shown a bidirectional association between depression and type 2 diabetes mellitus (T2DM); however, the prospective associations of anger and anxiety with T2DM have not been established. We hypothesized that trait anger and anxiety would predict incident T2DM, independently of depressive symptoms. Research Design and Methods In the Multi-ethnic Study of Atherosclerosis (MESA), we prospectively examined the association of trait anger and trait anxiety (assessed via the Spielberger Trait Anger and Anxiety Scales, respectively) with incident T2DM over 11.4 years in 5,598 White, Black, Hispanic, and Chinese participants (53.2% women, mean age 61.6 years) at baseline without prevalent T2DM or cardiovascular disease. We used Cox proportional hazards models to calculate the hazard ratios (HR) of incident T2DM by previously defined anger category (low, moderate, high), and anxiety quartile, as there were no previously defined categories. Results High total trait anger was associated with incident T2DM (HR 1.50; 95% CI 1.08–2.07) relative to low total trait anger. The association was attenuated following adjustment for waist circumference (HR 1.32; 95% CI 0.94–1.86). Higher anger reaction was also associated with incident T2DM (HR=1.07; 95% CI 1.03–1.11) that remained significant after adjusting for potential confounders/explanatory factors. In contrast, trait anxiety did not predict incident T2DM. Conclusions High total trait anger and anger reaction are potential modifiable risk factors for T2DM. Further research is needed to explore the mechanisms of the anger-diabetes relationship and to develop preventive interventions. PMID:26142567

Trait anger but not anxiety predicts incident type 2 diabetes: The Multi-Ethnic Study of Atherosclerosis (MESA).

PubMed

Abraham, Sherley; Shah, Nina G; Diez Roux, Ana; Hill-Briggs, Felicia; Seeman, Teresa; Szklo, Moyses; Schreiner, Pamela J; Golden, Sherita Hill

2015-10-01

Prior studies have shown a bidirectional association between depression and type 2 diabetes mellitus (T2DM); however, the prospective associations of anger and anxiety with T2DM have not been established. We hypothesized that trait anger and anxiety would predict incident T2DM, independently of depressive symptoms. In the Multi-ethnic Study of Atherosclerosis (MESA), we prospectively examined the association of trait anger and trait anxiety (assessed via the Spielberger Trait Anger and Anxiety Scales, respectively) with incident T2DM over 11.4 years in 5598 White, Black, Hispanic, and Chinese participants (53.2% women, mean age 61.6 years) at baseline without prevalent T2DM or cardiovascular disease. We used Cox proportional hazards models to calculate the hazard ratios (HR) of incident T2DM by previously defined anger category (low, moderate, high), and anxiety quartile, as there were no previously defined categories. High total trait anger was associated with incident T2DM (HR 1.50; 95% CI 1.08-2.07) relative to low total trait anger. The association was attenuated following adjustment for waist circumference (HR 1.32; 95% CI 0.94-1.86). Higher anger reaction was also associated with incident T2DM (HR=1.07; 95% CI 1.03-1.11) that remained significant after adjusting for potential confounders/explanatory factors. In contrast, trait anxiety did not predict incident T2DM. High total trait anger and anger reaction are potential modifiable risk factors for T2DM. Further research is needed to explore the mechanisms of the anger-diabetes relationship and to develop preventive interventions. Copyright © 2015 Elsevier Ltd. All rights reserved.

Distractor Devaluation Effect in the Attentional Blink: Direct Evidence for Distractor Inhibition

ERIC Educational Resources Information Center

Kihara, Ken; Yagi, Yoshihiko; Takeda, Yuji; Kawahara, Jun I.

2011-01-01

When two targets (T1 and T2) are embedded in rapid serial visual presentation (RSVP), T2 is often missed (attentional blink, AB) if T2 follows T1 by less than 500 ms. Some have proposed that inhibition of a distractor following T1 contributes to the AB, but no direct evidence supports this proposal. This study examined distractor inhibition by…

Analysis of White Matter Damage in Patients with Multiple Sclerosis via a Novel In Vivo MR Method for Measuring Myelin, Axons, and G-Ratio.

PubMed

Hagiwara, A; Hori, M; Yokoyama, K; Nakazawa, M; Ueda, R; Horita, M; Andica, C; Abe, O; Aoki, S

2017-10-01

Myelin and axon volume fractions can now be estimated via MR imaging in vivo, as can the g-ratio, which equals the ratio of the inner to the outer diameter of a nerve fiber. The purpose of this study was to evaluate WM damage in patients with MS via this novel MR imaging technique. Twenty patients with relapsing-remitting MS with a combined total of 149 chronic plaques were analyzed. Myelin volume fraction was calculated based on simultaneous tissue relaxometry. Intracellular and CSF compartment volume fractions were quantified via neurite orientation dispersion and density imaging. Axon volume fraction and g-ratio were calculated by combining these measurements. Myelin and axon volume fractions and g-ratio were measured in plaques, periplaque WM, and normal-appearing WM. All metrics differed significantly across the 3 groups ( P < .001, except P = .027 for g-ratio between periplaque WM and normal-appearing WM). Those in plaques differed most from those in normal-appearing WM. The percentage changes in plaque and periplaque WM metrics relative to normal-appearing WM were significantly larger in absolute value for myelin volume fraction than for axon volume fraction and g-ratio ( P < .001, except P = .033 in periplaque WM relative to normal-appearing WM for comparison between myelin and axon volume fraction). In this in vivo MR imaging study, the myelin of WM was more damaged than axons in plaques and periplaque WM of patients with MS. Myelin and axon volume fractions and g-ratio may potentially be useful for evaluating WM damage in patients with MS. © 2017 by American Journal of Neuroradiology.

Dissolution mechanism of crystalline cellulose in H3PO4 as assessed by high-field NMR spectroscopy and fast field cycling NMR relaxometry.

PubMed

Conte, Pellegrino; Maccotta, Antonella; De Pasquale, Claudio; Bubici, Salvatore; Alonzo, Giuseppe

2009-10-14

Many processes have been proposed to produce glucose as a substrate for bacterial fermentation to obtain bioethanol. Among others, cellulose degradation appears as the most convenient way to achieve reliable amounts of glucose units. In fact, cellulose is the most widespread biopolymer, and it is considered also as a renewable resource. Due to extended intra- and interchain hydrogen bonds that provide a very efficient packing structure, however, cellulose is also a very stable polymer, the degradation of which is not easily achievable. In the past decade, researchers enhanced cellulose reactivity by increasing its solubility in many solvents, among which concentrated phosphoric acid (H(3)PO(4)) played the major role because of its low volatility and nontoxicity. In the present study, the solubilization mechanism of crystalline cellulose in H(3)PO(4) has been elucidated by using high- and low-field NMR spectroscopy. In particular, high-field NMR spectra showed formation of direct bonding between phosphoric acid and dissolved cellulose. On the other hand, molecular dynamics studies by low-field NMR with a fast field cycling (FFC) setup revealed two different H(3)PO(4) relaxing components. The first component, described by the fastest longitudinal relaxation rate (R(1)), was assigned to the H(3)PO(4) molecules bound to the biopolymer. Conversely, the second component, characterized by the slowest R(1), was attributed to the bulk solvent. The understanding of cellulose dissolution in H(3)PO(4) represents a very important issue because comprehension of chemical mechanisms is fundamental for process ameliorations to produce bioenergy from biomasses.

MR fingerprinting for rapid quantification of myocardial T1 , T2 , and proton spin density.

PubMed

Hamilton, Jesse I; Jiang, Yun; Chen, Yong; Ma, Dan; Lo, Wei-Ching; Griswold, Mark; Seiberlich, Nicole

2017-04-01

To introduce a two-dimensional MR fingerprinting (MRF) technique for quantification of T 1 , T 2 , and M 0 in myocardium. An electrocardiograph-triggered MRF method is introduced for mapping myocardial T 1 , T 2 , and M 0 during a single breath-hold in as short as four heartbeats. The pulse sequence uses variable flip angles, repetition times, inversion recovery times, and T 2 preparation dephasing times. A dictionary of possible signal evolutions is simulated for each scan that incorporates the subject's unique variations in heart rate. Aspects of the sequence design were explored in simulations, and the accuracy and precision of cardiac MRF were assessed in a phantom study. In vivo imaging was performed at 3 Tesla in 11 volunteers to generate native parametric maps. T 1 and T 2 measurements from the proposed cardiac MRF sequence correlated well with standard spin echo measurements in the phantom study (R 2  > 0.99). A Bland-Altman analysis revealed good agreement for myocardial T 1 measurements between MRF and MOLLI (bias 1 ms, 95% limits of agreement -72 to 72 ms) and T 2 measurements between MRF and T 2 -prepared balanced steady-state free precession (bias, -2.6 ms; 95% limits of agreement, -8.5 to 3.3 ms). MRF can provide quantitative single slice T 1 , T 2 , and M 0 maps in the heart within a single breath-hold. Magn Reson Med 77:1446-1458, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Natural selection and type 2 diabetes-associated mortality in an isolated indigenous community in the valley of Oaxaca, southern Mexico.

PubMed

Little, Bertis B; Peña Reyes, Maria Eugenia; Malina, Robert M

2017-03-01

This study tests the hypothesis that natural selection is associated with type 2 diabetes (T2D)-associated mortality and fertility in a rural isolated Zapotec community in the Valley of Oaxaca, southern Mexico. Mortality data and related demographic and genealogic information were linked with data for fertility, prereproductive mortality and family history of mortality attributed to T2D. Physician verified T2D mortality (n = 27) between 1980 and 2009 and imputed T2D (n = 70) from cardiovascular mortality (68% random sample) and renal failure (44% random sample). Bootstrapping was used to obtain a robust variance estimate in survival analysis and multivariate analysis of variance. Estimated maximum natural selection by Crow's Index occurred circa 1930 and was relaxed after this time in the study population. Cox-regression survival analysis of T2D mortality with covariates (family history of T2D, cardiovascular disease, renal failure) indicated a significant hazard ratio (HR = 5.95, 95% CI: 1.38-25.67, p < .008) for the increase in T2D in 2000 to 2009. Survival analysis of imputed T2D resulted in a significant HR of 2.03 (95% CI: 1.08-3.85, p = .01) for the increase in T2D in the 2000 to 2009 cohort (reference group: 1980-1989). Mean number of live born offspring was lower among T2D (n = 27, 4.04 ± 3.85 SD) compared to non-T2D (n = 199, 5.30 ± 3.48) groups (p < .08). Mean number of live born offspring was lower (p = .003) among imputed T2D compared to non-T2D groups (4.10 ± 3.44 vs. 5.62 + 3.50). T2D-associated mortality increased in frequency as natural selection decreased, and favored offspring survival of non-T2D descedants. The results indicated statistically significant directional selection against T2D and imputed T2D to this population isolate. © 2016 Wiley Periodicals, Inc.

Probing the recognition surface of a DNA triplex: binding studies with intercalator-neomycin conjugates.

PubMed

Xue, Liang; Xi, Hongjuan; Kumar, Sunil; Gray, David; Davis, Erik; Hamilton, Paris; Skriba, Michael; Arya, Dev P

2010-07-06

Thermodynamic studies on the interactions between intercalator-neomycin conjugates and a DNA polynucleotide triplex [poly(dA).2poly(dT)] were conducted. To draw a complete picture of such interactions, naphthalene diimide-neomycin (3) and anthraquinone-neomycin (4) conjugates were synthesized and used together with two other analogues, previously synthesized pyrene-neomycin (1) and BQQ-neomycin (2) conjugates, in our investigations. A combination of experiments, including UV denaturation, circular dichroism (CD) titration, differential scanning calorimetry (DSC), and isothermal titration calorimetry (ITC), revealed that all four conjugates (1-4) stabilized poly(dA).2poly(dT) much more than its parent compound, neomycin. UV melting experiments clearly showed that the temperature (T(m3-->2)) at which poly(dA).2poly(dT) dissociated into poly(dA).poly(dT) and poly(dT) increased dramatically (>12 degrees C) in the presence of intercalator-neomycin conjugates (1-4) even at a very low concentration (2 muM). In contrast to intercalator-neomycin conjugates, the increment of T(m3-->2) of poly(dA).2poly(dT) induced by neomycin was negligible under the same conditions. The binding preference of intercalator-neomycin conjugates (1-4) to poly(dA).2poly(dT) was also confirmed by competition dialysis and a fluorescent intercalator displacement assay. Circular dichroism titration studies revealed that compounds 1-4 had slightly larger binding site size ( approximately 7-7.5) with poly(dA).2poly(dT) as compared to neomycin ( approximately 6.5). The thermodynamic parameters of these intercalator-neomycin conjugates with poly(dA).2poly(dT) were derived from an integrated van't Hoff equation using the T(m3-->2) values, the binding site size numbers, and other parameters obtained from DSC and ITC. The binding affinity of all tested ligands with poly(dA).2poly(dT) increased in the following order: neomycin < 1 < 3 < 4 < 2. Among them, the binding constant [(2.7 +/- 0.3) x 10(8) M(-1)] of 2 with poly(dA).2poly(dT) was the highest, almost 1000-fold greater than that of neomycin. The binding of compounds 1-4 with poly(dA).2poly(dT) was mostly enthalpy-driven and gave negative DeltaC(p) values. The results described here suggest that the binding affinity of intercalator-neomycin conjugates for poly(dA).2poly(dT) increases as a function of the surface area of the intercalator moiety.

Methionine Regulates mTORC1 via the T1R1/T1R3-PLCβ-Ca2+-ERK1/2 Signal Transduction Process in C2C12 Cells.

PubMed

Zhou, Yuanfei; Ren, Jiao; Song, Tongxing; Peng, Jian; Wei, Hongkui

2016-10-11

The mammalian target of rapamycin complex 1 (mTORC1) integrates amino acid (AA) availability to support protein synthesis and cell growth. Taste receptor type 1 member (T1R) is a G protein-coupled receptor that functions as a direct sensor of extracellular AA availability to regulate mTORC1 through Ca 2+ stimulation and extracellular signal-regulated kinases 1 and 2 (ERK1/2) activation. However, the roles of specific AAs in T1R1/T1R3-regulated mTORC1 are poorly defined. In this study, T1R1 and T1R3 subunits were expressed in C2C12 myotubes, and l-AA sensing was accomplished by T1R1/T1R3 to activate mTORC1. In response to l-AAs, such as serine (Ser), arginine (Arg), threonine (Thr), alanine (Ala), methionine (Met), glutamine (Gln), and glycine (Gly), Met induced mTORC1 activation and promoted protein synthesis. Met also regulated mTORC1 via T1R1/T1R3-PLCβ-Ca 2+ -ERK1/2 signal transduction. Results revealed a new role for Met-regulated mTORC1 via an AA receptor. Further studies should be performed to determine the role of T1R1/T1R3 in mediating extracellular AA to regulate mTOR signaling and to reveal its mechanism.

Are Eating Disorders Risk Factors for Type 2 Diabetes? A Systematic Review and Meta-analysis.

PubMed

Nieto-Martínez, Ramfis; González-Rivas, Juan P; Medina-Inojosa, José R; Florez, Hermes

2017-11-22

Eating disorders (ED) affect energy intake modifying body fat depots. Prior evidence suggests that binge eating disorder (BED) and bulimia nervosa (BN) could increase the risk for type 2 diabetes (T2D), while anorexia nervosa (AN) could reduce it. A systematic review and meta-analysis were conducted to evaluate if ED are risk factors for T2D. Ten studies were selected out of 1057 screened. Meta-analysis of six studies with T2D as outcome is reported. Among cross-sectional studies, both BED (OR 3.69, 95% CI [1.12-12.12]) and BN (OR 3.45 [1.92-6.1]) increased the risk of T2D, while AN was not associated with lower risk (OR 0.87 [0.40-1.88]). Cohort studies showed increased risk of T2D with BN (RR 1.7 [1.2-2.5]), and decreased risk with AN (RR 0.71 [0.52-0.98]), but for BED the association was less clear (OR 3.34 [0.85-13.12]). Limitations of studies and recommendations for future research are presented.

The clinical characteristics of patients with mitochondrial tRNA Leu(UUR)m.3243A > G mutation: Compared with type 1 diabetes and early onset type 2 diabetes.

PubMed

Zhu, Jie; Yang, Peng; Liu, Xiang; Yan, Li; Rampersad, Sharvan; Li, Feng; Li, Hong; Sheng, Chunjun; Cheng, Xiaoyun; Zhang, Manna; Qu, Shen

2017-08-01

This study presents nine patients with mitochondrial tRNA Leu (UUR) m.3243A>G mutation and compares the clinical characteristics and diabetes complications with type 1 diabetes (T1DM) or early onset type 2 diabetes (T2DM). The study covers 9 patients with MIDD, 33 patients with T1DM and 86 patients (age of onset ≤35years) with early onset T2DM, matched for sex, age at onset of diabetes, duration of diabetes. All patients with MIDD were confirmed as carrying the m.3243A>G mitochondrial DNA mutation. Serum HbA1c, beta-cell function, retinal and renal complications of diabetes, bone metabolic markers, lumbar spine and femoral neck BMD bone mineral density were compared to characterize the clinical features of all patients. Nine patients were from five unrelated families, and the mean (SD) onset age of those patients was 31.2±7.2year. Two patients required insulin at presentation, and six patients progressed to insulin requirement after a mean of 7.2years. β-Cell function in the MIDD group was intermediate between T1DM and early-onset T2DM. In MIDD, four patients were diagnosed as diabetic retinopathy (4/9) and five patients (5/9) had macroalbuminuria. The number of patients with diabetic retinopathy and macroalbuminuria in the MIDD group was comparable to T1DM or early-onset T2DM. The rate of osteoporosis (BMD T-score<-2.5 SD) in the patient with MIDD was higher than the T1DM or early-onset T2DM group. Our study indicates that of the nine subjects with MIDD, three patients (1-II-1, 1-II-3, 1-II-4) who came from the same family had a history of acute pancreatitis. Compared with T1DM or early-onset T2DM matched for sex, age, duration of diabetes, MIDD patients had the highest rate of osteoporosis. Copyright © 2017 Elsevier Inc. All rights reserved.

The role of NOS2A -954G/C and vascular endothelial growth factor +936C/T polymorphisms in type 2 diabetes mellitus and diabetic nonproliferative retinopathy risk management.

PubMed

Porojan, Mihai Dumitru; Cătană, Andreea; Popp, Radu A; Dumitrascu, Dan L; Bala, Cornelia

2015-01-01

Type 2 diabetes mellitus (T2DM) remains one of the major health problems in Europe. Retinopathy is one of the major causes of morbidity in T2DM, strongly influencing the evolution and prognosis of these patients. In the last 2 decades, several studies have been conducted to identify the possible genetic susceptibility factors involved in the pathogenesis of the disease. However, there is little data related to the involvement of vascular endothelial growth factor (VEGF) and nitric oxide synthase (NOS) gene polymorphisms in the T2DM Caucasian population. The objective of this study was to identify a possible connection between NOS2A -954G/C (rs2297518) and VEGF +936C/T (rs3025039) polymorphisms and the risk of developing T2DM and nonproliferative diabetic retinopathy in a Caucasian population group. We investigated 200 patients diagnosed with T2DM and 208 controls. Genotypes were determined by multiplex polymerase chain reaction-restriction fragment length polymorphism. Statistical and comparative analyses (Fisher's exact test) for dominant and recessive models of NOS2A -954G/C and VEGF +936C/T polymorphisms revealed an increased risk of T2DM (χ (2)=8.14, phi =0.141, P=0.004, odds ratio [OR] =2.795, 95% confidence interval [CI] =1.347-5.801; χ (2)=18.814, phi =0.215, P<0.001, OR =2.59, 95% CI =1.675-4.006, respectively). Also, comparative analysis for the recessive model (using Pearson's chi-square test [χ (2)] and the phi coefficient [phi]) reveals that the variant CC genotype of NOS2A gene is more frequently associated with T2DM without retinopathy (χ (2)=3.835, phi =-0.138, P=0.05, OR =0.447, 95% CI =0.197-1.015). In conclusion, the results of the study place VEGF +936C/T polymorphisms among the genetic risk factor for T2DM, whereas NOS2A -954G/C polymorphisms act like a protective individual factor for nonproliferative retinopathy.

The role of NOS2A −954G/C and vascular endothelial growth factor +936C/T polymorphisms in type 2 diabetes mellitus and diabetic nonproliferative retinopathy risk management

PubMed Central

Porojan, Mihai Dumitru; Cătană, Andreea; Popp, Radu A; Dumitrascu, Dan L; Bala, Cornelia

2015-01-01

Type 2 diabetes mellitus (T2DM) remains one of the major health problems in Europe. Retinopathy is one of the major causes of morbidity in T2DM, strongly influencing the evolution and prognosis of these patients. In the last 2 decades, several studies have been conducted to identify the possible genetic susceptibility factors involved in the pathogenesis of the disease. However, there is little data related to the involvement of vascular endothelial growth factor (VEGF) and nitric oxide synthase (NOS) gene polymorphisms in the T2DM Caucasian population. The objective of this study was to identify a possible connection between NOS2A −954G/C (rs2297518) and VEGF +936C/T (rs3025039) polymorphisms and the risk of developing T2DM and nonproliferative diabetic retinopathy in a Caucasian population group. We investigated 200 patients diagnosed with T2DM and 208 controls. Genotypes were determined by multiplex polymerase chain reaction-restriction fragment length polymorphism. Statistical and comparative analyses (Fisher’s exact test) for dominant and recessive models of NOS2A −954G/C and VEGF +936C/T polymorphisms revealed an increased risk of T2DM (χ2=8.14, phi =0.141, P=0.004, odds ratio [OR] =2.795, 95% confidence interval [CI] =1.347–5.801; χ2=18.814, phi =0.215, P<0.001, OR =2.59, 95% CI =1.675–4.006, respectively). Also, comparative analysis for the recessive model (using Pearson’s chi-square test [χ2] and the phi coefficient [phi]) reveals that the variant CC genotype of NOS2A gene is more frequently associated with T2DM without retinopathy (χ2=3.835, phi =−0.138, P=0.05, OR =0.447, 95% CI =0.197–1.015). In conclusion, the results of the study place VEGF +936C/T polymorphisms among the genetic risk factor for T2DM, whereas NOS2A −954G/C polymorphisms act like a protective individual factor for nonproliferative retinopathy. PMID:26664124

Longitudinal investigation of natural killer cells and cytokines in chronic fatigue syndrome/myalgic encephalomyelitis

PubMed Central

2012-01-01

Background Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) is an etiologically unexplained disorder characterised by irregularities in various aspects of the immunological function. Presently, it is unknown whether these immunological changes remain consistent over time. This study investigates Natural Killer (NK) cell cytotoxic activity, NK cell subsets (CD56brightCD16- and CD56dimCD16+) and cytokines, over the course of a12 month period in patients with CFS/ME. Methods The participants in the study comprised 65 (47.2 ± 11.5 years) CFS/ME participants and 21 (45.2 ±9.3 years) non-fatigued controls. Flow cytometry protocols were used to assess NK subsets and NK cytotoxic activity at various time points that included baseline (T1), 6 (T2) and 12 months (T3). Cytokine secretions were measured following mitogenic stimulation of peripheral blood mononuclear cells. Results NK cytotoxic activity was significantly decreased in the CFS/ME patients at T1, T2 and T3 compared to the non-fatigued group. Additionally, in comparison to the non-fatigued controls, the CFS/ME group had significantly lower numbers of CD56brightCD16- NK cells at both T1 and T2. Interestingly, following mitogenic stimulation, cytokine secretion revealed significant increases in IL-10, IFN-γ and TNF-α at T1 in the CFS/ME group. A significant decrease was observed at T2 in the CFS/ME group for IL-10 and IL-17A while at T3, IL-2 was increased in the CFS/ME group in comparison to the non-fatigued controls. Overall cytotoxic activity was significantly decreased at T3 compared to T1 and T2. CD56brightCD16- NK cells were much lower at T2 compared to T1 and T3. IL-10 and IL-17A secretion was elevated at T2 in comparison to T1 and T3. Conclusion These results confirm decreases in immune function in CFS/ME patients, suggesting an increased susceptibility to viral and other infections. Furthermore, NK cytotoxic activity may be a suitable biomarker for diagnosing CFS/ME as it was consistently decreased during the course of the 12 months study. PMID:22571715

Spatial analysis for prevalence of type 2 diabetes mellitus - A state investigation

NASA Astrophysics Data System (ADS)

Zainal, Siti Salsabilah Nabilah; Masnan, Maz Jamilah; Amin, Nor Azrita Mohd; Mohamed, Nordin

2017-11-01

Type 2 Diabetes Mellitus (T2DM) is a chronic and non-communicable disease, which is characterized as the cause of premature deaths in the world. Unfortunately, Malaysia is one of the many countries facing this epidemic. Based on the increasing current trend of T2DM patients' cases from the National Diabetes Registry (NDR) Report from 2009 to 2012, there were approximately 2.6 million adults aged 18 years and above living with diabetes disease in Malaysia. Thus, this study aims to (i) perform preliminary spatial analysis for the prevalence of T2DM patients based on some factors, (ii) map the findings of the analyses according to some spatial properties, and (iii) analyze the pattern of diagnosed T2DM patients based on the studied factors. The studied population is one of the highest prevalence states of T2DM in Malaysia. This study is expected to reveal some demographic patterns that probably significant to this alarming epidemic.

Early risk factors for being a bully, victim, or bully/victim in late elementary and early secondary education. The longitudinal TRAILS study

PubMed Central

2011-01-01

Background Data regarding the impact of early risk factors on later involvement in bullying are scarce. We investigated the impact of preschool behaviors, family characteristics (socio-economic status, family breakup) and parental mental health on bullying and victimization at age 11 (T1) and age 13.5 (T2). Methods longitudinal data from a subsample of the TRacking Adolescents' Individual Lives Survey (TRAILS) (T1: N = 982; T2: N = 977). TRAILS is a prospective study of adolescent mental health in a mixed urban and rural region of the Netherlands. At T1 parents reported on family characteristics, parental mental health and retrospectively on children's preschool behavior at age 4-5. Schoolmates reported involvement of adolescents in bullying or victimization at T1 and T2. Results Children with preschool anxiety were less likely to be bully/victim at T1. Children with preschool aggressiveness were more likely to be bully (T1), bully/victim (T1 and T2) and victim (T2) and children with good preschool motor functioning were more likely to be bully (T1) and less likely to be victim (T1 and T2). Children from low socioeconomic status families were more likely be to be bully, victim, or bully/victim and less likely to be uninvolved both at T1 and T2. Finally, children from intact two parent families were more likely to be uninvolved at T2. Conclusion Preschool behavioral, emotional and motor problems, socioeconomic status, and family breakup are related to involvement in bullying at a later age. Prevention of bullying and its consequences can be enhanced by focusing on risk groups in early life. PMID:21645403

Six-month open-label follow-up of risperidone long-acting injection use in pediatric bipolar disorder.

PubMed

Boarati, Miguel A; Wang, Yuan-Pang; Ferreira-Maia, Ana Paula; Cavalcanti, Ana Rosa S; Fu-I, Lee

2013-01-01

Recent studies suggest that risperidone long-acting injection (RLAI) may be considered for controlling mood episodes in bipolar disorder patients who have relapsed due to medication nonadherence or failure to respond to standard therapies. Currently, no study has reported the usefulness of RLAI in youths with bipolar disorder. The aim of this study was to evaluate short-term effects of RLAI in the naturalistic treatment of early-onset bipolar disorder and its role in symptomatic remission and adherence to treatment. Nineteen early-onset bipolar disorder outpatients receiving RLAI were observed in a 6-month naturalistic study at the outpatient clinic of the Child and Adolescent Affective Disorders Program at the Institute of Psychiatry of the University of São Paulo, São Paulo, Brazil. All patients met DSM-IV criteria for bipolar disorder. Clinical response to RLAI was evaluated using the Children's Global Assessment Scale (CGAS) and Clinical Global Impressions scale (CGI) across 3 time periods: index time (T0), 8 weeks after (T1), and 24 weeks after (T2). These subjects were recruited from May 2008 to December 2009. Patients receiving RLAI presented considerable improvement in global functioning (CGAS: T0 = 20.6; T1 = 42.9; and T2 = 49.2) and clinical severity (CGI: T0 = 5.9; T1 = 3.9; and T2 = 3.4). Global CGI mean scores of clinical improvement were 2.2 at T1 and 2.4 at T2. There were no significant changes in laboratory measurements and weight throughout follow-up. RLAI was shown to be an alternative treatment for youths with bipolar disorder failing to respond to prior medication trials or with adherence problems. Further blind, randomized controlled studies are necessary to confirm these initial findings. Sistema Nacional de Informaçōes Sobre Ética em Pesquisa Envolvendo Seres Humanos-Commisão Nacional de Ética em Pesquisa identifier: CAAE 0709.0.015.000-06.

Influence of endurance training on skeletal muscle mitophagy regulatory proteins in type 2 diabetic men.

PubMed

Brinkmann, Christian; Przyklenk, Axel; Metten, Alexander; Schiffer, Thorsten; Bloch, Wilhelm; Brixius, Klara; Gehlert, Sebastian

2017-11-01

Mitophagy is a form of autophagy for the elimination of mitochondria. Mitochondrial content and function are reduced in the skeletal muscle of patients with type 2 diabetes mellitus (T2DM). Physical training has been shown to restore mitochondrial capacity in T2DM patients, but the role of mitophagy has not been examined in this context. This study analyzes the impact of a 3-month endurance training on important skeletal muscle mitophagy regulatory proteins and oxidative phosphorylation (OXPHOS) complexes in T2DM patients. Muscle biopsies were obtained from eight overweight/obese T2DM men (61±10 years) at T1 (6 weeks pre-training), T2 (1 week pre-training), and T3 (3 to 4 days post-training). Protein contents were determined by Western blotting. The training increased mitochondrial complex II significantly (T2-T3: +29%, p = 0.037). The protein contents of mitophagy regulatory proteins (phosphorylated form of forkhead box O3A (pFOXO3A), mitochondrial E3 ubiquitin protein ligase-1 (MUL1), Bcl-2/adenovirus E1B 19-kD interacting protein-3 (BNIP3), microtubule-associated protein 1 light chain-3B (the ratio LC3B-II/LC3B-I was determined)) did not differ significantly between T1, T2, and T3. The results imply that training-induced changes in OXPHOS subunits (significant increase in complex II) are not accompanied by changes in mitophagy regulatory proteins in T2DM men. Future studies should elucidate whether acute exercise might affect mitophagic processes in T2DM patients (and whether a transient regulation of mitophagy regulatory proteins is evident) to fully clarify the role of physical activity and mitophagy for mitochondrial health in this particular patient group.

Evaluation of the reliability of clinical staging of T2 N0 esophageal cancer: a review of the Society of Thoracic Surgeons database.

PubMed

Crabtree, Traves D; Kosinski, Andrzej S; Puri, Varun; Burfeind, William; Bharat, Ankit; Patterson, G Alexander; Hofstetter, Wayne; Meyers, Bryan F

2013-08-01

Clinical staging of esophageal cancer has improved with positron-emission tomography/computed tomography and endoscopic ultrasound imaging. Despite such progress, small single-center studies have questioned the reliability of clinical staging of T2 N0 esophageal cancer. This study broadly examines the adequacy of clinical staging of T2 N0 disease using The Society of Thoracic Surgeons database. We retrospectively studied 810 clinical stage T2 N0 patients from 2002 to 2011, with 58 excluded because of incomplete pathologic staging data. Clinical stage, pathologic stage, and preoperative characteristics were recorded. Logistic regression analysis was used to identify factors associated with upstaging at the time of surgical intervention. Among 752 clinical stage T2 N0 patients, 270 (35.9%) received induction therapy before the operation. Of 482 patients who went directly to surgical intervention, 132 (27.4%) were confirmed as pathologic T2 N0, 125 (25.9%) were downstaged (ie, T0-1 N0), and 225 (46.7%) were upstaged at the operation (T3-4 N0 or Tany N1-3). Exclusive tumor upstaging (ie, pathologic T3-4 N0) accounted for 41 patients (18.2%), whereas exclusive nodal upstaging (ie, pathological T1-2 N1-3) accounted for 100 (44.5%). Combined tumor and nodal upstaging (ie, pathological T3-4 N1-3) accounted for 84 patients (37.3%). Among patients who received induction therapy, 103 (38.1%) were upstaged vs 225 (46.7%) without induction therapy (p = 0.026). Comparing the induction therapy group and the primary surgical group, postoperative 30-day mortality (3.7% vs 3.7%, p > 0.99) and morbidity (46.3% vs 45%, p = 0.76) were similar. Despite advances in staging techniques, clinical staging of T2 N0 esophageal cancer remains unreliable. Recognizing T2 N0 as a threshold for induction therapy in esophageal cancer, many surgeons have opted to treat T2 N0 disease with induction therapy, even though one-quarter of these patients will be pathologic T1 N0. Although this study demonstrated similar perioperative morbidity and mortality with and without induction therapy, further study is needed to examine the effect of upstaging on long-term survival. Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Association between ferritin and hepcidin levels and inflammatory status in patients with type 2 diabetes mellitus and obesity.

PubMed

Andrews, Mónica; Soto, Néstor; Arredondo-Olguín, Miguel

2015-01-01

The aim of this study was to determine the association between iron parameters and inflammation in obese individuals with and without type 2 diabetes mellitus (T2DM). We studied 132 obese individuals (OB), 60 individuals with T2DM, 106 obese individuals with T2DM (T2DOB), and 146 controls (C). All of were men aged >30 y. Biochemical, iron nutrition, and oxidative stress parameters were determined. Peripheral mononuclear cells were isolated and total RNA was extracted to quantify tumor necrosis factor (TNF)-α, nuclear factor (NF)-κB, interleukin (IL)-6, toll-like receptor (TLR)-2/4 and hepcidin by quantitative reverse transcription polymerase chain reaction. OB, T2DM, and T2DOB individuals had higher ferritin, retinol-binding protein 4, and thiobarbituric acid reactive substance (TBAR) levels than controls. T2DOB and T2DM individuals showed high high-sensitivity C-reactive protein (hsCRP) levels and OB with and without T2DM had elevated levels of serum hepcidin. Heme oxygenase activity was high in OB and T2DM and there were no differences observed in superoxide dismutase and glutathione parameters. A correlation between TBARS and ferritin in T2DOB was observed (r = 0.31; P < 0.006). Multiple linear regression analysis showed an association between diabetes and obesity with ferritin, TBARS, and hsCRP levels. The upper quartiles of ferritin, TBARS and hepcidin showed an adjusted odd ratio for T2DM of 1.782, 2.250, and 4.370, respectively. TNF-α, IL-6, hepcidin, NF-κB, TLR-2/4 mRNA abundances were increased in T2DM and T2DOB. Elevated hsCRP and hepcidin levels, and increased gene expression of TNF-α, IL-6, NF-κB, and TLR-2/4 in patients with diabetes, obesity, or both exacerbate and perpetuate the insulin resistance and inflammatory state. Copyright © 2015 Elsevier Inc. All rights reserved.

Effect of pregnancy on insulin requirements differs between type 1 and type 2 diabetes: A cohort study of 222 pregnancies.

PubMed

Padmanabhan, Suja; Jiang, Shan; Mclean, Mark; Cheung, N Wah

2016-08-01

Knowledge about expected insulin requirements during pregnancy, in women with pre-existing diabetes may assist clinicians to effectively respond to gestation-specific changes in glycemic pattern. Few studies have examined differences between type 1 (T1DM) and type 2 diabetes (T2DM). To compare patterns of insulin requirements in pregnancy for women with pre-existing T1DM and T2DM. A retrospective cohort study of 222 pregnancies was conducted in women with pre-existing diabetes, (67 with T1DM, 155 with T2DM). Total daily insulin dose (TID) at the end of each trimester, recorded as units and units per kilogram (median, 25th-75th percentile) as well as percentage increase in insulin dose per trimester were compared. Women with T1DM had higher insulin requirements in the first two trimesters than those with T2DM (0.69 (0.58-0.85) vs 0.36 (0.0-0.7) units/kg in first trimester; 0.80 (0.62-0.95) vs 0.61 (0.27-0.95) units/kg, P < 0.005) in second trimester), but requirements in late pregnancy were similar (0.97 (0.69-1.29) vs 0.95 (0.53-1.32) units/kg, P = 0.54). Women with T2DM needed much greater increases in insulin per trimester compared to T1DM (P < 0.001). Women with T1DM had a net fall in insulin requirements (3.7% in the first trimester and 4.1% in the late third trimester) while those with T2DM did not. This is the largest comparison study of insulin requirements in women with pre-existing diabetes, highlighting important trimester-specific differences between T1DM and T2DM to guide insulin titration during pregnancy. Our findings suggest a differential effect of pregnancy-mediated insulin resistance by type of diabetes. © 2016 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

Prospective study of a group of pre-university students evaluating anxiety and depression relationships with temporomandibular disorders

PubMed Central

de Lucena, Ieda M.; Rodrigues, Luciane L F R.; Teixeira, Marcelo L.; Guimaraes, Antonio S.

2012-01-01

Objectives: The aim of this prospective longitudinal study was to evaluate the relationships between anxiety, depression, and temporomandibular disorders (TMD) in a sample of pre-university students submitted to a stressful event. Study Design: 153 students from a pre-university course (82 females and 71 males between 16 and 31 years old) were given a survey about TMD symptoms and a survey about anxiety and depression scale at the beginning and the end of the preparatory course (August 2009-T1, and November 2009-T2). Results: Results were analyzed using a chi-square test and Odds Ratio (OR), significance level of α = 0.05. Statistical significance were found to depression rates in students with TMD (16% on T1 and 26% on T2, p = 0.001) as well as in general sample (12% on T1 and 22% on T2, p = 0.009), anxiety and TMD symptoms presented constant rates in both periods. Increased risk of having TMD were found in participants with anxiety (OR 2.6 in T2 and 5.6 in T1) and depression (2.0 in T2 and 3.3 in T1), but only anxiety reach statistical significance in both periods. Conclusions: TMD symptoms were a fluctuating variable that exchange between some individuals of this study. Independently of the TMD, depression rates significant increased in the evaluated period. Finally, anxiety was the psychological symptom related to the increased risk of having TMD. Key words:Temporomandibular disorders, anxiety, depression, orofacial pain, hospital anxiety and depression scale. PMID:24558533

Spatiotemporal Divergence of the Warming Hiatus over Land Based on Different Definitions of Mean Temperature

PubMed Central

Zhou, Chunlüe; Wang, Kaicun

2016-01-01

Existing studies of the recent warming hiatus over land are primarily based on the average of daily minimum and maximum temperatures (T2). This study compared regional warming rates of mean temperature based on T2 and T24 calculated from hourly observations available from 1998 to 2013. Both T2 and T24 show that the warming hiatus over land is apparent in the mid-latitudes of North America and Eurasia, especially in cold seasons, which is closely associated with the negative North Atlantic Oscillation (NAO) and Arctic Oscillation (AO) and cold air propagation by the Arctic-original northerly wind anomaly into mid-latitudes. However, the warming rates of T2 and T24 are significantly different at regional and seasonal scales because T2 only samples air temperature twice daily and cannot accurately reflect land-atmosphere and incoming radiation variations in the temperature diurnal cycle. The trend has a standard deviation of 0.43 °C/decade for T2 and 0.41 °C/decade for T24, and 0.38 °C/decade for their trend difference in 5° × 5° grids. The use of T2 amplifies the regional contrasts of the warming rate, i.e., the trend underestimation in the US and overestimation at high latitudes by T2. PMID:27531421

Development of an LC-MS/MS Determination Method for T-2 Toxin and Its Glucoside and Acetyl Derivatives for Estimating the Contamination of Total T-2 Toxins in Staple Flours.

PubMed

Nakagawa, Hiroyuki; Matsuo, Yosuke; McCormick, Susan; Lim, Chee Wei

2018-05-01

A determination method previously validated for trichothecenes and zearalenone by means of liquid chromatography-tandem mass spectrometry (LC-MS/MS) was adapted for the quantification of T-2 toxin (T-2) as well as its glucoside and acetyl derivatives, T-2-3-glucoside (T-2-3G) and 3-acetyl-T-2 (3A-T-2). HT-2 toxin (HT-2) and its acetyl derivative 3-acetyl-HT-2 (3A-HT-2) were also included as the target chemicals. Staple flours (56 samples collected from the Singapore market) were examined for contamination from T-2 and/or HT-2 and their derivatives. Among them, 16 flours were found to be contaminated with T-2 and/or HT-2, whereas none was contaminated with T-2-3G and 3A-HT-2, except for trace 3A-T-2 detected in 2 rye samples. Rye flour samples were frequently contaminated with both T-2 and HT-2. Some of the reference materials (RMs) were further analyzed, and T-2-3G and 3A-T-2 were quantitatively detected in corn and wheat RMs. The ratio of T-2-3G to T-2 in the RMs seemed to be much lower than the ratio of deoxynivalenol-3-glucoside to deoxynivalenol usually reported in former studies. To the best of our knowledge, the natural contamination of 3A-T-2 in staple flour is reported here for the first time.

Older adults' home- and community-based care service use and residential transitions: a longitudinal study.

PubMed

Chen, Ya-Mei; Berkowitz, Bobbie

2012-08-10

As Home-and Community-Based Services (HCBS), such as skilled nursing services or personal care services, have become increasingly available, it has become clear that older adults transit through different residential statuses over time. Older adults may transit through different residential statuses as the various services meet their needs. The purpose of this exploratory study was to better understand the interplay between community-dwelling older adults' use of home- and community-based services and their residential transitions. The study compared HCBS service-use patterns and residential transitions of 3,085 older adults from the Second Longitudinal Study of Aging. Based on older adults' residential status at the three follow-up interviews, four residential transitions were tracked: (1) Community-Community-Community (CCC: Resided in community during the entire study period); (2) Community-Institution-Community (CIC: Resided in community at T1, had lived in an institution at some time between T1 and T2, then had returned to community by T3); (3) Community-Community-Institution (CCI: Resided in community between at T1, and betweenT1 and T2, including at T2, but had used institutional services between T2 and T3); (4) Community-Institution-Institution (CII: Resided in community at T1 but in an institution at some time between T1 and T2, and at some time between T2 and T3.). Older adults' use of nondiscretionary and discretionary services differed significantly among the four groups, and the patterns of HCBS use among these groups were also different. Older adults' use of nondiscretionary services, such as skilled nursing care, may help them to return to communities from institutions. Personal care services (PCS) and senior center services may be the key to either support elders to stay in communities longer or help elders to return to their communities from institutions. Different combinations of PCS with other services, such as senior center services or meal services, were associated with different directions in residential transition, such as CIC and CII respectively. Older adults' differing HCBS use patterns may be the key to explaining older adults' transitions. Attention to older adults' HCBS use patterns is recommended for future practice. However, this was an exploratory study and the analyses cannot establish causal relationships.

Older adults’ home- and community-based care service use and residential transitions: a longitudinal study

PubMed Central

2012-01-01

Background As Home-and Community-Based Services (HCBS), such as skilled nursing services or personal care services, have become increasingly available, it has become clear that older adults transit through different residential statuses over time. Older adults may transit through different residential statuses as the various services meet their needs. The purpose of this exploratory study was to better understand the interplay between community-dwelling older adults’ use of home- and community-based services and their residential transitions. Methods The study compared HCBS service-use patterns and residential transitions of 3,085 older adults from the Second Longitudinal Study of Aging. Based on older adults’ residential status at the three follow-up interviews, four residential transitions were tracked: (1) Community-Community-Community (CCC: Resided in community during the entire study period); (2) Community-Institution-Community (CIC: Resided in community at T1, had lived in an institution at some time between T1 and T2, then had returned to community by T3); (3) Community-Community-Institution (CCI: Resided in community between at T1, and betweenT1 and T2, including at T2, but had used institutional services between T2 and T3); (4) Community-Institution-Institution (CII: Resided in community at T1 but in an institution at some time between T1 and T2, and at some time between T2 and T3.). Results Older adults’ use of nondiscretionary and discretionary services differed significantly among the four groups, and the patterns of HCBS use among these groups were also different. Older adults’ use of nondiscretionary services, such as skilled nursing care, may help them to return to communities from institutions. Personal care services (PCS) and senior center services may be the key to either support elders to stay in communities longer or help elders to return to their communities from institutions. Different combinations of PCS with other services, such as senior center services or meal services, were associated with different directions in residential transition, such as CIC and CII respectively. Conclusions Older adults’ differing HCBS use patterns may be the key to explaining older adults’ transitions. Attention to older adults’ HCBS use patterns is recommended for future practice. However, this was an exploratory study and the analyses cannot establish causal relationships. PMID:22877416

Soluble Forms of Intercellular and Vascular Cell Adhesion Molecules Independently Predict Progression to Type 2 Diabetes in Mexican American Families

PubMed Central

Kulkarni, Hemant; Mamtani, Manju; Peralta, Juan; Almeida, Marcio; Dyer, Thomas D.; Goring, Harald H.; Johnson, Matthew P.; Duggirala, Ravindranath; Mahaney, Michael C.; Olvera, Rene L.; Almasy, Laura; Glahn, David C.; Williams-Blangero, Sarah; Curran, Joanne E.; Blangero, John

2016-01-01

Objective While the role of type 2 diabetes (T2D) in inducing endothelial dysfunction is fairly well-established the etiological role of endothelial dysfunction in the onset of T2D is still a matter of debate. In the light of conflicting evidence in this regard, we conducted a prospective study to determine the association of circulating levels of soluble intercellular adhesion molecule 1 (sICAM-1) and soluble vessel cell adhesion molecule 1 (sVCAM-1) with incident T2D. Methods Data from this study came from 1,269 Mexican Americans of whom 821 initially T2D-free individuals were longitudinally followed up in the San Antonio Family Heart Study. These individuals were followed for 9752.95 person-years for development of T2D. Prospective association of sICAM-1 and sVCAM-1 with incident T2D was studied using Kaplan-Meier survival plots and mixed effects Cox proportional hazards modeling to account for relatedness among study participants. Incremental value of adhesion molecule biomarkers was studied using integrated discrimination improvement (IDI) and net reclassification improvement (NRI) indexes. Results Decreasing median values for serum concentrations of sICAM-1 and sVCAM-1 were observed in the following groups in this order: individuals with T2D at baseline, individuals who developed T2D during follow-up, individuals with prediabetes at baseline and normal glucose tolerant (NGT) individuals who remained T2D-free during follow-up. Top quartiles for sICAM-1 and sVCAM-1 were strongly and significantly associated with homeostatic model of assessment—insulin resistance (HOMA-IR). Mixed effects Cox proportional hazards modeling revealed that after correcting for important clinical confounders, high sICAM-1 and sVCAM-1 concentrations were associated with 2.52 and 1.99 times faster progression to T2D as compared to low concentrations, respectively. Individuals with high concentrations for both sICAM-1 and sVCAM-1 progressed to T2D 3.42 times faster than those with low values for both sICAM-1 and sVCAM-1. The results were similar in women in reproductive age group and the remainder of the cohort. Inclusion of sICAM-1 and sVCAM-1 in predictive models significantly improved reclassification and discrimination. The majority of these results were seen even when the analyses were restricted to NGT individuals. Conclusion Serum concentrations of sICAM-1 and sVCAM-1 independently and additively predict future T2D and represent important candidate biomarkers of T2D. PMID:27007680

On the Toxicity and Metabolism of the Trichothecene Mycotoxin T-2 Toxin,

DTIC Science & Technology

1988-06-20

on r~atiado d nfto..ayl --The present study deals witL1 toxicolegical effects anid :btoi of the trichothecene mycotoxin T-2 toxi.. T-2 toxin was shoeen...AND METABOLISM OF THE TRICHOTHECENE MYCOTOXIN T-2 TOXIN SUMMARY The present study deals with toxicological effects and metabolism of the trichothecene...directly related to this effect (McLaughlin et al., 1977). 15 1.4 DNA synthesis It is well established that trichothecene mycotoxins block DNA synthesis in

Diagnosis of glenoid labral tears using 3-tesla MRI vs. 3-tesla MRA: a systematic review and meta-analysis.

PubMed

Ajuied, Adil; McGarvey, Ciaran P; Harb, Ziad; Smith, Christian C; Houghton, Russell P; Corbett, Steven A

2018-05-01

Various protocols exist for magnetic resonance arthrogram (MRA) of the shoulder, including 3D isotropic scanning and positioning in neutral (2D neutral MRA), or abduction-external-rotation (ABER). MRA does not improve diagnostic accuracy for labral tears when compared to magnetic resonance imaging (MRI) performed using 3-Tesla (3T) magnets. Systematic review of the Cochrane, MEDLINE, and PubMed databases according to PRISMA guidelines. Included studies compared 3T MRI or 3T MRA (index tests) to arthroscopic findings (reference test). Methodological appraisal performed using QUADAS-2. Pooled sensitivity and specificity were calculated. Ten studies including 929 patients were included. Index test bias and applicability were a concern in the majority of studies. The use of arthroscopy as the reference test raised concern of verification bias in all studies. For anterior labral lesions, 3T MRI was less sensitive (0.83 vs. 0.87 p = 0.083) than 3T 2D neutral MRA. Compared to 3T 2D neutral MRA, both 3T 3D Isotropic MRA and 3T ABER MRA significantly improved sensitivity (0.87 vs. 0.95 vs. 0.94). For SLAP lesions, 3T 2D neutral MRA was of similar sensitivity to 3T MRI (0.84 vs. 0.83, p = 0.575), but less specific (0.99 vs. 0.92 p < 0.0001). For posterior labral lesions, 3T 2D neutral MRA had greater sensitivity than 3T 3D Isotropic MRA and 3T MRI (0.90 vs. 0.83 vs. 0.83). At 3-T, MRA improved sensitivity for diagnosis of anterior and posterior labral lesions, but reduced specificity in diagnosis of SLAP tears. 3T MRA with ABER positioning further improved sensitivity in diagnosis of anterior labral tears. IV.

Affecting behavior change in individuals with diabetes: findings from the Study to Help Improve Early Evaluation and Management of Risk Factors Leading to Diabetes (SHIELD).

PubMed

Bazata, Debbra D; Robinson, Jennifer G; Fox, Kathleen M; Grandy, Susan

2008-01-01

This study evaluated whether health knowledge, attitudes, and behaviors of individuals with type 1 (T1DM) or type 2 (T2DM) diabetes mellitus and those at high or low risk of T2DM were reflected in healthy behaviors and whether these attributes differed for T2DM respondents who did or did not see a health educator. SHIELD, a U.S. population-based study, included respondents (> or =18 years of age) with T1DM (n = 366), T2DM (n = 3897), high risk (HR, n = 5449) defined as > or =3 of the following: abdominal obesity, high body mass index, dyslipidemia, hypertension, cardiovascular disease, and low risk (LR, n = 5725) defined as < or =2 factors. T2DM respondents were more likely to receive health care professional recommendations to change their lifestyle habits (56%-62%) during their average 11 visits annually than the other groups (P < .0001). More T2DM and HR respondents tried losing weight, but fewer exercised regularly than T1DM and LR (P < .0001). T2DM respondents who saw a dietitian or health educator reported better current health and expectations for better future health, tried to make healthy food choices, and followed a prescribed eating plan than those who did not see these providers (P < .01). However, < or =30% of these T2DM respondents exercised regularly, or maintained desired weight. SHIELD findings show that respondents know and understand that improving their diet or exercise will affect their health, but the majority of respondents have not translated it into a behavior. Interaction with health educators and patient-empowering support may improve the transition to behavior change.

[Effects of carbon dioxide insufflation on regional cerebral oxygenation during laparoscopic surgery in children: a prospective study].

PubMed

Tuna, Ayca Tas; Akkoyun, Ibrahim; Darcin, Sevtap; Palabiyik, Onur

2016-01-01

Laparoscopic surgery has become a popular surgical tool when compared to traditional open surgery. There are limited data on pediatric patients regarding whether pneumoperitoneum affects cerebral oxygenation although end-tidal CO2 concentration remains normal. Therefore, this study was designed to evaluate the changes of cerebral oxygen saturation using near-infrared spectroscope during laparoscopic surgery in children. The study comprised forty children who were scheduled for laparoscopic (Group L, n=20) or open (Group O, n=20) appendectomy. Hemodynamic variables, right and left regional cerebral oxygen saturation (RrSO2 and LrSO2), fraction of inspired oxygen, end-tidal carbon dioxide pressure (PETCO2), peak inspiratory pressure (Ppeak), respiratory minute volume, inspiratory and end-tidal concentrations of sevoflurane and body temperature were recorded. All parameters were recorded after anesthesia induction and before start of surgery (T0, baseline), 15min after start of surgery (T1), 30min after start of surgery (T2), 45min after start of surgery (T3), 60min after start of surgery (T4) and end of the surgery (T5). There were progressive decreases in both RrSO2 and LrSO2 levels in both groups, which were not statistically significant at T1, T2, T3, T4. The RrSO2 levels of Group L at T5 were significantly lower than that of Group O. One patient in Group L had an rSO2 value <80% of the baseline value. Carbon dioxide insufflation during pneumoperitoneum in pediatric patients may not affect cerebral oxygenation under laparoscopic surgery. Copyright © 2015 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

Effects of carbon dioxide insufflation on regional cerebral oxygenation during laparoscopic surgery in children: a prospective study.

PubMed

Tuna, Ayca Tas; Akkoyun, Ibrahim; Darcin, Sevtap; Palabiyik, Onur

2016-01-01

Laparoscopic surgery has become a popular surgical tool when compared to traditional open surgery. There are limited data on pediatric patients regarding whether pneumoperitoneum affects cerebral oxygenation although end-tidal CO2 concentration remains normal. Therefore, this study was designed to evaluate the changes of cerebral oxygen saturation using near-infrared spectroscope during laparoscopic surgery in children. The study comprised forty children who were scheduled for laparoscopic (Group L, n=20) or open (Group O, n=20) appendectomy. Hemodynamic variables, right and left regional cerebral oxygen saturation (RrSO2 and LrSO2), fraction of inspired oxygen, end-tidal carbon dioxide pressure (PETCO2), peak inspiratory pressure (Ppeak), respiratory minute volume, inspiratory and end-tidal concentrations of sevoflurane and body temperature were recorded. All parameters were recorded after anesthesia induction and before start of surgery (T0, baseline), 15min after start of surgery (T1), 30min after start of surgery (T2), 45min after start of surgery (T3), 60min after start of surgery (T4) and end of the surgery (T5). There were progressive decreases in both RrSO2 and LrSO2 levels in both groups, which were not statistically significant at T1, T2, T3, T4. The RrSO2 levels of Group L at T5 were significantly lower than that of Group O. One patient in Group L had an rSO2 value <80% of the baseline value. Carbon dioxide insufflation during pneumoperitoneum in pediatric patients may not affect cerebral oxygenation under laparoscopic surgery. Copyright © 2015 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

Association of Genome-Wide Variation with Highly Sensitive Cardiac Troponin-T (hs-cTnT) Levels in European- and African-Americans: A Meta-Analysis from the Atherosclerosis Risk in Communities and the Cardiovascular Health Studies

PubMed Central

Yu, Bing; Barbalic, Maja; Brautbar, Ariel; Nambi, Vijay; Hoogeveen, Ron C.; Tang, Weihong; Mosley, Thomas H.; Rotter, Jerome I.; deFilippi, Christopher R.; O’Donnell, Christopher J.; Kathiresan, Sekar; Rice, Ken; Heckbert, Susan R.; Ballantyne, Christie M.; Psaty, Bruce M.; Boerwinkle, Eric

2013-01-01

Background High levels of cardiac troponin T measured by a highly sensitive assay (hs-cTnT) are strongly associated with incident coronary heart disease (CHD) and heart failure (HF). No large-scale genome-wide association study (GWAS) of hs-cTnT has been reported to date. We sought to identify novel genetic variants that are associated with hs-cTnT levels. Methods and Results We performed a GWAS in 9,491 European-Americans and 2,053 African-Americans free of CHD and HF from 2 prospective cohorts: the Atherosclerosis Risk in Communities Study (ARIC) and the Cardiovascular Health Study (CHS). GWASs were conducted in each study and race stratum. Fixed-effect meta-analyses combined the results of linear regression from 2 cohorts within each race stratum, and then across race strata to produce overall estimates and p-values. The meta-analysis identified a significant association at chromosome 8q13 (rs10091374, p = 9.06 × 10−9) near the nuclear receptor coactivator 2 (NCOA2) gene. Over-expression of NCOA2 can be detected in myoblasts An additional analysis using logistic regression and the clinically motivated 99th percentile cut-point detected a significant association at 1q32 (rs10091374, p = 9.06 × 10−8) in the gene TNNT2, which encodes the cardiac troponin T protein itself. The hs-cTnT-associated SNPs were not associated with CHD in a large case-control study, but rs12564445 was significantly associated with incident HF in ARIC European-Americans (HR = 1.16, p-value = 0.004). Conclusions We identified 2 loci, near NCOA2 and in the TNNT2 gene, at which variation was significantly associated with hs-cTnT levels. Further use of the new assay should enable replication of these results. PMID:23247143

Studying the Genetics of Complex Disease With Ancestry‐Specific Human Phenotype Networks: The Case of Type 2 Diabetes in East Asian Populations

PubMed Central

Qiu, Jingya; Darabos, Christian

2016-01-01

ABSTRACT Genome‐wide association studies (GWAS) have led to the discovery of over 200 single nucleotide polymorphisms (SNPs) associated with type 2 diabetes mellitus (T2DM). Additionally, East Asians develop T2DM at a higher rate, younger age, and lower body mass index than their European ancestry counterparts. The reason behind this occurrence remains elusive. With comprehensive searches through the National Human Genome Research Institute (NHGRI) GWAS catalog literature, we compiled a database of 2,800 ancestry‐specific SNPs associated with T2DM and 70 other related traits. Manual data extraction was necessary because the GWAS catalog reports statistics such as odds ratio and P‐value, but does not consistently include ancestry information. Currently, many statistics are derived by combining initial and replication samples from study populations of mixed ancestry. Analysis of all‐inclusive data can be misleading, as not all SNPs are transferable across diverse populations. We used ancestry data to construct ancestry‐specific human phenotype networks (HPN) centered on T2DM. Quantitative and visual analysis of network models reveal the genetic disparities between ancestry groups. Of the 27 phenotypes in the East Asian HPN, six phenotypes were unique to the network, revealing the underlying ancestry‐specific nature of some SNPs associated with T2DM. We studied the relationship between T2DM and five phenotypes unique to the East Asian HPN to generate new interaction hypotheses in a clinical context. The genetic differences found in our ancestry‐specific HPNs suggest different pathways are involved in the pathogenesis of T2DM among different populations. Our study underlines the importance of ancestry in the development of T2DM and its implications in pharmocogenetics and personalized medicine. PMID:27061195

Association between ACE (rs4646994), FABP2 (rs1799883), MTHFR (rs1801133), FTO (rs9939609) Genes Polymorphism and Type 2 Diabetes with Dyslipidemia.

PubMed

Raza, Syed Tasleem; Abbas, Shania; Siddiqi, Zeba; Mahdi, Farzana

2017-01-01

Diabetic dyslipidemia is one of the leading causes of coronary artery disease (CAD) death. Genetic and environmental factors play an important role in the development of type 2 diabetes mellitus (T2DM) and dyslipidemia. The present study was aimed to investigate the association of ACE (rs4646994), FABP2 (rs1799883), MTHFR (rs1801133) and FTO (rs9939609) genes polymorphism in T2DM with dyslipidemia. Totally, 559 subjects including 221 T2DM cases with dyslipidemia, 158 T2DM without dyslipidemia and 180 controls were enrolled. ACE genes polymorphism was evaluated by polymerase chain reaction (PCR), while MTHFR , FABP2 , FTO genes polymorphisms were evaluated by PCR and restriction fragment length polymorphism (RFLP). Significant association of ACE and MTHFR genes polymorphisms were found in both group of cases [T2DM with dyslipidemia (P<0.001, and P=0.008, respectively) and T2DM without dyslipidemia (P=0.003, and P=0.010, respectively)] while FABP2 and FTO genes polymorphisms were significantly associated with T2DM without dyslipidemia (P=0.038, and P= 0.019, respectively). This study concludes that ACE , FABP2 , FTO and MTHFR genes are associated with T2DM. Additionally, it also seems that ACE and MTHFR genes might be further associated with the development of dyslipidemia in T2DM cases.

Determinants of quality of life in adults with type 1 and type 2 diabetes

PubMed Central

2011-01-01

Background Limited evidence exists on the determinants of quality of life (QoL) specific to adults with type 1 diabetes (T1D). Further, it appears no study has compared the determinants of QoL between T1D and type 2 diabetes (T2D) groups. The objectives of this study were to examine: (1) determinants of QoL in adults with T1D; and, (2) differences in QoL determinants between T1D and T2D groups. Methods The Alberta Longitudinal Exercise and Diabetes Research Advancement (ALEXANDRA) study, a longitudinal study of adults with diabetes in Alberta, Canada. Adults (18 years and older) with T1D (N = 490) and T2D (N = 1,147) provided information on demographics (gender, marital status, education, and annual income), personality (activity trait), medical factors (diabetes duration, insulin use, number of comorbidities, and body mass index), lifestyle behaviors (smoking habits, physical activity, and diet), health-related quality of life (HRQL) and life satisfaction. Multiple regression models identified determinants of HRQL and life satisfaction in adults with T1D. These determinants were compared with determinants for T2D adults reported in a previous study from this population data set. Factors significantly associated with HRQL and life satisfaction in either T1D or T2D groups were further tested for interaction with diabetes type. Results In adults with T1D, higher activity trait (personality) score (β = 0.28, p < 0.01), fewer comorbidities (β = -0.27, p < 0.01), lower body mass index (BMI)(β = -0.12, p < 0.01), being a non-smoker (β = -0.14, p < 0.01), and higher physical activity levels (β = 0.16, p < 0.01) were associated with higher HRQL. Having a partner (β = 0.11, p < 0.05), high annual income (β = 0.16, p < 0.01), and high activity trait (personality) score (β = 0.27, p < 0.01) were significantly associated with higher life satisfaction. There was a significant age × diabetes type interaction for HRQL. The T2D group had a stronger positive relationship between advancing age and HRQL compared to the T1D group. No interaction was significant for life satisfaction. Conclusions Health services should target medical and lifestyle factors and provide support for T1D adults to increase their QoL. Additional social support for socioeconomically disadvantaged individuals living with this disease may be warranted. Health practitioners should also be aware that age has different effects on QoL between T1D and T2D adults. PMID:22182307

Serum Testosterone (T) Level Variability in T Gel-Treated Older Hypogonadal Men: Treatment Monitoring Implications

PubMed Central

Pak, Youngju; Wang, Christina; Liu, Peter Y.; Bhasin, Shalender; Gill, Thomas M.; Matsumoto, Alvin M.; Pahor, Marco; Surampudi, Prasanth; Snyder, Peter J.

2015-01-01

Context: The optimal frequency for on-treatment serum T measurement used for dose adjustment after transdermal T gel application is unknown, especially in older men with thinner skin and slower metabolic clearance. Objectives: The objectives of the study was to determine the variability of postgel application serum T concentrations and assess whether single levels are reflective of average serum T concentrations over 24 hours (Cavg0–24). Design: This was a double-blinded, placebo-controlled randomized trial. Setting: The study was conducted at five academic centers. Participants: Forty-seven symptomatic men 65 years old or older with an average of two morning T concentration less than 275 ng/dL participated in the study. Intervention(s): Transdermal T or placebo gel was applied for 120 ± 14 days. Monthly dose adjustments were made if necessary to target serum T between 400 and 500 to 800 ng/dL. Main Outcome Measures: Variability of serum T 2 hours after the gel application on two outpatient visits and at multiple time points over 24 hours during the inpatient day was measured. Results: On-treatment T levels varied substantially on the 2 ambulatory days and over 24 hours during the inpatient day. Ambulatory 2-hour postapplication T levels did not correlate significantly with either 2-hour postapplication serum T or Cavg0–24 measured during the inpatient day. Only 22.2% of men receiving T had a Cavg0–24 within the target range of 500–800 ng/dL; 81.5% had a Cavg0–24 within the broader 300–1000 ng/dL range. Conclusion: Large within-individual variations in serum T after T gel application render ambulatory 2-hour postapplication T level a poor indicator of average serum T on another day. Our data point out the limitations of dose adjustments based on a single postapplication serum T measurement. PMID:26120790

Presence of T3SS2β genes in trh⁺ Vibrio parahaemolyticus isolated from seafood harvested along Mangalore coast, India.

PubMed

Kumar, B K; Deekshit, V K; Rai, P; Shekar, M; Karunasagar, I; Karunasagar, I

2014-05-01

Vibrio parahaemolyticus is a seafood-borne pathogen autochthonous to the marine and estuarine ecosystem, responsible for gastroenteritis when contaminated raw seafood is consumed. The pathogenicity has been associated with thermostable direct haemolysin (TDH) and TDH-related haemolysin (TRH). Of late, the presence of T3SS2α and T3SS2β gene clusters has been well documented in clinical isolates of Vibrio parahaemolyticus and known to play an essential role in pathogenesis. However, reports on the presence of T3SSβ genes in V. parahaemolyticus isolated from the seafood and/or environmental samples are scanty. In this study, we have identified and analysed the distribution of the T3SS2β genes in V. parahaemolyticus isolated from seafood harvested along southwest coast of India. Results showed that T3SS2β genes are solely associated with trh⁺ and tdh⁺ /trh⁺ strains of V. parahaemolyticus. Reverse transcriptase PCR (RT-PCR) showed that the T3SS2β genes identified in trh⁺ V. parahaemolyticus were transcriptionally active. To our knowledge, this study appears to be the first description on the presence of T3SS2β-positive V. parahaemolyticus isolated from seafood in India. The study of T3SS2 along with other virulence factors will help in better understanding of the risk of seafood-borne illness due to V. parahaemolyticus. T3SSs (α or β) are the important virulence factors of Vibrio parahaemolyticus that contribute to their pathogenicity in humans. This study demonstrated the presence of T3SS2β genes in V. parahaemolyticus isolated from the seafood harvested along Mangalore coast. RT-PCR showed that the T3SS2β genes identified in seafood isolates of V. parahaemolyticus were found to be functional. To the best of our knowledge, this is the first description of T3SS2β genes in trh⁺ V. parahaemolyticus isolated from seafood in India. The presence of T3SS2 along with other virulence factors such as TDH and/or TRH highlights a potential health risk for seafood consumers. © 2013 The Society for Applied Microbiology.

Effects of simvastatin and ezetimibe in lowering low-density lipoprotein cholesterol in subjects with type 1 and type 2 diabetes mellitus.

PubMed

Ciriacks, Kevin; Coly, Gerard; Krishnaswami, Shanthi; Patel, Shailendra B; Kidambi, Srividya

2015-03-01

Statins are used to lower total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels among patients with type 1 (T1DM) and type 2 diabetes mellitus (T2DM). However, there are no studies of statin efficacy among T1DM patients. T1DM patients have higher gut cholesterol absorption than synthesis; hence cholesterol absorption inhibitors such as ezetimibe may also be effective in T1DM. Here, we compare the effects of simvastatin and ezetimibe among subjects with T1DM and T2DM. Subjects with T1DM (n=20, 45% female) or T2DM (n=27, 56% female) were assigned to alternating therapy with simvastatin (40 mg) or ezetimibe (10 mg) for 6 weeks in a crossover design. Among T2DM subjects, simvastatin lowered TC and LDL-C from the baseline (-25±4% and -40±5%, respectively, P<0.001), whereas ezetimibe was not as effective (-2±4% and -3±5%, respectively). Among T1DM subjects, both statin and ezetimibe showed significant decreases in TC and LDL-C from baseline, although ezetimibe lowered LDL-C much more than simvastatin (-32±12 (P<0.001) and -19±5% (P<0.01), respectively). Effect of simvastatin on LDL-C was much lower among T1DM subjects compared to T2DM subjects (P=0.02). This study shows that the cholesterol synthesis inhibitor simvastatin was less effective in lowering LDL-C in T1DM than T2DM subjects, whereas the cholesterol absorption inhibitor ezetimibe was at least as effective in lowering LDL-C as simvastatin among T1DM subjects.

Incidence of burnout in Spanish nursing professionals: a longitudinal study.

PubMed

Grau-Alberola, Ester; Gil-Monte, Pedro R; García-Juesas, Juan Antonio; Figueiredo-Ferraz, Hugo

2010-08-01

Burnout is a psychological response to chronic work-related stress of an interpersonal and emotional nature that appears in professionals in service organizations who work in direct contact with the clients or end-users of the organization. The purpose of this study was to examine the incidence of burnout in a sample of staff nurses. The study was longitudinal, and not randomized. The gap between time 1 (T1) and time 2 (T2) was 1 year. The data were gathered using an anonymous and self-applied questionnaire in different units of 13 Spanish hospitals. The sample consisted of 316 staff nurses, 53 males (16.8%) and 262 females (83.2%). The percentage of the response obtained was 31.37% of all the questionnaires distributed in T1, and 83.77% of all the questionnaires handed out in T2. The characteristics of the sample were stable over time. Burnout was evaluated by the Maslach Burnout Inventory (MBI-HSS). Descriptive statistics, percentages, and t-test analyses were conducted. The prevalence of burnout was different according to the approach used: (a) following the cut-off points from the American manual, the prevalence was 2.84% in T1 and 1.89% in T2; and considering the clinically derived cut-off points obtained in Holland, the percentage was 1.26% in T1 and .94% in T2. The results only confirmed the hypothesis formulated applying the American cut-off points in T1. There was a significant increase in the levels of emotional exhaustion from T1 to T2, but there were no significant changes in the levels of personal accomplishment or depersonalization from T1 to T2. When the scores on the three dimensions of the MBI were considered together, a decrease in the incidence of burnout was obtained from T1 to T2. The prevalence of burnout in staff nurses can be modified over time, depending on the criteria used to estimate the prevalence. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Core/shell Fe3O4/Gd2O3 nanocubes as T1-T2 dual modal MRI contrast agents

NASA Astrophysics Data System (ADS)

Li, Fenfen; Zhi, Debo; Luo, Yufeng; Zhang, Jiqian; Nan, Xiang; Zhang, Yunjiao; Zhou, Wei; Qiu, Bensheng; Wen, Longping; Liang, Gaolin

2016-06-01

T1-T2 dual modal magnetic resonance imaging (MRI) has attracted considerable interest because it offers complementary diagnostic information, leading to more precise diagnosis. To date, a number of nanostructures have been reported as T1-T2 dual modal MR contrast agents (CAs). However, hybrids of nanocubes with both iron and gadolinium (Gd) elements as T1-T2 dual modal CAs have not been reported. Herein, we report the synthesis of novel core/shell Fe3O4/Gd2O3 nanocubes as T1-T2 dual-modal CAs and their application for enhanced T1-T2 MR imaging of rat livers. A relaxivity study at 1.5 T indicated that our Fe3O4/Gd2O3 nanocubes have an r1 value of 45.24 mM-1 s-1 and an r2 value of 186.51 mM-1 s-1, which were about two folds of those of Gd2O3 nanoparticles and Fe3O4 nanocubes, respectively. In vivo MR imaging of rats showed both T1-positive and T2-negative contrast enhancements in the livers. We envision that our Fe3O4/Gd2O3 nanocubes could be applied as T1-T2 dual modal MR CAs for a wide range of theranostic applications in the near future.T1-T2 dual modal magnetic resonance imaging (MRI) has attracted considerable interest because it offers complementary diagnostic information, leading to more precise diagnosis. To date, a number of nanostructures have been reported as T1-T2 dual modal MR contrast agents (CAs). However, hybrids of nanocubes with both iron and gadolinium (Gd) elements as T1-T2 dual modal CAs have not been reported. Herein, we report the synthesis of novel core/shell Fe3O4/Gd2O3 nanocubes as T1-T2 dual-modal CAs and their application for enhanced T1-T2 MR imaging of rat livers. A relaxivity study at 1.5 T indicated that our Fe3O4/Gd2O3 nanocubes have an r1 value of 45.24 mM-1 s-1 and an r2 value of 186.51 mM-1 s-1, which were about two folds of those of Gd2O3 nanoparticles and Fe3O4 nanocubes, respectively. In vivo MR imaging of rats showed both T1-positive and T2-negative contrast enhancements in the livers. We envision that our Fe3O4/Gd2O3 nanocubes could be applied as T1-T2 dual modal MR CAs for a wide range of theranostic applications in the near future. Electronic supplementary information (ESI) available: Scheme S1, Fig. S1-S8, and Tables S1, S2. See DOI: 10.1039/c6nr02620f

Type 2 Diabetes Mellitus in Youth Exposed to Antipsychotics: A Systematic Review and Meta-analysis.

PubMed

Galling, Britta; Roldán, Alexandra; Nielsen, René E; Nielsen, Jimmi; Gerhard, Tobias; Carbon, Maren; Stubbs, Brendon; Vancampfort, Davy; De Hert, Marc; Olfson, Mark; Kahl, Kai G; Martin, Andres; Guo, Jeff J; Lane, Hsien-Yuan; Sung, Fung-Chang; Liao, Chun-Hui; Arango, Celso; Correll, Christoph U

2016-03-01

Antipsychotics are used increasingly in youth for nonpsychotic and off-label indications, but cardiometabolic adverse effects and (especially) type 2 diabetes mellitus (T2DM) risk have raised additional concern. To assess T2DM risk associated with antipsychotic treatment in youth. Systematic literature search of PubMed and PsycINFO without language restrictions from database inception until May 4, 2015. Data analyses were performed in July 2015, and additional analyses were added in November 2015. Longitudinal studies reporting on T2DM incidence in youth 2 to 24 years old exposed to antipsychotics for at least 3 months. Two independent investigators extracted study-level data for a random-effects meta-analysis and meta-regression of T2DM risk. The coprimary outcomes were study-defined T2DM, expressed as cumulative T2DM risk or as T2DM incidence rate per patient-years. Secondary outcomes included the comparison of the coprimary outcomes in antipsychotic-treated youth with psychiatric controls not receiving antipsychotics or with healthy controls. Thirteen studies were included in the meta-analysis, including 185,105 youth exposed to antipsychotics and 310,438 patient-years. The mean (SD) age of patients was 14.1 (2.1) years, and 59.5% were male. The mean (SD) follow-up was 1.7 (2.3) years. Among them, 7 studies included psychiatric controls (1,342,121 patients and 2,071,135 patient-years), and 8 studies included healthy controls (298,803 patients and 463,084 patient-years). Antipsychotic-exposed youth had a cumulative T2DM risk of 5.72 (95% CI, 3.45-9.48; P < .001) per 1000 patients. The incidence rate was 3.09 (95% CI, 2.35-3.82; P < .001) cases per 1000 patient-years. Compared with healthy controls, cumulative T2DM risk (odds ratio [OR], 2.58; 95% CI, 1.56-4.24; P < .0001) and incidence rate ratio (IRR) (IRR, 3.02; 95% CI, 1.71-5.35; P < .0001) were significantly greater in antipsychotic-exposed youth. Similarly, compared with psychiatric controls, antipsychotic-exposed youth had significantly higher cumulative T2DM risk (OR, 2.09; 95% CI, 1.50-52.90; P < .0001) and IRR (IRR, 1.79; 95% CI, 1.31-2.44; P < .0001). In multivariable meta-regression analyses of 10 studies, greater cumulative T2DM risk was associated with longer follow-up (P < .001), olanzapine prescription (P < .001), and male sex (P = .002) (r(2) = 1.00, P < .001). Greater T2DM incidence was associated with second-generation antipsychotic prescription (P ≤ .050) and less autism spectrum disorder diagnosis (P = .048) (r(2) = 0.21, P = .044). Although T2DM seems rare in antipsychotic-exposed youth, cumulative risk and exposure-adjusted incidences and IRRs were significantly higher than in healthy controls and psychiatric controls. Olanzapine treatment and antipsychotic exposure time were the main modifiable risk factors for T2DM development in antipsychotic-exposed youth. Antipsychotics should be used judiciously and for the shortest necessary duration, and their efficacy and safety should be monitored proactively.

Effects of beach-chair position and induced hypotension on cerebral oxygen saturation in patients undergoing arthroscopic shoulder surgery.

PubMed

Lee, Jae Hoon; Min, Kyeong Tae; Chun, Yong-Min; Kim, Eun Jung; Choi, Seung Ho

2011-07-01

We investigated the effects of the beach-chair position and induced hypotension on regional cerebral oxygen saturation (rSO(2)) in patients undergoing arthroscopic shoulder surgery by using near-infrared spectroscopy. Twenty-eight patients scheduled for arthroscopic shoulder surgery were enrolled prospectively. After induction of anesthesia, mechanical ventilation was controlled to maintain Paco(2) at 35 to 40 mm Hg. Anesthesia was maintained with sevoflurane and remifentanil. After radial artery cannulation, mean arterial pressure (MAP) was measured at the external auditory meatus level and maintained between 60 and 65 mm Hg. The rSO(2) was measured by use of near-infrared spectroscopy. MAP and rSO(2) were recorded at the following times: before induction (T(0)), immediately after induction (T(1) [baseline]), after beach-chair position (T(2)), immediately after induced hypotension (T(3)), 1 hour after induced hypotension (T(4)), and after supine position at the end of surgery (T(5)). Cerebral desaturation was defined as a reduction in rSO(2) to less than 80% of baseline value for 15 seconds or greater. A total of 27 patients were evaluated until the end of this study. The MAP at T(2) was significantly lower than that at T(1). The MAP values at T(3) and T(4) were significantly lower than those at T(1) and T(2). The rSO(2) at T(2) was significantly lower than that at T(1). Unlike the pattern of change in the MAP, there was no additional decrease in rSO(2) at T(3) and T(4). There were 2 patients who had an episode of cerebral desaturation. The beach-chair position combined with induced hypotension significantly decreases rSO(2) in patients undergoing shoulder arthroscopic surgery under general anesthesia. Level IV, study of nonconsecutive patients without consistently applied reference gold standard. Copyright © 2011 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Electronic properties of in-plane phase engineered 1T'/2H/1T' MoS2

NASA Astrophysics Data System (ADS)

Thakur, Rajesh; Sharma, Munish; Ahluwalia, P. K.; Sharma, Raman

2018-04-01

We present the first principles studies of semi-infinite phase engineered MoS2 along zigzag direction. The semiconducting (2H) and semi-metallic (1T') phases are known to be stable in thin-film MoS2. We described the electronic and structural properties of the infinite array of 1T'/2H/1T'. It has been found that 1T'phase induced semi-metallic character in 2H phase beyond interface but, only Mo atoms in 2H phase domain contribute to the semi-metallic nature and S atoms towards semiconducting state. 1T'/2H/1T' system can act as a typical n-p-n structure. Also high holes concentration at the interface of Mo layer provides further positive potential barriers.

Latent autoimmune diabetes in adults is perched between type 1 and type 2: evidence from adults in one region of Spain.

PubMed

Mollo, Angels; Hernandez, Marta; Marsal, Josep R; Esquerda, Aureli; Rius, Ferran; Blanco-Vaca, Francisco; Verdaguer, Joan; Pozzilli, Paolo; de Leiva, Alberto; Mauricio, Didac

2013-09-01

The aim of this study was to characterize the clinical characteristics and insulin secretion in adults with latent autoimmune diabetes in adults (LADA). We also compared these characteristics in subjects with antibody-negative type 2 diabetes (T2DM) or adult-onset type 1 diabetes (T1DM) to subjects with LADA. In this cross-sectional study, 82 patients with LADA, 78 with T1DM and 485 with T2DM were studied. Clinical and metabolic data, in particular those that related to metabolic syndrome, fasting C-peptide and islet-cell autoantibodies [glutamic acid decarboxylase (GADAb) and IA2 (IA2Ab)] were measured. The frequency of metabolic syndrome in patients with LADA (37.3%) was higher than in those with T1DM (15.5%; p = 0.005) and lower than in patients with T2DM (67.2%; p < 0.001). During the first 36 months of the disease, the C-peptide concentration in LADA patients was higher than in subjects with T1DM but was lower than in T2DM patients (p < 0.01 for comparisons). Glycemic control in LADA patients (HbA1c 8.1%) was worse than in patients with T2DM (HbA1c 7.6%; p =0.007). An inverse association between GADAb titers and C-peptide concentrations was found in subjects with LADA (p < 0.001). Finally, LADA patients rapidly progressed to insulin treatment. As in other European populations, patients with LADA in Spain have a distinct metabolic profile compared with patients with T1DM or T2DM. LADA is also associated with higher impairment of beta-cell function and has worse glycemic control than in T2DM. Beta cell function is related to GADAb titers in patients with LADA. Copyright © 2013 John Wiley & Sons, Ltd.

Pilot Study of the Use of Hybrid Multidimensional T2-Weighted Imaging-DWI for the Diagnosis of Prostate Cancer and Evaluation of Gleason Score.

PubMed

Sadinski, Meredith; Karczmar, Gregory; Peng, Yahui; Wang, Shiyang; Jiang, Yulei; Medved, Milica; Yousuf, Ambereen; Antic, Tatjana; Oto, Aytekin

2016-09-01

The objective of our study was to evaluate the role of a hybrid T2-weighted imaging-DWI sequence for prostate cancer diagnosis and differentiation of aggressive prostate cancer from nonaggressive prostate cancer. Twenty-one patients with prostate cancer who underwent preoperative 3-T MRI and prostatectomy were included in this study. Patients underwent a hybrid T2-weighted imaging-DWI examination consisting of DW images acquired with TEs of 47, 75, and 100 ms and b values of 0 and 750 s/mm(2). The apparent diffusion coefficient (ADC) and T2 were calculated for cancer and normal prostate ROIs at each TE and b value. Changes in ADC and T2 as a function of increasing the TE and b value, respectively, were analyzed. A new metric termed "PQ4" was defined as the percentage of voxels within an ROI that has increasing T2 with increasing b value and has decreasing ADC with increasing TE. ADC values were significantly higher in normal ROIs than in cancer ROIs at all TEs (p < 0.0001). With increasing TE, the mean ADC increased 3% in cancer ROIs and increased 12% in normal ROIs. T2 was significantly higher in normal ROIs than in cancer ROIs at both b values (p ≤ 0.0002). The mean T2 decreased with increasing b value in cancer ROIs (ΔT2 = -17 ms) and normal ROIs (ΔT2 = -52 ms). PQ4 clearly differentiated normal ROIs from prostate cancer ROIs (p = 0.0004) and showed significant correlation with Gleason score (ρ = 0.508, p < 0.0001). Hybrid MRI measures the response of ADC and T2 to changing TEs and b values, respectively. This approach shows promise for detecting prostate cancer and determining its aggressiveness noninvasively.

Distribution of Vesicular Glutamate Transporter 2 (VGluT2) in the Primary Visual Cortex of the Macaque and Human

PubMed Central

Garcia-Marin, Virginia; Ahmed, Tunazzina H.; Afzal, Yasmeen C.; Hawken, Michael J.

2014-01-01

The majority of thalamic terminals in V1 arise from lateral geniculate nucleus (LGN) afferents. Thalamic afferent terminals are preferentially labeled by an isoform of the vesicular glutamate transporter, VGluT2. The goal of our study was to determine the distribution of VGluT2-ir puncta in macaque and human visual cortex. First, we investigated the distribution of VGluT2-ir puncta in all layers of macaque monkey primary visual cortex (V1), and found a very close correspondence between the known distribution of LGN afferents from previous studies and the distribution of VGluT2-immunoreactive (-ir) puncta. There was also a close correspondence between cytochrome oxidase density and VGluT2-ir puncta distribution. After validating the correspondence in macaque, we made a comparative study in human V1. In many aspects, the distribution of VGluT2-ir puncta in human was qualitatively similar to that of the macaque: high densities in layer 4C, patches of VGluT2-ir puncta in the supragranular layer (2/3), lower but clear distribution in layers 1 and 6, and very few puncta in layers 5 and 4B. However, there were also important differences between macaques and humans. In layer 4A of human, there was a sparse distribution of VGluT2-ir puncta, whereas in macaque, there was a dense distribution with the characteristic honeycomb organization. The results suggest important changes in the pattern of cortical VGluT2 immunostaining that may be related to evolutionary differences in the cortical organization of LGN afferents between Old World monkeys and humans. PMID:22684983

Cleared for takeoff: The effects of hypobaric conditions on traumatic pneumothoraces.

PubMed

Majercik, Sarah; White, Thomas W; Van Boerum, Don H; Granger, Steven; Bledsoe, Joseph; Conner, Karen; Wilson, Emily; Weaver, Lindell K

2014-11-01

Current guidelines suggest that traumatic pneumothorax (tPTX) is a contraindication to commercial airline travel, and patients should wait at least 2 weeks after radiographic resolution of tPTX to fly. This recommendation is not based on prospective, physiologic study. We hypothesized that despite having a radiographic increase in pneumothorax size while at simulated altitude, patients with a recently treated tPTX would not exhibit any adverse physiologic changes and would not report any symptoms of cardiorespiratory compromise. This is a prospective, observational study of 20 patients (10 in Phase 1, 10 in Phase 2) with tPTX that has been treated by chest tube (CT) or high flow oxygen therapy. CT must have been removed within 48 hours of entering the study. Subjects were exposed to 2 hours of hypobaria (554 mm Hg in Phase 1, 471 mm Hg in Phase 2) in a chamber in Salt Lake City, Utah. Vital signs and subjective symptoms were recorded during the "flight." After 2 hours, while still at simulated altitude, a portable chest radiograph (CXR) was obtained. tPTX sizes on preflight, inflight, and postflight CXR were compared. Sixteen subjects (80%) were male. Mean (SD) age and ISS were 49 (5) years and 10.5 (4.6), respectively. Fourteen (70%) had a CT to treat tPTX, which had been removed 19 hours (range, 4-43 hours) before the study. No subject complained of any cardiorespiratory symptoms while at altitude. Radiographic increase in tPTX size at altitude was 5.6 (0.61) mm from preflight CXR. No subject developed a tension tPTX. No subject required procedural intervention during the flight. Four hours after the study, all tPTX had returned to baseline size. Patients with recently treated tPTX have a small increase in the size of tPTX when subjected to simulated altitude. This is clinically well tolerated. Current prohibitions regarding air travel following traumatic tPTX should be reconsidered and further studied. Therapeutic study, level IV.

Association between ADIPOQ +45T>G Polymorphism and Type 2 Diabetes: A Systematic Review and Meta-Analysis

PubMed Central

Fan, Yaofu; Wang, Kun; Xu, Shuhang; Chen, Guofang; Di, Hongjie; Cao, Meng; Liu, Chao

2014-01-01

Recently, a number of studies have reported the association between the single nucleotide polymorphisms (SNPs) +45T>G polymorphism in the adiponectin (ADIPOQ) gene and type 2 diabetes mellitus (T2DM) risk, though the results are inconsistent. In order to obtain a more precise estimation of the relationship, a meta-analysis was performed. In this current study, the Medline, Embase, Pubmed, ISI Web of Knowledge, Ovid, Science Citation Index Expanded Database, Wanfang Database, and China National Knowledge Infrastructure were searched for eligible studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to estimate the strength of association. Forty-five publications were included in the final meta-analysis with 9986 T2DM patients and 16,222 controls for ADIPOQ +45T>G polymorphism according to our inclusion and exclusion criteria. The +45T>G polymorphism was associated with an overall significantly increased risk of T2DM (G vs. T: OR = 1.18, 95% CI = 1.06–1.32; The dominant model: OR = 1.18, 95% CI = 1.03–1.33; The recessive model: OR = 1.47, 95% CI = 1.20–1.78; The homozygous model: OR = 1.62, 95% CI = 1.25–2.09; Except the heterozygous model: OR = 1.11, 95% CI = 0.98–1.24). Subgroup analysis revealed a significant association between the +45T>G polymorphism and T2D in an Asian population. Thus, this meta-analysis indicates that the G allele of the ADIPOQ +45T>G polymorphisms associated with a significantly increased risk of T2DM in the Asian population. PMID:25561226

Kinetics of the Reactions of Cl((sup 2)P(sub J)) and Br((sup 2)P(sub 3/2)) with O3

NASA Technical Reports Server (NTRS)

Nicovich, J. M.; Kreutter, K. D.; Wine, P. H.

1997-01-01

A laser flash photolysis-resonance fluorescence technique has been employed to study the kinetics of the important stratospheric reactions Cl((sup 2)P(sub J)) + O3 yields ClO + O2 and Br((sup 2)P(sub 3/2)) + O3 yields BrO + O2 as a function of temperature. The temperature dependence observed for the Cl((sup 2)P(sub J)) + O3 reaction is nonArrhenius, but can be adequately described by the following two Arrhenius expressions (units are cu cm/(molecule.s), errors are 2 sigma and represent precision only): k(sub 1)(T) = (1.19 +/- 0.21) x 10(exp -11) exp[(-33 +/- 37)/T] for T = 189-269 K and k(sub 1)(T) = (2.49 +/- 0.38) x 10(exp -11) exp[(-233 +/- 46)/T] for 269-385 K. At temperatures below 230 K, the rate coefficients determined in this study are faster than any reported previously. Incorporation of our values for k(sub 1)(T) into stratospheric models would increase calculated ClO levels and decrease calculated HCI levels; hence the calculated efficiency of ClO catalyzed ozone destruction would increase. The temperature dependence observed for the Br((sup 2)P(sub 3/2)) + O3 reaction is adequately described by the following Arrhenius expression (units are cu cm/(molecule.s), errors are 2 sigma and represent precision only): k(sub 2)(T) = (1.50 +/- 0.16) x 10(exp -11)exp[(-775 +/- 30)/T for 195-392 K. While not in quantitative agreement with Arrhenius parameters reported in most previous studies, our results almost exactly reproduce the average of all earlier studies and therefore will not affect the choice of k(sub 2)(T) for use in modeling stratospheric BrO2 chemistry.

A genome-wide association search for type 2 diabetes genes in African Americans.

PubMed

Palmer, Nicholette D; McDonough, Caitrin W; Hicks, Pamela J; Roh, Bong H; Wing, Maria R; An, S Sandy; Hester, Jessica M; Cooke, Jessica N; Bostrom, Meredith A; Rudock, Megan E; Talbert, Matthew E; Lewis, Joshua P; Ferrara, Assiamira; Lu, Lingyi; Ziegler, Julie T; Sale, Michele M; Divers, Jasmin; Shriner, Daniel; Adeyemo, Adebowale; Rotimi, Charles N; Ng, Maggie C Y; Langefeld, Carl D; Freedman, Barry I; Bowden, Donald W; Voight, Benjamin F; Scott, Laura J; Steinthorsdottir, Valgerdur; Morris, Andrew P; Dina, Christian; Welch, Ryan P; Zeggini, Eleftheria; Huth, Cornelia; Aulchenko, Yurii S; Thorleifsson, Gudmar; McCulloch, Laura J; Ferreira, Teresa; Grallert, Harald; Amin, Najaf; Wu, Guanming; Willer, Cristen J; Raychaudhuri, Soumya; McCarroll, Steve A; Langenberg, Claudia; Hofmann, Oliver M; Dupuis, Josée; Qi, Lu; Segrè, Ayellet V; van Hoek, Mandy; Navarro, Pau; Ardlie, Kristin; Balkau, Beverley; Benediktsson, Rafn; Bennett, Amanda J; Blagieva, Roza; Boerwinkle, Eric; Bonnycastle, Lori L; Boström, Kristina Bengtsson; Bravenboer, Bert; Bumpstead, Suzannah; Burtt, Noël P; Charpentier, Guillaume; Chines, Peter S; Cornelis, Marilyn; Couper, David J; Crawford, Gabe; Doney, Alex S F; Elliott, Katherine S; Elliott, Amanda L; Erdos, Michael R; Fox, Caroline S; Franklin, Christopher S; Ganser, Martha; Gieger, Christian; Grarup, Niels; Green, Todd; Griffin, Simon; Groves, Christopher J; Guiducci, Candace; Hadjadj, Samy; Hassanali, Neelam; Herder, Christian; Isomaa, Bo; Jackson, Anne U; Johnson, Paul R V; Jørgensen, Torben; Kao, Wen H L; Klopp, Norman; Kong, Augustine; Kraft, Peter; Kuusisto, Johanna; Lauritzen, Torsten; Li, Man; Lieverse, Aloysius; Lindgren, Cecilia M; Lyssenko, Valeriya; Marre, Michel; Meitinger, Thomas; Midthjell, Kristian; Morken, Mario A; Narisu, Narisu; Nilsson, Peter; Owen, Katharine R; Payne, Felicity; Perry, John R B; Petersen, Ann-Kristin; Platou, Carl; Proença, Christine; Prokopenko, Inga; Rathmann, Wolfgang; Rayner, N William; Robertson, Neil R; Rocheleau, Ghislain; Roden, Michael; Sampson, Michael J; Saxena, Richa; Shields, Beverley M; Shrader, Peter; Sigurdsson, Gunnar; Sparsø, Thomas; Strassburger, Klaus; Stringham, Heather M; Sun, Qi; Swift, Amy J; Thorand, Barbara; Tichet, Jean; Tuomi, Tiinamaija; van Dam, Rob M; van Haeften, Timon W; van Herpt, Thijs; van Vliet-Ostaptchouk, Jana V; Walters, G Bragi; Weedon, Michael N; Wijmenga, Cisca; Witteman, Jacqueline; Bergman, Richard N; Cauchi, Stephane; Collins, Francis S; Gloyn, Anna L; Gyllensten, Ulf; Hansen, Torben; Hide, Winston A; Hitman, Graham A; Hofman, Albert; Hunter, David J; Hveem, Kristian; Laakso, Markku; Mohlke, Karen L; Morris, Andrew D; Palmer, Colin N A; Pramstaller, Peter P; Rudan, Igor; Sijbrands, Eric; Stein, Lincoln D; Tuomilehto, Jaakko; Uitterlinden, Andre; Walker, Mark; Wareham, Nicholas J; Watanabe, Richard M; Abecasis, Goncalo R; Boehm, Bernhard O; Campbell, Harry; Daly, Mark J; Hattersley, Andrew T; Hu, Frank B; Meigs, James B; Pankow, James S; Pedersen, Oluf; Wichmann, H-Erich; Barroso, Inês; Florez, Jose C; Frayling, Timothy M; Groop, Leif; Sladek, Rob; Thorsteinsdottir, Unnur; Wilson, James F; Illig, Thomas; Froguel, Philippe; van Duijn, Cornelia M; Stefansson, Kari; Altshuler, David; Boehnke, Michael; McCarthy, Mark I; Soranzo, Nicole; Wheeler, Eleanor; Glazer, Nicole L; Bouatia-Naji, Nabila; Mägi, Reedik; Randall, Joshua; Johnson, Toby; Elliott, Paul; Rybin, Denis; Henneman, Peter; Dehghan, Abbas; Hottenga, Jouke Jan; Song, Kijoung; Goel, Anuj; Egan, Josephine M; Lajunen, Taina; Doney, Alex; Kanoni, Stavroula; Cavalcanti-Proença, Christine; Kumari, Meena; Timpson, Nicholas J; Zabena, Carina; Ingelsson, Erik; An, Ping; O'Connell, Jeffrey; Luan, Jian'an; Elliott, Amanda; McCarroll, Steven A; Roccasecca, Rosa Maria; Pattou, François; Sethupathy, Praveen; Ariyurek, Yavuz; Barter, Philip; Beilby, John P; Ben-Shlomo, Yoav; Bergmann, Sven; Bochud, Murielle; Bonnefond, Amélie; Borch-Johnsen, Knut; Böttcher, Yvonne; Brunner, Eric; Bumpstead, Suzannah J; Chen, Yii-Der Ida; Chines, Peter; Clarke, Robert; Coin, Lachlan J M; Cooper, Matthew N; Crisponi, Laura; Day, Ian N M; de Geus, Eco J C; Delplanque, Jerome; Fedson, Annette C; Fischer-Rosinsky, Antje; Forouhi, Nita G; Frants, Rune; Franzosi, Maria Grazia; Galan, Pilar; Goodarzi, Mark O; Graessler, Jürgen; Grundy, Scott; Gwilliam, Rhian; Hallmans, Göran; Hammond, Naomi; Han, Xijing; Hartikainen, Anna-Liisa; Hayward, Caroline; Heath, Simon C; Hercberg, Serge; Hicks, Andrew A; Hillman, David R; Hingorani, Aroon D; Hui, Jennie; Hung, Joe; Jula, Antti; Kaakinen, Marika; Kaprio, Jaakko; Kesaniemi, Y Antero; Kivimaki, Mika; Knight, Beatrice; Koskinen, Seppo; Kovacs, Peter; Kyvik, Kirsten Ohm; Lathrop, G Mark; Lawlor, Debbie A; Le Bacquer, Olivier; Lecoeur, Cécile; Li, Yun; Mahley, Robert; Mangino, Massimo; Manning, Alisa K; Martínez-Larrad, María Teresa; McAteer, Jarred B; McPherson, Ruth; Meisinger, Christa; Melzer, David; Meyre, David; Mitchell, Braxton D; Mukherjee, Sutapa; Naitza, Silvia; Neville, Matthew J; Oostra, Ben A; Orrù, Marco; Pakyz, Ruth; Paolisso, Giuseppe; Pattaro, Cristian; Pearson, Daniel; Peden, John F; Pedersen, Nancy L; Perola, Markus; Pfeiffer, Andreas F H; Pichler, Irene; Polasek, Ozren; Posthuma, Danielle; Potter, Simon C; Pouta, Anneli; Province, Michael A; Psaty, Bruce M; Rayner, Nigel W; Rice, Kenneth; Ripatti, Samuli; Rivadeneira, Fernando; Rolandsson, Olov; Sandbaek, Annelli; Sandhu, Manjinder; Sanna, Serena; Sayer, Avan Aihie; Scheet, Paul; Seedorf, Udo; Sharp, Stephen J; Shields, Beverley; Sijbrands, Eric J G; Silveira, Angela; Simpson, Laila; Singleton, Andrew; Smith, Nicholas L; Sovio, Ulla; Swift, Amy; Syddall, Holly; Syvänen, Ann-Christine; Tanaka, Toshiko; Tönjes, Anke; Uitterlinden, André G; van Dijk, Ko Willems; Varma, Dhiraj; Visvikis-Siest, Sophie; Vitart, Veronique; Vogelzangs, Nicole; Waeber, Gérard; Wagner, Peter J; Walley, Andrew; Ward, Kim L; Watkins, Hugh; Wild, Sarah H; Willemsen, Gonneke; Witteman, Jaqueline C M; Yarnell, John W G; Zelenika, Diana; Zethelius, Björn; Zhai, Guangju; Zhao, Jing Hua; Zillikens, M Carola; Borecki, Ingrid B; Loos, Ruth J F; Meneton, Pierre; Magnusson, Patrik K E; Nathan, David M; Williams, Gordon H; Silander, Kaisa; Salomaa, Veikko; Smith, George Davey; Bornstein, Stefan R; Schwarz, Peter; Spranger, Joachim; Karpe, Fredrik; Shuldiner, Alan R; Cooper, Cyrus; Dedoussis, George V; Serrano-Ríos, Manuel; Lind, Lars; Palmer, Lyle J; Franks, Paul W; Ebrahim, Shah; Marmot, Michael; Kao, W H Linda; Pramstaller, Peter Paul; Wright, Alan F; Stumvoll, Michael; Hamsten, Anders; Buchanan, Thomas A; Valle, Timo T; Rotter, Jerome I; Siscovick, David S; Penninx, Brenda W J H; Boomsma, Dorret I; Deloukas, Panos; Spector, Timothy D; Ferrucci, Luigi; Cao, Antonio; Scuteri, Angelo; Schlessinger, David; Uda, Manuela; Ruokonen, Aimo; Jarvelin, Marjo-Riitta; Waterworth, Dawn M; Vollenweider, Peter; Peltonen, Leena; Mooser, Vincent; Sladek, Robert

2012-01-01

African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.

Management of type 2 diabetes in Asian Indians: a review of the literature.

PubMed

Joseph, Letha M; Berry, Diane; Jessup, Ann

2015-04-01

Type 2 diabetes mellitus (T2DM) is increasing in Asian Indians globally. In this article, we review published studies of interventions designed to prevent T2DM or improve self-management in South Asian Indians. A PubMed, CINAHL, Medline, EMBASE, Psycinfo, Family & Society Studies Worldwide, Web of Science, and Consumer Health Complete search was conducted using the following search terms: type 2 diabetes mellitus, Asian Indian continental ancestry group, therapy, treatment, management, care, intervention, self-care, exercise, diet, and lifestyle. The review included pilot or full intervention studies examining the prevention and/or management of T2DM and qualitative studies analyzing the influence of various ethnic factors on the prevention and management of T2DM. Seventeen studies met the inclusion criteria. They examined the influence of culture and religion and the effectiveness of individual and community-based education and lifestyle improvement programs, exercise, and complementary therapies. Few programs led to the improved long-term management of T2DM. Further research is needed to develop ethnic-specific interventions. © The Author(s) 2014.

Changes in human pulp blood flow during canine retraction.

PubMed

Sabuncuoglu, Fidan Alakus; Ersahan, Seyda

2016-08-01

To evaluate the effects of maxillary canine retraction on pulpal blood flow (PBF) in humans as recorded by laser Doppler flowmetry (LDF). Maxillary canines of 24 participants were divided into two groups (n = 12 each). Teeth in the study group underwent maxillary canine retraction using mini-implants as anchorage for approximately 4 months, with 100 g of force applied via coil springs. Subjects in the control group received no orthodontic treatment. LDF measurements were recorded at baseline (T0); during retraction, at 24 hours (T1), 3 days (T2), 7 days (T3) and 1 month (T4); and at the end of retraction (T5) in the study group and at similar time-points in control subjects. Data were analyzed using the Friedman, Wilcoxon signed rank and Mann-Whitney U tests, with the significance level set at 0.05. No significant changes in PBF perfusion units (PU) were observed in the control group over the course of the study. However, PBF in the study group increased significantly from T0 (3.6 ± 0.2 PU) to T1 (3.7 ± 0.2 PU, p < 0.001) and decreased severely from T1 to T2 (3.3 ± 0.1, p < 0.001). PBF in the study group was still significantly lower at T3 (3.4 ± 0.1 PU, p < 0.001) in comparison to T0; however, at T4 and T5, PBF was found to have returned to pre-retraction levels. The fact that PBF values returned to initial levels within one month of the initiation of retraction despite short-term, hyperaemic, regressive changes demonstrates that the changes observed in PBF during canine retraction are reversible.

MRI-based quantification of Duchenne muscular dystrophy in a canine model

NASA Astrophysics Data System (ADS)

Wang, Jiahui; Fan, Zheng; Kornegay, Joe N.; Styner, Martin A.

2011-03-01

Duchenne muscular dystrophy (DMD) is a progressive and fatal X-linked disease caused by mutations in the DMD gene. Magnetic resonance imaging (MRI) has shown potential to provide non-invasive and objective biomarkers for monitoring disease progression and therapeutic effect in DMD. In this paper, we propose a semi-automated scheme to quantify MRI features of golden retriever muscular dystrophy (GRMD), a canine model of DMD. Our method was applied to a natural history data set and a hydrodynamic limb perfusion data set. The scheme is composed of three modules: pre-processing, muscle segmentation, and feature analysis. The pre-processing module includes: calculation of T2 maps, spatial registration of T2 weighted (T2WI) images, T2 weighted fat suppressed (T2FS) images, and T2 maps, and intensity calibration of T2WI and T2FS images. We then manually segment six pelvic limb muscles. For each of the segmented muscles, we finally automatically measure volume and intensity statistics of the T2FS images and T2 maps. For the natural history study, our results showed that four of six muscles in affected dogs had smaller volumes and all had higher mean intensities in T2 maps as compared to normal dogs. For the perfusion study, the muscle volumes and mean intensities in T2FS were increased in the post-perfusion MRI scans as compared to pre-perfusion MRI scans, as predicted. We conclude that our scheme successfully performs quantitative analysis of muscle MRI features of GRMD.

Optimizing hippocampal segmentation in infants utilizing MRI post-acquisition processing.

PubMed

Thompson, Deanne K; Ahmadzai, Zohra M; Wood, Stephen J; Inder, Terrie E; Warfield, Simon K; Doyle, Lex W; Egan, Gary F

2012-04-01

This study aims to determine the most reliable method for infant hippocampal segmentation by comparing magnetic resonance (MR) imaging post-acquisition processing techniques: contrast to noise ratio (CNR) enhancement, or reformatting to standard orientation. MR scans were performed with a 1.5 T GE scanner to obtain dual echo T2 and proton density (PD) images at term equivalent (38-42 weeks' gestational age). 15 hippocampi were manually traced four times on ten infant images by 2 independent raters on the original T2 image, as well as images processed by: a) combining T2 and PD images (T2-PD) to enhance CNR; then b) reformatting T2-PD images perpendicular to the long axis of the left hippocampus. CNRs and intraclass correlation coefficients (ICC) were calculated. T2-PD images had 17% higher CNR (15.2) than T2 images (12.6). Original T2 volumes' ICC was 0.87 for rater 1 and 0.84 for rater 2, whereas T2-PD images' ICC was 0.95 for rater 1 and 0.87 for rater 2. Reliability of hippocampal segmentation on T2-PD images was not improved by reformatting images (rater 1 ICC = 0.88, rater 2 ICC = 0.66). Post-acquisition processing can improve CNR and hence reliability of hippocampal segmentation in neonate MR scans when tissue contrast is poor. These findings may be applied to enhance boundary definition in infant segmentation for various brain structures or in any volumetric study where image contrast is sub-optimal, enabling hippocampal structure-function relationships to be explored.

[EzPAP® therapy of postoperative hypoxemia in the recovery room : experiences with the new compact system of end-expiratory positive airway pressure].

PubMed

Rieg, A D; Stoppe, C; Rossaint, R; Coburn, M; Hein, M; Schälte, G

2012-10-01

Postoperative hypoxemia is a common complication in the anesthesia recovery room (ARR), which is predominantly based on the development of atelectasis, excessive intraoperative fluid shift and insufficient ventilation. The goal of this prospective observational study was to compare the effect of standard oxygen administration via a face mask with oxygen administration using the EzPAP® system, a device which additionally provides a positive end-expiratory pressure (PEEP). This study included 210 patients with postoperative hypoxemia (S(p)O(2) < 93%) subdivided into the control group (105 patients) and the EzPAP group (105 patients). Postoperative residual paralysis was excluded using relaxometry and a train of four (TOF) ratio of 0.9 was assumed to ensure sufficient recovery of respiratory function from neuromuscular blockade. Patients who received a reversal of neuromuscular blockade were excluded. In cases of hypoxemia (S(p)O(2) < 93%) control patients were treated with oxygen (6 l/min) using a face mask, whereas the EzPAP group received oxygen using the EzPAP® system. In order to adjust the PEEP in the EzPAP group, the O(2) flow was verified and measured by a manometer. After 1 h of oxygen therapy, the oxygen supply was stopped. In cases of reoccurring hypoxemia (S(p)O(2) < 93%, persistence > 5 min), the oxygen therapy was restarted in both groups via a facemask. Both groups were compared using repeat measurement analysis of variance (ANOVA), the unpaired t-test, the Mann-Whitney U-test, Fisher's exact test and the χ(2)-test. The correlation of O(2) flow and PEEP was evaluated by regression analysis and p < 0.05 was considered to be statistically significant. Apart from this a subgroup analysis was performed depending on body-mass index (BMI), American Society of Anesthesiologists (ASA) classification, intraoperative airway management, the use of neuromuscular blocking agents and co-existing disorders, e.g. chronic obstructive lung disease (COLD), obesity and chronic heart failure. All patients were equally distributed between both groups with respect to demographic data, ASA classification, BMI, co-existing disorders and surgical procedures. The S(p)O(2) values did not differ between the EzPAP patients and the control group, except for 0.5 min after initiation of oxygen therapy: EzPAP group 96 ± 3.7% (mean ± standard deviation) versus the control group 93.8 ± 4.4% (p < 0.001). However, restarting oxygen therapy was less common in the EzPAP group (EzPAP group 25 versus control group 41, p = 0.03), as well as the occurrence of postoperative complications (EzPAP group 13 versus control group 25, p = 0.02), e.g. nosocomial pneumonia (0 versus 4) and wound infections (2 versus 3). Furthermore, patients with obesity and pulmonary disorders, such as COLD had a benefit from oxygen administration using the EzPAP device and showed higher postoperative than preoperative S(p)O(2) values. In contrast, the subgroup analysis of patients with heart failure did not reveal any differences between both groups and both groups did not differ in terms of time spent in the recovery room (EzPAP group 113 min versus control group 174.8 min, p = 0.2). In this observational study oxygen supply using the EzPAP® system appeared to be at least equally as effective in the therapy of postoperative hypoxemia compared to standard oxygen supply using a face mask. In patients with a high risk of postoperative hypoxemia, such as patients with obesity and/or pulmonary disorders, oxygen administration using the EzPAP® system possibly improves pulmonary oxygenation more effectively and is longer lasting compared to standard oxygen supply via a face mask. Hence, the EzPAP® system represents a well-tolerated, effective, cost-effective and easily operated tool to improve postoperative oxygenation. In order to investigate the possibilities of this promising tool more intensively, randomized clinical trials are warranted.

Factor VII and incidence of myocardial infarction in a Japanese population: The Jichi Medical School Cohort Study.

PubMed

Shiraishi, Takuya; Ishikawa, Shizukiyo; Kario, Kazuomi; Kayaba, Kazunori; Kajii, Eiji

2017-11-01

The role of factor VII (FVII) as a risk factor in myocardial infarction (MI) has been the subject of numerous studies. However, it remains uncertain whether the FVII levels are associated with development of MI. The subjects were 4142 men and women whose activated FVII (FVIIa) and FVII coagulant (FVIIc) levels were measured in the Jichi Medical School Cohort Study. Subjects were divided into tertiles by FVIIa and FVIIc levels, and Cox's proportional hazard model was used to calculate hazard ratios (HRs) for MI. The multivariate-adjusted HRs (95% confidential interval [CI]) for FVIIa in men were 0.67 (0.67-1.78) in tertile 2 (T2), and 0.52 (0.17-1.60) in T3. In women, the multivariate-adjusted HRs (95% CI) were 0.18 (0.02-1.60) in T2, and 0.39 (0.07-2.20) in T3. The multivariate-adjusted HRs (95% CI) for FVIIc in men were 0.54 (0.21-1.36) in T2, and 0.20 (0.04-0.91) in T3. In women, the multivariate-adjusted HRs (95% CI) were 0.44 (0.07-2.85) in T2, and 0.35 (0.06-2.22) in T3. We used T1 as a reference for all measures. Our findings revealed a significant association between low FVIIc level and incidence of MI in men. The FVIIa and FVIIc levels were inversely related to increased MI risk, but did not reach statistical significance. Future studies are needed to confirm this association. © 2017 Wiley Periodicals, Inc.

Early-Life Nutritional Programming of Type 2 Diabetes: Experimental and Quasi-Experimental Evidence.

PubMed

Vaiserman, Alexander M

2017-03-05

Consistent evidence from both experimental and human studies suggest that inadequate nutrition in early life can contribute to risk of developing metabolic disorders including type 2 diabetes (T2D) in adult life. In human populations, most findings supporting a causative relationship between early-life malnutrition and subsequent risk of T2D were obtained from quasi-experimental studies ('natural experiments'). Prenatal and/or early postnatal exposures to famine were demonstrated to be associated with higher risk of T2D in many cohorts around the world. Recent studies have highlighted the importance of epigenetic regulation of gene expression as a possible major contributor to the link between the early-life famine exposure and T2D in adulthood. Findings from these studies suggest that prenatal exposure to the famine may result in induction of persistent epigenetic changes that have adaptive significance in postnatal development but can predispose to metabolic disorders including T2D at the late stages of life. In this review, quasi-experimental data on the developmental programming of T2D are summarized and recent research findings on changes in DNA methylation that mediate these effects are discussed.

Implications of publicly available genomic data resources in searching for therapeutic targets of obesity and type 2 diabetes.

PubMed

Jung, Sungwon

2018-04-20

Obesity and type 2 diabetes (T2D) are two major conditions that are related to metabolic disorders and affect a large population. Although there have been significant efforts to identify their therapeutic targets, few benefits have come from comprehensive molecular profiling. This limited availability of comprehensive molecular profiling of obesity and T2D may be due to multiple challenges, as these conditions involve multiple organs and collecting tissue samples from subjects is more difficult in obesity and T2D than in other diseases, where surgical treatments are popular choices. While there is no repository of comprehensive molecular profiling data for obesity and T2D, multiple existing data resources can be utilized to cover various aspects of these conditions. This review presents studies with available genomic data resources for obesity and T2D and discusses genome-wide association studies (GWAS), a knockout (KO)-based phenotyping study, and gene expression profiles. These studies, based on their assessed coverage and characteristics, can provide insights into how such data can be utilized to identify therapeutic targets for obesity and T2D.

Early-Life Nutritional Programming of Type 2 Diabetes: Experimental and Quasi-Experimental Evidence

PubMed Central

Vaiserman, Alexander M.

2017-01-01

Consistent evidence from both experimental and human studies suggest that inadequate nutrition in early life can contribute to risk of developing metabolic disorders including type 2 diabetes (T2D) in adult life. In human populations, most findings supporting a causative relationship between early-life malnutrition and subsequent risk of T2D were obtained from quasi-experimental studies (‘natural experiments’). Prenatal and/or early postnatal exposures to famine were demonstrated to be associated with higher risk of T2D in many cohorts around the world. Recent studies have highlighted the importance of epigenetic regulation of gene expression as a possible major contributor to the link between the early-life famine exposure and T2D in adulthood. Findings from these studies suggest that prenatal exposure to the famine may result in induction of persistent epigenetic changes that have adaptive significance in postnatal development but can predispose to metabolic disorders including T2D at the late stages of life. In this review, quasi-experimental data on the developmental programming of T2D are summarized and recent research findings on changes in DNA methylation that mediate these effects are discussed. PMID:28273874

The Association of Type 2 Diabetes Loci Identified in Genome-Wide Association Studies with Metabolic Syndrome and Its Components in a Chinese Population with Type 2 Diabetes

PubMed Central

Xing, Xiaoyan; Zhang, Bo; Hong, Jing; Yang, Wenying

2015-01-01

Metabolic syndrome (MetS) is prevalent in type 2 diabetes (T2D) patients. The comorbidity of MetS and T2D increases the risk of cardiovascular complications. The aim of the present study was to determine the T2D-related genetic variants that contribute to MetS-related components in T2D patients of Chinese ancestry. We successfully genotyped 25 genome wide association study validated T2D-related single nucleotide polymorphisms (SNPs) among 5,169 T2D individuals and 4,560 normal glycemic controls recruited from the Chinese National Diabetes and Metabolic Disorders Study (DMS). We defined MetS in this population using the harmonized criteria (2009) combined with the Chinese criteria for abdominal obesity. The associations between SNPs and MetS-related components, as well as the associations between SNPs and risk for T2D with or without MetS, were subjected to logistic regression analysis adjusted for age and sex. Results showed that the T2D risk alleles of rs243021 located near BCL11A, rs10830963 in MTNR1B, and rs2237895 in KCNQ1 were related to a lower risk for abdominal obesity in T2D patients (rs243021: 0.92 (0.84, 1.00), P = 4.42 × 10−2; rs10830963: 0.92 (0.85, 1.00), P = 4.07 × 10−2; rs2237895: 0.89 (0.82, 0.98), P = 1.29 × 10−2). The T2D risk alleles of rs972283 near KLF14 contributed to a higher risk of elevated blood pressure (1.10 (1.00, 1.22), P = 4.48 × 10−2), while the T2D risk allele of rs7903146 in TCF7L2 was related to a lower risk for elevated blood pressure (0.74 (0.61, 0.90), P = 2.56 × 10−3). The T2D risk alleles of rs972283 near KLF14 and rs11634397 near ZFAND6 were associated with a higher risk for elevated triglycerides (rs972283: 1.11 (1.02, 1.24), P = 1.46 × 10−2; rs11634397: 1.14 (1.00, 1.29), P = 4.66 × 10−2), while the T2D risk alleles of rs780094 in GCKR and rs7903146 in TCF7L2 were related to a lower risk of elevated triglycerides (rs780094: 0.86 (0.80, 0.93), P = 1.35 × 10−4; rs7903146: 0.82 (0.69, 0.98), P = 3.18 × 10−2). The genotype risk score of the 25 T2D-related SNPs was related to a lower risk for abdominal obesity (P trend = 1.29 × 10−2) and lower waist circumference (P = 2.20 × 10−3). Genetic variants of WFS1, CDKAL1, CDKN2BAS, TCF7L2, HHEX, KCNQ1, TSPAN8/LGR5, FTO, and TCF2 were associated with the risk for T2D with MetS, as well as the risk for development of T2D with at least one of the MetS components (P < 0.05). In addition, genetic variants of BCL11A, GCKR, ADAMTS9, CDKAL1, KLF14, CDKN2BAS, TCF7L2, CDC123/CAMK1D, HHEX, MTNR1B, and KCNQ1 contributed to the risk for T2D without MetS (P < 0.05). In conclusion, these findings highlight the contribution of T2D-related genetic loci to MetS in a Chinese Han population. The study also provides insight into the pleotropic effects of genome-wide association loci of diabetes on metabolic regulation. PMID:26599349

Oxidative Stress, Obesity, and Breast Cancer Risk: Results From the Shanghai Women's Health Study

PubMed Central

Dai, Qi; Gao, Yu-Tang; Shu, Xiao-Ou; Yang, Gong; Milne, Ginger; Cai, Qiuyin; Wen, Wanqing; Rothman, Nathaniel; Cai, Hui; Li, Honglan; Xiang, Yongbing; Chow, Wong-Ho; Zheng, Wei

2009-01-01

Purpose Increased reactive oxygen species may exhaust the antioxidant capability of human defense systems, leading to oxidative stress and cancer development. Urinary F2-isoprostanes, secondary end products of lipid peroxidation, are more accurate markers of oxidative stress than other available biomarkers. No prospective study has investigated whether levels of 15-F2t-isoprostane (15-F2t-IsoP) and its metabolite 2,3-dinor-5,6-dihydro-15-F2t-IsoP (15-F2t-IsoPM) are related to breast cancer risk. Patients and Methods We conducted a nested case-control study within the Shanghai Women's Health Study, a population-based cohort study of 74,942 Chinese women between 40 and 70 years of age. Prediagnostic urinary 15-F2t-IsoP and 15-F2t-IsoPM were measured by gas chromatography mass spectrometry for 436 breast cancer cases and 852 individually matched controls. Results Urinary excretion of isoprostanes was not significantly different between cases and controls. However, among overweight women, levels of isoprostanes were positively associated with breast cancer risk, which became stronger with increasing body mass index (BMI). Among women with a BMI ≥ 29, the odds ratio (OR) increased to 10.27 (95% CI, 2.41 to 43.80) for the highest compared with the lowest tertile of 15-F2t-IsoPM (P for trend = .003; P for interaction = .0004). In contrast, 15-F2t-IsoP and 15-F2t-IsoPM were inversely associated with breast cancer risk among nonoverweight women. Among women with a BMI ≤ 23, breast cancer risk was reduced with increasing 15-F2t-IsoP levels in a dose-response manner (P for trend = .006), with an OR of 0.46 (95% CI, 0.26 to 0.80) for the highest tertile versus the lowest (P for interaction = .006). Conclusion Our results suggest that the role of oxidative stress in breast cancer development may depend on adiposity. PMID:19380446

Agreement between T2 and haste sequences in the evaluation of thoracolumbar intervertebral disc disease in dogs.

PubMed

Mankin, Joseph M; Hecht, Silke; Thomas, William B

2012-01-01

The purpose of this study was to compare half-Fourier-acquisition single-shot turbo spin-echo (HASTE) and T2-weighted (T2-W) sequences in dogs with thoracolumbar disc extrusion. MRI studies in 60 dogs (767 individual intervertebral disc spaces) were evaluated. Agreement between T2-W and HASTE sequences was assessed for two criteria: presence of an extradural lesion and treatment recommendation. There was moderate agreement between T2-W and HASTE sequences as to presence of an extradural lesion (kappa = 0.575). HASTE was in agreement in 96.1% of the sites where no extradural lesion was identified on T2-W images, but only in 58.1% of the sites where extradural lesions were identified on T2-W images. There was also moderate agreement between T2-W and HASTE sequences as to treatment recommendations (kappa = 0.476). HASTE was in agreement in 98.4% of the sites where a lesion was considered nonsurgical on T2 but only 82.1% of sites a lesion was considered surgical on T2. In 1.0% of sites considered not surgical and in 9.8% of sites considered equivocal based on T2-W images, a surgical lesion was identified on HASTE. Acquisition of a HASTE sequence in addition to conventional sequences may be beneficial in determining the severity of spinal cord compression in some cases when evaluating the canine spine.

Tension-compression-tension tertiary twins in coarse-grained polycrystalline pure magnesium at room temperature

DOE PAGES

Yu, Qin; Jiang, Yanyao; Wang, Jian

2015-04-07

Using electron backscatter diffraction, the microstructural features of tension–compression–tension (T–C–T) tertiary twins are studied in coarse-grained pure polycrystalline magnesium subjected to monotonic compression along the extrusion direction in ambient air. T–C–T tertiary twins are developed due to the formation of a compression–tension double twin inside a primary tension twin. All the observed T–C–T twin variants are of T iC jT j type. T iC i+1T i+1 (or T iC i–1T i–1) variants are observed more frequently than T iC i+2T i+2 (or T iC i–2T i–2) variants. Moreover, the number of tertiary twin lamellae increases with the applied compressive strain.

Comparison of β-cell dysfunction and insulin resistance correlating obesity with type 2 diabetes: A cross-sectional study.

PubMed

Liu, Jia; Wang, Ying; Hu, Yanjin; Leng, Song; Wang, Guang

2016-07-01

To assess the contribution of β-cell dysfunction and insulin resistance to type 2 diabetes (T2D) in obese and non-obese Chinese people. In this cross-sectional study, we recruited 1384 newly diagnosed T2D patients and 1712 healthy controls. Insulin resistance was estimated by homeostasis model assessment of insulin resistance (HOMA-IR). β-cell function was estimated by homeostasis model assessment of β-cell function (HOMA-β) and 60min insulinogenic index (IGI60). We compared the insulin resistance and β-cell function of obese and non-obese Chinese patients with and without T2D. 50.18% of control participants and 62.28% of T2D patients were obese (BMI≥25kg/m(2)). HOMA-IR, HOMA-β and IGI60 were significantly higher in obese than non-obese, irrespective of T2D. Non-obese T2D patients had significantly greater HOMA-IR, and lower HOMA-β and IGI60 than non-obese control participants. The obese T2D group had lower HOMA-β and IGI60 than the obese control group. There was no significant difference in HOMA-IR between the obese T2D and obese control groups. Multivariate logistic regression analysis revealed that HOMA-IR was associated with T2D only in non-obese group, and HOMA-β and IGI60 were associated with T2D in both non-obese and obese groups. HOMA-β and IGI60 were associated with T2D in obese and non-obese patients, but HOMA-IR was associated with T2D in non-obese Chinese. Copyright © 2016 Elsevier Inc. All rights reserved.

A comparative analysis of genetic diversity of candidate genes associated with type 2 diabetes in worldwide populations.

PubMed

Gong, Xian; Zhang, Chao; Yiliyasi·Aisa, Yiliyasi·Aisa; Shi, Ying; Yang, Xue-wei; NuersimanguliAosiman, NuersimanguliAosiman; Guan, Ya-qun; Xu, Shu-hua

2016-06-20

Over the last decade, a larger number of type 2 diabetes mellitus (T2DM) susceptible candidate genes have been reported by numerous genome-wide association studies (GWAS). Understanding the genetic diversity of these candidate genes among worldwide populations not only facilitates to elucidating the genetic mechanism of T2DM, but also provides guidance to further studies of pathogenesis of T2DM in any certain population. In this study, we identified 170 genes or genomic regions associated with T2DM by searching the GWAS databases and related literatures. We next analyzed the genetic diversity of these genes (or genomic regions) among present-day human populations by curetting the 1000 Genomes Projects phase1 dataset covering 14 worldwide populations. We further compared the characteristics of T2DM genes in different populations. No significant differences of genetic diversity were observed among the 14 worldwide populations between the T2DM candidate genes and the non-T2DM genes in terms of overall pattern. However, we observed some genes, such as IL20RA, RNMTL1-NXN, NOTCH2, ADRA2A-BTBD7P2, TBC1D4, RBM38-HMGB1P1, UBE2E2, and PPARD, show considerable differentiation between populations. In particular, IL20RA (FST=0.1521) displays the greatest population difference which is mainly contributed by that between Africans and non-Africans. Moreover, we revealed genetic differences between East Asians and Europeans on some candidate genes such as DGKB-AGMO (FST=0.173) and JAZF1 (FST=0.182). Our results indicate that some T2DM susceptible candidate genes harbor highly-differentiated variants between populations. These analyses, despite preliminary, should advance our understanding of the population difference of susceptibility to T2DM and provide insightful reference that future studies can relay on.

Disentangling the Role of Melatonin and its Receptor MTNR1B in Type 2 Diabetes: Still a Long Way to Go?

PubMed

Bonnefond, Amélie; Froguel, Philippe

2017-10-23

Type 2 diabetes (T2D) is a complex genetic metabolic disorder. T2D heritability has been estimated around 40-70%. In the last decade, exponential progress has been made in identifying T2D genetic determinants, through genome-wide association studies (GWAS). Among single-nucleotide polymorphisms mostly associated with T2D risk, rs10830963 is located in the MTNR1B gene, encoding one of the two receptors of melatonin, a neurohormone involved in circadian rhythms. Subsequent studies aiming to disentangle the role of MTNR1B in T2D pathophysiology led to controversies. In this review, we will tackle them and will try to give some directions to get a better view of MTNR1B contribution to T2D pathophysiology. Recent studies either based on genetic/genomic analyses, clinical/epidemiology data, functional analyses at rs10830963 locus, insulin secretion assays in response to melatonin (involving or not MTNR1B) or animal model analyses have led to strong controversies at each level of interpretation. We discuss possible caveats in these studies and present ways to go beyond these issues, towards a better understanding of T2D molecular mechanisms, keeping in mind that melatonin is a versatile hormone and regulates many functions via its primary role in the body clock.

Bitter taste receptor T2R1 activities were compatible with behavioral sensitivity to bitterness in chickens.

PubMed

Hirose, Nozomi; Kawabata, Yuko; Kawabata, Fuminori; Nishimura, Shotaro; Tabata, Shoji

2015-05-01

Clarification of the mechanism of the sense of taste in chickens will provide information useful for creating and improving new feedstuffs for chickens, because the character of the taste receptors in oral tissues affects feeding behavior in animals. In this study, we focused on the sensitivity to bitterness in chickens. We cloned one of the bitter taste receptors, T2R1, from the chicken palate, constructed several biosensor-cells expressing chicken T2R1 (cT2R1), and determined a highly sensitive biosensor of cT2R1 among them. By using Ca(2+) imaging methods, we identified two agonists of cT2R1, dextromethorphan (Dex) and diphenidol (Dip). Dex was a new agonist of cT2R1 that was more potent than Dip. In a behavioral drinking study, the intake volumes of solutions of these compounds were significantly lower than that of water in chickens. These aversive concentrations were identical to the concentrations that could activate cT2R1 in a cell-based assay. These results suggest that the cT2R1 activities induced by these agonists are linked to behavioral sensitivity to bitterness in chickens. Copyright © 2015 Elsevier Inc. All rights reserved.

Staging studies for cutaneous melanoma in the United States: a population-based analysis.

PubMed

Wasif, Nabil; Etzioni, David; Haddad, Dana; Gray, Richard J; Bagaria, Sanjay P; Pockaj, Barbara A

2015-04-01

Routine cross-sectional imaging for staging of early-stage cutaneous melanoma is not recommended. This study sought to investigate the use of imaging for staging of cutaneous melanoma in the United States. Patients with nonmetastatic cutaneous melanoma newly diagnosed between 2000 and 2007 were identified from the Surveillance Epidemiology End Results-Medicare registry. Any imaging study performed within 90 days after diagnosis was considered a staging study. The study identified 25,643 patients, 3,116 (12.2 %) of whom underwent cross-sectional imaging: positron emission tomography (PET) (7.2 %), computed tomography (CT) (5.9 %), and magnetic resonance imaging (MRI) (0.6 %). From 2000 to 2007, the use of cross-sectional imaging increased from 8.7 to 16.1 % (p < 0.001), driven predominantly by increased usage of PET (4.2-12.1 %). Stratification by T and N classification showed that cross-sectional imaging was used for 8.6 % of T1, 14.3 % of T2, 18.6 % of T3, and 26.7 % of T4 tumors (p < 0.001) and for 33.3 % of node-positive patients versus 11.1 % of node-negative patients (p < 0.001). Factors predictive of cross-sectional imaging included T classification [odds ratio (OR) for T4 vs T1, 2.66; 95 % confidence interval (CI) 2.33-3.03], node positivity (OR 2.70; 95 % CI 2.36-3.10), more recent year of diagnosis (OR 2.05 for 2007 vs 2000; 95 % CI 1.74-2.42), atypical histology, and non-Caucasian race (OR 1.32; 95 % CI 1.02-1.73). The use of cross-sectional imaging for staging of early-stage cutaneous melanoma is increasing in the Medicare population. Better dissemination of guidelines and judicious use of imaging should be encouraged.

Influence of the genetic polymorphism in the 5'-noncoding region of the CYP1A2 gene on CYP1A2 phenotype and urinary mutagenicity in smokers.

PubMed

Pavanello, Sofia; Pulliero, Alessandra; Lupi, Silvia; Gregorio, Pasquale; Clonfero, Erminio

2005-11-10

The functional significance of genetic polymorphisms on tobacco smoke-induced CYP1A2 activity was examined. The influence of three polymorphisms of the cytochrome P450 1A2 gene (CYP1A2) (-3860 G-->A (allele *1C), -2467 T-->delT (allele *1D), -163C-->A (allele *1F)), located in the 5'-noncoding promoter region of the gene, on CYP1A2 activity (measured as caffeine metabolic ratio, CMR), was studied in Caucasian current smokers (n=95). Tobacco smoke intake was calculated from the number of cigarettes/day. Also, studied was the influence of these CYP1A2 genotypes on smoking-associated urinary mutagenicity, detected in Salmonella typhimurium strain YG1024 with S9 mix, considering the urinary excretion of nicotine plus its metabolites as an internal indicator of tobacco smoke exposure. Smokers with at least one of the variant alleles CYP1A2 -3860A and -2467 delT showed a significantly increased CYP1A2 CMR (-3860 G/A versus G/G, p<0.05; -2467 delT/delT versus T/delT and T/T, p<0.01). Multiple regression analysis showed that the increase in CYP1A2 CMR (ln values) was again significantly related to the presence of CYP1A2 variants -2467delT and also to variant -163A (p<0.05), but moderately to -3860A (p=0.084). No influence of the number of cigarettes smoked per day by each subject was found. Heavy smokers (n=48, with urinary nicotine plus its metabolites>or=0.69 mg/mmol creatinine) with variant allele -2467delT or -163A had significantly increased urinary mutagenicity (p<0.01 and <0.05). CYP1A2 genetic polymorphisms are shown to influence the CYP1A2 phenotype in smokers, -2467 T-->delT having the main effect. This information is of interest for future studies assessing the possible role of tobacco smoke-inducible CYP1A2 genotypes as individual susceptibility factors in exposure to carcinogens.

A Genome-Wide Association Study Identifies GRK5 and RASGRP1 as Type 2 Diabetes Loci in Chinese Hans

PubMed Central

Li, Huaixing; Gan, Wei; Lu, Ling; Dong, Xiao; Han, Xueyao; Hu, Cheng; Yang, Zhen; Sun, Liang; Bao, Wei; Li, Pengtao; He, Meian; Sun, Liangdan; Wang, Yiqin; Zhu, Jingwen; Ning, Qianqian; Tang, Yong; Zhang, Rong; Wen, Jie; Wang, Di; Zhu, Xilin; Guo, Kunquan; Zuo, Xianbo; Guo, Xiaohui; Yang, Handong; Zhou, Xianghai; Zhang, Xuejun; Qi, Lu; Loos, Ruth J.F.; Hu, Frank B.; Wu, Tangchun; Liu, Ying; Liu, Liegang; Yang, Ze; Hu, Renming; Jia, Weiping; Ji, Linong; Li, Yixue; Lin, Xu

2013-01-01

Substantial progress has been made in identification of type 2 diabetes (T2D) risk loci in the past few years, but our understanding of the genetic basis of T2D in ethnically diverse populations remains limited. We performed a genome-wide association study and a replication study in Chinese Hans comprising 8,569 T2D case subjects and 8,923 control subjects in total, from which 10 single nucleotide polymorphisms were selected for further follow-up in a de novo replication sample of 3,410 T2D case and 3,412 control subjects and an in silico replication sample of 6,952 T2D case and 11,865 control subjects. Besides confirming seven established T2D loci (CDKAL1, CDKN2A/B, KCNQ1, CDC123, GLIS3, HNF1B, and DUSP9) at genome-wide significance, we identified two novel T2D loci, including G-protein–coupled receptor kinase 5 (GRK5) (rs10886471: P = 7.1 × 10−9) and RASGRP1 (rs7403531: P = 3.9 × 10−9), of which the association signal at GRK5 seems to be specific to East Asians. In nondiabetic individuals, the T2D risk-increasing allele of RASGRP1-rs7403531 was also associated with higher HbA1c and lower homeostasis model assessment of β-cell function (P = 0.03 and 0.0209, respectively), whereas the T2D risk-increasing allele of GRK5-rs10886471 was also associated with higher fasting insulin (P = 0.0169) but not with fasting glucose. Our findings not only provide new insights into the pathophysiology of T2D, but may also shed light on the ethnic differences in T2D susceptibility. PMID:22961080

Rescue of Tolerant CD8+ T Cells during Cancer Immunotherapy with IL2:Antibody Complexes.

PubMed

Klevorn, Lauryn E; Berrien-Elliott, Melissa M; Yuan, Jinyun; Kuehm, Lindsey M; Felock, Gregory D; Crowe, Sean A; Teague, Ryan M

2016-12-01

Interleukin-2 (IL2) was among the earliest reagents used for cancer immunotherapy due to its ability to support the survival and function of tumor-reactive T cells. However, treatment with IL2 is accompanied by off-target toxicity and low response rates in patients. In mouse models, these issues are largely overcome when IL2 is administered as a cytokine/antibody complex (IL2c). The complex has a longer serum half-life and can be designed for preferential cytokine delivery to specific cells of interest. Early studies showed IL2c could boost antitumor immunity in mice by activating tumor-reactive CD8 + T cells. But such functional T cells are often limited in the tumor microenvironment, where instead unresponsive tolerant T cells are eventually eliminated by apoptosis, representing a major obstacle to the success of cancer immunotherapy. We found that IL2c treatment rescued tumor-specific CD8 + T cells from a state of established tolerance, providing effective immunotherapy in tumor-bearing mice. Expression of the transcription factor T-bet was necessary to drive intratumoral IFNγ production and effector activity by T cells rescued with IL2c. Furthermore, IL2c promoted T-bet expression in human CD4 + and CD8 + T cells in humanized tumor-bearing mice, but also increased the frequency of Foxp3 + regulatory T cells. Our study reveals a novel role for IL2c as a powerful immunotherapeutic reagent capable of reversing tolerance in tumor-reactive T cells, and provides the first evidence that IL2c influences human T cells in vivo, highlighting the translational potential to modulate human antitumor immune responses. Cancer Immunol Res; 4(12); 1016-26. ©2016 AACR. ©2016 American Association for Cancer Research.

[Cardiovascular disease in patients with type 1 and type 2 diabetes in Spain].

PubMed

Ortega, Emilio; Amor, Antonio J; Rojo-Martínez, Gemma; Castell, Conxa; Giménez, Marga; Conget, Ignacio

2015-09-21

To describe the prevalence of cardiovascular disease (CVD) in type 1 diabetes (T1DM) and to compare it with that observed in type 2 diabetes (T2DM) and normal population in Spain. Cross-sectional study (18-70 years-old). Information on CVD was available from a nurse-administered questionnaire (Di@bet.es Study, NORMAL=3,430, T2DM=312) and from a physician reporting form (T1DM=1,382). Differences in the crude and adjusted prevalence of coronary heart (CHD), cerebrovascular (CNSD), peripheral vascular (PVD) and overall CV (CVD) disease were investigated between T1DM vs. NORMAL, and T1DM vs. T2DM groups. We found differences in age, body mass index, proportion of women, dyslipemia and antihypertensive medication between T1DM vs. NORMAL and T1DM vs. T2DM (all P<.001). Smoking prevalence was not different between T1DM vs. T2DM and it was lower in T1DM compared to NORMAL (P<.0001). The percentage of CHD, CNSD, PVD, and overall CVD in T1DM vs. NORMAL was 3.0 vs. 2.5 (P=.31), 0.70 vs. 1.10 (P=.22), 2.61 vs. 0.20 (P<.0001), and 5.1 vs. 3.44 (P<.01), respectively. The prevalence in T2DM (vs. T1DM) was 11.3 (P<.0001), 3.5 (P<.0001), 4.2 (P=.13), and 17% (P<.0001), respectively. Multiple logistic regression adjusted models showed a higher prevalence of CHD (odds ratio [OR] 2.27, 95% confidence interval [95% CI] 1.41-3.67), PVD (OR 15.35, 95% CI 5.61-42.04), and overall CVD (OR 2.32, 95% CI 1.55-3.46), but not for CNSD (OR 0.49, 95% CI 0.19-1.27) in T1DM compared to NORMAL. No differences were found between T1DM and T2DM. We found a higher prevalence of CVD in a Mediterranean population of T1DM individuals compared with non-diabetic subjects. This prevalence was similar to that observed in T2DM. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Eating patterns and type 2 diabetes risk in men: breakfast omission, eating frequency, and snacking1234

PubMed Central

Mekary, Rania A; Giovannucci, Edward; Willett, Walter C; van Dam, Rob M

2012-01-01

Background: Little is known about the association between eating patterns and type 2 diabetes (T2D) risk. Objective: The objective of this study was to prospectively examine associations between breakfast omission, eating frequency, snacking, and T2D risk in men. Design: Eating patterns were assessed in 1992 in a cohort of 29,206 US men in the Health Professionals Follow-Up Study who were free of T2D, cardiovascular disease, and cancer and were followed for 16 y. We used Cox proportional hazards analysis to evaluate associations with incident T2D. Results: We documented 1944 T2D cases during follow-up. After adjustment for known risk factors for T2D, including BMI, men who skipped breakfast had 21% higher risk of T2D than did men who consumed breakfast (RR: 1.21; 95% CI: 1.07, 1.35). Compared with men who ate 3 times/d, men who ate 1–2 times/d had a higher risk of T2D (RR: 1.25; 95% CI: 1.08, 1.45). These findings persisted after stratification by BMI or diet quality. Additional snacks beyond the 3 main meals (breakfast, lunch, and dinner) were associated with increased T2D risk, but these associations were attenuated after adjustment for BMI. Conclusions: Breakfast omission was associated with an increased risk of T2D in men even after adjustment for BMI. A direct association between snacking between meals and T2D risk was mediated by BMI. PMID:22456660

Magnetic resonance transverse relaxation time T2 of knee cartilage in osteoarthritis at 3-T: a cross-sectional multicentre, multivendor reproducibility study.

PubMed

Balamoody, Sharon; Williams, Tomos G; Wolstenholme, Chris; Waterton, John C; Bowes, Michael; Hodgson, Richard; Zhao, Sha; Scott, Marietta; Taylor, Chris J; Hutchinson, Charles E

2013-04-01

The transverse relaxation time (T2) in MR imaging has been identified as a potential biomarker of hyaline cartilage pathology. This study investigates whether MR assessments of T2 are comparable between 3-T scanners from three different vendors. Twelve subjects with symptoms of knee osteoarthritis and one or more risk factors had their knee scanned on each of the three vendors' scanners located in three sites in the U.K. MR data acquisition was based on the United States National Institutes of Health Osteoarthritis Initiative protocol. Measures of cartilage T2 and R2 (inverse of T2) were computed for precision error assessment. Intrascanner reproducibility was also assessed with a phantom (all three scanners) and a cohort of 5 subjects (one scanner only). Whole-organ magnetic resonance (WORM) semiquantitative cartilage scores ranged from minimal to advanced degradation. Intrascanner R2 root-mean-square coefficients of variation (RMSCOV) were low, within the range 2.6 to 6.3% for femoral and tibial regions. For one scanner pair, mean T2 differences ranged from -1.2 to 2.8 ms, with no significant difference observed for the medial tibia and patella regions (p < 0.05). T2 values from the third scanner were systematically lower, producing interscanner mean T2 differences within the range 5.4 to 10.0 ms. Significant interscanner cartilage T2 differences were found and should be accounted for before data from scanners of different vendors are compared.

The effectiveness of structured exercise in the south Asian population with type 2 diabetes: a systematic review.

PubMed

Albalawi, Hani; Coulter, Elaine; Ghouri, Nazim; Paul, Lorna

2017-11-01

The impact of exercise interventions on south Asians with type 2 diabetes (T2DM), who have a higher T2DM incidence rate compared to other ethnic groups, is inconclusive. This study aimed to systematically review the effect of exercise interventions in south Asians with T2DM. Five electronic databases were searched up to April 2017 for controlled trials investigating the impact of exercise interventions on south Asian adults with T2DM. The PEDro scale was used to assess the quality of the included studies. Eighteen trials examining the effect of aerobic, resistance, balance or combined exercise programs met the eligibility criteria. All types of exercise were associated with improvements in glycemic control, blood pressure, waist circumference, blood lipids, muscle strength, functional mobility, quality of life or neuropathy progression. The majority of included studies were of poor methodological quality. Few studies compared different types or dose of exercise. In conclusion, this review supports the benefits of exercise for south Asians with T2DM, although it was not possible to identify the most effective exercise prescription. Further studies of good methodological quality are required to determine the most effective dosage and type of exercise to manage T2DM in this population.

Functional genetic variants within the SIRT2 gene promoter in type 2 diabetes mellitus.

PubMed

Liu, Tingting; Yang, Wentao; Pang, Shuchao; Yu, Shipeng; Yan, Bo

2018-03-01

Type 2 diabetes mellitus (T2D) is a common and complex metabolic diseases caused by interactions between environmental and genetic factors. Genome-wide association studies have identified more than 80 common genetic variants for T2D, which account for only ∼10% of the heritability of T2D cases. SIRT2, a member of NAD(+)-dependent class III deacetylases, is involved in genomic stability, metabolism, inflammation, oxidative stress and autophagy. In maintaining metabolic homeostasis, SIRT2 regulates adipocyte differentiation, fatty acid oxidation, gluconeogenesis, and insulin sensitivity. Thus, we hypothesized that DNA sequence variants (DSVs) in SIRT2 gene promoter may change SIRT2 levels, contributing to T2D. SIRT2 gene promoter was genetically and functionally analyzed in large cohorts of T2D patients (n = 365) and ethnic-matched controls (n = 358). A total of 18 DSVs, including 5 SNPs, were identified in this study. Four novel heterozygous DSVs (g.38900912G > T, g.38900561C > T, g.38900359C > T and g.38900237G > A) were identified in four T2D patients, three of which (g.38900912G > T, g.38900359C > T and g.38900237G > A) significantly increased the transcriptional activity of the SIRT2 gene promoter in cultured pancreatic beta cells (P < .01). Seven novel heterozygous DSVs were only found in controls, and one heterozygous deletion DSV and five SNPs were found in both T2D patients and controls, which did not significantly affect SIRT2 gene promoter activity (P > .05). Our findings suggested that the DSVs may increase SIRT2 gene promoter activity and SIRT2 levels, contributing to T2D development as a risk factor. Copyright © 2018 Elsevier B.V. All rights reserved.

Doping evolution of the anisotropic upper critical fields in the iron-based superconductor Ba 1-xK xFe 2As 2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tanatar, Makariy A.; Liu, Yong; Jaroszynski, J.

In-plane resistivity measurements as a function of temperature and magnetic field up to 35 T with precise orientation within the crystallographic ac plane were used to study the upper critical field H c2 of the hole-doped iron-based superconductor Ba 1–xK xFe 2As 2. Compositions of the samples studied spanned from under- doped x=0.17 (T c=12 K) and x=0.22 (T c=20 K), both in the coexistence range of stripe magnetism and superconductivity, through optimal doping x=0.39 (T c=38.4 K) and x=0.47 (T c=37.2 K), to overdoped x=0.65 (T c=22 K) and x=0.83 (T c=10 K). Here, we find notable doping asymmetrymore » of the shapes of the anisotropic H c2(T), suggesting the important role of paramagnetic limiting effects in the H∥a configuration in overdoped compositions and multiband effects in underdoped compositions.« less

Doping evolution of the anisotropic upper critical fields in the iron-based superconductor Ba 1-xK xFe 2As 2

DOE PAGES

Tanatar, Makariy A.; Liu, Yong; Jaroszynski, J.; ...

2017-11-14

In-plane resistivity measurements as a function of temperature and magnetic field up to 35 T with precise orientation within the crystallographic ac plane were used to study the upper critical field H c2 of the hole-doped iron-based superconductor Ba 1–xK xFe 2As 2. Compositions of the samples studied spanned from under- doped x=0.17 (T c=12 K) and x=0.22 (T c=20 K), both in the coexistence range of stripe magnetism and superconductivity, through optimal doping x=0.39 (T c=38.4 K) and x=0.47 (T c=37.2 K), to overdoped x=0.65 (T c=22 K) and x=0.83 (T c=10 K). Here, we find notable doping asymmetrymore » of the shapes of the anisotropic H c2(T), suggesting the important role of paramagnetic limiting effects in the H∥a configuration in overdoped compositions and multiband effects in underdoped compositions.« less

Medical school predictors of later perceived mastery of clinical work among Norwegian doctors: a cohort study with 10-year and 20-year follow-up

PubMed Central

Belfrage, Anna; Grotmol, Kjersti Støen; Lien, Lars; Moum, Torbjørn; Wiese, Ragna Veslemøy; Tyssen, Reidar

2017-01-01

Objective Doctors’ self-perceived mastery of clinical work might have an impact on their career and patient care, in addition to their own health and well-being. The aim of this study is to identify predictors at medical school of perceived mastery later in doctors’ careers. Design A cohort of medical students (n=631) was surveyed in the final year of medical school in 1993/1994 (T1), and 10 (T2) and 20 (T3) years later. Setting Nationwide healthcare institutions. Participants Medical students from all universities in Norway. Main outcome measures Perceived mastery of clinical work was measured at T2 and T3. The studied predictors measured at T1 included personality traits, medical school stress, perceived medical recording skills, identification with the role of doctor, hazardous drinking and drinking to cope, in addition to age and gender. Effects were studied using multiple linear regression models. Results Response rates: T1, 522/631 (83%); T2, 390/522 (75%); and T3, 303/522 (58%). Mean scores at T2 and T3 were 22.3 (SD=4.2) and 24.5 (3.0) (t=8.2, p<0.001), with no gender difference. Adjusted associations at T2 were: role identification (β=0.16; p=0.006; 95% CI 0.05 to 0.28), perceived medical recording skills (β=0.13; p=0.02; 95% CI 0.02 to 0.24) and drinking to cope (β=–2.45; p=0.001; 95% CI –3.88 to –1.03). Adjusted association at T3 was perceived medical recording skills (β=0.11; p=0.015; 95% CI 0.02 to 0.21). Conclusions Perceived medical recording skills and role identification were associated with higher perceived mastery. Medical schools should provide experiences, teaching and assessment to enhance students’ physician role identification and confidence in their own skills. Drinking to cope was associated with lower perceived mastery, which indicates the importance of acquiring healthier coping strategies in medical school. PMID:28947437

Hybrid nanotrimers for dual T 1 and T 2-weighted magnetic resonance imaging

DOE PAGES

Cheng, Kai; Yang, Meng; Zhang, Ruiping; ...

2014-10-04

Development of multifunctional nanoparticle-based probes for dual T 1- and T 2-weighted magnetic resonance imaging (MRI) could allow us to image and diagnose the tumors or other abnormalities in an exceptionally accurate and reliable manner. In this study, by fusing distinct nanocrystals via solid-state interfaces, we built hybrid heteronanostructures to combine both T 1 and T 2- weighted contrast agents together for MRI with high accuracy and reliability. The resultant hybrid heterotrimers showed high stability in physiological conditions and could induce both simultaneous positive and negative contrast enhancements in MR images. Small animal positron emission tomography imaging study revealed thatmore » the hybrid heterostructures displayed favorable biodistribution and were suitable for in vivo imaging. Furthermore, their potential as dual contrast agents for T 1 and T 2-weighted MRI was further demonstrated by in vitro and in vivo imaging and relaxivity measurements.« less

Impact of a Serious Videogame Designed for Flexible Insulin Therapy on the Knowledge and Behaviors of Children with Type 1 Diabetes: The LUDIDIAB Pilot Study.

PubMed

Joubert, Michael; Armand, Coline; Morera, Julia; Tokayeva, Leyla; Guillaume, Aurore; Reznik, Yves

2016-02-01

Flexible (or functional) insulin therapy method is a self-management education approach for intensive insulin therapy in patients with type 1 diabetes. The serious game (or applied game) "L'Affaire Birman" ("Mr. Birman's File") (available at www.gluciweb.com ) was specifically designed as an educational tool for the flexible insulin therapy method. Its educational impact was evaluated in children with type 1 diabetes. This prospective multicenter pilot study evaluated the effect of this videogame on the therapeutic knowledge and behavior of children with type 1 diabetes. PedCarbQuiz (PCQ) and Diabetes Self-Management Profile (DSMP) questionnaires were used before (T0), immediately after (T1), and 6 months after (T2) the unstructured use of the videogame. The 38 children enrolled in the study were 42% boys and 58% girls; they had a mean age of 13.7 ± 2.1 years old, a diabetes duration of 6.0 ± 3.8 years, and hemoglobin A1c (HbA1c) levels of 8.5 ± 1.4% (69.4 ± 9.4 mmol/mol). The children connected to the game 3.3 ± 2.8 times during this 6-month study. Their PCQ score increased from 31.6 ± 4.9 at T0 to 36.0 ± 4.0 at T2 (P < 0.05). Two PCQ subscores also increased significantly: the insulin titration score at T1 and T2 and the carbohydrate quantification score at T2. Conversely, the DSMP score was not different at T0, T1, and T2 (59.1 ± 9.9, 60.2 ± 9.8, and 60.0 ± 10.0, respectively), and HbA1c levels also remained stable throughout the study (8.4 ± 1.3%, 8.4 ± 1.2%, and 8.5 ± 1.5% at T0, T1, and T2, respectively). Subgroup analysis found a greater impact of the game in children with poor glycemic control and low knowledge at baseline. Adherence to the game was rather low (half of the children played less than 2.5 bouts), but no criterion was found to be predictive of this low attractiveness. Nonsupervised usage of the serious game "L'Affaire Birman" was able to improve insulin titration and carbohydrate quantification in children with type 1 diabetes.

Burden, quality of life, and social support in caregivers of patients undergoing radiotherapy for head and neck cancer: A pilot study

PubMed Central

Nightingale, Chandylen L; Curbow, Barbara A; Wingard, John R; Pereira, Deidre B; Carnaby, Giselle D

2017-01-01

Objective The purpose of this pilot study was to (1) obtain preliminary data on changes in burden and quality of life in head and neck cancer caregivers during and shortly following patient radiotherapy, (2) assess the relationship between perceived social support and burden as well as perceived social support and quality of life in caregivers during radiotherapy, and (3) identify preferences for sources of support among caregivers during radiotherapy. Methods Caregivers completed burden and quality of life instruments at the start of patient radiotherapy (T1), 5 weeks into radiotherapy (T2), and 1 month post-radiotherapy (T3) and instruments for perceived social support and support preferences at T2 only. Results Caregivers showed a trend toward increased burden and worsened quality of life for the majority of subscales at T2 or T3 than at T1. Caregivers reported significantly lower esteem and significantly greater disruption at T2 than at T1 and significantly worse health at T3 than at T2. Higher perceived social support was typically associated with lower burden and higher quality of life at T2. Spouses/partners were the most commonly preferred source of support. Discussion These pilot findings suggest that caregivers experience psychosocial impairments during and shortly after patient radiotherapy, but more research using larger samples is warranted. PMID:27068111

Medical claims-based case-control study of temporal relationship between clinical visits for hand syndromes and subsequent diabetes diagnosis: implications for identifying patients with undiagnosed type 2 diabetes mellitus.

PubMed

Hou, Wen-Hsuan; Li, Chung-Yi; Chen, Lu-Hsuan; Wang, Liang-Yi; Kuo, Li-Chieh; Kuo, Ken N; Shen, Hsiu-Nien; Chiu, Chang-Ta

2016-10-20

To investigate whether a temporal relationship is present between clinical visits for diabetes-related hand syndromes (DHSs) and subsequent type 2 diabetes mellitus (T2DM) diagnosis and, accordingly, whether DHSs can be used for identifying patients with undiagnosed T2DM. This study had a case-control design nested within a cohort of 1 million people from the general population, which was followed from 2005 to 2010. The odds of prior clinical visits for DHSs, namely carpal tunnel syndrome (CTS), flexor tenosynovitis, limited joint mobility and Dupuytren's disease, were estimated for cases and controls. We used a conditional logistic regression model to estimate the OR and 95% CI of T2DM in association with a history of DHSs. The validity and predictive value of using the history of DHSs in predicting T2DM diagnosis were calculated. Taiwan National Health Insurance medical claims. We identified 33 571 patients receiving a new diagnosis of T2DM (cases) between 2005 and 2010. Each T2DM case was matched with 5 controls who had the same sex and birth year and were alive on the date of T2DM diagnosis. The primary outcome measure was T2DM diagnosis. The OR of T2DM in association with prior clinical visits was significantly increased for overall DHS and CTS, being 1.15 (95% CI 1.10 to 1.20) and 1.22 (95% CI 1.16 to 1.29), respectively. Moreover, 11% of patients with T2DM made clinical visits for CTS within 3 months prior to T2DM diagnosis. The history of DHSs had low sensitivity (<0.1% to 5.2%) and a positive predictive value (9.9% to 11.7%) in predicting T2DM. Despite the unsatisfactory validity and performance of DHSs as a clinical tool for detecting patients with undiagnosed T2DM, this study provided evidence that clinical visits for DHSs, particularly for CTS, can be a sign of undiagnosed T2DM. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Mud-bath therapy and oral glucosamine sulfate in patients with knee osteoarthritis: a randomized, controlled, crossover study.

PubMed

Peluso, Rosario; Caso, Francesco; Costa, Luisa; Sorbo, Dario; Carraturo, Nello; Di Minno, Matteo Nicola Dario; Carraturo, Federica; Oriente, Alfonso; Balestrieri, Umberto; Minicucci, Annamaria; Del Puente, Antonio; Scarpa, Raffaele

2016-01-01

To evaluate the efficacy and safety of combined treatment of mud-bath therapy and glucosamine crystalline sulfate (GlcN-S) in patients with knee osteoarthritis (OA). This study was a randomised, controlled, crossover investigation. Patients were randomly assigned (1:1) by the investigators to two groups, named group 1 and 2. Group 1 included twenty-three patients receiving oral GlcN-S treatment from the beginning of the study (T0) to the end of the 3rd month of treatment (T3) and a combined treatment of both mud-bath therapy and GlcN-S from T3 to the end of the study at six months (T6). Group 2 included twenty-two patients receiving a combined treatment of both mud-bath therapy and GlcN-S from T0 to T3 and that discontinued mud-bath therapy, receiving GlcN-S treatment alone, from T3 to T6. Primary endpoints of the study consisted of evaluating OA severity and activity at baseline and at follow-up visits. All 45 patients, eligible for the study, completed the period of the crossover. In group 1, no significant difference was shown in the comparison from T0 to T3, while from T3 to T6 most variables were significantly improved. In group 2, instead, the comparison between T0 and T3 showed a significant difference in different parameters. When comparing T3 and T6, despite an improvement of all the variables, no significant difference was shown. The association of GlcN-S and mud-bath therapy has a positive and safe role in improving pain, function and quality of life in knee OA patients.

Population specific impact of genetic variants in KCNJ11 gene to type 2 diabetes: a case-control and meta-analysis study.

PubMed

Phani, Nagaraja M; Guddattu, Vasudeva; Bellampalli, Ravishankara; Seenappa, Venu; Adhikari, Prabha; Nagri, Shivashankara K; D Souza, Sydney C; Mundyat, Gopinath P; Satyamoorthy, Kapaettu; Rai, Padmalatha S

2014-01-01

Potassium inwardly rectifying channel, subfamily J, member 11 (KCNJ11) gene have a key role in insulin secretion and is of substantial interest as a candidate gene for type 2 diabetes (T2D). The current work was performed to delineate the genetic influence of KCNJ11 polymorphisms on risk of T2D in South Indian population through case-control association study along with systematic review and meta-analysis. A case-control study of 400 T2D cases and controls of South Indian origin were performed to analyze the association of KCNJ11 polymorphisms (rs5219, rs5215, rs41282930, rs1800467) and copy number variations (CNV) on the risk of T2D. In addition a systematic review and meta-analysis for KCNJ11 rs5219 was conducted in 3,831 cases and 3,543 controls from 5 published reports from South-Asian population by searching various databases. Odds ratio with 95% confidence interval (CI) was used to assess the association strength. Cochran's Q, I2 statistics were used to study heterogeneity between the eligible studies. KCNJ11 rs5215, C-G-C-C haplotype and two loci analysis (rs5219 vs rs1800467) showed a significant association with T2D but CNV analysis did not show significant variation between T2D cases and control subjects. Lower age of disease onset (P = 0.04) and higher body mass index (BMI) (P = 0.04) were associated with rs5219 TT genotype in T2D patients. The meta-analysis of KCNJ11 rs5219 on South Asian population showed no association on susceptibility to T2D with an overall pooled OR = 0.98, 95% CI = 0.83-1.16. Stratification analysis showed East Asian population and global population were associated with T2D when compared to South Asians. KCNJ11 rs5219 is not independently associated with T2D in South-Indian population and our meta-analysis suggests that KCNJ11 polymorphism (rs5219) is associated with risk of T2D in East Asian population and global population but this outcome could not be replicated in South Asian sub groups.

The impact of common dopamine D2 receptor gene polymorphisms on D2/3 receptor availability: C957T as a key determinant in putamen and ventral striatum.

PubMed

Smith, C T; Dang, L C; Buckholtz, J W; Tetreault, A M; Cowan, R L; Kessler, R M; Zald, D H

2017-04-11

Dopamine function is broadly implicated in multiple neuropsychiatric conditions believed to have a genetic basis. Although a few positron emission tomography (PET) studies have investigated the impact of single-nucleotide polymorphisms (SNPs) in the dopamine D2 receptor gene (DRD2) on D2/3 receptor availability (binding potential, BP ND ), these studies have often been limited by small sample size. Furthermore, the most commonly studied SNP in D2/3 BP ND (Taq1A) is not located in the DRD2 gene itself, suggesting that its linkage with other DRD2 SNPs may explain previous PET findings. Here, in the largest PET genetic study to date (n=84), we tested for effects of the C957T and -141C Ins/Del SNPs (located within DRD2) as well as Taq1A on BP ND of the high-affinity D2 receptor tracer 18 F-Fallypride. In a whole-brain voxelwise analysis, we found a positive linear effect of C957T T allele status on striatal BP ND bilaterally. The multilocus genetic scores containing C957T and one or both of the other SNPs produced qualitatively similar striatal results to C957T alone. The number of C957T T alleles predicted BP ND in anatomically defined putamen and ventral striatum (but not caudate) regions of interest, suggesting some regional specificity of effects in the striatum. By contrast, no significant effects arose in cortical regions. Taken together, our data support the critical role of C957T in striatal D2/3 receptor availability. This work has implications for a number of psychiatric conditions in which dopamine signaling and variation in C957T status have been implicated, including schizophrenia and substance use disorders.

Population attributable fraction of type 2 diabetes due to physical inactivity in adults: a systematic review.

PubMed

Al Tunaiji, Hashel; Davis, Jennifer C; Mackey, Dawn C; Khan, Karim M

2014-05-18

Physical inactivity is a global pandemic. The population attributable fraction (PAF) of type 2 diabetes mellitus (T2DM) associated with physical inactivity ranges from 3% to 40%. The purpose of this systematic review was to determine the best estimate of PAF for T2DM attributable to physical inactivity and absence of sport participation or exercise for men and women. We conducted a systematic review that included a comprehensive search of MEDLINE, EMBASE, SportDiscus, and CINAHL (1946 to April 30 2013) limited by the terms adults and English. Two reviewers screened studies, extracted PAF related data and assessed the quality of the selected studies. We reconstructed 95% CIs for studies missing these data using a substitution method. Of the eight studies reporting PAF in T2DM, two studies included prospective cohort studies (3 total) and six were reviews. There were distinct variations in quality of defining and measuring physical inactivity, T2DM and adjusting for confounders. In the US, PAFs for absence of playing sport ranged from 13% (95% CI: 3, 22) in men and 29% (95% CI: 17, 41) in women. In Finland, PAFs for absence of exercise ranged from 3% (95% CI: -11, 16) in men to 7% (95% CI: -9, 20) in women. The PAF of physical inactivity due to T2DM is substantial. Physical inactivity is a modifiable risk factor for T2DM. The contribution of physical inactivity to T2DM differs by sex; PAF also differs if physical inactivity is defined as the absence of 'sport' or absence of 'exercise'.

Grip strength is not associated with incident type 2 diabetes mellitus in healthy adults: The CoLaus study.

PubMed

Marques-Vidal, Pedro; Vollenweider, Peter; Waeber, Gérard; Jornayvaz, François R

2017-10-01

We examined the association of grip strength with incident type 2 diabetes mellitus (T2DM) in healthy subjects initially aged 50 to 75years after a follow-up of 5.5years and 10.7years. This was a prospective, population-based study derived from the CoLaus (Cohorte Lausannoise) study including 2318 participants (aged 60.2y; 1354 women) free from T2DM at baseline. Grip strength was assessed using a handheld dynamometer. The effect of grip strength on the incidence of T2DM was analyzed by logistic regression. After a follow-up of 5.5years, 190 (8.2%) T2DM cases were identified. In bivariate analysis, participants who developed T2DM had a higher absolute grip strength (35.3±10.6 versus 33.2±10.7kg, P=0.013). Analysis between grip strength expressed in 5kg increment and incident TD2M showed a negative association when adjusted for age and sex [ORs (95% CI): 0.88 (0.79, 0.98)], or for age, sex and body mass index (BMI) [ORs (95% CI): 0.87 (0.78, 097)]. After a follow-up of 10.7years, 131 supplemental (7.3%) T2DM cases were identified, but there was no association between grip strength and incident T2DM in bivariate and multivariable analysis, potentially due to a lack of statistical power. In non elderly healthy adults, the risk of incident T2DM is overall not associated with grip strength over a maximum follow-up of 10.7years. Future studies are warranted to better assess the association between grip strength and incident T2DM in bigger and even younger cohorts. Copyright © 2017 Elsevier B.V. All rights reserved.

Predicting change over time in career planning and career exploration for high school students.

PubMed

Creed, Peter A; Patton, Wendy; Prideaux, Lee-Ann

2007-06-01

This study assessed 166 high school students in Grade 8 and again in Grade 10. Four models were tested: (a) whether the T1 predictor variables (career knowledge, indecision, decision-making self efficacy, self-esteem, demographics) predicted the outcome variable (career planning/exploration) at T1; (b) whether the T1 predictor variables predicted the outcome variable at T2; (c) whether the T1 predictor variables predicted change in the outcome variable from T1-T2; and (d) whether changes in the predictor variables from T1-T2 predicted change in the outcome variable from T1-T2. Strong associations (R(2)=34%) were identified for the T1 analysis (confidence, ability and paid work experience were positively associated with career planning/exploration). T1 variables were less useful predictors of career planning/exploration at T2 (R(2)=9%; having more confidence at T1 was associated with more career planning/exploration at T2) and change in career planning/exploration from T1-T2 (R(2)=11%; less confidence and no work experience were associated with change in career planning/exploration from T1-T2). When testing effect of changes in predictor variables predicting changes in outcome variable (R(2)=22%), three important predictors, indecision, work experience and confidence, were identified. Overall, results indicated important roles for self-efficacy and early work experiences in current and future career planning/exploration of high school students.

Metabolic Syndrome and Serum Liver Enzymes Level at Patients with Type 2 Diabetes Mellitus

PubMed Central

Music, Miralem; Dervisevic, Amela; Pepic, Esad; Lepara, Orhan; Fajkic, Almir; Ascic-Buturovic, Belma; Tuna, Enes

2015-01-01

Objectives: The aim of this study was to evaluate liver function in patients with type 2 diabetes mellitus (T2DM) with and without metabolic syndrome (MS) by determining serum levels of gamma glutamyltransferase (GGT), alanine aminotransferase (ALT) and aspartate aminotransferase (AST). We also investigated correlation between levels of liver enzymes and some components of MS in both groups of patients. Methods: This cross-sectional study included 96 patients (age 47–83 years) with T2DM. All patients were divided according to the criteria of the National Cholesterol Education Program (NCEP) in two groups: 50 patients with T2 DM and MS (T2DM-MS) and 46 patients with T2DM without MS (T2DM-Non MS). The analysis included blood pressure monitoring and laboratory tests: fasting blood glucose (FBG), total lipoprotein cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), fibrinogen and liver enzymes: GGT, ALT and AST. T2DM-MS group included patients which had FBG ≥ 6,1 mmol/L, TG ≥ 1,7 mmol/L and blood pressure ≥ 130/85 mm Hg. Results: T2DM-MS patients had significant higher values of systolic blood pressure, diastolic blood pressure and medium arterial pressure compared to T2DM-Non MS patients. Serum levels of TC, TG, LDL-C, VLDL-C and FBG were significantly higher in the T2DM-MS group compared to the T2DM-Non MS group. Serum fibrinogen level and GGT level were significantly higher in patients with T2DM-MS compared to the serum fibrinogen level and GGT level in T2DM-Non MS patients. Mean serum AST and ALT level were higher, but not significantly, in patients with T2DM and MS compared to the patients with T2DM without MS. Significant negative correlations were observed between TC and AST (r= -0,28, p<0,05), as well as between TC and ALT level (r= -0,29, p<0,05) in T2DM-MS group of patients. Conclusion: These results suggest that patients with T2DM and MS have markedly elevated liver enzymes. T2DM and MS probably play a role in increasing the risk of liver injury. PMID:26543313

TCF7L2 rs7903146 polymorphism and diabetic nephropathy association is not independent of type 2 diabetes--a study in a south Indian population and meta-analysis.

PubMed

Hussain, Hajarah; Ramachandran, Vinu; Ravi, Samathmika; Sajan, Teena; Ehambaram, Kiruthiha; Gurramkonda, Venkatesh Babu; Ramanathan, Gnanasambandan; Bhaskar, Lakkakula Venkata

2014-01-01

Diabetic nephropathy (DN) is a chronic microangiopathic complication of both type 1 (T1DM) and type 2 diabetes mellitus (T2DM). The TCF7L2 gene has been reported to be associated with type 2 diabetes risk. We aimed to investigate the impact of TCF7L2 gene on the susceptibility of T2DM and DN in a south Indian population. Plus to evaluate the association of rs7903146 in the TCF7L2 gene with T2DM in the Indian population. The subjects recruited for this included 55 diabetic cases with diabetic nephropathy, 68 diabetic cases without nephropathy, and 82 non-diabetic healthy controls. Genomic DNA was isolated from blood and genotyping of TCF7L2 rs7903146 was performed by PCR-RFLP analysis. A literature survey was carried out into the effect of rs7903146 on genetic susceptibility to T2DM in Indian populations and we then performed a meta-analysis in order to evaluate its association with T2DM. Analysis of TCF7L2 rs7903146 in normal controls and diabetics with or without nephropathy demonstrated that the 'T' allele is associated with both diabetes (p = 0.049) and DN (p = 0.024), but this association is not independent of T2DM. Meta-analysis showed that the mutant allele and genotypes are associated with T2DM in Indian populations. In summary, a significant association exists between the 'T' allele and DN, but this association is not independent of T2DM. Pooled meta-analysis of studies on rs7903146 and T2DM confirmed that rs7903146 is significantly associated with susceptibility to T2DM in Indian populations.

Biochemical and molecular study on interleukin-1β gene expression and relation of single nucleotide polymorphism in promoter region with Type 2 diabetes mellitus.

PubMed

Tayel, Safaa I; Fouda, Eman A M; Elshayeb, Elsayed I; Eldakamawy, Asmaa R A; El-Kousy, Salah M

2018-01-11

Interleukin-1β (IL-1β) assumes a centric role in the regulation of immune and inflammatory responses and thus has been recognized in immune mediated diseases like type 2 diabetes mellitus (T2DM). We aimed to investigate expressed level of IL-1β and its relation with IL-1β -511T>C polymorphism in T2DM patients. This study enrolled 80 subjects (50 patients with T2DM and 30 healthy control subjects). Laboratory investigations included fasting (FBG) and 2 h postprandial blood sugar (2 h PBG), HBA1c, lipid profile, and renal function tests. Genotyping of IL-1β -511T>C (rs16944) SNP assay by real-time PCR and relative quantitation of IL-1β gene expression transcript by real-time PCR. T2DM patients had significantly higher FBG and 2 h PBG, HBA1c, LDLc, TC, TG, systolic, and diastolic BP while lower HDLc compared with control group. IL 1- β -511 T>C, CC genotype and C allele were significantly associated with risk of T2DM with odds ratio (OR) 4.73, 95%CI (1.21-18.39) and OR 2.27, 95%CI (1.72-4.40), respectively. Moreover, diabetic patients had significantly higher IL 1- β gene transcript compared with control group (P < 0.001). CC genotype of IL 1- β -511 T > C had the highest significant level of IL 1- β gene transcript demonstrated compared with C/T and T/T genotypes (P < 0.001) in patients. C allele of IL-1 β -511 T >C could be considered risk factor contributor to T2DM and excess level of IL-1 β transcript may disclose to some degree the inflammatory role of cytokines in T2DM. © 2018 Wiley Periodicals, Inc.

Posttraumatic growth and depreciation six years after the 2004 tsunami.

PubMed

Michélsen, Hans; Therup-Svedenlöf, Charlotte; Backheden, Magnus; Schulman, Abbe

2017-01-01

Background : Posttraumatic growth (PTG) has been reported after various types of potentially traumatic events, as a part of the personal recovery process among survivors. Even negative changes in survivors' life view, known as posttraumatic depreciation (PTD), have been identified as an additional aspect in the personal recovery processes. Objective : To examine how the type of exposure experienced by survivors of a natural disaster, the 2004 Southeast Asia tsunami, influenced self-reported PTG and PTD six years later (T2). Additionally, the study examined the relations between psychological distress and posttraumatic stress symptoms (PTSS) 14 months after the disaster (T1), to PTG and PTD, respectively at T2. Finally, the study examined whether psychological distress and PTSS (T1) could have a mediating effect on PTG and PTD at T2. Method : The participants were 848 tsunami survivors living in Stockholm, Sweden who responded to a questionnaire at 14 months (T1) and six years (T2) after the tsunami. The material was analysed using linear regression and pathway analysis. PTG and PTD were measured on separate scales. Results : The type of exposure was significant related to both PTG and PTD six years later (T2). Those experiencing a combination of various types of exposure (including threat to life and bereavement) reported higher scores for both PTG and PTD. There were significant positive correlations between PTSS at T1 and PTG /PTD at T2, and somewhat lower correlations between psychological distress at T1 and PTG/PTD at T2. Both PTSS and psychological distress at T1 were significant mediating variables for both PTG and PTD at T2. Conclusions : Studying survivors' various types of exposure and subsequent changed view of life - both PTG and PTD - resulted in a broadened understanding of the complexity of reactions and the recovery process among survivors.

Posttraumatic growth and depreciation six years after the 2004 tsunami

PubMed Central

Michélsen, Hans; Therup-Svedenlöf, Charlotte; Backheden, Magnus; Schulman, Abbe

2017-01-01

ABSTRACT Background: Posttraumatic growth (PTG) has been reported after various types of potentially traumatic events, as a part of the personal recovery process among survivors. Even negative changes in survivors’ life view, known as posttraumatic depreciation (PTD), have been identified as an additional aspect in the personal recovery processes. Objective: To examine how the type of exposure experienced by survivors of a natural disaster, the 2004 Southeast Asia tsunami, influenced self-reported PTG and PTD six years later (T2). Additionally, the study examined the relations between psychological distress and posttraumatic stress symptoms (PTSS) 14 months after the disaster (T1), to PTG and PTD, respectively at T2. Finally, the study examined whether psychological distress and PTSS (T1) could have a mediating effect on PTG and PTD at T2. Method: The participants were 848 tsunami survivors living in Stockholm, Sweden who responded to a questionnaire at 14 months (T1) and six years (T2) after the tsunami. The material was analysed using linear regression and pathway analysis. PTG and PTD were measured on separate scales. Results: The type of exposure was significant related to both PTG and PTD six years later (T2). Those experiencing a combination of various types of exposure (including threat to life and bereavement) reported higher scores for both PTG and PTD. There were significant positive correlations between PTSS at T1 and PTG /PTD at T2, and somewhat lower correlations between psychological distress at T1 and PTG/PTD at T2. Both PTSS and psychological distress at T1 were significant mediating variables for both PTG and PTD at T2. Conclusions: Studying survivors’ various types of exposure and subsequent changed view of life – both PTG and PTD – resulted in a broadened understanding of the complexity of reactions and the recovery process among survivors. PMID:28451069