Parameterization retrieval of trace gas volume mixing ratios from Airborne MAX-DOAS

DOE PAGES

Dix, Barbara; Koenig, Theodore K.; Volkamer, Rainer

2016-11-28

We present a parameterization retrieval of volume mixing ratios (VMRs) from differential slant column density (dSCD) measurements by Airborne Multi-AXis Differential Optical Absorption Spectroscopy (AMAX-DOAS). The method makes use of the fact that horizontally recorded limb spectra (elevation angle 0°) are strongly sensitive to the atmospheric layer at instrument altitude. These limb spectra are analyzed using reference spectra that largely cancel out column contributions from above and below the instrument, so that the resulting limb dSCDs, i.e., the column integrated concentration with respect to a reference spectrum, are almost exclusively sensitive to the atmospheric layers around instrument altitude. The conversionmore » of limb dSCDs into VMRs is then realized by calculating box air mass factors (Box-AMFs) for a Rayleigh atmosphere and applying a scaling factor constrained by O 4 dSCDs to account for aerosol extinction. An iterative VMR retrieval scheme corrects for trace gas profile shape effects. Benefits of this method are (1) a fast conversion that only requires the computation of Box-AMFs in a Rayleigh atmosphere; (2) neither local aerosol extinction nor the slant column density in the DOAS reference (SCD ref) needs to be known; and (3) VMRs can be retrieved for every measurement point along a flight track, thus increasing statistics and adding flexibility to capture concentration gradients. Sensitivity studies are performed for bromine monoxide (BrO), iodine monoxide (IO) and nitrogen dioxide (NO 2), using (1) simulated dSCD data for different trace gas and aerosol profiles and (2) field measurements from the Tropical Ocean tRoposphere Exchange of Reactive halogen species and Oxygenated VOC (TORERO) field experiment. For simulated data in a Rayleigh atmosphere, the agreement between the VMR from the parameterization method (VMR para) and the true VMR (VMR true) is excellent for all trace gases. Offsets, slopes and R 2 values for the linear fit of VMR para over VMR true are, respectively (0.008 ± 0.001) pptv, 0.988 ± 0.001, 0.987 for BrO; (-0.0066 ± 0.0001) pptv, 1.0021 ± 0.0003, 0.9979 for IO; (-0.17 ± 0.03) pptv, 1.0036 ± 0.0001, 0.9997 for NO 2. The agreement for atmospheres with aerosol shows comparable R 2 values to the Rayleigh case, but slopes deviate a bit more from one: (0.093 ± 0.002) pptv, 0.933 ± 0.002, 0.907 for BrO; (0.0021 ± 0.0004) pptv, 0.887 ± 0.001, 0.973 for IO; (8.5 ± 0.1) pptv, 0.8302 ± 0.0006, 0.9923 for NO 2. VMR para from field data are further compared with optimal estimation retrievals (VMR OE). Least orthogonal distance fit of the data give the following equations: BrO para = (0.1 ± 0.2) pptv + (0.95 ± 0.14) × BrO OE; IO para = (0.01 ± 0.02) pptv + (1.00 ± 0.12) × IO OE; NO 2para = (3.9 ± 2.5) pptv + (0.87 ± 0.15) × NO 2OE. Overall, we conclude that the parameterization retrieval is accurate with an uncertainty of 20 % for IO, 30 % for BrO and NO 2, but not better than 0.05 pptv IO, 0.5 pptv BrO and 10 pptv NO 2. Finally, the retrieval is applicable over a wide range of atmospheric conditions and measurement geometries and not limited to the interpretation of vertical profile measurements in the remote troposphere.« less

Positron Emission Tomography With 18F-Fluorodeoxyglucose in Patients With Sickle Cell Acute Chest Syndrome

PubMed Central

de Prost, Nicolas; Sasanelli, Myriam; Deux, Jean-François; Habibi, Anoosha; Razazi, Keyvan; Galactéros, Frédéric; Meignan, Michel; Maître, Bernard; Brun-Buisson, Christian; Itti, Emmanuel; Dessap, Armand Mekontso

2015-01-01

Abstract The acute chest syndrome (ACS) is the main cause of mortality among adult patients with sickle cell disease (SCD). Its pathophysiology is still unclear. Using positron emission tomography (PET) with 18F-fluorodeoxyglucose [18F-fluorodeoxyglucose (18F-FDG)], we explored the relationship between regional lung density and lung metabolism, as a reflection of lung neutrophilic infiltration during ACS. Patients were prospectively enrolled in a single-center study. Dual modality chest PET/computed tomography (CT) scans were performed, with 18F-FDG emission scans for quantification of regional 18F-FDG uptake and CT scans with radiocontrast agent to check for pulmonary artery thrombosis. Regional lung 18F-FDG uptake was quantified in ACS patients and in SCD patients without ACS (SCD non-ACS controls). Maximal (SUVmax) and mean (SUVmean) standardized uptake values were computed. Seventeen patients with ACS (mean age 28.3 ± 6.4 years) were included. None died nor required invasive mechanical ventilation. The main lung opacity on CT scans was lower lobe consolidation. Lungs of patients with ACS exhibited higher SUVmax than those of SCD non-ACS controls (2.5 [2.1–2.9] vs 0.8 [0.6–1.0]; P < 0.0001). Regional SUVmax and SUVmean was higher in lower than in upper lobes of ACS patients (P < 0.001) with a significant correlation between lung density and SUVmax (R2 = 0.78). SUVmean was higher in upper lobes of ACS patients than in lungs of SCD non-ACS controls (P < 0.001). Patients with SUVmax >2.5 had longer intensive care unit (ICU) stay than others (7 [6–11] vs 4 [3–6] days; P = 0.016). Lungs of patients with ACS exhibited higher 18F-FDG uptake than SCD non-ACS controls. Lung apices had normal aeration and lower 18F-FDG uptake than lung bases, but higher 18F-FDG uptake than lungs of SCD non-ACS controls. Patients with higher lung 18F-FDG uptake had longer ICU stay than others. PMID:25950690

Effects of semen storage and separation techniques on sperm DNA fragmentation.

PubMed

Jackson, Robert E; Bormann, Charles L; Hassun, Pericles A; Rocha, André M; Motta, Eduardo L A; Serafini, Paulo C; Smith, Gary D

2010-12-01

To determine the effect of semen storage and separation techniques on sperm DNA fragmentation. Controlled clinical study. An assisted reproductive technology laboratory. Thirty normoozospermic semen samples obtained from patients undergoing infertility evaluation. One aliquot from each sample was immediately prepared (control) for the sperm chromatin dispersion assay (SCD). Aliquots used to assess storage techniques were treated in the following ways: snap frozen by liquid nitrogen immersion, slow frozen with Tris-yolk buffer and glycerol, kept on ice for 24 hours or maintained at room temperature for 4 and 24 hours. Aliquots used to assess separation techniques were processed by the following methods: washed and centrifuged in media, swim-up from washed sperm pellet, density gradient separation, density gradient followed by swim-up. DNA integrity was then measured by SCD. DNA fragmentation as measured by SCD. There was no significant difference in fragmentation among the snap frozen, slow frozen, and wet-ice groups. Compared to other storage methods short-term storage at room temperature did not impact DNA fragmentation yet 24 hours storage significantly increased fragmentation. Swim-up, density gradient and density gradient/swim-up had significantly reduced DNA fragmentation levels compared with washed semen. Postincubation, density gradient/swim-up showed the lowest fragmentation levels. The effect of sperm processing methods on DNA fragmentation should be considered when selecting storage or separation techniques for clinical use. Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

High-resolution airborne imaging DOAS measurements of NO2 above Bucharest during AROMAT

NASA Astrophysics Data System (ADS)

Meier, Andreas Carlos; Schönhardt, Anja; Bösch, Tim; Richter, Andreas; Seyler, André; Ruhtz, Thomas; Constantin, Daniel-Eduard; Shaiganfar, Reza; Wagner, Thomas; Merlaud, Alexis; Van Roozendael, Michel; Belegante, Livio; Nicolae, Doina; Georgescu, Lucian; Burrows, John Philip

2017-05-01

In this study we report on airborne imaging DOAS measurements of NO2 from two flights performed in Bucharest during the AROMAT campaign (Airborne ROmanian Measurements of Aerosols and Trace gases) in September 2014. These measurements were performed with the Airborne imaging Differential Optical Absorption Spectroscopy (DOAS) instrument for Measurements of Atmospheric Pollution (AirMAP) and provide nearly gapless maps of column densities of NO2 below the aircraft with a high spatial resolution of better than 100 m. The air mass factors, which are needed to convert the measured differential slant column densities (dSCDs) to vertical column densities (VCDs), have a strong dependence on the surface reflectance, which has to be accounted for in the retrieval. This is especially important for measurements above urban areas, where the surface properties vary strongly. As the instrument is not radiometrically calibrated, we have developed a method to derive the surface reflectance from intensities measured by AirMAP. This method is based on radiative transfer calculation with SCIATRAN and a reference area for which the surface reflectance is known. While surface properties are clearly apparent in the NO2 dSCD results, this effect is successfully corrected for in the VCD results. Furthermore, we investigate the influence of aerosols on the retrieval for a variety of aerosol profiles that were measured in the context of the AROMAT campaigns. The results of two research flights are presented, which reveal distinct horizontal distribution patterns and strong spatial gradients of NO2 across the city. Pollution levels range from background values in the outskirts located upwind of the city to about 4 × 1016 molec cm-2 in the polluted city center. Validation against two co-located mobile car-DOAS measurements yields good agreement between the datasets, with correlation coefficients of R = 0.94 and R = 0.85, respectively. Estimations on the NOx emission rate of Bucharest for the two flights yield emission rates of 15.1 ± 9.4 and 13.6 ± 8.4 mol s-1, respectively.

Limb-Nadir Matching Using Non-Coincident NO2 Observations: Proof of Concept and the OMI-minus-OSIRIS Prototype Product

NASA Technical Reports Server (NTRS)

Adams, Cristen; Normand, Elise N.; Mclinden, Chris A.; Bourassa, Adam E.; Lloyd, Nicholas D.; Degenstein, Douglas A.; Krotkov, Nickolay A.; Rivas, Maria Belmonte; Boersma, K. Folkert; Eskes, Henk

2016-01-01

A variant of the limb-nadir matching technique for deriving tropospheric NO2 columns is presented in which the stratospheric component of the NO2 slant column density (SCD) measured by the Ozone Monitoring Instrument (OMI) is removed using non-coincident profiles from the Optical Spectrograph and InfraRed Imaging System (OSIRIS). In order to correct their mismatch in local time and the diurnal variation of stratospheric NO2, OSIRIS profiles, which were measured just after sunrise, were mapped to the local time of OMI observations using a photochemical boxmodel. Following the profile time adjustment, OSIRIS NO2 stratospheric vertical column densities (VCDs) were calculated. For profiles that did not reach down to the tropopause, VCDs were adjusted using the photochemical model. Using air mass factors from the OMI Standard Product (SP), a new tropospheric NO2 VCD product - referred to as OMI-minus-OSIRIS (OmO) - was generated through limb-nadir matching. To accomplish this, the OMI total SCDs were scaled using correction factors derived from the next-generation SCDs that improve upon the spectral fitting used for the current operational products. One year, 2008, of OmO was generated for 60 deg S to 60 deg N and a cursory evaluation was performed. The OmO product was found to capture the main features of tropospheric NO2, including a background value of about 0.3 x 10(exp 15) molecules per sq cm over the tropical Pacific and values comparable to the OMI operational products over anthropogenic source areas. While additional study is required, these results suggest that a limb-nadir matching approach is feasible for the removal of stratospheric NO2 measured by a polar orbiter from a nadir-viewing instrument in a geostationary orbit such as Tropospheric Emissions: Monitoring of Pollution (TEMPO) or Sentinel-4.

The plasma environment, charge state, and currents of Saturn's C and D rings

NASA Technical Reports Server (NTRS)

Wilson, G. R.

1991-01-01

The charge state and associated currents of Saturn's C an D rings are studied by modeling the flow of ionospheric plasma from the mid- to low-latitude ionosphere to the vicinity of the rings. It is found that the plasma density near the C and D rings, at a given radial location, will experience a one to two order of magnitude diurnal variation. The surface charge density (SCD) of these rings can show significant radial and azimuthal variations due mainly to variation in the plasma density. The SCD also depends on structural features of the rings such as thickness and the nature of the particle size distribution. The associated azimuthal currents carried by these rings also show large diurnal variations resulting in field-aligned currents which close in the ionosphere. The resulting ionospheric electric field will probably not produce a significant amount of plasma convection in the topside ionosphere and inner plasmasphere.

Utilization of O4 slant column density to derive aerosol layer height from a space-borne UV-visible hyperspectral sensor: sensitivity and case study

NASA Astrophysics Data System (ADS)

Park, Sang Seo; Kim, Jhoon; Lee, Hanlim; Torres, Omar; Lee, Kwang-Mog; Lee, Sang Deok

2016-02-01

The sensitivities of oxygen-dimer (O4) slant column densities (SCDs) to changes in aerosol layer height are investigated using the simulated radiances by a radiative transfer model, the linearized pseudo-spherical vector discrete ordinate radiative transfer (VLIDORT), and the differential optical absorption spectroscopy (DOAS) technique. The sensitivities of the O4 index (O4I), which is defined as dividing O4 SCD by 1040 molecules2 cm-5, to aerosol types and optical properties are also evaluated and compared. Among the O4 absorption bands at 340, 360, 380, and 477 nm, the O4 absorption band at 477 nm is found to be the most suitable to retrieve the aerosol effective height. However, the O4I at 477 nm is significantly influenced not only by the aerosol layer effective height but also by aerosol vertical profiles, optical properties including single scattering albedo (SSA), aerosol optical depth (AOD), particle size, and surface albedo. Overall, the error of the retrieved aerosol effective height is estimated to be 1276, 846, and 739 m for dust, non-absorbing, and absorbing aerosol, respectively, assuming knowledge on the aerosol vertical distribution shape. Using radiance data from the Ozone Monitoring Instrument (OMI), a new algorithm is developed to derive the aerosol effective height over East Asia after the determination of the aerosol type and AOD from the MODerate resolution Imaging Spectroradiometer (MODIS). About 80 % of retrieved aerosol effective heights are within the error range of 1 km compared to those obtained from the Cloud-Aerosol Lidar with Orthogonal Polarization (CALIOP) measurements on thick aerosol layer cases.

Utilization of O4 Slant Column Density to Derive Aerosol Layer Height from a Space-Borne UV-Visible Hyperspectral Sensor: Sensitivity and Case Study

NASA Technical Reports Server (NTRS)

Park, Sang Seo; Kim, Jhoon; Lee, Hanlim; Torres, Omar; Lee, Kwang-Mog; Lee, Sang Deok

2016-01-01

The sensitivities of oxygen-dimer (O4) slant column densities (SCDs) to changes in aerosol layer height are investigated using the simulated radiances by a radiative transfer model, the linearized pseudo-spherical vector discrete ordinate radiative transfer (VLIDORT), and the differential optical absorption spectroscopy (DOAS) technique. The sensitivities of the O4 index (O4I), which is defined as dividing O4 SCD by 10(sup 40) molecules (sup 2) per centimeters(sup -5), to aerosol types and optical properties are also evaluated and compared. Among the O4 absorption bands at 340, 360, 380, and 477 nanometers, the O4 absorption band at 477 nanometers is found to be the most suitable to retrieve the aerosol effective height. However, the O4I at 477 nanometers is significantly influenced not only by the aerosol layer effective height but also by aerosol vertical profiles, optical properties including single scattering albedo (SSA), aerosol optical depth (AOD), particle size, and surface albedo. Overall, the error of the retrieved aerosol effective height is estimated to be 1276, 846, and 739 meters for dust, non-absorbing, and absorbing aerosol, respectively, assuming knowledge on the aerosol vertical distribution shape. Using radiance data from the Ozone Monitoring Instrument (OMI), a new algorithm is developed to derive the aerosol effective height over East Asia after the determination of the aerosol type and AOD from the MODerate resolution Imaging Spectroradiometer (MODIS). About 80 percent of retrieved aerosol effective heights are within the error range of 1 kilometer compared to those obtained from the Cloud-Aerosol Lidar with Orthogonal Polarization (CALIOP) measurements on thick aerosol layer cases.

Utilization of O4 Slant Column Density to Derive Aerosol Layer Height from a Spaceborne UV-Visible Hyperspectral Sensor: Sensitivity and Case Study

NASA Technical Reports Server (NTRS)

Park, Sang Seo; Kim, Jhoon; Lee, Hanlim; Torres, Omar; Lee, Kwang-Mog; Lee, Sang Deok

2016-01-01

The sensitivities of oxygen-dimer (O4) slant column densities (SCDs) to changes in aerosol layer height are investigated using the simulated radiances by a radiative transfer model, the linearized pseudo-spherical vector discrete ordinate radiative transfer (VLIDORT), and the Differential Optical Absorption Spectroscopy (DOAS) technique. The sensitivities of the O4 index (O4I), which is defined as dividing O4 SCD by 10(exp 40) sq molecules cm(exp -5), to aerosol types and optical properties are also evaluated and compared. Among the O4 absorption bands at 340, 360, 380, and 477 nm, the O4 absorption band at 477 nm is found to be the most suitable to retrieve the aerosol effective height. However, the O4I at 477 nm is significantly influenced not only by the aerosol layer effective height but also by aerosol vertical profiles, optical properties including single scattering albedo (SSA), aerosol optical depth (AOD), particle size, and surface albedo. Overall, the error of the retrieved aerosol effective height is estimated to be 1276, 846, and 739 m for dust, non-absorbing, and absorbing aerosol, respectively, assuming knowledge on the aerosol vertical distribution shape. Using radiance data from the Ozone Monitoring Instrument (OMI), a new algorithm is developed to derive the aerosol effective height over East Asia after the determination of the aerosol type and AOD from the MODerate resolution Imaging Spectroradiometer (MODIS). About 80% of retrieved aerosol effective heights are within the error range of 1 km compared to those obtained from the Cloud-Aerosol Lidar with Orthogonal Polarization (CALIOP) measurements on thick aerosol layer cases.

A Novel Index Using Soluble CD36 Is Associated with the Prevalence of Type 2 Diabetes Mellitus: Comparison Study with Triglyceride-Glucose Index.

PubMed

Kim, Ho Jin; Moon, Jun Sung; Park, Il Rae; Kim, Joong Hee; Yoon, Ji Sung; Won, Kyu Chang; Lee, Hyoung Woo

2017-09-01

Plasma soluble cluster determinant 36 (sCD36) level is closely related with insulin resistance and atherosclerosis, but little is known whether it could be a surrogate for estimating risk of developing diabetes or not. To address this, we evaluated association between sCD36 index, the product of sCD36 and fasting plasma glucose (FPG), and the prevalence of type 2 diabetes mellitus (T2DM), and then compared with triglyceride-glucose (TyG) index which has been suggested simple index for insulin resistance. This was cross-sectional study, and participants were classified as normal glucose tolerance (NGT), prediabetes, and T2DM according to glucose tolerance. The formula of TyG index was 'ln [FPG (mg/dL)×triglyceride (mg/dL)/2],' and the sCD36 index was 'ln [sCD36 (pg/mL)×FPG (mg/dL)/2].' One hundred and fifty-five subjects (mean age, 55.2 years) were enrolled, and patients with T2DM were 75. Both indexes were significantly increased in prediabetes and T2DM rather than NGT, and sCD36 index was positively correlated with both glycosylated hemoglobin and homeostasis model assessment of insulin resistance (r=0.767 and r=0.453, respectively; P<0.05) and negatively with homeostasis model assessment estimate of β-cell function (r=-0.317). The odds ratio (OR) of sCD36 index for T2DM was 4.39 (95% confidential interval, 1.51 to 12.77) after adjusting age, gender, blood pressure, smoking, alcohol, non-high density lipoprotein cholesterol and high-sensitivity C-reactive protein. However, OR of TyG index did not remained significance after adjustment. sCD36 index has an independent association with the risk of T2DM, and showed better correlation than TyG index. These results suggest sCD36 index might be useful surrogate marker for the risk of diabetes. Copyright © 2017 Korean Endocrine Society

Liquid Chromatographic Analysis of Nitrocellulose-Base Propellants

DTIC Science & Technology

1983-03-28

18 radial PkC column using 10 micron silica coated with octadecyl silane. The detector was a LC 85 variable wavelength UV detector from Perkin-Elmer...Snyder, L. R. J Chrom Scd i6, (1978), 223. i •2 Glatch, J. L., Kirkland, J. J., Squire, K. M., and Miner, J. M.; J. Chromatgography, 199, (1980), 57. 4...assuming non retained peaks elute at 1 minute). This produces 3 solvents of approximately the same strengths bnt greatly differing selectivities. Once

Parameterization retrieval of trace gas volume mixing ratios from Airborne MAX-DOAS

NASA Astrophysics Data System (ADS)

Dix, Barbara; Koenig, Theodore K.; Volkamer, Rainer

2016-11-01

We present a parameterization retrieval of volume mixing ratios (VMRs) from differential slant column density (dSCD) measurements by Airborne Multi-AXis Differential Optical Absorption Spectroscopy (AMAX-DOAS). The method makes use of the fact that horizontally recorded limb spectra (elevation angle 0°) are strongly sensitive to the atmospheric layer at instrument altitude. These limb spectra are analyzed using reference spectra that largely cancel out column contributions from above and below the instrument, so that the resulting limb dSCDs, i.e., the column integrated concentration with respect to a reference spectrum, are almost exclusively sensitive to the atmospheric layers around instrument altitude. The conversion of limb dSCDs into VMRs is then realized by calculating box air mass factors (Box-AMFs) for a Rayleigh atmosphere and applying a scaling factor constrained by O4 dSCDs to account for aerosol extinction. An iterative VMR retrieval scheme corrects for trace gas profile shape effects. Benefits of this method are (1) a fast conversion that only requires the computation of Box-AMFs in a Rayleigh atmosphere; (2) neither local aerosol extinction nor the slant column density in the DOAS reference (SCDref) needs to be known; and (3) VMRs can be retrieved for every measurement point along a flight track, thus increasing statistics and adding flexibility to capture concentration gradients. Sensitivity studies are performed for bromine monoxide (BrO), iodine monoxide (IO) and nitrogen dioxide (NO2), using (1) simulated dSCD data for different trace gas and aerosol profiles and (2) field measurements from the Tropical Ocean tRoposphere Exchange of Reactive halogen species and Oxygenated VOC (TORERO) field experiment. For simulated data in a Rayleigh atmosphere, the agreement between the VMR from the parameterization method (VMRpara) and the true VMR (VMRtrue) is excellent for all trace gases. Offsets, slopes and R2 values for the linear fit of VMRpara over VMRtrue are, respectively (0.008 ± 0.001) pptv, 0.988 ± 0.001, 0.987 for BrO; (-0.0066 ± 0.0001) pptv, 1.0021 ± 0.0003, 0.9979 for IO; (-0.17 ± 0.03) pptv, 1.0036 ± 0.0001, 0.9997 for NO2. The agreement for atmospheres with aerosol shows comparable R2 values to the Rayleigh case, but slopes deviate a bit more from one: (0.093 ± 0.002) pptv, 0.933 ± 0.002, 0.907 for BrO; (0.0021 ± 0.0004) pptv, 0.887 ± 0.001, 0.973 for IO; (8.5 ± 0.1) pptv, 0.8302 ± 0.0006, 0.9923 for NO2. VMRpara from field data are further compared with optimal estimation retrievals (VMROE). Least orthogonal distance fit of the data give the following equations: BrOpara = (0.1 ± 0.2) pptv + (0.95 ± 0.14) × BrOOE; IOpara = (0.01 ± 0.02) pptv + (1.00 ± 0.12) × IOOE; NO2para = (3.9 ± 2.5) pptv + (0.87 ± 0.15) × NO2OE. Overall, we conclude that the parameterization retrieval is accurate with an uncertainty of 20 % for IO, 30 % for BrO and NO2, but not better than 0.05 pptv IO, 0.5 pptv BrO and 10 pptv NO2. The retrieval is applicable over a wide range of atmospheric conditions and measurement geometries and not limited to the interpretation of vertical profile measurements in the remote troposphere.

Wave Probe - New Instrument For Space Research

NASA Astrophysics Data System (ADS)

Korepanov, V.; Dudkin, F.

2007-12-01

The dispersion relations are very important for the wave activity study in space plasmas. One of the most efficient methods for their analysis is the simultaneous measurements of spatial current density and magnetic field fluctuations during such a wave process. Whereas the measurement of the magnetic field is a routine task realized onboard practically every spacecraft (SC), the direct measurement of spatial current density (SCD) still remains a complicated scientific and technological problem. First attempt to solve it was executed in late 60-ties by a group headed by F. Mozer. They proposed and launched in a rocket experiment the device named "Split Langmuir Probe" (SLP) - two conducting plates separated by a thin insulated split. Unfortunately this experiment failed what diverted the attention of experimenters in space branch from this instrument for many years, practically till now. But the importance to know the SCD stimulated the development of new principles and devices to measure it. A short review of known versions is discussed. The newly evoked interest to this problem caused next attempt to improve the SLP construction and methodology of its application for SCD measurements, which resulted in first successful attempt in 1985: the measured SCD onboard Prognos-10 SC in the bow shock region was in rather good agreement with the calculated value. This attempt was continued onboard Interball-Tail SC (1995-2000) where again a qualitatively good coincidence of measured and calculated values was observed. The obtained experience and further theoretical research allowed developing a new instrument - Wave Probe - which is a combination of induction magnetometer and SLP in one body. Both on-ground tests in plasma chamber and the spatial experiment executed onboard Ukrainian "Sich-1M" SC (2004) showed that the combined in-situ simultaneous measurements of SCD and magnetic field fluctuations allowed obtaining the wave number of the whistler wave. The same wave number was calculated theoretically from dispersion relations of whistler wave using known ionosphere model and the comparison of measured and calculated values of both wave number and SCD gave a good quantitative agreement. The details of theoretical and experimental study are discussed in the report. There is a pleasant duty of the authors to thank Prof. F. Mozer and Prof. S. Klimov for continuous attention and practical support of this work. It was also supported by NSAU contract No 1-02/03.

Superior canal dehiscence length and location influences clinical presentation and audiometric and cervical vestibular-evoked myogenic potential testing.

PubMed

Niesten, Marlien E F; Hamberg, Leena M; Silverman, Joshua B; Lou, Kristina V; McCall, Andrew A; Windsor, Alanna; Curtin, Hugh D; Herrmann, Barbara S; Grolman, Wilko; Nakajima, Hideko H; Lee, Daniel J

2014-01-01

Superior canal dehiscence (SCD) is caused by an absence of bony covering of the arcuate eminence or posteromedial aspect of the superior semicircular canal. However, the clinical presentation of SCD syndrome varies considerably, as some SCD patients are asymptomatic and others have auditory and/or vestibular complaints. In order to determine the basis for these observations, we examined the association between SCD length and location with: (1) auditory and vestibular signs and symptoms; (2) air conduction (AC) loss and air-bone gap (ABG) measured by pure-tone audiometric testing, and (3) cervical vestibular-evoked myogenic potential (cVEMP) thresholds. 104 patients (147 ears) underwent SCD length and location measurements using a novel method of measuring bone density along 0.2-mm radial CT sections. We found that patients with auditory symptoms have a larger dehiscence (median length: 4.5 vs. 2.7 mm) with a beginning closer to the ampulla (median location: 4.8 vs. 6.4 mm from ampulla) than patients with no auditory symptoms (only vestibular symptoms). An increase in AC threshold was found as the SCD length increased at 250 Hz (95% CI: 1.7-4.7), 500 Hz (95% CI: 0.7-3.5) and 1,000 Hz (95% CI: 0.0-2.5), and an increase in ABG as the SCD length increased at 250 Hz (95% CI: 2.0-5.3), 500 Hz (95% CI: 1.6-4.6) and 1,000 Hz (95% CI: 1.3-3.3) was also seen. Finally, a larger dehiscence was associated with lowered cVEMP thresholds at 250 Hz (95% CI: -4.4 to -0.3), 500 Hz (95% CI: -4.1 to -1.0), 750 Hz (95% CI: -4.2 to -0.7) and 1,000 Hz (95% CI: -3.6 to -0.5) and a starting location closer to the ampulla at 250 Hz (95% CI: 1.3-5.1), 750 Hz (95% CI: 0.2-3.3) and 1,000 Hz (95% CI: 0.6-3.5). These findings may help to explain the variation of signs and symptoms seen in patients with SCD syndrome.

Changes in the cornea related to sickle cell disease: a pilot investigation.

PubMed

Coşkun, Mesut; İlhan, Özgür; İlhan, Nilüfer; Tuzcu, Esra Ayhan; Daglioğlu, Mutlu Cihan; Kahraman, Hilal; Elbeyli, Ahmet; Yarbağ, Abdulhekim; Helvaci, Mehmet Rami

2015-01-01

To investigate corneal structural changes (central corneal thickness, endothelial cell count, and cellular morphology) in patients with sickle cell disease (SCD). This prospective study included 56 patients with SCD and 50 age- and sex-matched healthy subjects without any eye disease aside from refractive errors. Endothelial cell density (ECD), percentage of hexagonality, and the coefficient of variation in cell size (CV) were measured using noncontact specular microscopy, and central corneal thickness (CCT) was measured by pachymetry. The mean CCT value was 509.6 ± 20.7 μm in the study group and 520.8 ± 23.6 μm in the control group. The mean ECD, CV, and percentage of hexagonality values in the study group were 2712 ± 335 cells/mm², 34.5 ± 5.3%, and 57.2 ± 6.6%, respectively, and 3030 ± 247 cells/mm², 31.6 ± 5.0%, and 60.4 ± 6.9% in the control group, respectively. Endothelial cell density (p = 0.001), CCT (p = 0.011), CV (p = 0.005), and percentage of hexagonality values (p = 0.018) were significantly different between the study and control groups. The results of the current study indicate that patients with SCD had considerable morphologic changes in the structure of the cornea when compared to healthy subjects.

Early elevation of soluble CD14 may help identify trauma patients at high risk for infection.

PubMed

Carrillo, E H; Gordon, L; Goode, E; Davis, E; Polk, H C

2001-05-01

Elevated levels of soluble CD14 (sCD14) have been implicated in both gram-positive and gram-negative sepsis, and it has been associated with high mortality in trauma patients who become infected. Eleven healthy volunteers and 25 adult trauma patients with multiple injuries and a mean Injury Severity Score of 32 participated. Whole blood was obtained at intervals. Immunohistochemistry was used to quantify membrane CD14 (mCD14), by flow cytometry and plasma levels of sCD14 by enzyme-linked immunosorbent assay. Analysis of variance and Student's T test with Mann-Whitney posttest were used to determine significance at p < 0.05. On posttrauma day 1, sCD14 was significantly different in the plasma of infected patients compared with normal controls (7.16 +/- 1.87 microg/mL vs. 4.4 +/- 0.92 microg/mL, p < 0.01), but not significantly different from noninfected patients. The percentage of monocytes expressing mCD14 in trauma patients did not differentiate them from normal controls; however, mCD14 receptor density did demonstrate significance in septic trauma patients (n = 15) versus normal controls on posttrauma day 3 (p = 0.0065). On the basis of our data, mCD14 did not differentiate infected and noninfected trauma patients, although trauma in general reduced mCD14 and elevated sCD14. Interestingly, 100% of patients who exceeded plasma levels of 8 microg/mL of sCD14 on day 1 after injury developed infections. Therefore, early high expressers of sCD14 may be at higher risk for infectious complications after trauma.

Soluble CD30 and ELISA-detected human leukocyte antigen antibodies for the prediction of acute rejection in pediatric renal transplant recipients.

PubMed

Billing, Heiko; Sander, Anja; Süsal, Caner; Ovens, Jörg; Feneberg, Reinhard; Höcker, Britta; Vondrak, Karel; Grenda, Ryszard; Friman, Stybjorn; Milford, David V; Lucan, Mihai; Opelz, Gerhard; Tönshoff, Burkhard

2013-03-01

Biomarker-based post-transplant immune monitoring for the prediction of impending graft rejection requires validation in specific patient populations. Serum of 28 pediatric renal transplant recipients within the framework of a well-controlled prospective randomized trial was analyzed pre- and post-transplant for soluble CD30 (sCD30), a biomarker reflecting mainly T-cell reactivity, and anti-human leukocyte antigen (anti-HLA) antibody reactivity, a biomarker for B-cell activation. A sCD30 concentration ≥40.3 U/ml on day 14 was able to discriminate between patients with or without biopsy-proven acute rejection (BPAR) with a sensitivity of 100% and a specificity of 76%. Six of seven patients (86%) with BPAR showed a sCD30 above this cut-off, whereas only 3/21 patients (14%) without BPAR had a sCD30 above this cut-off (P = 0.004). For pre- and post-transplant anti-HLA class II reactivities by enzyme-linked immunosorbent assay, a cut-off value of 140 optical density was able to discriminate rejecters from nonrejecters with a sensitivity of 86% or 71% and a specificity of 81% or 90%, respectively. Withdrawal of steroids was associated with a approximately twofold higher serum sCD30 compared to controls, but did not affect anti-HLA reactivities. An increased post-transplant sCD30 serum concentration and positive pre- and post-transplant anti-HLA class II reactivities are informative biomarkers for impending BPAR in pediatric renal transplant recipients. (TWIST, Clinical Trial No: FG-506-02-43). © 2012 The Authors Transplant International © 2012 European Society for Organ Transplantation. Published by Blackwell Publishing Ltd.

Polymorphisms in stearoyl coa desaturase and sterol regulatory element binding protein interact with N-3 polyunsaturated fatty acid intake to modify associations with anthropometric variables and metabolic phenotypes in Yup'ik people.

PubMed

Lemas, Dominick J; Klimentidis, Yann C; Aslibekyan, Stella; Wiener, Howard W; O'Brien, Diane M; Hopkins, Scarlett E; Stanhope, Kimber L; Havel, Peter J; Allison, David B; Fernandez, Jose R; Tiwari, Hemant K; Boyer, Bert B

2016-12-01

n-3 polyunsaturated fatty acid (n-3 PUFA) intake is associated with protection from obesity; however, the mechanisms of protection remain poorly characterized. The stearoyl CoA desaturase (SCD), insulin-sensitive glucose transporter (SLC2A4), and sterol regulatory element binding protein (SREBF1) genes are transcriptionally regulated by n-3 PUFA intake and harbor polymorphisms associated with obesity. The present study investigated how consumption of n-3 PUFA modifies associations between SCD, SLC2A4, and SREBF1 polymorphisms and anthropometric variables and metabolic phenotypes. Anthropometric variables and metabolic phenotypes were measured in a cross-sectional sample of Yup'ik individuals (n = 1135) and 33 polymorphisms were tested for main effects and interactions using linear models that account for familial correlations. n-3 PUFA intake was estimated using red blood cell nitrogen stable isotope ratios. SCD polymorphisms were associated with ApoA1 concentration and n-3 PUFA interactions with SCD polymorphisms were associated with reduced fasting cholesterol levels and waist-to-hip ratio. SLC2A4 polymorphisms were associated with hip circumference, high-density lipoprotein and ApoA1 concentrations. SREBF1 polymorphisms were associated with low-density lipoprotein and HOMA-IR and n-3 PUFA interactions were associated with reduced fasting insulin and HOMA-IR levels. The results suggest that an individual's genotype may interact with dietary n-3 PUFAs in ways that are associated with protection from obesity-related diseases in Yup'ik people. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Polymorphisms in stearoyl CoA desaturase and sterol regulatory element binding protein interact with N-3 polyunsaturated fatty acid intake to modify associations with anthropometric variables and metabolic phenotypes in Yup'ik people

PubMed Central

Lemas, Dominick J.; Klimentidis, Yann C.; Aslibekyan, Stella; Wiener, Howard W.; O’Brien, Diane M.; Hopkins, Scarlett E.; Stanhope, Kimber L.; Havel, Peter J.; Allison, David B.; Fernandez, Jose R.; Tiwari, Hemant K.; Boyer, Bert B.

2016-01-01

Scope n-3 polyunsaturated fatty acid (n-3 PUFA) intake is associated with protection from obesity, however, the mechanisms of protection remain poorly characterized. The stearoyl CoA desaturase (SCD), insulin sensitive glucose transporter (SLC2A4), and sterol regulatory element binding protein (SREBF1) genes are transcriptionally regulated by n-3 PUFA intake and harbor polymorphisms associated with obesity. The present study investigated how consumption of n-3 PUFA modifies associations between SCD, SLC2A4, and SREBF1 polymorphisms and anthropometric variables and metabolic phenotypes. Materials and Methods Anthropometric variables and metabolic phenotypes were measured in a cross-sectional sample of Yup’ik individuals (n=1135) and thirty-three polymorphisms were tested for main effects and interactions using linear models that account for familial correlations. n-3 PUFA intake was estimated using red blood cell nitrogen stable isotope ratios. SCD polymorphisms were associated with ApoA1 concentration and n-3 PUFA interactions with SCD polymorphisms were associated with reduced fasting cholesterol levels and waist-to-hip ratio. SLC2A4 polymorphisms were associated with hip circumference, high-density lipoprotein and ApoA1 concentrations. SREBF1 polymorphisms were associated with low-density lipoprotein and HOMA-IR and n-3 PUFA interactions were associated with reduced fasting insulin and HOMA-IR levels. Conclusion These results suggest that an individual’s genotype may interact with dietary n-3 PUFAs in ways that are associated with protection from obesity-related diseases in Yup’ik people. PMID:27467133

Morphometric analysis of cervical spinal canal diameter, transverse foramen, and pedicle width using computed tomography in Indian population.

PubMed

Sureka, Binit; Mittal, Aliza; Mittal, Mahesh K; Agarwal, Kanhaiya; Sinha, Mukul; Thukral, Brij Bhushan

2018-01-01

Accurate and detailed measurements of spinal canal diameter (SCD) and transverse foraminal morphometry are essential for understanding spinal column-related diseases and for surgical planning, especially for transpedicular screw fixation. This is especially because lateral cervical radiographs do not provide accurate measurements. This study was conducted to measure the dimensions of the transverse foramen sagittal and transverse diameters (SFD, TFD), SCD, and the distance of spinal canal from the transverse foramina (dSC-TF) at C1-C7 level in the Indian population. The study population comprised 84 male and 42 female subjects. The mean age of the study group was 44.63 years (range, 19-81 years). A retrospective study was conducted, and data were collected and analyzed for patients who underwent cervical spine computed tomography (CT) imaging for various reasons. One hundred and twenty-six patients were included in the study. Detailed readings were taken at all levels from C1-C7 for SCD, SFD, TFD, and dSc-TF. Values for male and female subjects were separately calculated and compared. For both the groups, the widest SCD were measured at the C1 level and the narrowest SCD at the C4 level. The narrowest SFD was measured at C7 for both male and female subjects on the right and left sides. The widest SFD was measured at C1 both for male and female subjects on the right and left side. The narrowest TFD on the left side was measured at C7 for male and at C1 for female subjects. The narrowest mean distance of dSC-TF was found to be at C4 for both male and female subjects on both left and right side. The computed tomographic (CT) imaging is better than conventional radiographs for the preoperative evaluation of cervical spine and for better understanding cervical spine morphometry. Care must be taken during transpedicular screw fixation, especially in female subjects, more so at the C2, C4, and C6 levels due to a decrease in the distance of dSC-TF.

Four weeks supplementation with Lactobacillus paracasei subsp. paracasei L. casei W8® shows modest effect on triacylglycerol in young healthy adults.

PubMed

Bjerg, A T; Kristensen, M; Ritz, C; Stark, K D; Holst, J J; Leser, T D; Wellejus, A; Astrup, A

2015-03-01

The microbiota has been shown to have the potential to affect appetite and blood lipids positively in animal studies. We investigated if four weeks supplementation with Lactobacillus paracasei subsp. paracasei L. casei W8® (L. casei W8) had an effect on subjective appetite sensation, ad libitum energy intake, glucagon-like peptide 1 (GLP-1), glucose and insulin response in humans. Secondarily, we explored potential effects on blood lipids, fatty acids and stearoyl-CoA desaturase-1 (SCD1) activity in humans as well as SCD1 expression in piglets given L. casei W8 for two weeks. 64 healthy participants completed the double-blinded, randomised, controlled, parallel four weeks study with supplementation of L. casei W8 (1010 cfu) or placebo capsules. A meal test was conducted before and after the intervention, where subjective appetite, ad libitum energy intake, GLP-1, glucose and insulin response were measured. Additionally fasting blood lipids and fatty acids concentrations were measured. Sixteen piglets were randomised into two groups: L. casei W8 (1010 cfu/day) as top dressing on morning fed or no treatment. After two weeks piglets were sacrificed and tissue from ileum, jejunum and skeletal muscle were sampled for mRNA analyses of SCD1 expression. Compared to placebo, L. casei W8 did not affect appetite, ad libitum energy intake, GLP-1, glucose and insulin response and total, high-density or low-density lipoprotein cholesterol levels after four weeks intervention. Triacylglycerol decreased in the L. casei W8 group compared to placebo at week 4 (P=0.03). The C16:1n-7/C16:0 ratio, reflecting SCD1 activity, tended to decrease when having L. casei W8 (P=0.06) compared to placebo. Muscle SCD1 expression decreased in piglets supplemented with L. casei W8 compared to control. In conclusion, supplementation with L. casei W8 did not affect appetite parameters, glucose or insulin responses; but appear to be able to lower triacylglycerol levels, possibly by reducing its production.

On the Origin of the High Column Density Turnover in the HI Column Density Distribution

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

Erkal, Denis; Gnedin, Nickolay Y.; Kravtsov, Andrey V.

We study the high column density regime of the HI column density distribution function and argue that there are two distinct features: a turnover at NHI ~ 10^21 cm^-2 which is present at both z=0 and z ~ 3, and a lack of systems above NHI ~ 10^22 cm^-2 at z=0. Using observations of the column density distribution, we argue that the HI-H2 transition does not cause the turnover at NHI ~ 10^21 cm^-2, but can plausibly explain the turnover at NHI > 10^22 cm^-2. We compute the HI column density distribution of individual galaxies in the THINGS sample andmore » show that the turnover column density depends only weakly on metallicity. Furthermore, we show that the column density distribution of galaxies, corrected for inclination, is insensitive to the resolution of the HI map or to averaging in radial shells. Our results indicate that the similarity of HI column density distributions at z=3 and z=0 is due to the similarity of the maximum HI surface densities of high-z and low-z disks, set presumably by universal processes that shape properties of the gaseous disks of galaxies. Using fully cosmological simulations, we explore other candidate physical mechanisms that could produce a turnover in the column density distribution. We show that while turbulence within GMCs cannot affect the DLA column density distribution, stellar feedback can affect it significantly if the feedback is sufficiently effective in removing gas from the central 2-3 kpc of high-redshift galaxies. Finally, we argue that it is meaningful to compare column densities averaged over ~ kpc scales with those estimated from quasar spectra which probe sub-pc scales due to the steep power spectrum of HI column density fluctuations observed in nearby galaxies.« less

The serum level of soluble CD26/dipeptidyl peptidase 4 increases in response to acute hyperglycemia after an oral glucose load in healthy subjects: association with high-molecular weight adiponectin and hepatic enzymes.

PubMed

Aso, Yoshimasa; Terasawa, Tomoko; Kato, Kanako; Jojima, Teruo; Suzuki, Kunihiro; Iijima, Toshie; Kawagoe, Yoshiaki; Mikami, Shigeru; Kubota, Yoshiro; Inukai, Toshihiko; Kasai, Kikuo

2013-11-01

A soluble form of CD26/dipeptidyl peptidase 4 (sCD26/DPP4) is found in serum and it has DPP4 enzymatic activity. We investigated whether the serum level of sCD26/DPP4 was influenced by the oral glucose tolerance test (OGTT) in healthy subjects. The serum sCD26/DPP4 level increased significantly from 824.5 ng/mL (interquartile range, from 699.0 to 1050 ng/mL) at baseline to a peak of 985.0 ng/mL (interquartile range, from 796.5 to 1215 ng/mL) during the OGTT (P < 0.0001). The peak sCD26/DPP4 level correlated positively with the baseline age and body mass index, and fasting plasma glucose (FPG), homeostasis model assessment of insulin resistance (HOMA-IR), triglycerides (TG), alanine aminotransferase, and γ-glutamyl transpeptidase (GGT) levels whereas it correlated negatively with high-density lipoprotein (HDL) cholesterol and the serum levels of total and high-molecular weight (HMW) adiponectin. Stepwise regression analysis was done with forward selection of variables, including age, FPG, HOMA-IR, TG, HDL cholesterol, uric acid, GGT, C-reactive protein, and HMW adiponectin. In a model that explained 57.5% of the variation of the peak sCD26/DPP4 level, GGT (β = 0.382, P = 0.007) and HOMA-IR (β = 0.307, P = 0.034) were independent determinants of the peak serum level of sCD26/DPP4. Serum HMW adiponectin decreased significantly from 4.43 μg/mL (interquartile range, from 2.80 to 6.65 μg/mL) at baseline to 4.17 μg/mL (interquartile range, from 2.48 to 6.96 μg/mL) 120 minutes after the oral glucose load (P < 0.0001). The baseline serum level of sCD26/DPP4 showed a significant negative correlation with the percent change of HMW adiponectin during the OGTT. In conclusion, the serum level of sCD26/DPP4 increased acutely after an oral glucose load in apparently healthy subjects. The abrupt increase of serum sCD26/DPP4 after a glucose load may be a marker of insulin resistance that could come from liver or muscle. Copyright © 2013 Mosby, Inc. All rights reserved.

Single fiber lignin distributions based on the density gradient column method

Treesearch

Brian Boyer; Alan W. Rudie

2007-01-01

The density gradient column method was used to determine the effects of uniform and non-uniform pulping processes on variation in individual fiber lignin concentrations of the resulting pulps. A density gradient column uses solvents of different densities and a mixing process to produce a column of liquid with a smooth transition from higher density at the bottom to...

The relation between the column density structures and the magnetic field orientation in the Vela C molecular complex

NASA Astrophysics Data System (ADS)

Soler, J. D.; Ade, P. A. R.; Angilè, F. E.; Ashton, P.; Benton, S. J.; Devlin, M. J.; Dober, B.; Fissel, L. M.; Fukui, Y.; Galitzki, N.; Gandilo, N. N.; Hennebelle, P.; Klein, J.; Li, Z.-Y.; Korotkov, A. L.; Martin, P. G.; Matthews, T. G.; Moncelsi, L.; Netterfield, C. B.; Novak, G.; Pascale, E.; Poidevin, F.; Santos, F. P.; Savini, G.; Scott, D.; Shariff, J. A.; Thomas, N. E.; Tucker, C. E.; Tucker, G. S.; Ward-Thompson, D.

2017-07-01

We statistically evaluated the relative orientation between gas column density structures, inferred from Herschel submillimetre observations, and the magnetic field projected on the plane of sky, inferred from polarized thermal emission of Galactic dust observed by the Balloon-borne Large-Aperture Submillimetre Telescope for Polarimetry (BLASTPol) at 250, 350, and 500 μm, towards the Vela C molecular complex. First, we find very good agreement between the polarization orientations in the three wavelength-bands, suggesting that, at the considered common angular resolution of 3.´0 that corresponds to a physical scale of approximately 0.61 pc, the inferred magnetic field orientation is not significantly affected by temperature or dust grain alignment effects. Second, we find that the relative orientation between gas column density structures and the magnetic field changes progressively with increasing gas column density, from mostly parallel or having no preferred orientation at low column densities to mostly perpendicular at the highest column densities. This observation is in agreement with previous studies by the Planck collaboration towards more nearby molecular clouds. Finally, we find a correspondencebetween (a) the trends in relative orientation between the column density structures and the projected magnetic field; and (b) the shape of the column density probability distribution functions (PDFs). In the sub-regions of Vela C dominated by one clear filamentary structure, or "ridges", where the high-column density tails of the PDFs are flatter, we find a sharp transition from preferentially parallel or having no preferred relative orientation at low column densities to preferentially perpendicular at highest column densities. In the sub-regions of Vela C dominated by several filamentary structures with multiple orientations, or "nests", where the maximum values of the column density are smaller than in the ridge-like sub-regions and the high-column density tails of the PDFs are steeper, such a transition is also present, but it is clearly less sharp than in the ridge-like sub-regions. Both of these results suggest that the magnetic field is dynamically important for the formation of density structures in this region.

High-Density SNP Genotyping to Define β-Globin Locus Haplotypes

PubMed Central

Liu, Li; Muralidhar, Shalini; Singh, Manisha; Sylvan, Caprice; Kalra, Inderdeep S.; Quinn, Charles T.; Onyekwere, Onyinye C.; Pace, Betty S.

2014-01-01

Five major β-globin locus haplotypes have been established in individuals with sickle cell disease (SCD) from the Benin, Bantu, Senegal, Cameroon, and Arab-Indian populations. Historically, β-haplotypes were established using restriction fragment length polymorphism (RFLP) analysis across the β-locus, which consists of five functional β-like globin genes located on chromosome 11. Previous attempts to correlate these haplotypes as robust predictors of clinical phenotypes observed in SCD have not been successful. We speculate that the coverage and distribution of the RFLP sites located proximal to or within the globin genes are not sufficiently dense to accurately reflect the complexity of this region. To test our hypothesis, we performed RFLP analysis and high-density single nucleotide polymorphism (SNP) genotyping across the β-locus using DNA samples from either healthy African Americans with normal hemoglobin A (HbAA) or individuals with homozygous SS (HbSS) disease. Using the genotyping data from 88 SNPs and Haploview analysis, we generated a greater number of haplotypes than that observed with RFLP analysis alone. Furthermore, a unique pattern of long-range linkage disequilibrium between the locus control region and the β-like globin genes was observed in the HbSS group. Interestingly, we observed multiple SNPs within the HindIII restriction site located in the Gγ-globin intervening sequence II which produced the same RFLP pattern. These findings illustrated the inability of RFLP analysis to decipher the complexity of sequence variations that impacts genomic structure in this region. Our data suggest that high density SNP mapping may be required to accurately define β-haplotypes that correlate with the different clinical phenotypes observed in SCD. PMID:18829352

Quantitative on-line analysis of sulfur compounds in complex hydrocarbon matrices.

PubMed

Djokic, Marko R; Ristic, Nenad D; Olahova, Natalia; Marin, Guy B; Van Geem, Kevin M

2017-08-04

An improved method for on-line measurement of sulfur containing compounds in complex matrices is presented. The on-line system consists of a specifically designed sampling system connected to a comprehensive two-dimensional gas chromatograph (GC×GC) equipped with two capillary columns (Rtx ® -1 PONA×SGE BPX50), a flame ionization detector (FID) and a sulfur chemiluminescence detector (SCD). The result is an unprecedented sensitivity down to ppm level (1 ppm-w) for various sulfur containing compounds in very complex hydrocarbon matrices. In addition to the GC×GC-SCD, the low molecular weight sulfur containing compounds such as hydrogen sulfide (H 2 S) and carbonyl sulfide (COS) can be analyzed using a thermal conductivity detector of a so-called refinery gas analyzer (RGA). The methodology was extensively tested on a continuous flow pilot plant for steam cracking, in which quantification of sulfur containing compounds in the reactor effluent was carried out using 3-chlorothiophene as internal standard. The GC×GC-FID/-SCD settings were optimized for ppm analysis of sulfur compounds in olefin-rich (ethylene- and propylene-rich) hydrocarbon matrices produced by steam cracking of petroleum feedstocks. Besides that is primarily used for analysis of the hydrocarbon matrix, FID of the GC×GC-FID/-SCD set-up serves to double check the amount of added sulfur internal standard which is crucial for a proper quantification of sulfur compounds. When vacuum gas oil containing 780 ppm-w of elemental sulfur in the form of benzothiophenes and dibenzothiophenes is subjected to steam cracking, the sulfur balance was closed, with 75% of the sulfur contained in the feed is converted to hydrogen sulfide, 13% to alkyl homologues of thiophene while the remaining 12% is present in the form of alkyl homologues of benzothiophenes. The methodology can be applied for many other conversion processes which use sulfur containing feeds such as hydrocracking, catalytic cracking, kerogen evolution, bio-waste pyrolysis, supercritical water treatment, etc. Copyright © 2017 Elsevier B.V. All rights reserved.

Using Neuropsychological Process Scores to Identify Subtle Cognitive Decline and Predict Progression to Mild Cognitive Impairment.

PubMed

Thomas, Kelsey R; Edmonds, Emily C; Eppig, Joel; Salmon, David P; Bondi, Mark W

2018-05-26

We previously operationally-defined subtle cognitive decline (SCD) in preclinical Alzheimer's disease (AD) using total scores on neuropsychological (NP) tests. NP process scores (i.e., provide information about how a total NP score was achieved) may be a useful tool for identifying early cognitive inefficiencies prior to objective impairment seen in mild cognitive impairment (MCI) and dementia. We aimed to integrate process scores into the SCD definition to identify stages of SCD and improve early detection of those at risk for decline. Cognitively "normal" participants from the Alzheimer's Disease Neuroimaging Initiative were classified as "early" SCD (E-SCD; >1 SD below mean on 2 process scores or on 1 process score plus 1 NP total score), "late" SCD (L-SCD; existing SCD criteria of >1 SD below norm-adjusted mean on 2 NP total scores in different domains), or "no SCD" (NC). Process scores considered in the SCD criteria were word-list intrusion errors, retroactive interference, and learning slope. Cerebrospinal fluid AD biomarkers were used to examine pathologic burden across groups. E-SCD and L-SCD progressed to MCI 2.5-3.4 times faster than the NC group. Survival curves for E-SCD and L-SCD converged at 7-8 years after baseline. The combined (E-SCD+L-SCD) group had improved sensitivity to detect progression to MCI relative to L-SCD only. AD biomarker positivity increased across NC, SCD, and MCI groups. Process scores can be integrated into the SCD criteria to allow for increased sensitivity and earlier identification of cognitively normal older adults at risk for decline prior to frank impairment on NP total scores.

Adenylyl Cyclase 9 Polymorphisms Reveal Potential Link to HDL Function and Cardiovascular Events in Multiple Pathologies: Potential Implications in Sickle Cell Disease.

PubMed

Niesor, Eric J; Benghozi, Renée; Amouyel, Philippe; Ferdinand, Keith C; Schwartz, Gregory G

2015-12-01

Adenylyl cyclase 9 (ADCY9) mediates β2-adrenoceptor (β2-AR) signalling. Both proteins are associated with caveolae, specialized cholesterol-rich membrane substructures. Apolipoprotein A1 (ApoA1), the major protein component of high-density lipoprotein (HDL), removes cholesterol from cell membrane and caveolae and may thereby influence β2-AR signalling, shown in vitro to be modulated by cholesterol. Patients with Sickle Cell Disease (SCD) typically have low HDL and ApoA1 levels. In patients, mainly of African origin, with SCD, β2-AR activation may trigger adhesion of red blood cells to endothelial cells, leading to vascular occlusive events. Moreover, ADCY9 polymorphism is associated with risk of stroke in SCD. In recent clinical trials, ADCY9 polymorphism was found to be a discriminant factor associated with the risk of cardiovascular (CV) events in Caucasian patients treated with the HDL-raising compound dalcetrapib. We hypothesize that these seemingly disparate observations share a common mechanism related to interaction of HDL/ApoA1 and ADCY9 on β2-AR signalling. This review also raises the importance of characterizing polymorphisms that determine the response to HDL-raising and -mimicking agents in the non-Caucasian population at high risk of CV diseases and suffering from SCD. This may facilitate personalized CV treatments.

Pharmacological inhibition of calpain-1 prevents red cell dehydration and reduces Gardos channel activity in a mouse model of sickle cell disease.

PubMed

De Franceschi, Lucia; Franco, Robert S; Bertoldi, Mariarita; Brugnara, Carlo; Matté, Alessandro; Siciliano, Angela; Wieschhaus, Adam J; Chishti, Athar H; Joiner, Clinton H

2013-02-01

Sickle cell disease (SCD) is a globally distributed hereditary red blood cell (RBC) disorder. One of the hallmarks of SCD is the presence of circulating dense RBCs, which are important in SCD-related clinical manifestations. In human dense sickle cells, we found reduced calpastatin activity and protein expression compared to either healthy RBCs or unfractionated sickle cells, suggesting an imbalance between activator and inhibitor of calpain-1 in favor of activator in dense sickle cells. Calpain-1 is a nonlysosomal cysteine proteinase that modulates multiple cell functions through the selective cleavage of proteins. To investigate the relevance of this observation in vivo, we evaluated the effects of the orally active inhibitor of calpain-1, BDA-410 (30 mg/kg/d), on RBCs from SAD mice, a mouse model for SCD. In SAD mice, BDA-410 improved RBC morphology, reduced RBC density (D(20); from 1106 ± 0.001 to 1100 ± 0.001 g/ml; P<0.05) and increased RBC-K(+) content (from 364 ± 10 to 429 ± 12.3 mmol/kg Hb; P<0.05), markedly reduced the activity of the Ca(2+)-activated K(+)channel (Gardos channel), and decreased membrane association of peroxiredoxin-2. The inhibitory effect of calphostin C, a specific inhibitor of protein kinase C (PKC), on the Gardos channel was eliminated after BDA-410 treatment, which suggests that calpain-1 inhibition affects the PKC-dependent fraction of the Gardos channel. BDA-410 prevented hypoxia-induced RBC dehydration and K(+) loss in SAD mice. These data suggest a potential role of BDA-410 as a novel therapeutic agent for treatment of SCD.

TOPSIS based parametric optimization of laser micro-drilling of TBC coated nickel based superalloy

NASA Astrophysics Data System (ADS)

Parthiban, K.; Duraiselvam, Muthukannan; Manivannan, R.

2018-06-01

The technique for order of preference by similarity ideal solution (TOPSIS) approach was used for optimizing the process parameters of laser micro-drilling of nickel superalloy C263 with Thermal Barrier Coating (TBC). Plasma spraying was used to deposit the TBC and a pico-second Nd:YAG pulsed laser was used to drill the specimens. Drilling angle, laser scan speed and number of passes were considered as input parameters. Based on the machining conditions, Taguchi L8 orthogonal array was used for conducting the experimental runs. The surface roughness and surface crack density (SCD) were considered as the output measures. The surface roughness was measured using 3D White Light Interferometer (WLI) and the crack density was measured using Scanning Electron Microscope (SEM). The optimized result achieved from this approach suggests reduced surface roughness and surface crack density. The holes drilled at an inclination angle of 45°, laser scan speed of 3 mm/s and 400 number of passes found to be optimum. From the Analysis of variance (ANOVA), inclination angle and number of passes were identified as the major influencing parameter. The optimized parameter combination exhibited a 19% improvement in surface finish and 12% reduction in SCD.

Cellular biophysical markers of hydroxyurea treatment in sickle cell disease

NASA Astrophysics Data System (ADS)

So, Peter T. C.; Hosseini, Poorya; Abidi, Sabia Z.; Du, E.; Papageorgiou, Dimitrios P.; Park, YongKeun; Higgins, John; Kato, Gregory J.; Suresh, Subra; Dao, Ming; Yaqoob, Zahid

2017-04-01

Using a common-path interferometric technique, we measure biomechanical and morphological properties of individual red blood cells in SCD patients as a function of cell density, and investigate the correlation of these biophysical properties with drug intake as well as other clinically measured parameters.

Implementation of Subjective Cognitive Decline criteria in research studies

PubMed Central

Molinuevo, José L; Rabin, Laura A.; Amariglio, Rebecca; Buckley, Rachel; Dubois, Bruno; Ellis, Kathryn A.; Ewers, Michael; Hampel, Harald; Klöppel, Stefan; Rami, Lorena; Reisberg, Barry; Saykin, Andrew J.; Sikkes, Sietske; Smart, Colette M.; Snitz, Beth E.; Sperling, Reisa; van der Flier, Wiesje M.; Wagner, Michael; Jessen, Frank

2017-01-01

INTRODUCTION Subjective Cognitive Decline (SCD) manifesting prior to clinical impairment could serve as a target population for early intervention trials in Alzheimer’s disease (AD). A working group, the Subjective Cognitive Decline Initiative (SCD-I), published SCD research criteria in the context of preclinical AD. To successfully apply them, a number of issues regarding assessment and implementation of SCD needed to be addressed. METHODS Members of the SCD-I met to identify and agree upon topics relevant to SCD criteria operationalization in research settings. Initial ideas and recommendations were discussed with other SCD-I working group members and modified accordingly. RESULTS Topics included SCD inclusion and exclusion criteria, together with the informant’s role in defining SCD presence and the impact of demographic factors. DISCUSSION Recommendations for the operationalization of SCD in differing research settings, with the aim of harmonization of SCD measurement across studies are proposed, to enhance comparability and generalizability across studies. PMID:27825022

Detection of BrO plumes over various sources using OMI and GOME-2 measurements

NASA Astrophysics Data System (ADS)

Seo, Sora; Richter, Andreas; Blechschmidt, Anne-Marlene; Burrows, John P.

2017-04-01

Reactive halogen species (RHS) play important roles in the chemistry of the stratosphere and troposphere. They are responsible for ozone depletion through catalytic reaction cycles, changes in the OH/HO2 and NO/NO2 ratios, and oxidation of compounds such as gaseous elemental mercury (GEM) and dimethyl sulphide (DMS). Thus, monitoring of halogen oxides is important for understanding global atmospheric oxidation capacity and climate change. Bromine monoxide (BrO) is one of the most common active halogen oxides. In the troposphere, large amounts of bromine are detected in Polar Regions in spring, over salt lakes, and in volcanic plumes. In this study, we analyse BrO column densities using OMI and GOME-2 observations. The measured spectra from both UV-visible nadir satellites were analyzed using the differential optical absorption spectroscopy (DOAS) method with different settings depending on the instrumental characteristics. Large amounts of volcanic BrO from the Kasatochi eruption in 2008 were detected for 6 days from August 8 to August 13. Especially large BrO amounts were found in the plume center for 3 days from August 9 to 11 with slant column densities (SCD) of up to ˜1.6x1015 molecules cm-2 and ˜5.5x1014 molecules cm-2 in OMI and GOME-2 measurements, respectively. In addition to the volcanic sources, events of widespread BrO enhancements were also observed over the Arctic and Antarctic coastal regions during the spring time by both satellites. As the overpass time of the two instruments is not the same, differences between the two data sets are expected. In this study, the agreement between OMI and GOME-2 BrO data is investigated using both the operational products and different DOAS fits. Systematic differences are found in BrO slant columns and fitting residuals, both being larger in the case of OMI data. In addition, results are sensitive to the choice of fitting window. From a monitoring point of view, due to the higher spatial resolution of OMI compared to GOME-2, OMI results are better suited for observing the shape variation and transport pattern of volcanic BrO. This will be further improved with upcoming the European Sentinel 5 Precursor satellite which has an even higher spatial resolution (3.5 / 7x7 km2).

Sudden Cardiac Death During Sports Activities in the General Population.

PubMed

Narayanan, Kumar; Bougouin, Wulfran; Sharifzadehgan, Ardalan; Waldmann, Victor; Karam, Nicole; Marijon, Eloi; Jouven, Xavier

2017-12-01

Regular exercise reduces cardiovascular and overall mortality. Participation in sports is an important determinant of cardiovascular health and fitness. Regular sports activity is associated with a smaller risk of sudden cardiac death (SCD). However, there is a small risk of sports-related SCD. Sports-related SCD accounts for approximately 5% of total SCD. SCD among athletes comprises only a fraction of all sports-related SCD. Sport-related SCD has a male predominance and an average age of affliction of 45 to 50 years. Survival is better than for other SCD. This review summarizes links between sports and SCD and discusses current knowledge and controversies. Copyright © 2017 Elsevier Inc. All rights reserved.

Impact of NO2 horizontal heterogeneity on tropospheric NO2 vertical columns retrieved from satellite, multi-axis differential optical absorption spectroscopy, and in situ measurements

NASA Astrophysics Data System (ADS)

Mendolia, D.; D'Souza, R. J. C.; Evans, G. J.; Brook, J.

2013-01-01

Tropospheric NO2 vertical column densities were retrieved for the first time in Toronto, Canada using three methods of differing spatial scales. Remotely-sensed NO2 vertical column densities, retrieved from multi-axis differential optical absorption spectroscopy and satellite remote sensing, were evaluated by comparison with in situ vertical column densities derived using a pair of chemiluminescence monitors situated 0.01 and 0.5 km above ground level. The chemiluminescence measurements were corrected for the influence of NOz, which reduced the NO2 concentrations at 0.01 and 0.5 km by 8 ± 1% and 12 ± 1%, respectively. The average absolute decrease in the chemiluminescence NO2 measurement as a result of this correction was less than 1 ppb. Good correlation was observed between the remotely sensed and in situ NO2 vertical column densities (Pearson R ranging from 0.68 to 0.79), but the in situ vertical column densities were 27% to 55% greater than the remotely-sensed columns. These results indicate that NO2 horizontal heterogeneity strongly impacted the magnitude of the remotely-sensed columns. The in situ columns reflected an urban environment with major traffic sources, while the remotely-sensed NO2 vertical column densities were representative of the region, which included spatial heterogeneity introduced by residential neighbourhoods and Lake Ontario. Despite the difference in absolute values, the reasonable correlation between the vertical column densities determined by three distinct methods increased confidence in the validity of the values provided by each of the methods.

Sickle cell disease in pregnancy: trend and pregnancy outcomes at a tertiary hospital in Tanzania.

PubMed

Muganyizi, Projestine S; Kidanto, Hussein

2013-01-01

SCD in pregnancy is associated with increased adverse fetal and maternal outcomes. In Tanzania where the frequency of sickle cell trait is 13% there has been scanty data on SCD in pregnancy. With progressive improvement in childhood survival the burden of SCD in pregnancy will increase. We analyzed all deliveries at Muhimbili National Hospital (MNH) from 1999 to 2011. Fetal and maternal outcomes of SCD deliveries were compared with non-SCD. Data were analyzed using IBM SPSS statistics version 19. Chi square and Fisher Exact tests were used to compare proportions and the independent t-test for continuous data. To predict risks of adverse effects, odds ratios were determined using multivariate logistic regression. A p-value<0.05 was considered significant. In total, 157,473 deliveries occurred at MNH during the study period, of which 149 were SCD (incidence of 95 SCD per 100,000 deliveries). The incidence of SCD had increased from 76 per 100,000 deliveries in the 1999-2002 period to over 100 per 100,000 deliveries in recent years. The mean maternal age at delivery was lower in SCD (24.0±5.5 years) than in non-SCD deliveries (26.2±6.0 years), p<0.001. Compared with non-SCD (2.9±0.7 Kg), SCD deliveries had less mean birth-weight (2.6±0.6 Kg), p<0.001. SCD were more likely than non-SCD to deliver low APGAR score at 5 minutes (34.5% Vs 15.0%, OR = 3.0, 95%CI: 2.1-4.2), stillbirths (25.7% Vs 7.5%, OR = 4.0, 95%CI: 2.8-5.8). There was excessive risk of maternal deaths in SCD compared to non-SCD (11.4% Vs 0.4%, OR = 29, 95%CI: 17.3-48.1). The leading cause of deaths in SCD was infections in wholly 82% in contrast to only 32% in non-SCD. In conclusion SCD in pregnancy is an emerging problem at MNH with increased adverse fetal outcomes and excessive maternal mortality mainly due to infections.

Head circumference of children with sickle cell disease in Lagos, Nigeria.

PubMed

Senbanjo, Idowu Odunayo; Oshikoya, Kazeem Adeola; Salisu, Mohammed; Diaku-Akinwumi, Ijeoma Nnenna

2016-01-01

Growth retardation and under-nutrition are common in children with sickle cell disease (SCD). The aim of this study was to compare the head circumference (HC) of SCD children and non-SCD children and to determine the effect of malnutrition on head circumference of children with SCD. This was a prospective case-control study conducted at the Lagos State University Teaching Hospital, Nigeria, involving SCD children (subject, n = 118) and non-SCD children (control, n = 118) matched for age, sex, and socioeconomic status. Weight, height and HC were measured using standard techniques. The mean ages of children with and without SCD were 7.46 ± 3.69 years and 7.01 ± 3.58 years, respectively. The HC increased significantly with age in both males and females (r = 0.75, p = < 0.001; r = 0.70, p < 0.001 respectively). There was no significant difference in HC between males and females (p > 0.05). At all ages, the mean head circumference of SCD children was not significantly (p > 0.05) different from non-SCD children. The In the age group 11-15 years, the prevalence of stunting was significantly higher among SCD children than non-SCD children. The mean HC of SCD children with stunting was significantly lower than those not stunted (51.7 vs. 53.5; P= 0.006) in age group 11.15 years. The head circumference of children with SCD is not significantly different from that of non-SCD children. Therefore, the HC chart for the general population is also applicable for monitoring head growth in children with SCD. The effect of malnutrition on head circumference of SCD children is most marked in age group 11-15 years.

Head circumference of children with sickle cell disease in Lagos, Nigeria

PubMed Central

Senbanjo, Idowu Odunayo; Oshikoya, Kazeem Adeola; Salisu, Mohammed; Diaku-Akinwumi, Ijeoma Nnenna

2016-01-01

Introduction Growth retardation and under-nutrition are common in children with sickle cell disease (SCD). The aim of this study was to compare the head circumference (HC) of SCD children and non-SCD children and to determine the effect of malnutrition on head circumference of children with SCD. Methods This was a prospective case-control study conducted at the Lagos State University Teaching Hospital, Nigeria, involving SCD children (subject, n = 118) and non-SCD children (control, n = 118) matched for age, sex, and socioeconomic status. Weight, height and HC were measured using standard techniques. Results The mean ages of children with and without SCD were 7.46 ± 3.69 years and 7.01 ± 3.58 years, respectively. The HC increased significantly with age in both males and females (r = 0.75, p = < 0.001; r = 0.70, p < 0.001 respectively). There was no significant difference in HC between males and females (p > 0.05). At all ages, the mean head circumference of SCD children was not significantly (p > 0.05) different from non-SCD children. The In the age group 11-15 years, the prevalence of stunting was significantly higher among SCD children than non-SCD children. The mean HC of SCD children with stunting was significantly lower than those not stunted (51.7 vs. 53.5; P= 0.006) in age group 11.15 years. Conclusion The head circumference of children with SCD is not significantly different from that of non-SCD children. Therefore, the HC chart for the general population is also applicable for monitoring head growth in children with SCD. The effect of malnutrition on head circumference of SCD children is most marked in age group 11-15 years. PMID:28154697

Understanding star formation in molecular clouds. I. Effects of line-of-sight contamination on the column density structure

NASA Astrophysics Data System (ADS)

Schneider, N.; Ossenkopf, V.; Csengeri, T.; Klessen, R. S.; Federrath, C.; Tremblin, P.; Girichidis, P.; Bontemps, S.; André, Ph.

2015-03-01

Column-density maps of molecular clouds are one of the most important observables in the context of molecular cloud- and star-formation (SF) studies. With the Herschel satellite it is now possible to precisely determine the column density from dust emission, which is the best tracer of the bulk of material in molecular clouds. However, line-of-sight (LOS) contamination from fore- or background clouds can lead to overestimating the dust emission of molecular clouds, in particular for distant clouds. This implies values that are too high for column density and mass, which can potentially lead to an incorrect physical interpretation of the column density probability distribution function (PDF). In this paper, we use observations and simulations to demonstrate how LOS contamination affects the PDF. We apply a first-order approximation (removing a constant level) to the molecular clouds of Auriga and Maddalena (low-mass star-forming), and Carina and NGC 3603 (both high-mass SF regions). In perfect agreement with the simulations, we find that the PDFs become broader, the peak shifts to lower column densities, and the power-law tail of the PDF for higher column densities flattens after correction. All corrected PDFs have a lognormal part for low column densities with a peak at Av ~ 2 mag, a deviation point (DP) from the lognormal at Av(DP) ~ 4-5 mag, and a power-law tail for higher column densities. Assuming an equivalent spherical density distribution ρ ∝ r- α, the slopes of the power-law tails correspond to αPDF = 1.8, 1.75, and 2.5 for Auriga, Carina, and NGC 3603. These numbers agree within the uncertainties with the values of α ≈ 1.5,1.8, and 2.5 determined from the slope γ (with α = 1-γ) obtained from the radial column density profiles (N ∝ rγ). While α ~ 1.5-2 is consistent with a structure dominated by collapse (local free-fall collapse of individual cores and clumps and global collapse), the higher value of α > 2 for NGC 3603 requires a physical process that leads to additional compression (e.g., expanding ionization fronts). From the small sample of our study, we find that clouds forming only low-mass stars and those also forming high-mass stars have slightly different values for their average column density (1.8 × 1021 cm-2 vs. 3.0 × 1021 cm-2), and they display differences in the overall column density structure. Massive clouds assemble more gas in smaller cloud volumes than low-mass SF ones. However, for both cloud types, the transition of the PDF from lognormal shape into power-law tail is found at the same column density (at Av ~ 4-5 mag). Low-mass and high-mass SF clouds then have the same low column density distribution, most likely dominated by supersonic turbulence. At higher column densities, collapse and external pressure can form the power-law tail. The relative importance of the twoprocesses can vary between clouds and thus lead to the observed differences in PDF and column density structure. Appendices are available in electronic form at http://www.aanda.orgHerschel maps as FITS files are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/575/A79

Serum sCD30 in monitoring of alloresponse in well HLA-matched cadaveric kidney transplantations.

PubMed

Matinlauri, Irma H; Kyllönen, Lauri E J; Salmela, Kaija T; Helin, Heikki; Pelzl, Steffen; Süsal, Caner

2005-12-27

In kidney transplantation, pretransplant serum sCD30 testing has been proposed in immunological risk estimation together with anti-HLA antibodies. We evaluated the risks associated with high pretransplant serum sCD30 in well HLA-matched cadaveric kidney recipients recruited in a clinical study comparing different immunosuppressive regimens. Rejection rate was similar in 37 recipients with high pretransplant serum sCD30 compared to 117 recipients with low serum sCD30 (16% vs. 15%, P=NS). Compared to pretransplant levels, the posttransplant sCD30 levels generally decreased, also in patients with rejection, although on day 21 posttransplant, rejecting patients had significantly higher relative sCD30 than nonrejecting patients (P<0.01). However, steroid-resistant rejection was associated with increasing posttransplant sCD30 levels. High pretransplant sCD30 values were associated with tubulointerstitial rejection. There was no correlation of sCD30 with delayed graft function. Good HLA matching seems to be effective in neutralizing the negative effect of a high pretransplant serum sCD30.

Characterization of electrophysiological propagation by multichannel sensors

PubMed Central

Bradshaw, L. Alan; Kim, Juliana H.; Somarajan, Suseela; Richards, William O.; Cheng, Leo K.

2016-01-01

Objective The propagation of electrophysiological activity measured by multichannel devices could have significant clinical implications. Gastric slow waves normally propagate along longitudinal paths that are evident in recordings of serosal potentials and transcutaneous magnetic fields. We employed a realistic model of gastric slow wave activity to simulate the transabdominal magnetogastrogram (MGG) recorded in a multichannel biomagnetometer and to determine characteristics of electrophysiological propagation from MGG measurements. Methods Using MGG simulations of slow wave sources in a realistic abdomen (both superficial and deep sources) and in a horizontally-layered volume conductor, we compared two analytic methods (Second Order Blind Identification, SOBI and Surface Current Density, SCD) that allow quantitative characterization of slow wave propagation. We also evaluated the performance of the methods with simulated experimental noise. The methods were also validated in an experimental animal model. Results Mean square errors in position estimates were within 2 cm of the correct position, and average propagation velocities within 2 mm/s of the actual velocities. SOBI propagation analysis outperformed the SCD method for dipoles in the superficial and horizontal layer models with and without additive noise. The SCD method gave better estimates for deep sources, but did not handle additive noise as well as SOBI. Conclusion SOBI-MGG and SCD-MGG were used to quantify slow wave propagation in a realistic abdomen model of gastric electrical activity. Significance These methods could be generalized to any propagating electrophysiological activity detected by multichannel sensor arrays. PMID:26595907

Leukoreduced red blood cell transfusions do not induce platelet glycoprotein antibodies in patients with sickle cell disease.

PubMed

Nickel, Robert Sheppard; Winkler, Anne M; Horan, John T; Hendrickson, Jeanne E

2016-09-01

Alloimmunization to red blood cell (RBC) antigens after transfusion is well described in patients with sickle cell disease (SCD). We recently demonstrated that leukocyte-reduced RBC transfusions appeared to induce human leukocyte antigen (HLA) antibodies in some children with SCD; now, we hypothesize that residual platelets contained in transfused RBC products may lead to platelet glycoprotein antibody formation. A cross-sectional study was conducted among never pregnant pediatric patients with SCD who either had received many RBC transfusions or had never received any transfusions. Serum was tested for antibodies to platelet-specific glycoproteins using a commercial enzyme immunoassay. Platelet-specific glycoprotein antibodies were found in 12 of 90 patients (13%) in the transfused group versus 5 of 24 patients (21%) in the never transfused group (p = 0.35). The prevalence of antibodies as well as the median standardized optical density for these two groups was not significantly different for any of the studied platelet glycoprotein antigens. There was no association with the presence of platelet-specific glycoprotein antibodies with either RBC or HLA antibodies. Leukocyte-reduced RBC transfusions do not appear to induce platelet-specific glycoprotein antibodies. The positive platelet-specific glycoprotein antibody results from this study may represent platelet autoantibodies, platelet alloantibodies, or false-positive reactions. A better understanding of the immunobiology of patients with SCD at baseline and after blood product exposure may help improve future transfusion and transplantation. © 2016 AABB.

Analysis of Mexico City urban air pollution using nitrogen dioxide column density measurements from UV/Visible spectroscopy

NASA Astrophysics Data System (ADS)

Garcia Payne, D. G.; Grutter, M.; Melamed, M. L.

2010-12-01

The differential optical absorption spectroscopy method (DOAS) was used to get column densities of nitrogen dioxide (NO2) from the analysis of zenith sky UV/visible spectra. Since the optical path length provides critical information in interpreting NO2 column densities, in conjunction with NO2 column densities, the oxygen dimer (O4) column density was retrieved to give insight into the optical path length. We report observations of year round NO2 and O4 column densities (from august 2009 to september 2010) from which the mean seasonal levels and the daily evolution, as well as the occurrence of elevated pollution episodes are examined. Surface nitric oxide (NO) and NO2 from the local monitoring network, as well as wind data and the vertical aerosol density from continuous Lidar measurements are used in the analysis to investigate specific events in the context of local emissions from vehicular traffic, photochemical production and transport from industrial emissions. The NO2 column density measurements will enhance the understanding Mexico City urban air pollution. Recent research has begun to unravel the complexity of the air pollution problem in Mexico City and its effects not only locally but on a regional and global scale as well.

Scd5p and Clathrin Function Are Important for Cortical Actin Organization, Endocytosis, and Localization of Sla2p in Yeast

PubMed Central

Henry, Kenneth R.; D'Hondt, Kathleen; Chang, JiSuk; Newpher, Thomas; Huang, Kristen; Hudson, R. Tod; Riezman, Howard; Lemmon, Sandra K.

2002-01-01

SCD5 was identified as a multicopy suppressor of clathrin HC-deficient yeast. SCD5 is essential, but an scd5-Δ338 mutant, expressing Scd5p with a C-terminal truncation of 338 amino acids, is temperature sensitive for growth. Further studies here demonstrate that scd5-Δ338 affects receptor-mediated and fluid-phase endocytosis and normal actin organization. The scd5-Δ338 mutant contains larger and depolarized cortical actin patches and a prevalence of G-actin bars. scd5-Δ338 also displays synthetic negative genetic interactions with mutations in several other proteins important for cortical actin organization and endocytosis. Moreover, Scd5p colocalizes with cortical actin. Analysis has revealed that clathrin-deficient yeast also have a major defect in cortical actin organization and accumulate G-actin. Overexpression of SCD5 partially suppresses the actin defect of clathrin mutants, whereas combining scd5-Δ338 with a clathrin mutation exacerbates the actin and endocytic phenotypes. Both Scd5p and yeast clathrin physically associate with Sla2p, a homologue of the mammalian huntingtin interacting protein HIP1 and the related HIP1R. Furthermore, Sla2p localization at the cell cortex is dependent on Scd5p and clathrin function. Therefore, Scd5p and clathrin are important for actin organization and endocytosis, and Sla2p may provide a critical link between clathrin and the actin cytoskeleton in yeast, similar to HIP1(R) in animal cells. PMID:12181333

Cortical Recruitment and Nuclear–Cytoplasmic Shuttling of Scd5p, a Protein Phosphatase-1-targeting Protein Involved in Actin Organization and EndocytosisD⃞

PubMed Central

Chang, Ji Suk; Henry, Kenneth; Geli, María Isabel; Lemmon, Sandra K.

2006-01-01

Scd5p regulates endocytosis and cortical actin organization as a targeting subunit for the Ser/Thr protein phosphatase-1 (PP1) in yeast. To identify localization signals in Scd5p required for cell surface recruitment, visualization of GFP-tagged Scd5 truncations and deletions was performed. Scd5p contains a PP1 binding site, a 3-repeat region of 20 amino acids (3R), and a 9-repeat region of 12 amino acids (9R). We found that the 9R is critical for cortical localization of Scd5p, but cortical recruitment is not essential for Scd5p's function in actin organization and endocytosis. We propose that Scd5p can target PP1 to endocytic factors in the cytoplasm that have been disassembled and/or inactivated by phosphorylation. We also found that Scd5p undergoes nuclear-cytoplasmic shuttling in a Crm1p-dependent manner. Scd5p-ΔCT lacking the 9R region and its nuclear export signal (NES) accumulates in the nucleus, causing cortical actin and endocytic defects. Cytoplasmic localization and function of Scd5p-ΔCT is restored by NES addition. However, removal of Scd5p's nuclear localization signal prevents nuclear entry, but endocytosis and actin organization remain relatively normal. These results indicate that nuclear-cytoplasmic shuttling is not required for regulation of Scd5p's cortical function and suggest that Scd5p has an independent nuclear function. PMID:16251346

Activated effector and memory T cells contribute to circulating sCD30: potential marker for islet allograft rejection.

PubMed

Saini, D; Ramachandran, S; Nataraju, A; Benshoff, N; Liu, W; Desai, N; Chapman, W; Mohanakumar, T

2008-09-01

T-cell activation up-regulates CD30 resulting in an increase in serum soluble CD30 (sCD30). CD4+ T cells, a major source for sCD30, play a significant role in the pathogenesis of rejection. In this study, sCD30 was measured pre- and posttransplant in mouse islet allograft models and human islet allograft recipients. sCD30 was measured by ELISA in diabetic C57BL/6, CD4Knockout (KO) and CD8KO islet allograft recipients. sCD30 increased significantly prior to rejection (1.8 +/- 1 days) in 80% of allograft recipients. Sensitization with donor splenocytes, or a second graft, further increased sCD30 (282.5 +/- 53.5 for the rejecting first graft vs. 374.6 +/- 129 for the rejecting second graft) prior to rejection suggesting memory CD4+ T cells contribute to sCD30. CD4KO failed to reject islet allograft and did not demonstrate sCD30 increase. CD8KO showed elevated (227 +/- 107) sCD30 (1 day) prior to rejection. High pretransplant sCD30 (>20 U/ml) correlated with poor outcome in human islet allograft recipients. Further, increase in sCD30 posttransplant preceded (3-4 months) loss of islet function. We conclude that sCD30 is released from activated CD4 T cells prior to islet allograft rejection and monitoring sCD30 can be a valuable adjunct in the follow-up of islet transplant recipients.

Elevated pretransplantation soluble CD30 is associated with decreased early allograft function after human lung transplantation.

PubMed

Shah, Ashish S; Leffell, M Sue; Lucas, Donna; Zachary, Andrea A

2009-02-01

Early allograft function after lung transplantation is variable. Clinical criteria have limited predictive value for early graft function. Recipient immunologic state before LTx may affect early lung function. We investigated the association between pretransplantation soluble CD30 (sCD30), a marker of Th2-type T-cell activation, and early clinical parameters of allograft function. Between September 2002 and January 2007, a total of 80 transplantations were performed at Johns Hopkins Hospital. Of the patients, 43 had a pretransplantation sCD30 level determined. Pre- and postoperative patient variables were collected, and patients were stratified into two groups: sCD30 <20 (low sCD30) and >20 (high sCD30). High sCD30 (n = 26) and low sCD30 (n = 17) groups were similar in age, gender, and ischemia time. In the high sCD30 group, a higher percentage of patients had pulmonary fibrosis and a lower percentage had emphysema. Oxygenation at 48 hours was significantly worse in the high sCD30 group as compared with the low sCD30 (p = 0.003). Moreover, prolonged intubation and 90-day mortality were greater in the high sCD30 group. This represents the first report of the use of sCD30 as a marker for early allograft function in human lung transplanation. Increased pretransplantation recipient sCD30 appears to be associated with decreased early post-transplantation gas exchange, prolonged intubation, and early mortality.

Transient lateral photovoltaic effect in synthetic single crystal diamond

NASA Astrophysics Data System (ADS)

Prestopino, G.; Marinelli, M.; Milani, E.; Verona, C.; Verona-Rinati, G.

2017-10-01

A transient lateral photovoltaic effect (LPE) is reported for a metal-semiconductor structure of synthetic single crystal diamond (SCD). A SCD Schottky photodiode was specifically designed to measure a LPE under collimated irradiation from a tunable pulsed laser. A transient lateral photovoltage parallel to the Schottky junction was indeed detected. LPE on the p-type doped SCD side showed a non-linearity of 2% and a fast response time, with a rise time of 2 μs and a decay time of 12 μs. The position sensitivity (up to 30 mV/mm at a laser wavelength of 220 nm and a pulse energy density of 2.9 μJ/mm2) was measured as a function of laser wavelength, and an ultraviolet (UV)-to-visible contrast ratio of about four orders of magnitude with a sharp cutoff at 225 nm was observed. Our results demonstrate that a large LPE at UV wavelengths is achievable in synthetic single crystal diamond, potentially opening opportunities for the study and application of LPE in diamond and for the fabrication of high performance visible blind UV position sensitive detectors with high sensitivity and microsecond scale response time.

Differential Risk of Incident Alzheimer's Disease Dementia in Stable Versus Unstable Patterns of Subjective Cognitive Decline.

PubMed

Wolfsgruber, Steffen; Kleineidam, Luca; Wagner, Michael; Mösch, Edelgard; Bickel, Horst; Lϋhmann, Dagmar; Ernst, Annette; Wiese, Birgitt; Steinmann, Susanne; König, Hans-Helmut; Brettschneider, Christian; Luck, Tobias; Stein, Janine; Weyerer, Siegfried; Werle, Jochen; Pentzek, Michael; Fuchs, Angela; Maier, Wolfgang; Scherer, Martin; Riedel-Heller, Steffi G; Jessen, Frank

2016-10-04

It is unknown whether longitudinal stability versus instability in subjective cognitive decline (SCD) is a modifying factor of the association between SCD and risk of incident Alzheimer's disease (AD) dementia. We tested the modifying role of temporal stability of the SCD report on AD dementia risk in cognitively normal elderly individuals. We analyzed data of 1,990 cognitively normal participants from the longitudinal AgeCoDe Study. We assessed SCD with/without associated worries both at baseline and first follow-up 18 months later. Participants were then classified either as (a) Controls (CO, with no SCD at both baseline and follow-up 1, n = 613), (b) inconsistent SCD (with SCD reported only at baseline or at follow-up 1, n = 637), (c) consistent SCD but without/or with inconsistent worries (n = 610) or (d) consistent SCD with worries (n = 130). We estimated incident AD dementia risk over up to 6 years for each group with Cox-Proportional Hazard Regression analyses adjusted for age, gender, education, ApoE4 status, and depression. Compared to CO, inconsistent SCD was not associated with increased risk of incident AD dementia. In contrast, risk was doubled in the group of consistent SCD without/ with inconsistent worries, and almost 4-fold in the group of consistent SCD with worries. These results could be replicated when using follow-up 1 to follow-up 2 response patterns for group definition. These findings suggest that longitudinal stability versus instability is an important modifying factor of the association between SCD and AD dementia risk. Worrisome SCD that is also consistently reported over time is associated with greatly increased risk of AD dementia.

Stearoyl CoA Desaturase (SCD) Facilitates Proliferation of Prostate Cancer Cells through Enhancement of Androgen Receptor Transactivation

PubMed Central

Kim, Seung-Jin; Choi, Hojung; Park, Sung-Soo; Chang, Chawnshang; Kim, Eungseok

2011-01-01

Stearoyl-CoA desaturase (SCD), the rate-limiting enzyme in the biosynthesis of monounsaturated fatty acids, is highly expressed in prostate cancer although the SCD protein has been known to be rapidly turned over by proteolytic cleavage. The present data demonstrate that SCD can promote proliferation of androgen receptor (AR)-positive LNCaP prostate cancer cells and enhance dihydrotestosterone (DHT)-induced AR transcriptional activity, resulting in increased expression of prostatespecific antigen (PSA) and kallikrein-related peptidase 2 (KLK2). Interestingly, among the previously reported SCDderived peptides produced by proteolytic cleavage of SCD, a peptide spanning amino acids 130-162 of SCD (SCDCoRNR) contained the CoRNR box motif (LFLII) and enhanced AR transcriptional activity. In contrast, a mutant SCD-CoRNR in which Leu136 was replaced by Ala had no effect on AR transcriptional activity. Moreover, SCDCoRNR directly interacted with AR and inhibited RIP140 suppression of AR transactivation. Knockdown of the SCD gene by SCD microRNA suppressed AR transactivation with decreased cell proliferation, suggesting that SCD may regulate the proliferation of LNCaP cells via modulation of AR transcriptional activity. Moreover, ectopic expression of SCD in LNCaP cells facilitated LNCaP tumor formation and growth in nude mice. Together, the data indicate that SCD plays a key role in the regulation of AR transcriptional activity in prostate cancer cells. PMID:21331774

Helicobacter pylori infection among a pediatric population with sickle cell disease.

PubMed

Senbanjo, Idowu; Akinbami, Akinsegun; Diaku-Akinwumi, Ijeoma; Oshikoya, Kazeem; Adeyemo, Titilope; Dada, Olufemi; Dosunmu, Adedoyin; Oshinaike, Olajumoke

2010-11-01

Recurrent abdominal pain (RAP) is a common presenting symptom in children with sickle cell disease (SCD). This may be as a result of complications of the disease, surgical problems, or Helicobacter pylori gastritis. The prevalence of H pylori infection in SCD children is not known. This study aimed to determine the prevalence and association of H pylori infection with RAP in SCD children. This was a prospective case-control study conducted at the Lagos State University Teaching Hospital, Nigeria, involving SCD children (subject, n = 118) and non-SCD children (control, n = 118) matched for age, sex, and socioeconomic status. Seroprevalence status of the children was determined by measuring immunoglobulin G antibodies against H pylori using enzyme-linked immunosorbent assay that had been validated for pediatric use. The overall prevalence of H pylori infection was 155 of 236 (SCD, 67.8%; non-SCD, 63.6%; OR, 1.1; 95% CI, 0.89-1.28; p = .493). The prevalence increased with age in both SCD and non-SCD children and was significantly highest at the age of 6 to 10 years (p < .001 in each case). H pylori infection was significantly associated with socioeconomic status of the parents (OR, 4.25; 95% CI, 1.49-12.1; p = .004) but not significantly associated with RAP in SCD children (OR, 1.21: 95% CI, 0.55-2.66; p = .632). Prevalence of H pylori infection is high in SCD and non-SCD children in Lagos, Nigeria. There was no significant association between H pylori infection and recurrent abdominal pain in SCD children.

Pharmacological inhibition of calpain-1 prevents red cell dehydration and reduces Gardos channel activity in a mouse model of sickle cell disease

PubMed Central

De Franceschi, Lucia; Franco, Robert S.; Bertoldi, Mariarita; Brugnara, Carlo; Matté, Alessandro; Siciliano, Angela; Wieschhaus, Adam J.; Chishti, Athar H.; Joiner, Clinton H.

2013-01-01

Sickle cell disease (SCD) is a globally distributed hereditary red blood cell (RBC) disorder. One of the hallmarks of SCD is the presence of circulating dense RBCs, which are important in SCD-related clinical manifestations. In human dense sickle cells, we found reduced calpastatin activity and protein expression compared to either healthy RBCs or unfractionated sickle cells, suggesting an imbalance between activator and inhibitor of calpain-1 in favor of activator in dense sickle cells. Calpain-1 is a nonlysosomal cysteine proteinase that modulates multiple cell functions through the selective cleavage of proteins. To investigate the relevance of this observation in vivo, we evaluated the effects of the orally active inhibitor of calpain-1, BDA-410 (30 mg/kg/d), on RBCs from SAD mice, a mouse model for SCD. In SAD mice, BDA-410 improved RBC morphology, reduced RBC density (D20; from 1106±0.001 to 1100±0.001 g/ml; P<0.05) and increased RBC-K+ content (from 364±10 to 429±12.3 mmol/kg Hb; P<0.05), markedly reduced the activity of the Ca2+-activated K+channel (Gardos channel), and decreased membrane association of peroxiredoxin-2. The inhibitory effect of calphostin C, a specific inhibitor of protein kinase C (PKC), on the Gardos channel was eliminated after BDA-410 treatment, which suggests that calpain-1 inhibition affects the PKC-dependent fraction of the Gardos channel. BDA-410 prevented hypoxia-induced RBC dehydration and K+ loss in SAD mice. These data suggest a potential role of BDA-410 as a novel therapeutic agent for treatment of SCD.—De Franceschi, L., Franco, R. S., Bertoldi, M., Brugnara, C., Matté, A., Siciliano, A., Wieschhaus, A. J., Chishti, A. H., Joiner, C. H. Pharmacological inhibition of calpain-1 prevents red cell dehydration and reduces Gardos channel activity in a mouse model of sickle cell disease. PMID:23085996

Genomic analyses of pneumococci from children with sickle cell disease expose host-specific bacterial adaptations and deficits in current interventions

PubMed Central

Muller, Martha; Obert, Caroline; Burnham, Corinna; Mann, Beth; Li, Yimei; Hayden, Randall T; Pestina, Tamara; Persons, Derek; Camilli, Andrew

2014-01-01

Summary Sickle cell disease (SCD) patients are at high risk of contracting pneumococcal infection. To address this risk, they receive pneumococcal vaccines, and antibiotic prophylaxis and treatment. To assess the impact of SCD and these interventions on pneumococcal genetic architecture, we examined the genomes of over 300 pneumococcal isolates from SCD patients over 20 years. Modern SCD strains retained invasive capacity but shifted away from the serotypes used in vaccines. These strains had specific genetic changes related to antibiotic resistance, capsule biosynthesis, metabolism and metal transport. A murine SCD model coupled with Tn-seq mutagenesis identified 60 non-capsular pneumococcal genes under differential selective pressure in SCD, which correlated with aspects of SCD pathophysiology. Further, virulence determinants in the SCD context were distinct from the general population and protective capacity of potential antigens was lost over time in SCD. This highlights the importance of understanding bacterial pathogenesis in the context of high-risk individuals. PMID:24832453

Soluble CD30 is more relevant to disease activity of atopic dermatitis than soluble CD26

PubMed Central

Katoh, N; Hirano, S; Suehiro, M; Ikenaga, K; Yamashita, T; Sugawara, N; Yasuno, H

2000-01-01

It is suggested that CD30 and CD26 are surface molecules expressed on activated Th2 and Th1 cells, respectively. We examined plasma levels of soluble CD26 (sCD26) and sCD30 in patients with atopic dermatitis (AD) when their eruptions were aggravated and in non-atopic healthy controls, and then analysed the possible correlation between these values and the levels of several clinical markers. The plasma levels of both sCD30 and sCD26 were significantly higher in AD patients than in controls, both in exacerbation status and after conventional treatment. Multiple regression analyses showed that plasma sCD30 was a much better predictor of the levels of serum IgE, serum LDH and plasma sCD25, and the area and the score of AD eruption than sCD26, although elevated levels of both sCD30 and sCD26 are associated with these clinical predictors of AD. Importantly, sCD30 plasma levels decreased significantly in AD patients after conventional treatment, while no significant transition was noted in the concentration of sCD26. Moreover, a significant reduction of sCD30 levels was observed in the group of patients whose eruption score was reduced > 50%, whereas it was not in those < 50%. These findings provide evidence that the successful treatment of AD is associated with down-activation of Th2. PMID:10931130

Persistent high plasma levels of sCD163 and sCD14 in adult patients with measles virus infection.

PubMed

Mascia, Claudia; Pozzetto, Irene; Kertusha, Blerta; Marocco, Raffaella; Del Borgo, Cosmo; Tieghi, Tiziana; Vita, Serena; Savinelli, Stefano; Iannetta, Marco; Vullo, Vincenzo; Lichtner, Miriam; Mastroianni, Claudio Maria

2018-01-01

Measles is an infectious disease that represents a serious public health problem worldwide, being associated with increased susceptibility to secondary infections, especially in the respiratory and gastrointestinal tracts. The aim of this study was to evaluate sCD163 and sCD14 levels in measles virus (MV) infected patients, as markers of immune activation, in order to better understand their role in the pathogenesis of the disease. TNF-α plasma levels were also evaluated. sCD163, sCD14 and TNF-α were measured by ELISA in plasma samples of 27 MV infected patients and 27 healthy donors (HD) included as controls. At the time of hospital admission, sCD163 and sCD14 levels were significantly higher in MV infected patients than in HD, while a decrease in TNF-α levels were found even if without statistical significance. sCD163 and sCD14 levels were significantly decreased after two months from acute infection compared to hospital admission although they remained significantly higher compared to HD. TNF-α levels increased significantly during the follow-up period. Considering clinical parameters, sCD163 levels positively correlated with aspartate aminotransferase, white blood cell count and neutrophils rate, while negatively correlated with the lymphocyte percentage. sCD14 levels positively correlated with the neutrophil and lymphocyte percentages. These results indicate that, despite the resolution of symptoms, an important macrophage/monocyte activation persists in measles patients, even after two months from infection.

Sickle cell in Latin America and the United States [corrected].

PubMed

Huttle, Alexandra; Maestre, Gladys E; Lantigua, Rafael; Green, Nancy S

2015-07-01

Latin Americans are an underappreciated population affected by sickle cell disease (SCD). Sickle trait and SCD exist throughout Latin America and U.S. Latino communities. We describe the epidemiology and genetic heterogeneity of SCD among Latin Americans, and fetal hemoglobin expression. National population-based newborn screening for SCD is limited to Brazil, Costa Rica, and the U.S. Available and extrapolated data suggest that over 6,000 annual births and 100,000-150,000 Latin Americans are affected by SCD. This comprehensive review highlights the substantial numbers and population distribution of SCD and sickle trait in Latin America, and where national newborn screening programs for SCD exist. © 2015 Wiley Periodicals, Inc.

Soluble CD30 and Cd27 levels in patients undergoing HLA antibody-incompatible renal transplantation.

PubMed

Hamer, Rizwan; Roche, Laura; Smillie, David; Harmer, Andrea; Mitchell, Daniel; Molostvov, Guerman; Lam, For T; Kashi, Habib; Tan, Lam Chin; Imray, Chris; Fletcher, Simon; Briggs, David; Lowe, David; Zehnder, Daniel; Higgins, Rob

2010-08-01

HLA antibody-incompatible transplantation has a higher risk of rejection when compared to standard renal transplantation. Soluble CD30 (sCD30) has been shown in many, but not all, studies to be a biomarker for risk of rejection in standard renal transplant recipients. We sought to define the value of sCD30 and soluble CD27 (sCD27) in patients receiving HLA antibody-incompatible transplants. Serum taken at different time points from 32 HLA antibody-incompatible transplant recipients was retrospectively assessed for sCD30 and sCD27 levels by enzyme-linked immunosorbent assay (ELISA). This was compared to episodes of acute rejection, post-transplant donor-specific antibody (DSA) levels and 12 month serum creatinine levels. No association was found between sCD27 and sCD30 levels and risk of acute rejection or DSA levels. Higher sCD30 levels at 4-6 weeks post-transplantation were associated with a higher serum creatinine at 12 months. Conclusion patients undergoing HLA antibody-incompatible transplantation are at a high risk of rejection but neither sCD30 (unlike in standard transplantation) nor sCD27 was found to be a risk factor. High sCD30 levels measured at 4-6 weeks post-transplantation was associated with poorer graft function at one year. Copyright © 2010 Elsevier B.V. All rights reserved.

Soluble CD163 is an indicator of liver inflammation and fibrosis in patients chronically infected with the hepatitis B virus.

PubMed

Dultz, G; Gerber, L; Farnik, H; Berger, A; Vermehren, J; Pleli, T; Zeuzem, S; Piiper, A; Kronenberger, B; Waidmann, O

2015-04-01

Soluble CD163 (sCD163), a marker for macrophage activation, was found to be associated with the severity of liver cirrhosis. The aim of the current study was to investigate whether serum sCD163 levels correlate with liver inflammation and fibrosis in patients with chronic hepatitis B virus (HBV) infection. In a retrospective cohort study, serum sCD163 levels were assessed by ELISA together with clinical and laboratory data in 186 patients with chronic HBV infection and 15 healthy controls. The relation between parameters for liver fibrosis and necroinflammation and sCD163 levels was analysed. Additionally, sCD163 was quantified in a subset of follow-up serum samples after initiation of antiviral treatment. sCD163 levels differed among phases of chronic HBV infection (P < 0.0001), and sCD163 concentrations were associated with inflammatory activity and fibrosis in the liver. sCD163 levels ≥ 1961 ng/l had a high specificity in the identification of subjects with substantial fibrosis (F ≥ 2). sCD163 concentrations decreased significantly after initiation of antiviral treatment. The correlation of sCD163 levels with necroinflammation and fibrosis and the sCD163 decline under treatment indicates that macrophage activation plays a role in HBV-related liver pathogenesis. © 2014 John Wiley & Sons Ltd.

Identification of conserved cis-elements and transcription factors required for sterol-regulated transcription of stearoyl-CoA desaturase 1 and 2.

PubMed

Tabor, D E; Kim, J B; Spiegelman, B M; Edwards, P A

1999-07-16

We previously identified stearoyl-CoA desaturase 2 (SCD2) as a new member of the family of genes that are transcriptionally regulated in response to changing levels of nuclear sterol regulatory element binding proteins (SREBPs) or adipocyte determination and differentiation factor 1 (ADD1). A novel sterol regulatory element (SRE) (5'-AGCAGATTGTG-3') identified in the proximal promoter of the mouse SCD2 gene is required for induction of SCD2 promoter-reporter genes in response to cellular sterol depletion (Tabor, D. E., Kim, J. B., Spiegelman, B. M., and Edwards, P. A. (1998) J. Biol. Chem. 273, 22052-22058). In this report, we demonstrate that this novel SRE is both present in the promoter of the SCD1 gene and is critical for the sterol-dependent transcription of SCD1 promoter-reporter genes. Two conserved cis elements (5'-CCAAT-3') lie 5 and 48 base pairs 3' of the novel SREs in the promoters of both the SCD1 and SCD2 murine genes. Mutation of either of these putative NF-Y binding sites attenuates the transcriptional activation of SCD1 or SCD2 promoter-reporter genes in response to cellular sterol deprivation. Induction of both reporter genes is also attenuated when cells are cotransfected with dominant-negative forms of either NF-Y or SREBP. In addition, we demonstrate that the induction of SCD1 and SCD2 mRNAs that occurs during the differentiation of 3T3-L1 preadipocytes to adipocytes is paralleled by an increase in the levels of ADD1/SREBP-1c and that the SCD1 and SCD2 mRNAs are induced to even higher levels in response to ectopic expression of ADD1/SREBP-1c. We conclude that transcription of both SCD1 and SCD2 genes is responsive to cellular sterol levels and to the levels of nuclear SREBP/ADD1 and that transcriptional induction requires three spatially conserved cis elements, that bind SREBP and NF-Y. Additional studies demonstrate that maximal transcriptional repression of SCD2 reporter genes in response to an exogenous polyunsaturated fatty acid is dependent upon the SRE and the adjacent CCAAT motif.

LDL-cholesterol-lowering effect of a dietary supplement with plant extracts in subjects with moderate hypercholesterolemia.

PubMed

Ogier, Nicolas; Amiot, Marie-Josèphe; Georgé, Stéphane; Maillot, Matthieu; Mallmann, Cécilia; Maraninchi, Marie; Morange, Sophie; Lescuyer, Jean-François; Peltier, Sébastien L; Cardinault, Nicolas

2013-03-01

Red yeast rice (RYR), sugar cane-derived policosanols (SCdP) and artichoke leaf extracts (ALEs) are currently incorporated alone or in combination into dietary supplements for their potential low-density-lipoprotein cholesterol (LDL-cholesterol)-lowering effects. Yet, there is no information supporting the efficacy of this association on the reduction in LDL-cholesterol. The main objective of this study was to investigate the effects of a new dietary supplement (DS) with RYR, SCdP and ALEs on LDL-cholesterol. In a double-blind, randomized, parallel controlled study, 39 subjects from 21 to 55 years with moderate hypercholesterolemia without drug treatment were assigned to 2 groups and then consumed either a DS containing RYR, SCdP and ALEs or a placebo over a 16-week period. Plasma concentrations of lipids [LDL-cholesterol, total cholesterol (TC), high-density-lipoprotein cholesterol (HDL-cholesterol), triacylglycerols (TG)] and plasma levels of vitamins C and E, total polyphenols and malondialdehyde were determined at baseline and after 4, 8, 12 and 16 weeks. LDL-cholesterol and TC were reduced by, respectively, 21.4 % (95 % CI, -13.3 to -24.9 %, p < 0.001) and 14.1 % (95 % CI, -10.1 to -18.0 %, p < 0.001) at week 16 in the DS group compared with baseline. Similar results were obtained at weeks 4, 8 and 12. TG decreased by 12.2 % after 16 weeks in the DS group (95 % CI: -24.4 to -0.1 %, p < 0.05). For the vitamin E/TC ratio, a difference was observed between groups at week 16 (p < 0.05). Other parameters were not modified. Daily consumption of this new DS decreased LDL-cholesterol and TC and is therefore an interesting, convenient aid in managing mild to moderate hypercholesterolemia.

Non-survivor septic patients have persistently higher serum sCD40L levels than survivors.

PubMed

Lorente, Leonardo; Martín, María M; Pérez-Cejas, Antonia; Ferreres, José; Solé-Violán, Jordi; Labarta, Lorenzo; Díaz, César; Jiménez, Alejandro

2017-10-01

Soluble CD40 ligand (sCD40L) is a protein with proinflammatory and prothrombotic effects. Previously we found higher circulating sCD40L levels in non-survivor than in survivor patients at sepsis diagnosis. Now some questions arise such as how are serum sCD40L levels during the first week of severe sepsis?, is there an association between serum sCD40L levels during the first week and mortality?, and serum sCD40L levels during the first week could be used as sepsis mortality biomarker?. This study was developed to answer these asks. Study from 6 Spanish Intensive Care Units with 291 severe septic patients. There were determined serum levels of sCD40L and tumor necrosis factor (TNF)-alpha during the first week. The end-point study was 30-day mortality. We found that serum sCD40L at days 1, 4, and 8 could predict mortality at 30days, and are associated with mortality. The novel findings of our study were that there were higher serum sCD40L levels persistently during the first week in non-survivor than in survivor patients, that there is an association between serum sCD40L levels during the first week and sepsis mortality, and that serum sCD40L levels during the first week could be used as sepsis mortality biomarker. Copyright © 2017 Elsevier Inc. All rights reserved.

The shapes of column density PDFs. The importance of the last closed contour

NASA Astrophysics Data System (ADS)

Alves, João; Lombardi, Marco; Lada, Charles J.

2017-10-01

The probability distribution function of column density (PDF) has become the tool of choice for cloud structure analysis and star formation studies. Its simplicity is attractive, and the PDF could offer access to cloud physical parameters otherwise difficult to measure, but there has been some confusion in the literature on the definition of its completeness limit and shape at the low column density end. In this letter we use the natural definition of the completeness limit of a column density PDF, the last closed column density contour inside a surveyed region, and apply it to a set of large-scale maps of nearby molecular clouds. We conclude that there is no observational evidence for log-normal PDFs in these objects. We find that all studied molecular clouds have PDFs well described by power laws, including the diffuse cloud Polaris. Our results call for a new physical interpretation of the shape of the column density PDFs. We find that the slope of a cloud PDF is invariant to distance but not to the spatial arrangement of cloud material, and as such it is still a useful tool for investigating cloud structure.

A differential impact of mycophenolic acid, prednisolone, and tacrolimus exposure on sCD30 levels in adult kidney transplant recipients.

PubMed

Barraclough, Katherine A; Staatz, Christine E; Johnson, David W; Gillis, David; Lee, Katie J; McWhinney, Brett C; Ungerer, Jacobus P J; Campbell, Scott B; Isbel, Nicole M

2013-04-01

Soluble CD30 (sCD30) has been associated with rejection and graft loss in kidney transplantation, leading to the suggestion that sCD30 might be a useful biomarker to adjust immunosuppressant medication dosing. However, there has been minimal study of the influence of individual immunosuppressive drugs on sCD30 levels. To evaluate the influence of mycophenolic acid (MPA), prednisolone, and tacrolimus exposure on sCD30 levels in adult kidney transplant recipients. The sCD30 levels were measured pretransplant and 30 days posttransplant. Area under the concentration-time curve (AUC) for each drug was estimated on day 30 using validated, multiple regression-derived limited sampling strategies. One hundred twenty-five subjects were included. Median (interquartile range) sCD30 levels were lower on day 30 posttransplant compared with pretransplant [10.7 (3.7-20.1) pg/mL versus 66.5 (46.0-95.1) pg/mL; P < 0.0001]. On univariate analyses, day 30 sCD30 levels were negatively correlated with MPA exposure and positively correlated with tacrolimus exposure. Using multivariate logistic regression, higher tacrolimus exposure was independently associated with higher day 30 sCD30 levels (2.2 change in odds for an SD increase in tacrolimus AUC 0-12, P = 0.01; 5.5 change in odds for an SD increase in tacrolimus predose concentration, P < 0.0001). In contrast, MPA and total and free prednisolone exposures were not independently associated with sCD30 levels. The sCD30 levels are significantly reduced in the presence of combination immunosuppression but are differentially affected by different immunosuppressant agents. More research is required before introduction of sCD30 measurement into clinical practice can be considered.

From Subjective Cognitive Decline to Alzheimer's Disease: The Predictive Role of Neuropsychological Assessment, Personality Traits, and Cognitive Reserve. A 7-Year Follow-Up Study.

PubMed

Bessi, Valentina; Mazzeo, Salvatore; Padiglioni, Sonia; Piccini, Carolina; Nacmias, Benedetta; Sorbi, Sandro; Bracco, Laura

2018-01-01

The aim of this study was to evaluate the accuracy of neuropsychological assessment in predicting conversion from subjective cognitive decline (SCD) and mild cognitive impairment (MCI) to Alzheimer's disease (AD) and the effect of personality traits and cognitive reserve in progression from SCD to MCI. As part of a longitudinal, clinical-neuropsychological-genetic survey on SCD and MCI, 284 patients referred to our hospital between 1990 and 2017 were included. All patients underwent clinical-extensive neuropsychological evaluation and Apolipoprotein E genotyping; personality traits were assessed in a subgroup. Each patient underwent clinical-neuropsychological follow-up. Subjects with a follow-up shorter than two years were excluded. A total of 212 subjects were, after exclusions, considered: 26 out of 109 SCD subjects progressed to MCI (SCD-p), 15 converted to AD (SCD-c), and 68 remained stable (SCD-s). Of 103 MCI subjects, 39 converted to AD (MCI-c) and 64 remained stable (MCI-s). At baseline, SCD-c performed significantly worse than SCD-s in tests assessing long-term verbal memory. MCI-c showed worse performance on neuropsychological tests for short- and long-term verbal memory and for ecological evaluation of memory (RBMT). These tests provided good accuracy in distinguishing MCI-c and MCI-s. Emotional stability was significantly lower in SCD-s than in SCD-p while higher intellectual activities were associated with a lower risk of conversion to MCI. Our results suggest that memory neuropsychological tests may represent a reliable tool to estimate the risk of progression to AD. Personality and lifestyle factors could provide useful information to identify SCD subjects who may develop an objective cognitive impairment.

Incident Subjective Cognitive Decline Does Not Predict Mortality in the Elderly--Results from the Longitudinal German Study on Ageing, Cognition, and Dementia (AgeCoDe).

PubMed

Roehr, Susanne; Luck, Tobias; Heser, Kathrin; Fuchs, Angela; Ernst, Annette; Wiese, Birgitt; Werle, Jochen; Bickel, Horst; Brettschneider, Christian; Koppara, Alexander; Pentzek, Michael; Lange, Carolin; Prokein, Jana; Weyerer, Siegfried; Mösch, Edelgard; König, Hans-Helmut; Maier, Wolfgang; Scherer, Martin; Jessen, Frank; Riedel-Heller, Steffi G

2016-01-01

Subjective cognitive decline (SCD) might represent the first symptomatic representation of Alzheimer's disease (AD), which is associated with increased mortality. Only few studies, however, have analyzed the association of SCD and mortality, and if so, based on prevalent cases. Thus, we investigated incident SCD in memory and mortality. Data were derived from the German AgeCoDe study, a prospective longitudinal study on the epidemiology of mild cognitive impairment (MCI) and dementia in primary care patients over 75 years covering an observation period of 7.5 years. We used univariate and multivariate Cox regression analyses to examine the relationship of SCD and mortality. Further, we estimated survival times by the Kaplan Meier method and case-fatality rates with regard to SCD. Among 971 individuals without objective cognitive impairment, 233 (24.0%) incidentally expressed SCD at follow-up I. Incident SCD was not significantly associated with increased mortality in the univariate (HR = 1.0, 95% confidence interval = 0.8-1.3, p = .90) as well as in the multivariate analysis (HR = 0.9, 95% confidence interval = 0.7-1.2, p = .40). The same applied for SCD in relation to concerns. Mean survival time with SCD was 8.0 years (SD = 0.1) after onset. Incident SCD in memory in individuals with unimpaired cognitive performance does not predict mortality. The main reason might be that SCD does not ultimately lead into future cognitive decline in any case. However, as prevalence studies suggest, subjectively perceived decline in non-memory cognitive domains might be associated with increased mortality. Future studies may address mortality in such other cognitive domains of SCD in incident cases.

High pretransplantation soluble CD30 levels: impact in renal transplantation.

PubMed

Giannoli, C; Bonnet, M C; Perrat, G; Houillon, A; Reydet, S; Pouteil-Noble, C; Villar, E; Lefrançois, N; Morelon, E; Dubois, V

2007-10-01

In a retrospective study, the impact of the level of pretransplantation soluble CD30 molecule (sCD30) was evaluated on 3 year transplant survival, as well as the number and grade of acute rejection episodes among kidney recipients engrafted between 2000 and 2002. One hundred and ninety sera of 190 patients sampled on the cross-match day were tested for sCD30 concentrations using an enzyme-linked immunosorbent assay (ELISA) kit (Biotest). For the analysis, a sCD30 cutoff level of 100 U/mL was chosen: 87 (46%) recipients had a level >100, and 103 (54%) <100. All cases (5) of immunological graft loss showed a high sCD30 level. The rate of biopsy-proven acute rejection was 26% in the sCD30 >100 group versus 22% in the sCD30 <100 groups. Among the first graft population (n = 157), the rate was 27% for sCD30 >100 versus 20% for the lower level. The difference was more important for grade II acute rejection (Banff criteria): 6/87 (7%) showed high sCD30 versus 2/103 (2%) with sCD30 <100. This analysis became significant for anti-HLA immunization: 11 (13%) recipients developed anti-HLA class II antibodies in the first group (sCD30 >100) versus 1 (1%) in the second group (sCD30 <100; P < .01). A high pretransplantation sCD30 was not a significant risk factor for an acute rejection episode, but it seemed to be more predictive for antibody-mediated acute rejection and immunological graft loss. However, many recipients showed an increased pretransplantation concentration without any rejection episode or graft loss. Consequently, sCD30 pregraft measurements cannot be used as a predictor for acute kidney rejection among our transplant center, nor as an aid to adapt the immunosuppressive regimen.

Plasma CXCL10, sCD163 and sCD14 Levels Have Distinct Associations with Antiretroviral Treatment and Cardiovascular Disease Risk Factors

PubMed Central

Castley, Alison; Williams, Leah; James, Ian; Guelfi, George; Berry, Cassandra; Nolan, David

2016-01-01

We investigate the associations of three established plasma biomarkers in the context of HIV and treatment-related variables including a comprehensive cardiovascular disease risk assessment, within a large ambulatory HIV cohort. Patients were recruited in 2010 to form the Royal Perth Hospital HIV/CVD risk cohort. Plasma sCD14, sCD163 and CXCL10 levels were measured in 475 consecutive patients with documented CVD risk (age, ethnicity, gender, smoking, blood pressure, BMI, fasting metabolic profile) and HIV treatment history including immunological/virological outcomes. The biomarkers assessed showed distinct associations with virological response: CXCL10 strongly correlated with HIV-1 RNA (p<0.001), sCD163 was significantly reduced among ‘aviraemic’ patients only (p = 0.02), while sCD14 was unaffected by virological status under 10,000 copies/mL (p>0.2). Associations between higher sCD163 and protease inhibitor therapy (p = 0.05) and lower sCD14 with integrase inhibitor therapy (p = 0.02) were observed. Levels of sCD163 were also associated with CVD risk factors (age, ethnicity, HDL, BMI), with a favourable influence of Framingham score <10% (p = 0.04). Soluble CD14 levels were higher among smokers (p = 0.002), with no effect of other CVD risk factors, except age (p = 0.045). Our findings confirm CXCL10, sCD163 and sCD14 have distinct associations with different aspects of HIV infection and treatment. Levels of CXCL10 correlated with routinely monitored variables, sCD163 levels reflect a deeper level of virological suppression and influence of CVD risk factors, while sCD14 levels were not associated with routinely monitored variables, with evidence of specific effects of smoking and integrase inhibitor therapy warranting further investigation. PMID:27355513

Emergency Medicine Management of Sickle Cell Disease Complications: An Evidence-Based Update.

PubMed

Simon, Erica; Long, Brit; Koyfman, Alex

2016-10-01

Sickle cell disease (SCD) affects approximately 100,000 individuals in the United States. Due to alterations in the structural conformation of hemoglobin molecules under deoxygenated conditions, patients with SCD are predisposed to numerous sequelae, many of which require acute intervention. Our aim was to provide emergency physicians with an evidence-based update regarding the diagnosis and management of SCD complications. SCD patients experience significant morbidity and mortality secondary to cerebrovascular accident, acute chest syndrome, acute vaso-occlusive pain crises, SCD-related multi-organ failure, cholecystitis, acute intrahepatic cholestasis, acute sickle hepatic crisis, acute hepatic sequestration, priapism, and renal disease. Emergency physicians must recognize acute manifestations of SCD in order to deliver timely management and determine patient disposition. A comprehensive review of the emergency department management of acute SCD complications is provided. Comprehensive understanding of these aspects of SCD can assist physicians in expediting patient evaluation and treatment, thus decreasing the morbidity and mortality associated with this hemoglobinopathy. Copyright © 2016 Elsevier Inc. All rights reserved.

Exploring family communication about sickle cell disease in adolescence.

PubMed

Graff, J Carolyn; Hankins, Jane; Graves, Rebecca J; Robitaille, Kimberly Y; Roberts, Ruth; Cejda, Katherine; Hardy, Belinda T; Johnson, Margery; Porter, Jerlym S

2012-01-01

Sickle cell disease (SCD) is a lifelong disorder that involves progressive organ damage and requires ongoing medical attention to prevent and treat episodic acute complications. Children with SCD need ongoing monitoring and extra attention that may be stressful to family members. Communication within families can help resolve family stress and may be associated with medical follow-up and management of SCD. Focus groups were conducted with 12 African American families to explore the communication that occurred within and outside of the family from the perspectives of adolescents with SCD, siblings, and parents. Factors that influence family communication were explored. The extended family was an important social network and resource to adolescents, siblings, and parents. Family member knowledge of SCD was an important factor that influenced communication about SCD; adolescents and parents communicated more easily than siblings and also reported having more knowledge of SCD than siblings. Future research focusing on the knowledge of immediate and extended family members and their recognition of their contribution to the child with SCD is recommended.

Serum and CSF soluble CD26 and CD30 concentrations in healthy pediatric surgical outpatients.

PubMed

Delezuch, W; Marttinen, P; Kokki, H; Heikkinen, M; Vanamo, K; Pulkki, K; Matinlauri, I

2012-10-01

Activated T-helper type 1 (Th1) lymphocytes induce a cellular type immune response, and Th2 lymphocytes, a humoral or antibody-mediated type immune response. Soluble CD26 (sCD26) and soluble CD30 (sCD30) are regarded as markers of Th1 and Th2 lymphocyte activation, respectively. Serum from 112 generally healthy pediatric surgical patients and cerebrospinal fluid (CSF) from 39, aged 1-17 years were measured for sCD26 and sCD30 using an enzyme-linked immunosorbent assay method. The detection limit for sCD26 was 6.8 ng/ml and for sCD30, 1.9 IU/ml. For serum sCD26 and sCD30, 2.5% and 97.5% percentiles constituted the reference limits, and the 95% credible intervals for the percentiles were calculated using regression models with a Bayesian approach. A significant between-gender difference was observed (P = 0.015) in serum sCD26 concentration, of which the lower limits ranged between 273 and 716 ng/ml for girls and 235 and 797 ng/ml for boys. The upper limits ranged between 1456 and 1898 ng/ml for girls and between 1419 and 1981 ng/ml for boys. Moreover, the concentrations of sCD26 increased in infants and children up to 10 years in girls and 12 years in boys. After this however, the values decreased. The serum sCD30 concentration was highest among the youngest infants aged 1 year (80-193 IU/ml), after which a consistent age-related decrease was found. The lowest values were found at the age of 17 years (10-89 IU/ml). A significant between-gender difference in sCD30 concentration was observed (P = 0.019). sCD26 and sCD30 concentrations were low in the CSF samples analyzed: 13.3 ng/ml (median); range 8.3-51.5 ng/ml and 7.6 IU/ml; 2.1-18.5 IU/ml, respectively. Reference limits for serum sCD26 in children aged 1-17 years were established as being 235-1800 ng/ml in toddlers and 400-1800 ng/ml in female adolescents and 700-2000 ng/ml in male adolescents. For sCD30; reference limits of 80-190 IU/ml were established in the youngest age group and 10-90 IU/ml in adolescents. © 2012 John Wiley & Sons A/S.

Lack of Mucosal Healing From Modified Specific Carbohydrate Diet in Pediatric Patients With Crohn Disease.

PubMed

Wahbeh, Ghassan T; Ward, Brian T; Lee, Dale Y; Giefer, Matthew J; Suskind, David L

2017-09-01

Exclusive enteral nutrition is effective in pediatric Crohn disease but challenging as maintenance therapy. There is interest in food-based therapies such as the specific carbohydrate diet (SCD) but paucity of data on efficacy and effect on mucosal healing, an evolving target of IBD therapy. We conducted a retrospective review of the mucosal healing effect of the SCD in pediatric Crohn disease (CD). The endoscopic findings for children younger than 18 years with CD treated exclusively with the SCD or modified SCD (mSCD; SCD + addition of "illegal foods") were reviewed before and after the diet. Ileocolonoscopic examinations were scored according to the Simple Endoscopic Score for CD and findings on upper endoscopy were described. Seven subjects were identified, all on mSCD. The average age at starting the SCD was 11 ± 3.4 years and median duration of SCD/mSCD therapy was 26 months. All subjects reported no active symptoms before repeat endoscopic evaluation on mSCD, the majority had consistently normal C-reactive protein, albumin and hematocrit assessments, and mildly elevated fecal calprotectin (>50 μg/g, median 201, range 65-312) at any point within 3 months before the repeat endoscopy. One patient showed complete ileocolonic healing but persistent upper gastrointestinal tract ulceration. Complete macroscopic mucosal healing of both the ileocolon and upper gastrointestinal tract was not seen in any patient.

Comparison of tropospheric NO2 vertical columns in an urban environment using satellite, multi-axis differential optical absorption spectroscopy, and in situ measurements

NASA Astrophysics Data System (ADS)

Mendolia, D.; D'Souza, R. J. C.; Evans, G. J.; Brook, J.

2013-10-01

Tropospheric NO2 vertical column densities have been retrieved and compared for the first time in Toronto, Canada, using three methods of differing spatial scales. Remotely sensed NO2 vertical column densities, retrieved from multi-axis differential optical absorption spectroscopy and satellite remote sensing, were evaluated by comparison with in situ vertical column densities estimated using a pair of chemiluminescence monitors situated 0.01 and 0.5 km a.g.l. (above ground level). The chemiluminescence measurements were corrected for the influence of NOz, which reduced the NO2 concentrations at 0.01 and 0.5 km by an average of 8 ± 1% and 12 ± 1%, respectively. The average absolute decrease in the chemiluminescence NO2 measurement as a result of this correction was less than 1 ppb. The monthly averaged ratio of the NO2 concentration at 0.5 to 0.01 km varied seasonally, and exhibited a negative linear dependence on the monthly average temperature, with Pearson's R = 0.83. During the coldest month, February, this ratio was 0.52 ± 0.04, while during the warmest month, July, this ratio was 0.34 ± 0.04, illustrating that NO2 is not well mixed within 0.5 km above ground level. Good correlation was observed between the remotely sensed and in situ NO2 vertical column densities (Pearson's R value ranging from 0.72 to 0.81), but the in situ vertical column densities were 52 to 58% greater than the remotely sensed columns. These results indicate that NO2 horizontal heterogeneity strongly impacted the magnitude of the remotely sensed columns. The in situ columns reflected an urban environment with major traffic sources, while the remotely sensed NO2 vertical column densities were representative of the region, which included spatial heterogeneity introduced by residential neighbourhoods and Lake Ontario. Despite the difference in absolute values, the reasonable correlation between the vertical column densities determined by three distinct methods increased confidence in the validity of the values provided by each measurement technique.

Elevated serum levels of soluble CD30 in patients with atopic dermatitis (AD).

PubMed

Bengtsson, A; Holm, L; Bäck, O; Fransson, J; Scheynius, A

1997-09-01

The immunopathology of AD is still unclear, but evidence for an immune response polarized towards Th2 activity has been provided. The CD30 molecule belongs to the tumour necrosis factor (TNF) receptor family and is expressed on activated T cells with a sustained expression in Th2 cells. This molecule also exists in a soluble form (sCD30). Elevated serum levels of sCD30 have been found in patients with Hodgkin's disease, chronic hepatitis B infection and HIV infection. Studies were undertaken to compare the serum levels of sCD30 in patients with AD (n=49) and healthy non-atopic controls (n=94). The presence of sCD30 was analysed with ELISA. A significantly higher concentration of sCD30 was noted in AD patients, median sCD30 level 29 U/ml (range 1-708 U/ml), compared with healthy non-atopic controls (P<0.001), where the median level was 11 U/ml with a range of 1-1042 U/ml. No correlation was found between sCD30 levels and total serum IgE, or between the AD patients' SCORAD values and concentration of sCD30. sCD30 levels were also analysed in 20 AD patients, which during ketoconazole treatment had improved their clinical scores and reduced their serum IgE and eosinophil cationic protein levels. However, no significant decrease in sCD30 levels was noted after treatment. The results show that patients with AD have elevated levels of sCD30, but without correlation to total serum IgE or disease activity.

Proceedings of a Sickle Cell Disease Ontology workshop - Towards the first comprehensive ontology for Sickle Cell Disease.

PubMed

Mulder, Nicola; Nembaware, Victoria; Adekile, Adekunle; Anie, Kofi A; Inusa, Baba; Brown, Biobele; Campbell, Andrew; Chinenere, Furahini; Chunda-Liyoka, Catherine; Derebail, Vimal K; Geard, Amy; Ghedira, Kais; Hamilton, Carol M; Hanchard, Neil A; Haendel, Melissa; Huggins, Wayne; Ibrahim, Muntaser; Jupp, Simon; Kamga, Karen Kengne; Knight-Madden, Jennifer; Lopez-Sall, Philomène; Mbiyavanga, Mamana; Munube, Deogratias; Nirenberg, Damian; Nnodu, Obiageli; Ofori-Acquah, Solomon Fiifi; Ohene-Frempong, Kwaku; Opap, Kenneth Babu; Panji, Sumir; Park, Miriam; Pule, Gift; Royal, Charmaine; Sangeda, Raphael; Tayo, Bamidele; Treadwell, Marsha; Tshilolo, Léon; Wonkam, Ambroise

2016-06-01

Sickle cell disease (SCD) is a debilitating single gene disorder caused by a single point mutation that results in physical deformation (i.e. sickling) of erythrocytes at reduced oxygen tensions. Up to 75% of SCD in newborns world-wide occurs in sub-Saharan Africa, where neonatal and childhood mortality from sickle cell related complications is high. While SCD research across the globe is tackling the disease on multiple fronts, advances have yet to significantly impact on the health and quality of life of SCD patients, due to lack of coordination of these disparate efforts. Ensuring data across studies is directly comparable through standardization is a necessary step towards realizing this goal. Such a standardization requires the development and implementation of a disease-specific ontology for SCD that is applicable globally. Ontology development is best achieved by bringing together experts in the domain to contribute their knowledge. The SCD community and H3ABioNet members joined forces at a recent SCD Ontology workshop to develop an ontology covering aspects of SCD under the classes: phenotype, diagnostics, therapeutics, quality of life, disease modifiers and disease stage. The aim of the workshop was for participants to contribute their expertise to development of the structure and contents of the SCD ontology. Here we describe the proceedings of the Sickle Cell Disease Ontology Workshop held in Cape Town South Africa in February 2016 and its outcomes. The objective of the workshop was to bring together experts in SCD from around the world to contribute their expertise to the development of various aspects of the SCD ontology.

Outcomes of Inpatients With and Without Sickle Cell Disease After High-Volume Surgical Procedures

PubMed Central

Dinan, Michaela A.; Chou, Chia-Hung; Hammill, Bradley G.; Graham, Felicia L.; Schulman, Kevin A.; Telen, Marilyn J.; Reed, Shelby D.

2009-01-01

In this study, we examined differences in inpatient costs, length of stay, and in-hospital mortality between hospitalizations for patients with and without sickle cell disease (SCD) undergoing high-volume surgical procedures. We used Clinical Classification Software (CCS) codes to identify discharges in the 2002–2005 Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project for patients who had undergone either cholecystectomy or hip replacement. We limited the non-SCD cohort to hospitals where patients with SCD had undergone the same procedure. We compared inpatient outcomes using summary statistics and generalized linear regression analysis to adjust for patient, hospital, and procedural characteristics. Overall, the median age of surgical patients with SCD was more than 3 decades less than the median age of patients without SCD undergoing the same procedure. In recognition of the age disparity, we limited the analyses to patients aged 18 to 64 years. Nonetheless, patients with SCD undergoing cholecystectomy or hip replacement were 12.1 and 14.4 years younger, had inpatient stays that were 73% and 82% longer, and incurred costs that were 46% and 40% higher per discharge than patients without SCD, respectively. Inpatient mortality for these procedures was low, approximately 0.6% for cholecystectomy and 0.2% for hip replacement, and did not differ significantly between patients with and without SCD. Multivariable regression analyses revealed that higher inpatient costs among patients with SCD were primarily attributable to longer hospital stays. Patients with SCD who underwent cholecystectomy or hip replacement required more health care resources than patients without SCD. PMID:19787790

Structural pathways and prevention of heart failure and sudden death.

PubMed

Pacifico, Antonio; Henry, Philip D

2003-07-01

We review the macroscopic and microscopic anatomy of myocardial disease associated with heart failure (HF) and sudden cardiac death (SCD) and focus on the prevention of SCD in light of its structural pathways. Compared to patients without SCD, patients with SCD exhibit 5- to 6-fold increases in the risks of ventricular arrhythmias and SCD. Epidemiologically, left ventricular hypertrophy by ECG or echocardiography acts as a potent dose-dependent SCD predictor. Dyslipidemia, a coronary disease risk factor, independently predicts echocardiographic hypertrophy. In adult SCD autopsy studies, increases in heart weight and severe coronary disease are constant findings, whereas rates of acute coronary thrombi vary remarkably. The microscopic myocardial anatomy of SCD is incompletely defined but may include prevalent changes of advanced myocardial disease, including cardiomyocyte hypertrophy, cardiomyocyte apoptosis, fibroblast hyperplasia, diffuse and focal matrix protein accumulation, and recruitment of inflammatory cells. Hypertrophied cardiomyocytes express "fetospecific" genetic programs that can account for acquired long QT physiology with risk for polymorphic ventricular arrhythmias. Structural heart disease associated with HF and high SCD risk is causally related to an up-regulation of the adrenergic renin-angiotensin-aldosterone pathway. In outcome trials, suppression of this pathway with combinations of beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin-II receptor blockers, and mineralocorticoid receptor blockers have achieved substantial total mortality and SCD reductions. Contrarily, trials with ion channel-active agents that are not known to reduce structural heart disease have failed to reduce these risks. Device therapy effectively prevents SCD, but whether biventricular pacing-induced remodeling decreases left ventricular mass remains uncertain.

The AOTF-based NO2 camera

NASA Astrophysics Data System (ADS)

Dekemper, Emmanuel; Vanhamel, Jurgen; Van Opstal, Bert; Fussen, Didier

2016-12-01

The abundance of NO2 in the boundary layer relates to air quality and pollution source monitoring. Observing the spatiotemporal distribution of NO2 above well-delimited (flue gas stacks, volcanoes, ships) or more extended sources (cities) allows for applications such as monitoring emission fluxes or studying the plume dynamic chemistry and its transport. So far, most attempts to map the NO2 field from the ground have been made with visible-light scanning grating spectrometers. Benefiting from a high retrieval accuracy, they only achieve a relatively low spatiotemporal resolution that hampers the detection of dynamic features. We present a new type of passive remote sensing instrument aiming at the measurement of the 2-D distributions of NO2 slant column densities (SCDs) with a high spatiotemporal resolution. The measurement principle has strong similarities with the popular filter-based SO2 camera as it relies on spectral images taken at wavelengths where the molecule absorption cross section is different. Contrary to the SO2 camera, the spectral selection is performed by an acousto-optical tunable filter (AOTF) capable of resolving the target molecule's spectral features. The NO2 camera capabilities are demonstrated by imaging the NO2 abundance in the plume of a coal-fired power plant. During this experiment, the 2-D distribution of the NO2 SCD was retrieved with a temporal resolution of 3 min and a spatial sampling of 50 cm (over a 250 × 250 m2 area). The detection limit was close to 5 × 1016 molecules cm-2, with a maximum detected SCD of 4 × 1017 molecules cm-2. Illustrating the added value of the NO2 camera measurements, the data reveal the dynamics of the NO to NO2 conversion in the early plume with an unprecedent resolution: from its release in the air, and for 100 m upwards, the observed NO2 plume concentration increased at a rate of 0.75-1.25 g s-1. In joint campaigns with SO2 cameras, the NO2 camera could also help in removing the bias introduced by the NO2 interference with the SO2 spectrum.

Gender differences in lateralization of mismatch negativity in dichotic listening tasks.

PubMed

Ikezawa, Satoru; Nakagome, Kazuyuki; Mimura, Masaru; Shinoda, Junko; Itoh, Kenji; Homma, Ikuo; Kamijima, Kunitoshi

2008-04-01

With the aim of investigating gender differences in the functional lateralization subserving preattentive processing of language stimuli, we compared auditory mismatch negativities (MMNs) using dichotic listening tasks. Forty-four healthy volunteers, including 23 males and 21 females, participated in the study. MMNs generated by pure-tone and phonetic stimuli were compared, to check for the existence of language-specific gender differences in lateralization. Both EEG amplitude and scalp current density (SCD) data were analyzed. With phonetic MMNs, EEG findings revealed significantly larger amplitude in females than males, especially in the right hemisphere, while SCD findings revealed left hemisphere dominance and contralateral dominance in males alone. With pure-tone MMNs, no significant gender differences in hemispheric lateralization appeared in either EEG or SCD findings. While males exhibited left-lateralized activation with phonetic MMNs, females exhibited more bilateral activity. Further, the contralateral dominance of the SCD distribution associated with the ear receiving deviant stimuli in males indicated that ipsilateral input as well as interhemispheric transfer across the corpus callosum to the ipsilateral side was more suppressed in males than in females. The findings of the present study suggest that functional lateralization subserving preattentive detection of phonetic change differs between the genders. These results underscore the significance of considering the gender differences in the study of MMN, especially when phonetic stimulus is adopted. Moreover, they support the view of Voyer and Flight [Voyer, D., Flight, J., 2001. Gender differences in laterality on a dichotic task: the influence of report strategies. Cortex 37, 345-362.] in that the gender difference in hemispheric lateralization of language function is observed in a well-managed-attention condition, which fits the condition adopted in the MMN measurement; subjects are required to focus attention to a distraction task and thereby ignore the phonetic stimuli that elicit MMN.

Interstellar C2, CH, and CN in translucent molecular clouds

NASA Technical Reports Server (NTRS)

Black, John H.; Van Dishoeck, Ewine F.

1989-01-01

Optical absorption-line techniques have been applied to the study of a number of translucent molecular clouds in which the total column densities are large enough that substantial molecular abundances can be maintained. Results are presented for a survey of absorption lines of interstellar C2, CH, and CN. Detections of CN through the A 2Pi-X 2Sigma(+) (1,O) and (2,O) bands of the red system are reported and compared with observations of the violet system for one line of sight. The population distributions in C2 provide diagnostic information on temperature and density. The measured column densities of the three species can be used to test details of the theory of molecule formation in clouds where photoprocesses still play a significant role. The C2 and CH column densities are strongly correlated with each other and probably also with the H2 column density. In contrast, the CN column densities are found to vary greatly from cloud to cloud. The observations are discussed with reference to detailed theoretical models.

Post-transplant increased levels of serum sCD30 is a marker for prediction of kidney allograft loss in a 5-year prospective study.

PubMed

Delgado, Julio C; Pavlov, Igor Y; Shihab, Fuad S

2009-12-01

Levels of sCD30 represent a biomarker for early outcome in kidney transplantation. The purpose of this study was to determine the role of sCD30 levels for prediction of graft loss in the late post-transplant period. Sera were collected immediately pre-transplant and yearly thereafter for up to 5-year post-transplant in 37 primary renal transplant recipients. Levels of serum sCD30 were tested using a fluorescent microsphere assay. Levels of sCD30 significantly decreased after transplantation and remained normal in 34 patients without graft loss up to 5-year post-transplant. Elevated levels of serum sCD30 preceded the increase of serum creatinine in patients with subsequent graft loss. Elevated levels of serum sCD30 post-transplant might be a marker for predicting subsequent graft loss in the post-transplant period.

Identification of patients at risk of acute rejection by pretransplantation and posttransplantation monitoring of soluble CD30 levels in kidney transplantation.

PubMed

Sengul, Sule; Keven, Kenan; Gormez, Ulku; Kutlay, Sim; Erturk, Sehsuvar; Erbay, Bulent

2006-04-27

In this study, we investigated the impact of pre- and posttransplantation sCD30 monitoring on early (<6 months) acute rejection (AR) risk and analyzed the effect of different immunosuppressive regimens on posttransplantation sCD30 levels in kidney recipients. Fifty patients receiving kidney allograft and 10 healthy donors were included in this retrospective cohort study. Eight patients developed biopsy-proven AR (19%). In pretransplantation samples, patients showed a significantly higher sCD30 than healthy controls. The pretransplantation and posttransplantation (day-15) sCD30 levels were significantly elevated in rejecting patients compared to non-rejecting patients. No significant differences among immunosuppressive regimens were found in posttransplantation sCD30 levels. High pretransplantation and posttransplantation (day 15) sCD30 levels are associated with increased risk of early AR, and sCD30 can be another tool to evaluate immunological risk prior to kidney transplantation. There was no difference in immunosuppressive regimens used in this study on posttransplantation sCD30 levels at the first month.

Chemokine (c-c motif) receptor 2 mediates mechanical and cold hypersensitivity in sickle cell disease mice.

PubMed

Sadler, Katelyn E; Zappia, Katherine J; O'Hara, Crystal L; Langer, Sarah N; Weyer, Andy D; Hillery, Cheryl A; Stucky, Cheryl L

2018-04-23

Approximately one third of individuals with sickle cell disease (SCD) develop chronic pain. This debilitating pain is inadequately treated because the underlying mechanisms driving the pain are poorly understood. In addition to persistent pain, SCD patients are also in a tonically pro-inflammatory state. Previous studies have revealed that there are elevated plasma levels of many inflammatory mediators including chemokine (c-c motif) ligand 2 (CCL2) in individuals with SCD. Using a transgenic mouse model of SCD, we investigated the contributions of CCL2 signaling to SCD-related pain. Inhibition of the chemokine receptor 2 (CCR2), but not CCR4, alleviated the behavioral mechanical and cold hypersensitivity in SCD. Further, acute CCR2 blockade reversed both the behavioral and the in vitro responsiveness of sensory neurons to an agonist of TRPV1, a neuronal ion channel previously implicated in SCD pain. These results provide insight into the immune-mediated regulation of hypersensitivity in SCD and could inform future development of analgesics or therapeutic measures to prevent chronic pain.

Age-dependent changes of serum soluble CD30 concentration in children.

PubMed

Chrul, Slawomir; Polakowska, Ewa

2011-08-01

  CD30 was originally described as a marker on Reed-Sternberg cells in Hodgkin lymphoma. The extracellular portion of CD30 is proteolytically cleaved from CD30+ cells, to produce a soluble form of the molecule (sCD30) detectable in serum. Measurement of sCD30 concentration in serum has been suggested to be a potential tool in monitoring of inflammatory status in variety of diseases. Several investigators reported the relevance for sCD30 as a predictive marker for allograft rejection following organ transplantation. The aim of the study was to verify whether sCD30 serum concentrations may be affected by an age in healthy children. Heparinized venous blood was taken from 78 healthy children. For the analysis of sCD30 levels, the commercially available sCD30 ELISA was used. The sCD30 was detected in all serum samples and concentrations ranged from 6.75 to 68.07ng/mL. The statistical analysis of all individuals showed that sCD30 concentration was significantly age depended (r=-0.618, p<0.0001). When sCD30 concentrations were analyzed in regard to gender, no significant differences were identified in age subgroups. © 2011 John Wiley & Sons A/S.

Simulating the effect of high column density absorbers on the one-dimensional Lyman α forest flux power spectrum

NASA Astrophysics Data System (ADS)

Rogers, Keir K.; Bird, Simeon; Peiris, Hiranya V.; Pontzen, Andrew; Font-Ribera, Andreu; Leistedt, Boris

2018-03-01

We measure the effect of high column density absorbing systems of neutral hydrogen (H I) on the one-dimensional (1D) Lyman α forest flux power spectrum using cosmological hydrodynamical simulations from the Illustris project. High column density absorbers (which we define to be those with H I column densities N(H I) > 1.6 × 10^{17} atoms cm^{-2}) cause broadened absorption lines with characteristic damping wings. These damping wings bias the 1D Lyman α forest flux power spectrum by causing absorption in quasar spectra away from the location of the absorber itself. We investigate the effect of high column density absorbers on the Lyman α forest using hydrodynamical simulations for the first time. We provide templates as a function of column density and redshift, allowing the flexibility to accurately model residual contamination, i.e. if an analysis selectively clips out the largest damping wings. This flexibility will improve cosmological parameter estimation, for example, allowing more accurate measurement of the shape of the power spectrum, with implications for cosmological models containing massive neutrinos or a running of the spectral index. We provide fitting functions to reproduce these results so that they can be incorporated straightforwardly into a data analysis pipeline.

Reduced sCD36 following weight loss corresponds to improved insulin sensitivity, dyslipidemia and liver fat in obese children.

PubMed

Knøsgaard, L; Kazankov, K; Birkebæk, N H; Holland-Fischer, P; Lange, A; Solvig, J; Hørlyck, A; Kristensen, K; Rittig, S; Vilstrup, H; Grønbæk, H; Handberg, A

2016-09-01

Childhood obesity is a major health problem with serious long-term metabolic consequences. CD36 is important for the development of obesity-related complications among adults. We aimed to investigate circulating sCD36 during weight loss in childhood obesity and its associations with insulin resistance, dyslipidemia, hepatic fat accumulation and low-grade inflammation. The impact of a 10-week weight loss camp for obese children (N=113) on plasma sCD36 and further after a 12-month follow-up (N=68) was investigated. Clinical and biochemical data were collected, and sCD36 was measured by an in-house assay. Liver fat was estimated by ultrasonography and insulin resistance by the homeostasis model assessment (HOMA-IR). Along with marked weight loss, sCD36 was reduced by 21% (P=0.0013) following lifestyle intervention, and individual sCD36 reductions were significantly associated with the corresponding decreases in HOMA-IR, triglycerides and total cholesterol. The largest sCD36 decrease occurred among children who reduced HOMA-IR and liver fat. After 12 months of follow-up, sCD36 was increased (P=0.014) and the metabolic improvements were largely lost. Weight-loss-induced sCD36 reduction, coincident with improved insulin resistance, circulating lipids and hepatic fat accumulation, proposes that sCD36 may be an early marker of long-term health risk associated with obesity-related complications.

Spontaneous circulation of myeloid-lymphoid-initiating cells and SCID-repopulating cells in sickle cell crisis.

PubMed

Lamming, Christopher E D; Augustin, Lance; Blackstad, Mark; Lund, Troy C; Hebbel, Robert P; Verfaillie, Catherine M

2003-03-01

The only curative therapy for sickle cell disease (SCD) is allogeneic hematopoietic stem cell (HSC) transplantation. Gene therapy approaches for autologous HSC transplantation are being developed. Although earlier engraftment is seen when cells from GCSF-mobilized blood are transplanted than when bone marrow is transplanted, administration of GCSF to patients with SCD can cause significant morbidity. We tested whether primitive hematopoietic progenitors are spontaneously mobilized in the blood of patients with SCD during acute crisis (AC-SCD patients). The frequency of myeloid-lymphoid-initiating cells (ML-ICs) and SCID-repopulating cells (SRCs) was significantly higher in blood from AC-SCD patients than in blood from patients with steady-state SCD or from normal donors. The presence of SRCs in peripheral blood was not associated with detection of long-term culture-initiating cells, consistent with the notion that SRCs are more primitive than long-term culture-initiating cells. As ML-ICs and SRCs were both detected in blood of AC-SCD patients only, these assays may both measure primitive progenitors. The frequency of ML-ICs also correlated with increases in stem cell factor, GCSF, and IL-8 levels in AC-SCD compared with steady-state SCD and normal-donor sera. Because significant numbers of ML-ICs and SRCs are mobilized in the blood without exogenous cytokine treatment during acute crisis of SCD, collection of peripheral blood progenitors during crisis may yield a source of autologous HSCs suitable for ex-vivo correction by gene therapy approaches and subsequent transplantation.

Posttransplant sCD30 as a predictor of kidney graft outcome.

PubMed

Süsal, Caner; Döhler, Bernd; Sadeghi, Mahmoud; Salmela, Kaija T; Weimer, Rolf; Zeier, Martin; Opelz, Gerhard

2011-06-27

Reliable markers for assessing the biological effect of immunosuppressive drugs and identification of transplant recipients at risk of developing rejection are not available. In a prospective multicenter study, we investigated whether posttransplant measurement of the T-cell activation marker soluble CD30 (sCD30) can be used for estimating the risk of graft loss in kidney transplant recipients. Pre- and posttransplant sera of 2322 adult deceased-donor kidney recipients were tested for serum sCD30 content using a commercial enzyme-linked immunosorbent assay. sCD30 decreased posttransplant and reached a nadir on day 30. Patients with a high sCD30 of more than or equal to 40 U/mL on day 30 showed a subsequent graft survival rate after 3 years of 78.3±4.1%, significantly lower than the 90.3±1.0% rate in recipients with a low sCD30 on day 30 of less than 40 U/mL (log-rank P<0.001; Cox hazard ratio 2.02, P<0.001). Although an association was found between pre- and posttransplant sCD30 levels, patients with high sCD30 on posttransplant day 30 demonstrated significantly lower 3-year graft survival irrespective of the pretransplant level. Our data suggest that posttransplant measurement of sCD30 on day 30 is a predictor of subsequent graft loss in kidney transplant recipients and that sCD30 may potentially serve as an indicator for adjustment of immunosuppressive medication.

A Biopsychosocial-Spiritual Model of Chronic Pain in Adults with Sickle Cell Disease

PubMed Central

Taylor, Lou Ella V.; Stotts, Nancy A.; Humphreys, Janice; Treadwell, Marsha J.; Miaskowski, Christine

2011-01-01

Chronic pain in adults with sickle cell disease (SCD) is a complex multidimensional experience that includes biological, psychological, sociological, and spiritual factors. To date, three models of pain associated with SCD (i.e., biomedical model; biopsychosocial model for SCD pain; Health Belief Model) are published. The biopsychosocial (BPS) multidimensional approach to chronic pain developed by Turk and Gatchel is a widely used model of chronic pain. However, this model has not been applied to chronic pain associated with SCD. In addition, a spiritual/religious dimension is not included in this model. Because spirituality/religion is central to persons affected by SCD, this dimension needs to be added to any model of chronic pain in adults with SCD. In fact, data from one study suggest that spirituality/religiosity is associated with decreased pain intensity in adults with chronic pain from SCD. A BPS-Spiritual model is proposed for adults with chronic pain from SCD since it embraces the whole person. This model includes the biological, psychological, sociological, and spiritual factors relevant to adults with SCD based on past and current research. The purpose of this paper is to describe an adaptation of Turk and Gatchel’s model of chronic pain for adults with SCD and to summarize research findings that support each component of the revised model (i.e., biological, psychological, sociological, spiritual). The paper concludes with a discussion of implications for the use of this model in research. PMID:24315252

National registry of hemoglobinopathies in Spain (REPHem).

PubMed

Cela, Elena; Bellón, José M; de la Cruz, María; Beléndez, Cristina; Berrueco, Rubén; Ruiz, Anna; Elorza, Izaskun; Díaz de Heredia, Cristina; Cervera, Aurea; Vallés, Griselda; Salinas, J Antonio; Coll, M Teresa; Bermúdez, Mar; Prudencio, Marta; Argilés, Bienvenida; Vecilla, Cruz

2017-07-01

Although highly prevalent throughout the world, the accurate prevalence of hemoglobinopathies in Spain is unknown. This study presents data on the national registry of hemoglobinopathies of patients with thalassemia major (TM), thalassemia intermedia (TI), and sickle cell disease (SCD) in Spain created in 2014. Fifty centers reported cases retrospectively. Data were registered from neonatal screening or from the first contact at diagnosis until last follow-up or death. Data of the 715 eligible patients were collected: 615 SCD (497 SS, 64 SC, 54 SBeta phenotypes), 73 thalassemia, 9 CC phenotype, and 18 other variants. Most of the SCD patients were born in Spain (65%), and 51% of these were diagnosed at newborn screening. Median age at the first diagnosis was 0.4 years for thalassemia and 1.0 years for SCD. The estimated incidence was 0.002 thalassemia cases and 0.03 SCD cases/1,000 live births. Median age was 8.9 years (0.2-33.7) for thalassemia and 8.1 years (0.2-32.8) for SCD patients. Stroke was registered in 16 SCD cases. Transplantation was performed in 43 TM and 23 SCD patients at a median age of 5.2 and 7.8 years, respectively. Twenty-one patients died (3 TM, 17 SCD, 1 CC) and 200 were lost to follow-up. Causes of death were related to transplantation in three patients with TM and three patients with SCD. Death did not seem to be associated with SCD in six patients, but nine patients died secondary to disease complications. Overall survival was 95% at 15 years of age. The registry provides data about the prevalence of hemoglobinopathies in Spain and will permit future cohort studies and the possibility of comparison with other registries. © 2016 Wiley Periodicals, Inc.

Sudden cardiac death in non-dialysis chronic kidney disease patients.

PubMed

Caravaca, Francisco; Chávez, Edgar; Alvarado, Raúl; García-Pino, Guadalupe; Luna, Enrique

2016-01-01

A relatively high proportion of deaths in dialysis patients occur suddenly and unexpectedly. The incidence of sudden cardiac death (SCD) in non-dialysis advanced chronic kidney disease (CKD) stages has been less well investigated. This study aims to determine the incidence and predictors of SCD in a cohort of 1078 patients with CKD not yet on dialysis. Prospective observational cohort study, which included patients with advanced CKD not yet on dialysis (stage 4-5). The association between baseline variables and SCD was assessed using Cox and competing-risk (Fine and Grey) regression models. Demographic, clinical information, medication use, and baseline biochemical parameters of potential interest were included as covariates. During the study period (median follow-up time 12 months), 210 patients died (19%), and SCD occurred in 34 cases (16% of total deaths). All-cause mortality and SCD incidence rates were 113 (95% CI: 99-128), and 18 (95% CI: 13-26) events per 1000 patients/year, respectively. By Cox regression analysis, covariates significantly associated with SCD were: Age, comorbidity index, and treatment with antiplatelet drugs. This latter covariate showed a beneficial effect over the development of SCD. By competing-risk regression, in which the competing event was non-sudden death from any cause, only age and comorbidity index remained significantly associated with SCD. SCD is relatively common in non-dialysis advanced CKD patients. SCD was closely related to age and comorbidity, and some indirect data from this study suggest that unrecognised or undertreated cardiovascular disease may predispose to a higher risk of SCD. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Sudden cardiac death in adults with congenital heart disease: does QRS-complex fragmentation discriminate in structurally abnormal hearts?

PubMed

Vehmeijer, Jim T; Koyak, Zeliha; Bokma, Jouke P; Budts, Werner; Harris, Louise; Mulder, Barbara J M; de Groot, Joris R

2018-06-01

Sudden cardiac death (SCD) causes a large portion of all mortality in adult congenital heart disease (ACHD) patients. However, identification of high-risk patients remains challenging. Fragmented QRS-complexes (fQRS) are a marker for SCD in patients with acquired heart disease but data in ACHD patients are lacking. We therefore aim to evaluate the prognostic value of fQRS for SCD in ACHD patients. From a multicentre cohort of 25 790 ACHD patients, we included tachyarrhythmic SCD cases (n = 147), and controls (n = 266) matched by age, gender, congenital defect and (surgical) intervention. fQRS was defined as ≥1 discontinuous deflection in narrow QRS-complexes, and ≥2 in wide QRS-complexes (>120 ms), in two contiguous ECG leads. We calculated odds ratios (OR) using univariable and multivariable conditional logistic regression models correcting for impaired systemic ventricular function, heart failure and QRS duration >120 ms. ECGs of 147 SCD cases (65% male, median age of death 34 years) and of 266 controls were assessed. fQRS was present in 51% of cases and 34% of controls (OR 2.0, P = 0.003). In multivariable analysis, fQRS was independently associated with SCD (OR 1.9, P = 0.01). The most common diagnose of SCD cases was tetralogy of Fallot (ToF, 34 cases). In ToF, fQRS was present in 71% of cases vs. 43% of controls (OR for SCD 2.8, P = 0.03). fQRS was independently associated with SCD in ACHD patients in a cohort of SCD patients and matched controls. fQRS may therefore contribute to the decision when evaluating ACHD patients for primary prevention of SCD.

Lifetime Risk for Sudden Cardiac Death in the Community.

PubMed

Bogle, Brittany M; Ning, Hongyan; Mehrotra, Sanjay; Goldberger, Jeffrey J; Lloyd-Jones, Donald M

2016-06-29

Sudden cardiac death (SCD) is a leading cause of death in the United States and often occurs without previous cardiac symptoms. Lifetime risk for SCD and the influence of established risk factors on lifetime risks for SCD have not been estimated previously. We followed Framingham Heart Study participants who were free of cardiovascular disease before their earliest examination. SCD was defined as death attributed to coronary heart disease within 1 hour of symptom onset without another probable cause of death, as adjudicated by a panel of 3 physicians. Lifetime risk for SCD was estimated to 85 years of age for men and women, with death attributed to other causes as the competing risk, and stratified by risk factor levels. We followed 2294 men and 2785 women for 160 396 person-years; 375 experienced SCD. At 45 years of age, lifetime risks were 10.9% (95% CI, 9.4-12.5) for men and 2.8% (95% CI, 2.1-3.5) for women. Greater aggregate burden of established risk factors was associated with a higher lifetime risk for SCD. Categorizing men and women solely by blood pressure levels resulted in a clear stratification of lifetime risk curves. We present the first lifetime risk estimates for SCD. Greater aggregate risk factor burden, or blood pressure level alone, is associated with higher lifetime risks for SCD. This high risk of premature death attributed to SCD (approximately 1 in 9 men and 1 in 30 women) should serve as a motivator of public health efforts in preventing and responding to SCD. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Pretransplant soluble CD30 level has limited effect on acute rejection, but affects graft function in living donor kidney transplantation.

PubMed

Kim, Myoung Soo; Kim, Hae Jin; Kim, Soon Il; Ahn, Hyung Joon; Ju, Man Ki; Kim, Hyun Jung; Jeon, Kyung Ock; Kim, Yu Seun

2006-12-27

Serum soluble CD30 (sCD30) levels might be a useful marker of immunologic status in pre transplant (Tx) recipients. We retrospectively correlated preTx sCD30 levels (high versus low) on postTx graft survival, incidence of acute rejection, and graft function using stored preTx serum. Of 254 recipients who underwent kidney Tx, 120 recipients were enrolled under the uniform criteria (living donor, age >25 years, viral hepatitis free, diabetes free). The preTx sCD30 was not significantly associated with differences in graft survival rate during 47.5+/-11.4 months of follow-up (P = 0.5901). High sCD30 (> or =115 U/ml) was associated with a higher incidence of clinically or pathologically defined acute rejection than low sCD30, but the difference was not statistically significant (33.9% vs. 22.4%, P = 0.164). The response rate to antirejection therapy in patients with high sCD30 was inferior to those with low sCD30, but also was not statistically significant (33.3% vs. 7.7%, P = 0.087). However, mean serum creatinine levels in high sCD30 patients at one month, one year, and three years postTx were significantly different from those with low sCD30 (P < 0.05). In multiple regression analysis, acute rejection episodes, donor age, kidney weight/recipient body weight ratio, and preTx sCD30 levels were independent variables affecting the serum creatinine level three years postTx. PreTx sCD30 level has a limited effect on the incidence of acute rejection and response to antirejection treatment, but inversely and independently affects serum creatinine level after living donor kidney transplantation.

Regulation of palmitoyl-CoA chain elongation by clofibric acid in the liver of Zucker fa/fa rats.

PubMed

Toyama, Tomoaki; Kudo, Naomi; Mitsumoto, Atsushi; Kawashima, Yoichi

2005-05-01

The regulation of palmitoyl-CoA chain elongation (PCE) by clofibric acid [2-(4-chlorophenoxy)-2-methylpropionic acid] was investigated in comparison with stearoyl-CoA desaturase (SCD) in the liver of obese Zucker fa/fa rats. The proportion of oleic acid in the hepatic lipids of Zucker obese rats is 2.7 times higher than that of lean littermates. The activities of PCE and SCD in the liver of Zucker obese rats were markedly higher than in lean rats, and the hepatic uptake of 2-deoxyglucose (2-DG) was also higher in Zucker obese rats compared with lean rats. The increased activities of SCD and PCE in Zucker obese rats were due to the enhanced expression of mRNA of both SCD1 and rat FA elongase 2 (rELO2), but not SCD2 or rELO1. The proportion of oleic acid in the liver was significantly increased by the administration of clofibric acid to Zucker obese rats, and the hepatic PCE activity and rELO2 mRNA expression, but not the SCD activity or SCD1 mRNA expression, were increased in response to clofibric acid treatment. By contrast, the activities of both PCE and SCD and the mRNA expression of SCD1 and rELO2 in the liver were increased by the treatment of Zucker lean rats with clofibric acid. Multiple regression analysis, which was performed to determine the relationships involving PCE activity, SCD activity, and the proportion of oleic acid, revealed that the three parameters were significantly correlated and that the standardized partial regression coefficient of PCE was higher than that of SCD. These results indicate that oleic acid is synthesized by the concerted action of PCE and SCD and that PCE plays a crucial role in the formation of oleic acid when Zucker fa/fa rats are given clofibric acid.

Soluble CD14 inhibits contractile function and insulin action in primary adult rat cardiomyocytes.

PubMed

Overhagen, Sabrina; Blumensatt, Marcel; Fahlbusch, Pia; Herzfeld de Wiza, Daniella; Müller, Heidi; Maxhera, Bujar; Akhyari, Payam; Ouwens, D Margriet

2017-02-01

Epicardial adipose tissue (EAT) from patients with type 2 diabetes (T2D) is characterized by monocyte infiltrations and displays an elevated release of the monocyte marker soluble cluster of differentiation 14 (sCD14) versus EAT from patients without T2D. We propose that an increased abundance of sCD14 in EAT from patients with T2D may impair the function and insulin sensitivity of the adjacent cardiomyocytes. To examine this, primary adult rat cardiomyocytes were incubated with increasing concentrations of sCD14 in the presence and absence of the co-receptor lipopolysaccharide (LPS), and analyzed for effects on determinants of contractile function, activation of inflammation signalling and insulin action. Exposing cardiomyocytes to sCD14 increased the phosphorylation of the stress kinases p38 and extracellular-signal regulated kinase (ERK). In contrast, insulin-mediated phosphorylation of Akt on Thr308 and Ser473 was inhibited. Furthermore, sCD14 impaired sarcomere shortening and cytosolic Ca 2+ -fluxes. All responses were concentration-dependent and became significant at 1ng/ml sCD14. LPS, either alone or in complex with sCD14, did not affect contractile function or the activation of stress kinases and insulin signalling pathways. Similar data on protein phosphorylation were obtained when exposing human umbilical vein endothelial cells to sCD14. Finally, pharmacological inhibition of p38 reversed the detrimental effects of sCD14 on contractile function, but not on sCD14-induced insulin resistance. Collectively, these data show that sCD14 impairs the function and insulin sensitivity of cardiomyocytes, suggesting that an enhanced sCD14 release from EAT in patients with T2D may contribute to the pathogenesis of diabetes-related cardiometabolic complications. Copyright © 2016 Elsevier B.V. All rights reserved.

Pre-transplant and post-transplant soluble CD30 for prediction and diagnosis of acute kidney allograft rejection.

PubMed

Nafar, Mohsen; Farrokhi, Farhat; Vaezi, Mohammad; Entezari, Amir-Ebrahim; Pour-Reza-Gholi, Fatemeh; Firoozan, Ahmad; Eniollahi, Behzad

2009-01-01

Serum levels of soluble CD30 (sCD30) have been considered as a predictor of acute kidney allograft rejection. We have evaluated the pre-transplant and post-transplant levels of sCD30 with the aim of determining its value in predicting and diagnosing kidney rejection. We measured sCD30 serum levels before kidney transplantation, 5 days post-operatively, and at creatinine elevation episodes. The predictive value of sCD30 for diagnosing acute rejection (AR) within the first 6 post-operative months was assessed in 203 kidney recipients from living donors. Pre-transplant and post-operative levels of serum sCD30 were 58.10 +/- 52.55 and 51.55 +/- 49.65 U/ml, respectively (P = 0.12). Twenty-three patients experienced biopsy-proven acute rejection, and 28 had acute allograft dysfunction due to non-immunologic diseases. The pre-transplant sCD30 level was not different between patients with and without AR. However, post-transplant sCD30 was higher in the AR group. The median serum level of post-transplant sCD30 was 52 U/ml in the AR group and 26.3 U/ml in a control group (P < 0.001). The relative changes of sCD30 on day 5 were higher in patients with AR (P = 0.003). Based on post-transplant sCD30 levels, we were able to differentiate between kidney recipients who experienced an AR within 6 months post-surgery and those without an AR (cutoff value 41 U/ml; sensitivity 70%; specificity 71.7%). The level of sCD30 during periods of elevated serum creatinine was not independently associated with the diagnosis of AR. Post-transplant sCD30 levels and their relative changes are higher in patients experiencing AR. We propose further studies on the post-transplant trend of this marker for the prediction of AR.

Soluble CD40-ligand (sCD40L, sCD154) plays an immunosuppressive role via regulatory T cell expansion in HIV infection

PubMed Central

Jenabian, M-A; Patel, M; Kema, I; Vyboh, K; Kanagaratham, C; Radzioch, D; Thébault, P; Lapointe, R; Gilmore, N; Ancuta, P; Tremblay, C; Routy, J-P

2014-01-01

CD40/CD40-ligand (CD40L) signalling is a key stimulatory pathway which triggers the tryptophan (Trp) catabolizing enzyme IDO in dendritic cells and is immunosuppressive in cancer. We reported IDO-induced Trp catabolism results in a T helper type 17 (Th17)/regulatory T cell (Treg) imbalance, and favours microbial translocation in HIV chronic infection. Here we assessed the link between sCD40L, Tregs and IDO activity in HIV-infected patients with different clinical outcomes. Plasmatic sCD40L and inflammatory cytokines were assessed in anti-retroviral therapy (ART)-naive, ART-successfully treated (ST), elite controllers (EC) and healthy subjects (HS). Plasma levels of Trp and its metabolite Kynurenine (Kyn) were measured by isotope dilution tandem mass spectrometry and sCD14 was assessed by enzyme-linked immunosorbent assay (ELISA). IDO-mRNA expression was quantified by reverse transcription–polymerase chain reaction (RT–PCR). The in-vitro functional assay of sCD40L on Treg induction and T cell activation were assessed on peripheral blood mononuclear cells (PBMCs) from HS. sCD40L levels in ART-naive subjects were significantly higher compared to ST and HS, whereas EC showed only a minor increase. In ART-naive alone, sCD40L was correlated with T cell activation, IDO-mRNA expression and CD4 T cell depletion but not with viral load. sCD40L was correlated positively with IDO enzymatic activity (Kyn/Trp ratio), Treg frequency, plasma sCD14 and inflammatory soluble factors in all HIV-infected patients. In-vitro functional sCD40L stimulation induced Treg expansion and favoured Treg differentiation by reducing central memory and increasing terminal effector Treg proportion. sCD40L also increased T cell activation measured by co-expression of CD38/human leucocyte antigen D-related (HLA-DR). These results indicate that elevated sCD40L induces immunosuppression in HIV infection by mediating IDO-induced Trp catabolism and Treg expansion. PMID:24924152

Soluble CD40-ligand (sCD40L, sCD154) plays an immunosuppressive role via regulatory T cell expansion in HIV infection.

PubMed

Jenabian, M-A; Patel, M; Kema, I; Vyboh, K; Kanagaratham, C; Radzioch, D; Thébault, P; Lapointe, R; Gilmore, N; Ancuta, P; Tremblay, C; Routy, J-P

2014-10-01

CD40/CD40-ligand (CD40L) signalling is a key stimulatory pathway which triggers the tryptophan (Trp) catabolizing enzyme IDO in dendritic cells and is immunosuppressive in cancer. We reported IDO-induced Trp catabolism results in a T helper type 17 (Th17)/regulatory T cell (Treg ) imbalance, and favours microbial translocation in HIV chronic infection. Here we assessed the link between sCD40L, Tregs and IDO activity in HIV-infected patients with different clinical outcomes. Plasmatic sCD40L and inflammatory cytokines were assessed in anti-retroviral therapy (ART)-naive, ART-successfully treated (ST), elite controllers (EC) and healthy subjects (HS). Plasma levels of Trp and its metabolite Kynurenine (Kyn) were measured by isotope dilution tandem mass spectrometry and sCD14 was assessed by enzyme-linked immunosorbent assay (ELISA). IDO-mRNA expression was quantified by reverse transcription-polymerase chain reaction (RT-PCR). The in-vitro functional assay of sCD40L on Treg induction and T cell activation were assessed on peripheral blood mononuclear cells (PBMCs) from HS. sCD40L levels in ART-naive subjects were significantly higher compared to ST and HS, whereas EC showed only a minor increase. In ART-naive alone, sCD40L was correlated with T cell activation, IDO-mRNA expression and CD4 T cell depletion but not with viral load. sCD40L was correlated positively with IDO enzymatic activity (Kyn/Trp ratio), Treg frequency, plasma sCD14 and inflammatory soluble factors in all HIV-infected patients. In-vitro functional sCD40L stimulation induced Treg expansion and favoured Treg differentiation by reducing central memory and increasing terminal effector Treg proportion. sCD40L also increased T cell activation measured by co-expression of CD38/human leucocyte antigen D-related (HLA-DR). These results indicate that elevated sCD40L induces immunosuppression in HIV infection by mediating IDO-induced Trp catabolism and Treg expansion. © 2014 British Society for Immunology.

Plasma-soluble CD30 in childhood tuberculosis: effects of disease severity, nutritional status, and vitamin A therapy.

PubMed

Hanekom, W A; Hussey, G D; Hughes, E J; Potgieter, S; Yogev, R; Check, I J

1999-03-01

Plasma-soluble CD30 (sCD30) is the result of proteolytic splicing from the membrane-bound form of CD30, a putative marker of type 2 cytokine-producing cells. We measured sCD30 levels in children with tuberculosis, a disease characterized by prominent type 1 lymphocyte cytokine responses. We postulated that disease severity and nutritional status would alter cytokine responses and therefore sCD30 levels. Samples from South African children enrolled prospectively at the time of diagnosis of tuberculosis were analyzed. (Patients were originally enrolled in a randomized, double-blind placebo-controlled study of the effects of oral vitamin A supplementation on prognosis of tuberculosis.) Plasma samples collected at the time of diagnosis and 6 and 12 weeks later (during antituberculosis therapy) were analyzed. sCD30 levels were measured by enzyme immunoassay. The 91 children included in the study demonstrated high levels of sCD30 at diagnosis (median, 98 U/liter; range, 11 to 1,569 U/liter). Although there was a trend toward higher sCD30 levels in more severe disease (e.g., culture-positive disease or miliary disease), this was not statistically significant. Significantly higher sCD30 levels were demonstrated in the presence of nutritional compromise: the sCD30 level was higher in patients with a weight below the third percentile for age, in those with clinical signs of kwashiorkor, and in those with a low hemoglobin content. There was minimal change in the sCD30 level after 12 weeks of therapy, even though patients improved clinically. However, changes in sCD30 after 12 weeks differed significantly when 46 patients (51%) who received vitamin A were compared with those who had received a placebo. Vitamin A-supplemented children demonstrated a mean (+/- standard error of the mean) decrease in sCD30 by a factor of 0.99 +/- 0.02 over 12 weeks, whereas a factor increase of 1.05 +/- 0.02 was demonstrated in the placebo group (P = 0.02). We conclude that children with tuberculosis had high sCD30 levels, which may reflect the presence of a type 2 cytokine response. Nutritional compromise was associated with higher sCD30 levels. Vitamin A therapy resulted in modulation of sCD30 levels over time.

Plasma-Soluble CD30 in Childhood Tuberculosis: Effects of Disease Severity, Nutritional Status, and Vitamin A Therapy

PubMed Central

Hanekom, W. A.; Hussey, G. D.; Hughes, E. J.; Potgieter, S.; Yogev, R.; Check, I. J.

1999-01-01

Plasma-soluble CD30 (sCD30) is the result of proteolytic splicing from the membrane-bound form of CD30, a putative marker of type 2 cytokine-producing cells. We measured sCD30 levels in children with tuberculosis, a disease characterized by prominent type 1 lymphocyte cytokine responses. We postulated that disease severity and nutritional status would alter cytokine responses and therefore sCD30 levels. Samples from South African children enrolled prospectively at the time of diagnosis of tuberculosis were analyzed. (Patients were originally enrolled in a randomized, double-blind placebo-controlled study of the effects of oral vitamin A supplementation on prognosis of tuberculosis.) Plasma samples collected at the time of diagnosis and 6 and 12 weeks later (during antituberculosis therapy) were analyzed. sCD30 levels were measured by enzyme immunoassay. The 91 children included in the study demonstrated high levels of sCD30 at diagnosis (median, 98 U/liter; range, 11 to 1,569 U/liter). Although there was a trend toward higher sCD30 levels in more severe disease (e.g., culture-positive disease or miliary disease), this was not statistically significant. Significantly higher sCD30 levels were demonstrated in the presence of nutritional compromise: the sCD30 level was higher in patients with a weight below the third percentile for age, in those with clinical signs of kwashiorkor, and in those with a low hemoglobin content. There was minimal change in the sCD30 level after 12 weeks of therapy, even though patients improved clinically. However, changes in sCD30 after 12 weeks differed significantly when 46 patients (51%) who received vitamin A were compared with those who had received a placebo. Vitamin A-supplemented children demonstrated a mean (± standard error of the mean) decrease in sCD30 by a factor of 0.99 ± 0.02 over 12 weeks, whereas a factor increase of 1.05 ± 0.02 was demonstrated in the placebo group (P = 0.02). We conclude that children with tuberculosis had high sCD30 levels, which may reflect the presence of a type 2 cytokine response. Nutritional compromise was associated with higher sCD30 levels. Vitamin A therapy resulted in modulation of sCD30 levels over time. PMID:10066655

Clinical Significance of Soluble Hemoglobin Scavenger Receptor CD163 (sCD163) in Sepsis, a Prospective Study

PubMed Central

Feng, Lin; Zhou, Xin; Su, Long-Xiang; Feng, Dan; Jia, Yan-Hong; Xie, Li-Xin

2012-01-01

Objective We investigated serum soluble CD163 (sCD163) levels for use in the diagnosis, severity assessment, and prognosis of sepsis in the critical ill patients and compared sCD163 with other infection-related variables. Methods During july 2010 and April 2011, serum was obtained from 102 sepsis patients (days 1, 3, 5, 7, and 10 after admission to an ICU) and 30 systemic inflammatory response syndrome (SIRS) patients with no sepsis diagnosed. Serum levels of sCD163, procalcitonon (PCT), and C reactive protein (CRP) were determined respectively. Sequential organ failure assessment (SOFA) scores for sepsis patients were also recorded. Then evaluated their roles in sepsis. Results The sCD163 levels were 0.88(0.78–1.00)ug/mL for SIRS patients, 1.50(0.92–2.00)ug/mL for moderate sepsis patients, and 2.95(2.18–5.57)ug/mL for severe sepsis patients on day1. The areas under the ROC curves for sCD163, CRP, and PCT for the diagnosis of sepsis were, respectively, 0.856(95%CI: 0.791–0.921), 0.696(95%CI: 0.595–0.797), and 0.629(95%CI: 0.495–0.763), At the recommended cut-off 1.49 ug/mL for sCD163, the sensitivity is 74.0% with 93.3% specificity. Based on 28-day survivals, sCD163 levels in the surviving group stay constant, while they tended to gradually increase in the non-surviving group.The area under the ROC curve for sCD163 for sepsis prognosis was 0.706(95%CI 0.558–0.804). Levels of sCD163 with cut-off point >2.84 ug/mL have sensitivity of 55.8.0%, specificity 80.4%.Common risk factors for death and sCD163 were included in multivariate logistic regression analysis; the odds ratios (OR) for sCD163 and SOFA scores for sepsis prognosis were 1.173 and 1.396, respectively (P<0.05). Spearman rank correlation analysis showed that sCD163 was weakly, but positively correlated with CRP, PCT, and SOFA scores (0.2< r <0.4, P<0.0001), but not with leukocyte counts (r <0.2, P = 0.450). Conclusion Serum sCD163 is superior to PCT and CRP for the diagnosis of sepsis and differentiate the severity of sepsis. sCD163 levels were more sensitive for dynamic evaluations of sepsis prognosis. Serum sCD163 and SOFA scores are prognostic factors for sepsis. Trial Registration www.chictr.org ChiCTR-ONC-10000812 PMID:22911680

Pressure, temperature and density drops along supercritical fluid chromatography columns. I. Experimental results for neat carbon dioxide and columns packed with 3- and 5-micron particles.

PubMed

Poe, Donald P; Veit, Devon; Ranger, Megan; Kaczmarski, Krzysztof; Tarafder, Abhijit; Guiochon, Georges

2012-08-10

The pressure drop and temperature drop on columns packed with 3- and 5-micron particles were measured using neat CO(2) at a flow rate of 5 mL/min, at temperatures from 20°C to 100°C, and outlet pressures from 80 to 300 bar. The density drop was calculated based on the temperature and pressure at the column inlet and outlet. The columns were suspended in a circulating air bath either bare or covered with foam insulation. The results show that the pressure drop depends on the outlet pressure, the operating temperature, and the thermal environment. A temperature drop was observed for all conditions studied. The temperature drop was relatively small (less than 3°C) for combinations of low temperature and high pressure. Larger temperature drops and density drops occurred at higher temperatures and low to moderate pressures. Covering the column with thermal insulation resulted in larger temperature drops and corresponding smaller density drops. At 20°C the temperature drop was never more than a few degrees. The largest temperature drops occurred for both columns when insulated at 80°C and 80 bar, reaching a maximum value of 21°C for the 5-micron column, and 26°C for the 3-micron column. For an adiabatic column, the temperature drop depends on the pressure drop, the thermal expansion coefficient, and the density and the heat capacity of the mobile phase fluid, and can be described by a simple mathematical relationship. For a fixed operating temperature and outlet pressure, the temperature drop increases monotonically with the pressure drop. Copyright © 2012 Elsevier B.V. All rights reserved.

Density Gradient Columns for Chemical Displays.

ERIC Educational Resources Information Center

Guenther, William B.

1986-01-01

Procedures for preparing density gradient columns for chemical displays are presented. They include displays illustrating acid-base reactions, metal ion equilibria, and liquid density. The lifetime of these metastable displays is surprising, some lasting for months in display cabinets. (JN)

Combating Weapons of Mass Destruction: Models, Complexity, and Algorithms in Complex Dynamic and Evolving Networks

DTIC Science & Technology

2015-11-01

NLP Blondel Oslom Infomap 0 0.2 0.4 0.6 0.8 1 0 0.2 0.4 0.6 0.8 1 N M I (N = 5 0 0 0 ) µ SCD SCD- NLP Blondel Oslom Infomap A...Networks with minC ,maxC unconstrained. 0 0.2 0.4 0.6 0.8 1 0 0.2 0.4 0.6 0.8 1 N M I (N = 1 0 0 0 ) µ SCD SCD- NLP Blondel Oslom Infomap 0...0.2 0.4 0.6 0.8 1 0 0.2 0.4 0.6 0.8 1 N M I (N = 5 0 0 0 ) µ SCD SCD- NLP Blondel Oslom Infomap B

Isoelectric focusing of red blood cells in a density gradient stabilized column

NASA Technical Reports Server (NTRS)

Smolka, A. J. K.; Miller, T. Y.

1980-01-01

The effects of Ficoll and cell application pH on red blood cell electrophoretic mobility and focusing pH were investigated by focusing cells in a density gradient stabilized column. Sample loading, cell dispersion, column conductivity, resolution of separation, and the effect of Ampholines were examined.

Contribution of Sickle Cell Disease to the Pediatric Stroke Burden Among Hospital Discharges of African-Americans—United States, 1997–2012

PubMed Central

Baker, Charlotte; Grant, Althea M.; George, Mary G.; Grosse, Scott D.; Adamkiewicz, Thomas V.

2015-01-01

Background Approximately 10–20% of children with sickle cell disease (SCD) develop stroke, but few consistent national estimates of the stroke burden for children with SCD exist. The purpose of this study is to determine the proportion of diagnosed stroke among African-American pediatric discharges with and without SCD. Procedure Records for African-Americans aged 1–18 years in the Kids' Inpatient Database (KID) 1997–2012 with ≥1 ICD-9-CM diagnosis code for stroke were included. Data were weighted to provide national estimates. A total of 2,994 stroke cases among African-American children were identified. Diagnoses co-existing with ischemic or hemorrhagic stroke were frequency ranked separately. Results From 1997 through 2012, SCD was present in 24% of stroke discharges, with 89% being ischemic stroke. For hospital discharges of African-American children, SCD is the highest co-existing risk factor for ischemic stroke (29%). Stroke in children with SCD occurred predominantly in children aged 5–9 years, older than previously reported. The trend of stroke discharges significantly decreased for children with SCD from 1997 to 2012 for children aged 10–14 years. Conclusions SCD is a leading risk factor to pediatric stroke in African-American children. Reducing the number of strokes among children with SCD would have a significant impact on the rate of strokes among African-American children. Preventative intervention may be modifying initial age of presentation of stroke in children with SCD. PMID:26174777

The epidemiology of sickle cell disease in Germany following recent large-scale immigration.

PubMed

Kunz, Joachim B; Cario, Holger; Grosse, Regine; Jarisch, Andrea; Lobitz, Stephan; Kulozik, Andreas E

2017-07-01

The epidemiology of sickle cell disease (SCD) in Germany is currently changing fundamentally with ongoing immigration. Here, we address the challenges resulting from the increased frequency, that is, the morbidity, and mortality of SCD in this population. The number of immigrants with SCD was estimated based on the data of the German central registry of migrants (2007-2015) and published epidemiologic data. Additional data analysis was based on nationwide aggregated data from the diagnosis-related groups' (DRG) statistics of the German Federal Statistical Office. The total number of patients with SCD among migrants was estimated at 2,016 in 2007 and 3,216 in 2015, thus showing a 60% increase, which was particularly remarkable during 2014 and 2015. The countries of origin included those of West sub-Saharan Africa, followed by Syria, and other countries of the Middle East. In parallel, the number of SCD inpatient treatments increased from 780 in 2002 to 1,340 in 2015. Between 2012 and 2014, 42 patients with SCD died in hospital, mostly at an age of less than 5 years (n = 7) or over 30 years (n = 29). More than 3,000 patients with SCD are estimated to live among the immigrant population in Germany. In addition, the number of SCD patients of German nationality is not known. The increasing number of inpatient treatments and the death of young children from SCD indicate the need for a general newborn screening program and an increased awareness of this disease among medical practitioners in a country in which SCD used to be rare. © 2017 Wiley Periodicals, Inc.

Hemin controls T cell polarization in sickle cell alloimmunization.

PubMed

Zhong, Hui; Bao, Weili; Friedman, David; Yazdanbakhsh, Karina

2014-07-01

Patients with sickle cell disease (SCD) often require transfusions to treat and prevent worsening anemia and other SCD complications. However, transfusions can trigger alloimmunization against transfused RBCs with serious clinical sequelae. Risk factors for alloimmunization in SCD remain poorly understood. We recently reported altered regulatory T cell (Treg) and Th responses with higher circulating Th1 (IFN-γ(+)) cytokines in chronically transfused SCD patients with alloantibodies as compared with those without alloantibodies. Because monocytes play a critical role in polarization of T cell subsets and participate in clearance of transfused RBCs, we tested the hypothesis that in response to the RBC breakdown product hemin, monocyte control of T cell polarization will differ between alloimmunized and non-alloimmunized SCD patients. Exogenous hemin induced Treg polarization in purified T cell/monocyte cocultures from healthy volunteers through the monocyte anti-inflammatory heme-degrading enzyme heme oxygenase-1. Importantly, hemin primarily through its effect on CD16+ monocytes induced an anti-inflammatory (higher Treg/lower Th1) polarization state in the non-alloimmunized SCD group, whereas it had little effect in the alloimmunized group. Non-alloimmunized SCD CD16+ monocytes expressed higher basal levels of heme oxygenase-1. Furthermore, IL-12, which contributed to a proinflammatory polarization state (low Treg/high Th1) in SCD, was dampened in hemin-treated stimulated monocytes from non-alloimmunized SCD patients, but not in the alloimmunized group. These data suggest that unlike alloimmunized patients, non-alloimmunized SCD CD16+ monocytes in response to transfused RBC breakdown products promote an anti-inflammatory state that is less conducive to alloimmunization. Copyright © 2014 by The American Association of Immunologists, Inc.

Spontaneous circulation of myeloid-lymphoid–initiating cells and SCID-repopulating cells in sickle cell crisis

PubMed Central

Lamming, Christopher E.D.; Augustin, Lance; Blackstad, Mark; Lund, Troy C.; Hebbel, Robert P.; Verfaillie, Catherine M.

2003-01-01

The only curative therapy for sickle cell disease (SCD) is allogeneic hematopoietic stem cell (HSC) transplantation. Gene therapy approaches for autologous HSC transplantation are being developed. Although earlier engraftment is seen when cells from GCSF-mobilized blood are transplanted than when bone marrow is transplanted, administration of GCSF to patients with SCD can cause significant morbidity. We tested whether primitive hematopoietic progenitors are spontaneously mobilized in the blood of patients with SCD during acute crisis (AC-SCD patients). The frequency of myeloid-lymphoid–initiating cells (ML-ICs) and SCID-repopulating cells (SRCs) was significantly higher in blood from AC-SCD patients than in blood from patients with steady-state SCD or from normal donors. The presence of SRCs in peripheral blood was not associated with detection of long-term culture–initiating cells, consistent with the notion that SRCs are more primitive than long-term culture–initiating cells. As ML-ICs and SRCs were both detected in blood of AC-SCD patients only, these assays may both measure primitive progenitors. The frequency of ML-ICs also correlated with increases in stem cell factor, GCSF, and IL-8 levels in AC-SCD compared with steady-state SCD and normal-donor sera. Because significant numbers of ML-ICs and SRCs are mobilized in the blood without exogenous cytokine treatment during acute crisis of SCD, collection of peripheral blood progenitors during crisis may yield a source of autologous HSCs suitable for ex-vivo correction by gene therapy approaches and subsequent transplantation. PMID:12639987

Cardiometabolic risk factors are influenced by Stearoyl-CoA Desaturase (SCD) -1 gene polymorphisms and n-3 polyunsaturated fatty acid supplementation.

PubMed

Rudkowska, Iwona; Julien, Pierre; Couture, Patrick; Lemieux, Simone; Tchernof, André; Barbier, Olivier; Vohl, Marie-Claude

2014-05-01

To determine if single nucleotide polymorphisms (SNPs) in stearoyl-CoA desaturase (SCD)-1 gene that encodes a key enzyme for fatty acid metabolism are associated with the response of cardiometabolic risk factors to n-3 PUFA supplementation. Two hundred and ten subjects completed a 2-week run-in period followed by 6-week supplementation with 5 g of fish oil (1.9-2.2 g eicosapentaenoic acid and 1.1 g docosahexaenoic acid). Risk factors were measured pre and post n-3 supplementation. Fatty acid composition of plasma phospholipids was analyzed by GC and the desaturase indices SCD16 (16:1n-7/16:0) and SCD18 (18:1n-9/18:0) were calculated. Genotyping of eight SNPs of the SCD1 gene was performed. N-3 PUFA supplementation decreased plasma triglycerides, as well as SCD16 and SCD18 indices, but increased fasting plasma glucose concentrations. SNPs in SCD1-modified cardiometabolic risk factors pre and post n-3 PUFA supplementation: triglyceride (rs508384, p = 0.0086), IL6 (rs3071, p = 0.0485), C-reactive protein (rs3829160, p = 0.0489), and SCD18 indices (rs2234970, p = 0.0337). A significant interaction effect between the SNP and n-3 PUFA supplementation was also observed for fasting plasma glucose levels (rs508384, p = 0.0262). These results suggest that cardiometabolic risk factors are modulated by genetic variations in the SCD1 gene alone or in combination with n-3 PUFA supplementation. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Subjective Cognitive Decline, Objective Cognition, and Depression in Older Hispanics Screened for Memory Impairment.

PubMed

Zlatar, Zvinka Z; Muniz, Martha C; Espinoza, Sarah G; Gratianne, Roberto; Gollan, Tamar H; Galasko, Douglas; Salmon, David P

2018-01-01

Subjective cognitive decline (SCD) is common in older adults and may be an early marker of future cognitive decline. Research suggest that SCD is more closely related to concurrent symptoms of depression than to objective cognitive performance in non-Hispanic Whites, but it is unknown whether the associations of SCD, cognition, and depression manifest differently in Hispanic older adults. We examined if SCD is associated with objective cognitive performance or with depression symptoms in 145 Hispanic individuals ages 60 or older referred by community health clinics for screening of cognitive complaints. All participants lived near the U.S.-Mexico border, spoke Spanish only, or were Spanish-English bilingual. Memory-only and global cognitive composites were created from scores on Spanish versions of several neuropsychological tests. The Geriatric Depression Scale (GDS) and a five-item SCD questionnaire developed by our group were also completed. Multiple regression analyses showed no significant associations between SCD and memory or global cognitive composite scores after adjusting for age, sex, education, and GDS score. In contrast, there was a significant association between GDS and SCD after adjusting for age, sex, education, global and memory composite scores. Findings suggest that SCD does not accurately reflect current cognitive status in older Hispanics who present to their primary care physician with cognitive complaints. Clinicians should interpret SCD in this population within the context of information about symptoms of depression. Longitudinal research is needed in older Hispanics to better characterize SCD in this population and to determine if it can predict future cognitive decline.

Self-control depletion and nicotine deprivation as precipitants of smoking cessation failure: A human laboratory model.

PubMed

Heckman, Bryan W; MacQueen, David A; Marquinez, Nicole S; MacKillop, James; Bickel, Warren K; Brandon, Thomas H

2017-04-01

The need to understand potential precipitants of smoking relapse is exemplified by relapse rates as high as 95%. The Self-Control Strength model, which proposes that self-control is dependent upon limited resources and susceptible to fatigue, may offer insight into relapse processes. The current study tested the hypothesis that self-control depletion (SCD), produced from engagement in emotional suppression, would serve as a novel antecedent for cessation failure, as indexed by a validated laboratory analogue of smoking lapse and relapse. We also examined whether SCD effects interacted with those of a well-established relapse precipitant (i.e., nicotine deprivation). Craving and behavioral economic indices (delay discounting and demand) were tested as hypothesized mechanisms for increased cessation failure. Ultimately, a moderated mediation model was used to test nicotine deprivation as a hypothesized moderator of SCD effects. We used a 2 × 2 (12-hr deprivation vs. no deprivation; SCD vs. no SCD) factorial between-subjects design (N = 128 smokers). The primary hypothesis of the study was supported, as SCD increased lapse behavior (p = .04). Nicotine deprivation significantly increased craving, cigarette demand, delay discounting, and lapse behavior. No main effects were found for SCD on putative mediators (i.e., craving, demand, and discounting), but the SCD and deprivation manipulations interacted upon craving (p = .04). The moderated mediation model was significant. SCD was found to increase craving among nicotine deprived smokers, which mediated effects on lapse behavior. SCD appears to play an important role in smoking relapse and may be a viable target for intervention. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Self-Control Depletion and Nicotine Deprivation as Precipitants of Smoking Cessation Failure: A Human Laboratory Model

PubMed Central

Heckman, Bryan W.; MacQueen, David A.; Marquinez, Nicole S.; MacKillop, James; Bickel, Warren K.; Brandon, Thomas H.

2017-01-01

Objective The need to understand potential precipitants of smoking relapse is exemplified by relapse rates as high as 95%. The Self-Control Strength model, which proposes that self-control is dependent upon limited resources and susceptible to fatigue, may offer insight into relapse processes. The current study tested the hypothesis that self-control depletion (SCD), produced from engagement in emotional suppression, would serve as a novel antecedent for cessation failure, as indexed by a validated laboratory analogue of smoking lapse and relapse. We also examined whether SCD effects interacted with those of a well-established relapse precipitant (i.e., nicotine deprivation). Craving and behavioral economic indices (delay discounting and demand) were tested as hypothesized mechanisms for increased cessation failure. Ultimately, a moderated mediation model was used to test nicotine deprivation as a hypothesized moderator of SCD effects. Method We used a 2 ×2 (12-hour deprivation vs. no deprivation; SCD vs. no SCD) factorial between-subjects design (N = 128 smokers). Results The primary hypothesis of the study was supported, as SCD increased lapse behavior (p = .04). Nicotine deprivation significantly increased craving, cigarette demand, delay discounting, and lapse behavior. No main effects were found for SCD on putative mediators (i.e., craving, demand, discounting), but the SCD and deprivation manipulations interacted upon craving (p = .04). The moderated mediation model was significant. SCD was found to increase craving among nicotine deprived smokers, which mediated effects on lapse behavior. Conclusions SCD appears to play an important role in smoking relapse and may be a viable target for intervention. PMID:28333537

Sickle cell disease pain management in adolescents: a literature review.

PubMed

Wilson, Bridget H; Nelson, Jessica

2015-04-01

Sickle cell disease (SCD) pain continues to emerge in adolescents. More than 98,000 individuals are believed to have SCD in the United States. In fact, 1 in 500 Black infants will be affected by SCD. Identifying standards of care for this unique population can improve pain management and treatment. A significant effect of vaso-occlusive crisis is a decrease in the quality of life in children. Therefore, pain management is multidimensional and includes pharmacologic, physical, and psychological strategies. A review of the literature was conducted to identify best practices regarding pain management in adolescents with sickle cell anemia. Key words such as pain, pain management, adolescent sickle cell anemia, and acute sickle cell pain were entered into databases to reveal qualitative and quantitative studies from 2009 to the present. Many of the research articles identified poor SCD pain management. Studies showed that acute SCD pain management is essential and should be evaluated and robustly managed to achieve optimum pain relief for patients. Acute SCD pain usually occurs as a result of vaso-occlusive crisis. Untreated acute SCD pain can result in morbidity and mortality in adolescents. Nursing knowledge is critical to reducing the stigma and improving management of SCD pain. Nurses play a vital role in the introduction of evidence-based practice within the clinical setting. In an effort to educate nurses and other health care professionals about SCD, this article is a literature review of studies concerning SCD and pain management in emergency rooms. Copyright © 2015 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

Sequential compression devices in postoperative urologic patients: an observational trial and survey study on the influence of patient and hospital factors on compliance.

PubMed

Ritsema, David F; Watson, Jennifer M; Stiteler, Amanda P; Nguyen, Mike M

2013-04-11

Sequential compression devices (SCDs) are commonly used for thromboprophylaxis in postoperative patients but compliance is often poor. We investigated causes for noncompliance, examining both hospital and patient related factors. 100 patients undergoing inpatient urologic surgery were enrolled. All patient had SCD sleeves placed preoperatively. Postoperative observations determined SCD compliance and reasons for non-compliance. Patient demographics, length of stay, inpatient unit type, and surgery type were recorded. At discharge, a patient survey gauged knowledge and attitudes regarding SCDs and bother with SCDs. Statistical analysis was performed to correlate SCD compliance with patient demographics; patient knowledge and attitudes regarding SCDs; and patient self-reported bother with SCDs. Observed overall compliance was 78.6%. The most commonly observed reasons for non-compliance were SCD machines not being initially available on the ward (71% of non-compliant observations on post-operative day 1) and SCD use not being restarted promptly after return to bed (50% of non-compliant observations for entire hospital stay). Mean self-reported bother scores related to SCDs were low, ranging from 1-3 out of 10 for all 12 categories of bother assessed. Patient demographics, knowledge, attitudes and bother with SCD devices were not significantly associated with non-compliance. Patient self-reported bother with SCD devices was low. Hospital factors, including SCD machine availability and timely restarting of devices by nursing staff when a patient returns to bed, played a greater role in SCD non-compliance than patient factors. Identifying and addressing hospital related causes for poor SCD compliance may improve postoperative urologic patient safety.

Post-transplant sCD30 and neopterin as predictors of chronic allograft nephropathy: impact of different immunosuppressive regimens.

PubMed

Weimer, R; Süsal, C; Yildiz, S; Staak, A; Pelzl, S; Renner, F; Dietrich, H; Daniel, V; Kamali-Ernst, S; Ernst, W; Padberg, W; Opelz, G

2006-08-01

Immunological monitoring for chronic allograft nephropathy (CAN) is of great potential interest. We assessed serum soluble CD30 (sCD30) together with in vitro Th2-type responses (IL-4, IL-10, CD4 helper activity) and neopterin in a prospective study of 84 renal transplant recipients with 2-year follow-up. Patients were randomized to CsA/Aza, CsA/MMF and Tacr/Aza, respectively, to analyze the effect of immunosuppression on posttransplant sCD30 and neopterin. ATG induction and acute rejections did not alter sCD30 levels whereas CMV disease was associated with transient upregulation of sCD30 (p = 0.003 at 4 months) and sustained upregulation of neopterin (corrected for graft function (Neo/CR) p = 0.005 at 2 years). Tacr versus CsA treatment proved to be an independent variable associated with downregulation of 1-year sCD30, which was positively related to Neo/CR (p = 0.007 and 0.01, respectively; logistic regression). Importantly, increased 1-year sCD30 and Neo/CR were associated with decreased glomerular filtration rate at 2 years (p = 0.02 and p < 0.0005, respectively) and evidence of CAN (p < 0.0005). High 1-year sCD30 could not be attributed to enhanced Th2-type responses and was not associated with HLA antibody formation. Our data suggest that elevated sCD30 and neopterin predict graft deterioration by CAN. Tacr effectively downregulates these responses and might be of advantage in patients with elevated sCD30 or neopterin.

Ocular vestibular evoked myogenic potentials to vertex low frequency vibration as a diagnostic test for superior canal dehiscence.

PubMed

Verrecchia, Luca; Westin, Magnus; Duan, Maoli; Brantberg, Krister

2016-04-01

To explore ocular vestibular evoked myogenic potentials (oVEMP) to low-frequency vertex vibration (125 Hz) as a diagnostic test for superior canal dehiscence (SCD) syndrome. The oVEMP using 125 Hz single cycle bone-conducted vertex vibration were tested in 15 patients with unilateral superior canal dehiscence (SCD) syndrome, 15 healthy controls and in 20 patients with unilateral vestibular loss due to vestibular neuritis. Amplitude, amplitude asymmetry ratio, latency and interaural latency difference were parameters of interest. The oVEMP amplitude was significantly larger in SCD patients when affected sides (53 μVolts) were compared to non-affected (17.2 μVolts) or compared to healthy controls (13.6 μVolts). Amplitude larger than 33.8 μVolts separates effectively the SCD ears from the healthy ones with sensitivity of 87% and specificity of 93%. The other three parameters showed an overlap between affected SCD ears and non-affected as well as between SCD ears and those in the two control groups. oVEMP amplitude distinguishes SCD ears from healthy ones using low-frequency vibration stimuli at vertex. Amplitude analysis of oVEMP evoked by low-frequency vertex bone vibration stimulation is an additional indicator of SCD syndrome and might serve for diagnosing SCD patients with coexistent conductive middle ear problems. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

[Influence of pre-transplant serum level of soluble CD30 on the long-term survival rates of kidney transplant recipients and grafts].

PubMed

Chen, Jiang-hua; Lü, Rong; Chen, Ying; Wu, Jian-yong; He, Qiang; Huang, Hong-feng; Qu, Li-hui

2005-06-15

To investigate the influence of pre-transplant sCD30 level on the long-term survival rates of kidney transplant recipients and grafts among Chinese. A retrospective cohort of 707 patients undergoing cadaver renal transplants between Dec.1998 and Aug 2003, 467 males and 240 females, aged 40 +/- 11, with their blood samples preserved was studied. The plasma levels of sCD30 were determined by ELISA. The 5-year graft survival/functional rates of the high sCD30 group were 77.7% +/- 3.5%/85.0% +/- 3.2%, significantly lower than those of the low and intermediate groups, 84.7% +/- 2.1%/98.9% +/- 1.1% and 88.1% +/- 2.9%/95.1% +/- 1.6% respectively (all P < 0.05). The 5-year recipient survival rate of the intermediate sCD30 group was 92.4% +/- 1.6%, higher than those of the low and high sCD30 groups, 84.7% +/- 3.9% and 87.1% +/- 2.7% respectively with a significant difference between the intermediate and high sCD30 groups (P = 0.032). Pre-transplant serum level of sCD30 reflects the immune status. Recipients with high sCD30 are prone to rejection while those with low sCD30 are prone to infections.

High serum level of the soluble CD30 identifies Chinese kidney transplant recipients at high risk of unfavorable outcome.

PubMed

Iv, R; He, Q; Wang, H P; Jin, J; Chen, Y; Chen, J H

2008-12-01

We sought to investigate the relationship between serum level of sCD30 and recipient/graft survival rates, rejection types, as well as other prognostic factors among Chinese kidney transplant patients. We performed enzyme-linked immunosorbent assays of serum sCD30 levels in duplicate among retrospective cohort of 707 renal transplant patients. The incidences of rejection increased in relation to the pretransplant sCD30 level. The reversal rates of rejection were 100%, 90.6%, and 78.6% for the low, intermediate, and high sCD30 groups. This observation suggested that high levels of sCD30 and pretransplant panel-reactive antibody (PRA)-positive patients are risk factors for acute rejection with odds ratios of 6.862 and 1.756. High sCD30 was an independent risk factor for functional graft survival. The 5-year graft survival rates were 99.39% +/- 6.1%, 93.11% +/- 1.93%, and 82.07% +/- 3.97% among the low, intermediate, and high sCD30 groups, while the 5-year recipient survival rates were 89.25% +/- 2.41%, 91.82% +/- 1.64%, and 88.85% +/- 2.36%, respectively. Increased sCD30 levels were observed among patients who were PRA-positive, cytomegalovirus antigens or antibodies positive, on long-term dialysis, and

Association of elevated pretransplant sCD30 levels with graft loss in 206 patients treated with modern immunosuppressive therapies after renal transplantation.

PubMed

Heinemann, Falko M; Rebmann, Vera; Witzke, Oliver; Philipp, Thomas; Broelsch, Christoph E; Grosse-Wilde, Hans

2007-03-27

Recent reports suggest that high pretransplant serum levels of soluble CD30 (sCD30) are a risk factor for rejections after kidney transplantation. The aim of our study was to elucidate the predictive value of pretransplant sCD30 levels for kidney transplantation outcome in a single-center patient cohort that has been treated with modern immunosuppressive therapies after transplantation. We retrospectively analyzed sCD30 in multiple pretransplant sera from 206 patients, of whom 174 were transplanted with a cadaveric kidney and 32 patients received an allograft from a living donor. Renal function after transplantation was estimated by measuring serum creatinine and by rejection diagnosis. We could demonstrate a statistically significant association between increased pretransplant sCD30 values and graft failures (P=0.005). Receiver operating curve analysis revealed a cutoff value of 124 U/mL pretransplant sCD30. A multivariate analysis confirmed pretransplant sCD30 values >124 U/mL (P=0.011) and rejection episodes (P<0.0001) as independent risk factors for graft loss. Our study revealed a strong correlation between pretransplant sCD30 levels and the incidence of graft failure, but we could not confirm that the development of rejection episodes is correlated with pretransplant sCD30 values.

Mothers raising children with sickle cell disease at the intersection of race, gender, and illness stigma.

PubMed

Burnes, David P R; Antle, Beverley J; Williams, Charmaine C; Cook, Lisa

2008-08-01

This qualitative study used the long interview method with Canadian mothers of African and Caribbean descent to understand the underresearched experience of raising a child with sickle cell disease (SCD). Mothers' realities were explored through three levels of social organization: daily caregiver coping (micro level); community views of SCD, such as stigma (meso level); and systemic SCD health care provision (macro level). Through the use of population health and structural social work perspectives, mothers' experiences were examined in the context of perceived gender and racial oppression. Saturation was achieved after initial interviews with 10 participants and a four-month postinterview with half of the participants. Mothers commonly reported several daily coping challenges: fear of their children's death, separation anxiety, loss of control over life, helplessness, and loneliness/isolation. SCD stigma interacted with racism, contributed to social isolation, and prevented families from organizing as a group. All mothers perceived racism as a salient factor behind inadequate mainstream SCD health care. Recommendations to improve SCD health care and implications for social work practice and research are discussed. This is the first known Canadian psychosocial study of SCD and investigation into SCD stigma outside of rural Nigeria.

The Traveler with Sickle Cell Disease

PubMed Central

Willen, Shaina M.; Thornburg, Courtney D.; Lantos, Paul M.

2014-01-01

Background Sickle cell disease (SCD) is the most common genetic disease among persons with African ancestry. This article provides a background on SCD and reviews many important aspects of travel preparation in this population. Methods The medical literature was searched for studies about travel-associated preparedness and complications in individuals with SCD. Topics researched included malaria, bacterial infections, vaccinations, dehydration, altitude, air travel, and travel preparedness. Results There is very little published literature that specifically addresses the risks faced by travelers with SCD. Rates of medical complications during travel appear to be high. There is a body of literature that describes complications of SCD in indigenous populations, particularly within Africa. The generalizability of these data to a traveler are uncertain. Combining these sources of data and the broader medical literature we address major travel-related questions that may face a provider preparing an individual with SCD for safe travel. Conclusions Travelers with SCD face considerable medical risks when traveling to developing tropical countries; these include malaria, bacterial infections, hypovolemia, and sickle cell-associated vaso-occlusive crises. Frank counseling about risks, vigilant preventative measures, and contingency planning for illness while abroad are necessary parts of the pre-travel visit for individuals with SCD. PMID:24947546

Soluble CD26 and CD30 plasma levels in HIV infected patients with and without GB virus type C coinfection.

PubMed

Mostafa, Haji-Molla-Hoseini; Ali-Akbar, Pourfathollah; Zahra, Soheili; Minoo, Mohraz; Sedigheh, Amini; Mahnaz, Aghaiepour; Shahram, Samiee; Mahin, Nikoogoftar; Mina, Moghtadaie

2007-06-15

GB virus type C (GBV-C) probably influences HIV infection associated disease by either directly inhibiting HIV replication or enhancing the immune competence to cope with HIV. Still the definitive mechanisms of this inhibitory effect need to be identified. To address the possibility of immune modulating effects of GBV-C coinfection in HIV patients we evaluated plasma levels of soluble (s) CD26 and CD30 in HIV infected patients with and without GBV-C. Cross-sectional comparison of sCD26 and sCD30 levels among 6 HIV/GBV-C coinfected, 11 HIV mono-infected and 13 healthy controls was carried out. We used a commercial EIA to evaluate sCD26 and scD30 and a RT-PCR assay to detect active GBV-C infection. The Mann-Whitney U test was used for statistical analysis. No statistically significant differences were observed in levels of sCD26 and sCD30 in plasma of HIV infected patients with and without GBV-C viremia. GBV-C infection does not appear to influence the sCD26 and sCD30 levels.

Developmental Changes in Soluble CD40 Ligand

PubMed Central

Cholette, Jill M.; Blumberg, Neil; Phipps, Richard P.; McDermott, Michael P.; Gettings, Kelly F.; Lerner, Norma B.

2008-01-01

Objectives To determine if soluble CD40 ligand (sCD40L; formally CD154) levels vary with age and to identify age-dependent ranges in healthy pediatric and adult populations. Study design sCD40L was measured in 25 neonates, 74 children (3 months –15 years) and 20 adults using an enzyme-linked immunosorbent assay. For age group comparisons, Mann-Whitney tests were performed. Correlation coefficients assessed relationships between plasma and serum sCD40L. Results Plasma sCD40L levels were higher in neonates than in all other age groups, (p<0.001). All grouped pediatric plasma levels were significantly higher than in adults (p<0.0001). There were no significant differences in plasma sCD40L between pediatric age groups. Serum levels were significantly higher in neonates than in any other age group (p <0.0001). Pediatric and adult serum sCD40L levels were not significantly different. Conclusions Plasma sCD40L levels are highest at birth and remain higher than those in adults throughout childhood. Reasons for such developmental changes remain to be investigated. Age appropriate reference ranges should be used when sCD40L is being evaluated in pediatric disorders. PMID:18154898

Demands and challenges for patients with sickle-cell disease requiring hematopoietic stem cell transplantation in Saudi Arabia.

PubMed

Alsultan, Abdulrahman; Jastaniah, Wasil; Al Afghani, Sameera; Al Bagshi, Muneer H; Nasserullah, Zaki; Al-Suliman, Ahmed M; Alabdulaali, Mohammed K

2016-09-01

Allogeneic HSCT is the only curative treatment for SCD. In this study, we estimated the number of Saudi patients with SCD who are candidates for HSCT. We used the presence of overt stroke, recurrent ACS, and frequent severe pain crisis as indications for HSCT. We calculated the frequencies of these complications among a Saudi SCD cohort of 376 patients with SCD, 250 from SW and 126 from Eastern (E) provinces. We found that 59 (23.6%) of SW patients were transplant candidates compared to 22 (17.4%) from E province. It is estimated that about 61 000 patients with SCD live in Saudi Arabia. Thus, the projected number of Saudi patients with SCD who are candidates for HSCT is 10 536 patients. Of those, 2148 are children. The burden of SCD on HSCT centers in Saudi Arabia is substantial and is difficult currently to meet the demand. We recommend recruiting/training more transplant physicians and nurses, expand current capacity of centers if feasible, and open new transplant centers to make HSCT a practical therapeutic option for patients with severe SCD in Saudi Arabia. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Soluble CD30 as a prognostic factor for outcome following renal transplantation.

PubMed

Platt, R E; Wu, K S T; Poole, K; Newstead, C G; Clark, B

2009-07-01

To determine whether measurement of soluble CD30 (sCD30) levels predicts for early rejection in a cohort of first deceased kidney transplant recipients. Pre-transplant serum samples were analysed for sCD30 levels using a commercial ELISA kit (Biotest). A 100 U/ml cut-off for "high sCD30" was applied. Clinical outcome parameters were biopsy-proven rejection episodes, creatinine levels and glomerular filtration rate. In the cohort of patients who experienced at least one episode of rejection in the first 6 months post-transplant, levels of pre-transplant sCD30 were significantly higher than in those who did not experience rejection. Despite this association, the occurrence of a high sCD30 level did not predict for rejection on an individual basis. The prognostic value of pre-transplant sCD30 testing is diminished by the large number of patients with high sCD30 levels who do not develop rejection. Although this limits the utility of the test in informing clinical management of individual patients, a high pre-transplant sCD30 level should still be considered a risk factor for poorer outcome.

[The relationship between acute rejection and expression of sCD30 for the patients after kidney transplantation].

PubMed

Yang, Jian-Lin; Hao, Hong-Jun; Qin, Bin; Bang, Ling-Qing; Zhang, Zhi-Hong; Xin, Dian-Qi; Guo, Ying-Lu; Na, Yan-Qun

2005-03-16

To study the relationship between the sCD30 and acute rejection. We tested the sCD30 level in serum for 58 cases with kidney transplantation before and the 7th day and 28th day after operation by ELISA. 31 healthy individual for control group, and simultaneously recorded the incidence of rejection after kidney transplantation. The results showed that there is an obviously relation before kidney transplantation between the sCD30 level in serum and the incidence of acute rejection (chi = 4.843, P = 0.028, P < 0.05). There is a significantly relation at the 7th day after kidney transplantation between the sCD30 level in serum and the incidence of acute rejection (chi = 7.201, P = 0.007, P < 0.01). There is no obviously relation at 28th day after kidney transplantation between the sCD30 level in serum and the incidence of acute rejection (chi = 2.095, P = 0.148, P > 0.05). The results suggested that the expressions of sCD30 are related to acute rejection. We speculated that the expressions of sCD30 could play an important role in acute rejection.

Systemic Down-Regulation of Delta-9 Desaturase Promotes Muscle Oxidative Metabolism and Accelerates Muscle Function Recovery following Nerve Injury

PubMed Central

Henriques, Alexandre; Lequeu, Thiebault; Rene, Frederique; Bindler, Françoise; Dirrig-Grosch, Sylvie; Oudart, Hugues; Palamiuc, Lavinia; Metz-Boutigue, Marie-Helene; Dupuis, Luc; Marchioni, Eric; Gonzalez De Aguilar, Jose-Luis; Loeffler, Jean-Philippe

2013-01-01

The progressive deterioration of the neuromuscular axis is typically observed in degenerative conditions of the lower motor neurons, such as amyotrophic lateral sclerosis (ALS). Neurodegeneration in this disease is associated with systemic metabolic perturbations, including hypermetabolism and dyslipidemia. Our previous gene profiling studies on ALS muscle revealed down-regulation of delta-9 desaturase, or SCD1, which is the rate-limiting enzyme in the synthesis of monounsaturated fatty acids. Interestingly, knocking out SCD1 gene is known to induce hypermetabolism and stimulate fatty acid beta-oxidation. Here we investigated whether SCD1 deficiency can affect muscle function and its restoration in response to injury. The genetic ablation of SCD1 was not detrimental per se to muscle function. On the contrary, muscles in SCD1 knockout mice shifted toward a more oxidative metabolism, and enhanced the expression of synaptic genes. Repressing SCD1 expression or reducing SCD-dependent enzymatic activity accelerated the recovery of muscle function after inducing sciatic nerve crush. Overall, these findings provide evidence for a new role of SCD1 in modulating the restorative potential of skeletal muscles. PMID:23785402

Combined therapy of dietary fish oil and stearoyl-CoA desaturase 1 inhibition prevents the metabolic syndrome and atherosclerosis.

PubMed

Brown, J Mark; Chung, Soonkyu; Sawyer, Janet K; Degirolamo, Chiara; Alger, Heather M; Nguyen, Tam M; Zhu, Xuewei; Duong, My-Ngan; Brown, Amanda L; Lord, Caleb; Shah, Ramesh; Davis, Matthew A; Kelley, Kathryn; Wilson, Martha D; Madenspacher, Jennifer; Fessler, Michael B; Parks, John S; Rudel, Lawrence L

2010-01-01

Stearoyl-CoA desaturase 1 (SCD1) is a critical regulator of energy metabolism and inflammation. We have previously reported that inhibition of SCD1 in hyperlipidemic mice fed a saturated fatty acid (SFA)-enriched diet prevented development of the metabolic syndrome, yet surprisingly promoted severe atherosclerosis. In this study we tested whether dietary fish oil supplementation could prevent the accelerated atherosclerosis caused by SCD1 inhibition. LDLr(-/-), ApoB(100/100) mice were fed diets enriched in saturated fat or fish oil in conjunction with antisense oligonucleotide (ASO) treatment to inhibit SCD1. As previously reported, in SFA-fed mice, SCD1 inhibition dramatically protected against development of the metabolic syndrome, yet promoted atherosclerosis. In contrast, in mice fed fish oil, SCD1 inhibition did not result in augmented macrophage inflammatory response or severe atherosclerosis. In fact, the combined therapy of dietary fish oil and SCD1 ASO treatment effectively prevented both the metabolic syndrome and atherosclerosis. SCD1 ASO treatment in conjunction with dietary fish oil supplementation is an effective combination therapy to comprehensively combat the metabolic syndrome and atherosclerosis in mice.

Asthma Management in Sickle Cell Disease

PubMed Central

Morris, Claudia R.

2013-01-01

Asthma is a common comorbid factor in sickle cell disease (SCD). However, the incidence of asthma in SCD is much higher than expected compared to rates in the general population. Whether “asthma” in SCD is purely related to genetic and environmental factors or rather is the consequence of the underlying hemolytic and inflammatory state is a topic of recent debate. Regardless of the etiology, hypoxemia induced by bronchoconstriction and inflammation associated with asthma exacerbations will contribute to a cycle of sickling and subsequent complications of SCD. Recent studies confirm that asthma predisposes to complications of SCD such as pain crises, acute chest syndrome, and stroke and is associated with increased mortality. Early recognition and aggressive standard of care management of asthma may prevent serious pulmonary complications and reduce mortality. However, data regarding the management of asthma in SCD is very limited. Clinical trials are needed to evaluate the effectiveness of current asthma therapy in patients with SCD and coincident asthma, while mechanistic studies are needed to delineate the underlying pathophysiology. PMID:24324967

Single-case synthesis tools I: Comparing tools to evaluate SCD quality and rigor.

PubMed

Zimmerman, Kathleen N; Ledford, Jennifer R; Severini, Katherine E; Pustejovsky, James E; Barton, Erin E; Lloyd, Blair P

2018-03-03

Tools for evaluating the quality and rigor of single case research designs (SCD) are often used when conducting SCD syntheses. Preferred components include evaluations of design features related to the internal validity of SCD to obtain quality and/or rigor ratings. Three tools for evaluating the quality and rigor of SCD (Council for Exceptional Children, What Works Clearinghouse, and Single-Case Analysis and Design Framework) were compared to determine if conclusions regarding the effectiveness of antecedent sensory-based interventions for young children changed based on choice of quality evaluation tool. Evaluation of SCD quality differed across tools, suggesting selection of quality evaluation tools impacts evaluation findings. Suggestions for selecting an appropriate quality and rigor assessment tool are provided and across-tool conclusions are drawn regarding the quality and rigor of studies. Finally, authors provide guidance for using quality evaluations in conjunction with outcome analyses when conducting syntheses of interventions evaluated in the context of SCD. Copyright © 2018 Elsevier Ltd. All rights reserved.

Parental Problem-Solving Abilities and the Association of Sickle Cell Disease Complications with Health-related Quality of Life for School-age Children

PubMed Central

Barakat, Lamia P.; Daniel, Lauren C.; Smith, Kelsey; Robinson, M. Renée; Patterson, Chavis A.

2013-01-01

Children with sickle cell disease (SCD) are at risk for poor health-related quality of life (HRQOL). The current analysis sought to explore parent problem-solving abilities/skills as a moderator between SCD complications and HRQOL to evaluate applicability to pediatric SCD. At baseline, 83 children ages 6–12 years and their primary caregiver completed measures of the child HRQOL. Primary caregivers also completed a measure of social problem-solving. A SCD complications score was computed from medical record review. Parent problem-solving abilities significantly moderated the association of SCD complications with child self-report psychosocial HRQOL (p = .006). SCD complications had a direct effect on parent proxy physical and psychosocial child HRQOL. Enhancing parent problem-solving abilities may be one approach to improve HRQOL for children with high SCD complications; however, modification of parent perceptions of HRQOL may require direct intervention to improve knowledge and skills involved in disease management. PMID:24222378

Level of soluble CD30 after kidney transplantation correlates with acute rejection episodes.

PubMed

Yang, J L; Hao, H J; Zhang, B; Liu, Y X; Chen, S; Na, Y Q

2008-12-01

Measurement of soluble CD30 (sCD30) levels may predict acute rejection episodes (ARE). To explore the value of sCD30 after transplantation, we tested serum sCD30 levels in 58 kidney transplant cases at 1 day before and 7 and 28 days after transplantation by enzyme-linked immunosorbent assay (ELISA). The incidences of ARE after kidney transplantation were recorded simultaneously. Meanwhile, 31 healthy individuals were selected as a control group. The results showed a relationship between sCD30 level in serum before kidney transplantation and the incidence of ARE. However, the relationship was more significant between serum sCD30 levels at day 7 after kidney transplantation and the incidence of ARE. There was no obvious relationship between serum sCD30 levels at day 28 after kidney transplantation and the incidence of ARE. These results suggested that the level of sCD30 at day 7 posttransplantation provides valuable data to predict ARE.

Sudden cardiac death in the soccer field: a retrospective study in young soccer players from 2000 to 2013.

PubMed

Davogustto, Giovanni; Higgins, John

2014-11-01

Soccer is the most popular sport in the world, with over 200 million active players. Sudden cardiac death (SCD) represents the most striking as well as the most common cause of death in the soccer field. Underlying cardiovascular pathologies predispose to life threatening ventricular arrhythmias and SCD in soccer players. Up to thousands to hundred thousands players might have an underlying condition that predisposes them for SCD. After several media striking SCD events in soccer players the Fédération Internationale de Football Association (FIFA) has made screening recommendations that are more thorough than the ones recommended for the American Heart Association and the European Society of Cardiology. We present a retrospective search through Internet databases that resulted in 54 soccer players with SCD events from 2000 until 2013. In this article, we will describe and discuss the conditions of those cases of SCD in order to provide more knowledge of the factors that may precipitate SCD in young soccer players.

Parental problem-solving abilities and the association of sickle cell disease complications with health-related quality of life for school-age children.

PubMed

Barakat, Lamia P; Daniel, Lauren C; Smith, Kelsey; Renée Robinson, M; Patterson, Chavis A

2014-03-01

Children with sickle cell disease (SCD) are at risk for poor health-related quality of life (HRQOL). The current analysis sought to explore parent problem-solving abilities/skills as a moderator between SCD complications and HRQOL to evaluate applicability to pediatric SCD. At baseline, 83 children ages 6-12 years and their primary caregiver completed measures of child HRQOL. Primary caregivers also completed a measure of social problem-solving. A SCD complications score was computed from medical record review. Parent problem-solving abilities significantly moderated the association of SCD complications with child self-report psychosocial HRQOL (p = .006). SCD complications had a direct effect on parent proxy physical and psychosocial child HRQOL. Enhancing parent problem-solving abilities may be one approach to improve HRQOL for children with high SCD complications; however, modification of parent perceptions of HRQOL may require direct intervention to improve knowledge and skills involved in disease management.

The Effect of AGN Heating on the Low-redshift Lyα Forest

NASA Astrophysics Data System (ADS)

Gurvich, Alex; Burkhart, Blakesley; Bird, Simeon

2017-02-01

We investigate the effects of AGN heating and the ultraviolet background on the low-redshift Lyα forest column density distribution (CDD) using the Illustris simulation. We show that Illustris reproduces observations at z = 0.1 in the column density range {10}12.5{--}{10}13.5 cm-2, relevant for the “photon underproduction crisis.” We attribute this to the inclusion of AGN feedback, which changes the gas distribution so as to mimic the effect of extra photons, as well as the use of the Faucher-Giguère ultraviolet background, which is more ionizing at z = 0.1 than the Haardt & Madau background previously considered. We show that the difference between simulations run with smoothed particle hydrodynamics and simulations using a moving mesh is small in this column density range but can be more significant at larger column densities. We further consider the effect of supernova feedback, Voigt profile fitting, and finite resolution, all of which we show to have little influence on the CDD. Finally, we identify a discrepancy between our simulations and observations at column densities {10}14{--}{10}16 cm-2, where Illustris produces too few absorbers, which suggests the AGN feedback model should be further refined. Since the “photon underproduction crisis” primarily affects lower column density systems, we conclude that AGN feedback and standard ionizing background models can resolve the crisis.

Serum Levels of Soluble CD26/Dipeptidyl Peptidase-IV in Type 2 Diabetes Mellitus and Its Association with Metabolic Syndrome and Therapy with Antidiabetic Agents in Malaysian Subjects.

PubMed

Ahmed, Radwan H; Huri, Hasniza Zaman; Al-Hamodi, Zaid; Salem, Sameer D; Muniandy, Sekaran

2015-01-01

A soluble form of CD26/dipeptidyl peptidase-IV (sCD26/DPP-IV) induces DPP-IV enzymatic activity that degrades incretin. We investigated fasting serum levels of sCD26/DPP-IV and active glucagon-like peptide-1 (GLP-1) in Malaysian patients with type 2 diabetes mellitus (T2DM) with and without metabolic syndrome (MetS), as well as the associations between sCD26/DPP-IV levels, MetS, and antidiabetic therapy. We assessed sCD26/DPP-IV levels, active GLP-1 levels, body mass index (BMI), glucose, insulin, A1c, glucose homeostasis indices, and lipid profiles in 549 Malaysian subjects (including 257 T2DM patients with MetS, 57 T2DM patients without MetS, 71 non-diabetics with MetS, and 164 control subjects without diabetes or metabolic syndrome). Fasting serum levels of sCD26/DPP-IV were significantly higher in T2DM patients with and without MetS than in normal subjects. Likewise, sCD26/DPP-IV levels were significantly higher in patients with T2DM and MetS than in non-diabetic patients with MetS. However, active GLP-1 levels were significantly lower in T2DM patients both with and without MetS than in normal subjects. In T2DM subjects, sCD26/DPP-IV levels were associated with significantly higher A1c levels, but were significantly lower in patients using monotherapy with metformin. In addition, no significant differences in sCD26/DPP-IV levels were found between diabetic subjects with and without MetS. Furthermore, sCD26/DPP-IV levels were negatively correlated with active GLP-1 levels in T2DM patients both with and without MetS. In normal subjects, sCD26/DPP-IV levels were associated with increased BMI, cholesterol, and LDL-cholesterol (LDL-c) levels. Serum sCD26/DPP-IV levels increased in T2DM subjects with and without MetS. Active GLP-1 levels decreased in T2DM patients both with and without MetS. In addition, sCD26/DPP-IV levels were associated with Alc levels and negatively correlated with active GLP-1 levels. Moreover, metformin monotherapy was associated with reduced sCD26/DPP-IV levels. In normal subjects, sCD26/DPP-IV levels were associated with increased BMI, cholesterol, and LDL-c.

Soluble CD14 in cerebrospinal fluid is associated with markers of inflammation and axonal damage in untreated HIV-infected patients: a retrospective cross-sectional study.

PubMed

Jespersen, Sofie; Pedersen, Karin Kæreby; Anesten, Birgitta; Zetterberg, Henrik; Fuchs, Dietmar; Gisslén, Magnus; Hagberg, Lars; Trøseid, Marius; Nielsen, Susanne Dam

2016-04-21

HIV-associated cognitive impairment has declined since the introduction of combination antiretroviral treatment (cART). However, milder forms of cognitive impairment persist. Inflammation in the cerebrospinal fluid (CSF) has been associated with cognitive impairment, and CSF neurofilament light chain protein (NFL) and CSF neopterin concentrations are increased in those patients. Microbial translocation in HIV infection has been suggested to contribute to chronic inflammation, and lipopolysaccharide (LPS) and soluble CD14 (sCD14) are markers of microbial translocation and the resulting monocyte activation, respectively. We hypothesised that microbial translocation contributes to inflammation and axonal damage in the central nervous system (CNS) in untreated HIV infection. We analyzed paired samples of plasma and CSF from 62 HIV-infected, untreated patients without cognitive symptoms from Sahlgrenska University Hospital, Gothenburg, Sweden. Measurements of neopterin and NFL in CSF were available from previous studies. Plasma and CSF sCD14 was measured using ELISA (R&D, Minneapolis, MN), and plasma and CSF LPS was measured using LAL colorimetric assay (Lonza, Walkersville, MD, USA). Univariate and multivariate regression analyses were performed. LPS in plasma was associated with plasma sCD14 (r = 0.31, P = 0.015), and plasma sCD14 was associated with CSF sCD14 (r = 0.32, P = 0.012). Furthermore, CSF sCD14 was associated with NFL (r = 0.32, P = 0.031) and neopterin (r = 0.32, P = 0.012) in CSF. LPS was not detectable in CSF. In a multivariate regression model CSF sCD14 remained associated with NFL and neopterin after adjusting for age, CD4+ cell count, and HIV RNA in CSF. In a group of untreated, HIV-infected patients LPS was associated with sCD14 in plasma, and plasma sCD14 was associated CSF sCD14. CSF sCD14 were associated with markers of CNS inflammation and axonal damage. This suggest that microbial translocation might be a driver of systemic and CNS inflammation. However, LPS was not detectable in the CSF, and since sCD14 is a marker of monocyte activation sCD14 may be increased due to other causes than microbial translocation. Further studies regarding cognitive impairment and biomarkers are warranted to fully understand causality.

Sudden cardiac death and geomagnetic activity: links to age, gender and agony time.

PubMed

Stoupel, Eliahu; Domarkiene, Stase; Radishauskas, Richardas; Abramson, Evgeny

2002-01-01

In previous studies, we analyzed sudden cardiac death (SCD) of shorter and longer agony time with geomagnetic activity (GMA) levels, with controversial results. The goals of the present study were (1) to study SCD at ages below 65 and 65 and older for each gender on days of low (Io) and higher (IIo-IVo) GMA; (2) to compare links between SCD and GMA with death at 1 h and from 1 to 24 h. We studied 1327 SCD, 392 (29.5%) females and 935 (70.5%) males, from the Kaunas Registry (part of the MONICA Study): 785 deaths during 1826 consecutive days (1994-1998) at ages 25 to 64 years and 524 deaths at ages 65 and older during 732 consecutive days (1996-1997). Of these, 261 SCD occurred at 1 h, 1076 between 1 h and 24 h without prodromes. GMA data were obtained from the National Geophysical Data Center and the National Space Services Center, USA. Student t-test and its probabilities for daily SCD at Io and IIo-IVo GMA were compared. The daily number of SCD was significantly different for most of the compared groups at lowest and higher GMA levels. For all SCD, both at age <65 and at >65, the frequency was significantly higher on days of IIo-IVo GMA than on days of Io GMA (p=0.00067-0.03). A strong trend for more SCD on days of Io GMA was seen in males aged <65 who died within 1 h (p=0.06); females aged <65 who died within >1 h to 24 h (p=0.06), and females >65 who died within 1 h (p=0.0267). Females below the age of 65 who died in less than 1 h showed a trend toward higher SCD frequency at IIo-IVo GMA that did not achieve significance (p=0.057). The distribution of SCD, with short (< or =1h) and longer (1-24 h) time of death, on days of lowest (Io) GMA differs from that on days of unsettled, active, or stormy (IIo-IVo) GMA. Despite the general trend to higher SCD frequency at IIo-IVo GMA, certain rapidly dying groups (< 65 y males, > 65 y females) showed a strong trend toward higher numbers of SCD at the lowest GMA.

MAVEN/IUVS Apoapse Observations of the Martian FUV Dayglow

NASA Astrophysics Data System (ADS)

Correira, J.; Evans, J. S.; Stevens, M. H.; Schneider, N. M.; Stewart, I. F.; Deighan, J.; Jain, S.; Chaffin, M.; Crismani, M. M. J.; McClintock, B.; Holsclaw, G.; Lefèvre, F.; Lo, D.; Stiepen, A.; Clarke, J. T.; Mahaffy, P. R.; Bougher, S. W.; Bell, J. M.; Jakosky, B. M.

2015-12-01

We present FUV data (115 - 190 nm) from MAVEN/IUVS apoapse mode observations for the Oct 2014 through Feb 2015 time period. During apoapse mode the highly elliptical orbit of MAVEN allows for up to four apoapse disk images by IUVS per day. Maps of FUV feature intensities and intensity ratios as well as derived CO/CO2 and O/CO2 column density ratios will be shown. Column density ratios are derived from lookup tables created using the Atmospheric Ultraviolet Radiance Integrated Code [Strickland et al., 1999] in conjunction with observed intensity ratios. Column density ratios provide a measure of composition changes in the Martian atmosphere. Due to MAVEN's orbital geometry the observations from this time period focus on the southern hemisphere. The broad view provided by apoapse observations allows for the investigation of spatial and temporal variations (both long term and local time) of the atmospheric composition (via the column density ratios). IUVS FUV intensities and derived column density ratios will also be compared with model results from Mars Global Ionosphere/Thermosphere Model (MGITM) and the Mars Climate Database (MCD).

StearoylCoA Desaturase-5: A Novel Regulator of Neuronal Cell Proliferation and Differentiation

PubMed Central

Sinner, Debora I.; Kim, Gretchun J.; Henderson, Gregory C.; Igal, R. Ariel

2012-01-01

Recent studies have demonstrated that human stearoylCoA desaturase-1 (SCD1), a Δ9-desaturase that converts saturated fatty acids (SFA) into monounsaturated fatty acids, controls the rate of lipogenesis, cell proliferation and tumorigenic capacity in cancer cells. However, the biological function of stearoylCoA desaturase-5 (SCD5), a second isoform of human SCD that is highly expressed in brain, as well as its potential role in human disease, remains unknown. In this study we report that the constitutive overexpression of human SCD5 in mouse Neuro2a cells, a widely used cell model of neuronal growth and differentiation, displayed a greater n-7 MUFA-to-SFA ratio in cell lipids compared to empty-vector transfected cells (controls). De novo synthesis of phosphatidylcholine and cholesterolesters was increased whereas phosphatidylethanolamine and triacylglycerol formation was reduced in SCD5-expressing cells with respect to their controls, suggesting a differential use of SCD5 products for lipogenic reactions. We also observed that SCD5 expression markedly accelerated the rate of cell proliferation and suppressed the induction of neurite outgrowth, a typical marker of neuronal differentiation, by retinoic acid indicating that the desaturase plays a key role in the mechanisms of cell division and differentiation. Critical signal transduction pathways that are known to modulate these processes, such epidermal growth factor receptor (EGFR)Akt/ERK and Wnt, were affected by SCD5 expression. Epidermal growth factor-induced phosphorylation of EGFR, Akt and ERK was markedly blunted in SCD5-expressing cells. Furthermore, the activity of canonical Wnt was reduced whereas the non-canonical Wnt was increased by the presence of SCD5 activity. Finally, SCD5 expression increased the secretion of recombinant Wnt5a, a non-canonical Wnt, whereas it reduced the cellular and secreted levels of canonical Wnt7b. Our data suggest that, by a coordinated modulation of key lipogenic pathways and transduction signaling cascades, SCD5 participates in the regulation of neuronal cell growth and differentiation. PMID:22745828

Impact of skin capsular distance on the performance of controlled attenuation parameter in patients with chronic liver disease.

PubMed

Shen, Feng; Zheng, Rui-Dan; Shi, Jun-Ping; Mi, Yu-Qiang; Chen, Guo-Feng; Hu, Xiqi; Liu, Yong-Gang; Wang, Xiao-Ying; Pan, Qin; Chen, Guang-Yu; Chen, Jian-Neng; Xu, Liang; Zhang, Rui-Nan; Xu, Lei-Ming; Fan, Jian-Gao

2015-11-01

Controlled attenuation parameter (CAP) is a non-invasive method for evaluating hepatic steatosis. However, larger skin capsular distance (SCD) can affect the accuracy. The aim of this study was to investigate the impact of SCD on the diagnostic performance of CAP and liver stiffness measurement (LSM). Of 101 patients with non-alcoholic fatty liver disease (NAFLD) and 280 patients with chronic hepatitis B (CHB) who underwent liver biopsy were prospectively recruited. CAP, LSM and SCD were performed using FibroScan with M probe. The areas under receiver operating characteristics curves (AUROCs) were calculated to determine the diagnostic efficacy. The optimal thresholds were defined by the maximum Youden index. SCD (B 30.34, P < 0.001) and hepatic steatosis (B 23.04, P < 0.001) were independently associated with CAP by multivariate analysis. The AUROCs were slightly higher for SCD <25 mm compared to those for SCD ≥25 mm for steatosis ≥5% (0.88 vs. 0.81), >33% (0.90 vs. 0.85) and >66% (0.84 vs. 0.72). For SCD <25 mm, the optimal CAP cut-offs for differentiating steatosis ≥5%, >33% and >66% were 255.0 dB/m, 283.5 dB/m and 293.5 dB/m. However, cut-offs were elevated by approximately 60-70 dB/m for SCD ≥25 mm. When stratified by fibrosis grade, LSM was significantly affected by SCD ≥25 mm for advanced fibrosis (≥F3) in NAFLD, but not in CHB. CAP is a promising tool for detecting and quantifying hepatic steatosis. SCD ≥25 mm may cause overestimation of steatosis. Similarly, SCD ≥25 mm affects the detection of advanced fibrosis by LSM in NAFLD patients. © 2015 The Authors. Liver International Published by John Wiley & Sons Ltd.

Sudden Cardiac Death in Women With Suspected Ischemic Heart Disease, Preserved Ejection Fraction, and No Obstructive Coronary Artery Disease: A Report From the Women's Ischemia Syndrome Evaluation Study.

PubMed

Mehta, Puja K; Johnson, B Delia; Kenkre, Tanya S; Eteiba, Wafia; Sharaf, Barry; Pepine, Carl J; Reis, Steven E; Rogers, William J; Kelsey, Sheryl F; Thompson, Diane V; Bittner, Vera; Sopko, George; Shaw, Leslee J; Bairey Merz, C Noel

2017-08-21

Sudden cardiac death (SCD) is often the first presentation of ischemic heart disease; however, there is limited information on SCD among women with and without obstructive coronary artery disease (CAD). We evaluated SCD incidence in the WISE (Women's Ischemia Syndrome Evaluation) study. Overall, 904 women with suspected ischemic heart disease with preserved ejection fraction and core laboratory coronary angiography were followed for outcomes. In case of death, a death certificate and/or a physician or family narrative of the circumstances of death was obtained. A clinical events committee rated all deaths as cardiovascular or noncardiovascular and as SCD or non-SCD. In total, 96 women (11%) died over a median of 6 years (maximum: 8 years). Among 65 cardiovascular deaths, 42% were SCD. Mortality per 1000 person-hours increased linearly with CAD severity (no CAD: 5.8; minimal: 15.9; obstructive: 38.6; P <0.0001). However, the proportion of SCD was similar across CAD severity: 40%, 58%, and 38% for no, minimal, and obstructive CAD subgroups, respectively ( P value not significant). In addition to traditional risk factors (age, diabetes mellitus, smoking), a history of depression ( P =0.018) and longer corrected QT interval ( P =0.023) were independent SCD predictors in the entire cohort. Corrected QT interval was an independent predictor of SCD in women without obstructive CAD ( P =0.033). SCD contributes substantially to mortality in women with and without obstructive CAD. Corrected QT interval is the single independent SCD risk factor in women without obstructive CAD. In addition to management of traditional risk factors, these data indicate that further investigation should address mechanistic understanding and interventions targeting depression and corrected QT interval in women. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Sports-related sudden cardiac deaths in the young population of Switzerland.

PubMed

Asatryan, Babken; Vital, Cristina; Kellerhals, Christoph; Medeiros-Domingo, Argelia; Gräni, Christoph; Trachsel, Lukas D; Schmied, Christian M; Saguner, Ardan M; Eser, Prisca; Herzig, David; Bolliger, Stephan; Michaud, Katarzyna; Wilhelm, Matthias

2017-01-01

In Switzerland, ECG screening was first recommended for national squad athletes in 1998. Since 2001 it has become mandatory in selected high-risk professional sports. Its impact on the rates of sports-related sudden cardiac death (SCD) is unknown. We aimed to study the incidence, causes and time trends of sports-related SCD in comparison to SCD unrelated to exercise in Switzerland. We reviewed all forensic reports of SCDs of the German-speaking region of Switzerland in the age group of 10 to 39 years, occurring between 1999 and 2010. Cases were classified into three categories based on whether or not deaths were associated with sports: no sports (NONE), recreational sports (REC), and competitive sports (COMP). Over the 12-year study period, 349 SCD cases were recorded (mean age 30±7 years, 76.5% male); 297 cases were categorized as NONE, 31 as REC, and 21 as COMP. Incidences of SCD per 100,000 person-years [mean (95% CI)] were the lowest in REC [0.43 (0.35-0.56)], followed by COMP [1.19 (0.89-1.60)] and NONE [2.46 (2.27-2.66)]. In all three categories, coronary artery disease (CAD) with or without acute myocardial infarction (MI) was the most common cause of SCD. Three professional athletes were identified in COMP category which all had SCD due to acute MI. There were no time trends, neither in overall, nor in cause-specific incidences of SCD. The incidence of SCD in young individuals in Switzerland is low, both related and unrelated to sports. In regions, like Switzerland, where CAD is the leading cause of SCD associated with competitions, screening for cardiovascular risk factors in addition to the current PPS recommendations might be indicated to improve detection of silent CAD and further decrease the incidence of SCD.

Validation of the 2014 European Society of Cardiology guidelines risk prediction model for the primary prevention of sudden cardiac death in hypertrophic cardiomyopathy.

PubMed

Vriesendorp, Pieter A; Schinkel, Arend F L; Liebregts, Max; Theuns, Dominic A M J; van Cleemput, Johan; Ten Cate, Folkert J; Willems, Rik; Michels, Michelle

2015-08-01

The recently released 2014 European Society of Cardiology guidelines of hypertrophic cardiomyopathy (HCM) use a new clinical risk prediction model for sudden cardiac death (SCD), based on the HCM Risk-SCD study. Our study is the first external and independent validation of this new risk prediction model. The study population consisted of a consecutive cohort of 706 patients with HCM without prior SCD event, from 2 tertiary referral centers. The primary end point was a composite of SCD and appropriate implantable cardioverter-defibrillator therapy, identical to the HCM Risk-SCD end point. The 5-year SCD risk was calculated using the HCM Risk-SCD formula. Receiver operating characteristic curves and C-statistics were calculated for the 2014 European Society of Cardiology guidelines, and risk stratification methods of the 2003 American College of Cardiology/European Society of Cardiology guidelines and 2011 American College of Cardiology Foundation/American Heart Association guidelines. During follow-up of 7.7±5.3 years, SCD occurred in 42 (5.9%) of 706 patients (ages 49±16 years; 34% women). The C-statistic of the new model was 0.69 (95% CI, 0.57-0.82; P=0.008), which performed significantly better than the conventional risk factor models based on the 2003 guidelines (C-statistic of 0.55: 95% CI, 0.47-0.63; P=0.3), and 2011 guidelines (C-statistic of 0.60: 95% CI, 0.50-0.70; P=0.07). The HCM Risk-SCD model improves the risk stratification of patients with HCM for primary prevention of SCD, and calculating an individual risk estimate contributes to the clinical decision-making process. Improved risk stratification is important for the decision making before implantable cardioverter-defibrillator implantation for the primary prevention of SCD. © 2015 American Heart Association, Inc.

International External Validation Study of the 2014 European Society of Cardiology Guidelines on Sudden Cardiac Death Prevention in Hypertrophic Cardiomyopathy (EVIDENCE-HCM).

PubMed

O'Mahony, Constantinos; Jichi, Fatima; Ommen, Steve R; Christiaans, Imke; Arbustini, Eloisa; Garcia-Pavia, Pablo; Cecchi, Franco; Olivotto, Iacopo; Kitaoka, Hiroaki; Gotsman, Israel; Carr-White, Gerald; Mogensen, Jens; Antoniades, Loizos; Mohiddin, Saidi A; Maurer, Mathew S; Tang, Hak Chiaw; Geske, Jeffrey B; Siontis, Konstantinos C; Mahmoud, Karim D; Vermeer, Alexa; Wilde, Arthur; Favalli, Valentina; Guttmann, Oliver P; Gallego-Delgado, Maria; Dominguez, Fernando; Tanini, Ilaria; Kubo, Toru; Keren, Andre; Bueser, Teofila; Waters, Sarah; Issa, Issa F; Malcolmson, James; Burns, Tom; Sekhri, Neha; Hoeger, Christopher W; Omar, Rumana Z; Elliott, Perry M

2018-03-06

Identification of people with hypertrophic cardiomyopathy (HCM) who are at risk of sudden cardiac death (SCD) and require a prophylactic implantable cardioverter defibrillator is challenging. In 2014, the European Society of Cardiology proposed a new risk stratification method based on a risk prediction model (HCM Risk-SCD) that estimates the 5-year risk of SCD. The aim was to externally validate the 2014 European Society of Cardiology recommendations in a geographically diverse cohort of patients recruited from the United States, Europe, the Middle East, and Asia. This was an observational, retrospective, longitudinal cohort study. The cohort consisted of 3703 patients. Seventy three (2%) patients reached the SCD end point within 5 years of follow-up (5-year incidence, 2.4% [95% confidence interval {CI}, 1.9-3.0]). The validation study revealed a calibration slope of 1.02 (95% CI, 0.93-1.12), C-index of 0.70 (95% CI, 0.68-0.72), and D-statistic of 1.17 (95% CI, 1.05-1.29). In a complete case analysis (n= 2147; 44 SCD end points at 5 years), patients with a predicted 5-year risk of <4% (n=1524; 71%) had an observed 5-year SCD incidence of 1.4% (95% CI, 0.8-2.2); patients with a predicted risk of ≥6% (n=297; 14%) had an observed SCD incidence of 8.9% (95% CI, 5.96-13.1) at 5 years. For every 13 (297/23) implantable cardioverter defibrillator implantations in patients with an estimated 5-year SCD risk ≥6%, 1 patient can potentially be saved from SCD. This study confirms that the HCM Risk-SCD model provides accurate prognostic information that can be used to target implantable cardioverter defibrillator therapy in patients at the highest risk of SCD. © 2017 American Heart Association, Inc.

High variation of individual soluble serum CD30 levels of pre-transplantation patients: sCD30 a feasible marker for prediction of kidney allograft rejection?

PubMed

Altermann, Wolfgang; Schlaf, Gerald; Rothhoff, Anita; Seliger, Barbara

2007-10-01

Previous studies have suggested that the pre-transplant levels of the soluble CD30 molecule (sCD30) represent a non-invasive tool which can be used as a biomarker for the prediction of kidney allograft rejections. In order to evaluate the feasibility of sCD30 for pre-transplantation monitoring the sera of potential kidney recipients (n = 652) were collected four times in a 3 months interval. Serum from healthy blood donors (n = 203) served as controls. The sCD30 concentrations of all samples were determined using a commercially available ELISA. This strategy allowed the detection of possible variations of individual sCD30 levels over time. Heterogeneous sCD30 concentrations were found in the samples obtained from individual putative kidney transplant recipients when quarterly measured over 1 year. Total 95% of serum samples obtained from healthy controls exhibited sCD30 values <30 U/ml, whereas most recipients displayed higher serum levels (>30 U/ml). Total 524 patients (80.4%) constantly exhibited serum concentrations of <100 U/ml during the period investigated, whereas 109 patients (16.7%) showed variations by exceeding the proposed 'cut off' of 100 U/ml for one to three times. The frequency of samples exhibiting sCD30 values >100 U/ml was significantly lower than that previously reported. The high degree of variation does not allow the stratification of patients into high and low immunological risk groups based on a single sCD30 value > 100 U/ml. Due to the heterogeneity of sCD30 levels during time course and the high values of SD, its implementation as a pre-transplant marker cannot be justified to generate special provisions for the organ allocation to patients with single sCD30 values > 100 U/ml.

Observations of circumstellar carbon monoxide and evidence for multiple ejections in red giants

NASA Technical Reports Server (NTRS)

Bernat, A. P.

1981-01-01

Observations of the fundamental 4.6 micron band of CO in nine red giants are presented. A common feature is multiple absorption lines which are identified as products of separate components or shells. Column densities are derived; the relative values should be free of the uncertainties inherent in determining the absolute scale. These column densities are well fitted by single excitation temperatures for each absorption component; these excitation temperatures are identified with the local kinetic temperatures. There is no correlation of CO column density with either gas or dust column density nor of the expansion velocity of the component with its distance from the star. The evidence is reviewed, and it is concluded that mass loss from red giants is most likely episodic in nature.

Soluble immune receptor serum levels are associated with age, but not with clinical phenotype or disease severity in childhood atopic dermatitis.

PubMed

Ott, H; Wilke, J; Baron, J M; Höger, P H; Fölster-Holst, R

2010-04-01

Soluble immune receptors (SIRs) have been proposed as biomarkers in patients with atopic dermatitis (AD). However, their clinical applicability in affected children has rarely been studied. To assess the diagnostic usefulness of serum SIRs in childhood AD by correlating the obtained receptor profiles with serological parameters and clinical features such as age, AD phenotype and disease severity. We investigated 100 children with AD. The sCD14, sCD23, sCD25, sCD30, total IgE (tIgE) and eosinophilic cationic protein (ECP) were determined using sera of all children. The clinical phenotype was classified as extrinsic AD (ADe) or intrinsic AD (ADi) by the presence of allergen-specific IgE antibodies. A total of 55 male and 45 female children were recruited. The sCD23, sCD25 and sCD30 serum levels revealed significant age-dependency. At a mean SCORAD of 40 (range 8-98), none of the evaluated SIRs was correlated to disease severity. In all, 73% of patients suffered from ADe while 27% showed the ADi phenotype. None of the analysed SIRs differed significantly between ADe and ADi patients, while tIgE and ECP levels were elevated in the ADe subgroup. The current study provides evidence that sCD23, sCD25 and sCD30 serum levels are highly age-dependent. Serum concentrations of all investigated SIRs did not significantly correlate with disease severity in children with AD and were not differentially expressed in patients of different AD phenotypes. Therefore, we believe that the studied SIRs cannot be regarded as clinically useful biomarkers for the assessment of childhood AD.

SCD1 activity in muscle increases triglyceride PUFA content, exercise capacity, and PPARδ expression in mice[S

PubMed Central

Rogowski, Michael P.; Flowers, Matthew T.; Stamatikos, Alexis D.; Ntambi, James M.; Paton, Chad M.

2013-01-01

Stearoyl-CoA desaturase (SCD)1 converts saturated fatty acids into monounsaturated fatty acids. Using muscle overexpression, we sought to determine the role of SCD1 expression in glucose and lipid metabolism and its effects on exercise capacity in mice. Wild-type C57Bl/6 (WT) and SCD1 muscle transgenic (SCD1-Tg) mice were generated, and expression of the SCD1 transgene was restricted to skeletal muscle. SCD1 overexpression was associated with increased triglyceride (TG) content. The fatty acid composition of the muscle revealed a significant increase in polyunsaturated fatty acid (PUFA) content of TG, including linoleate (18:2n6). Untrained SCD1-Tg mice also displayed significantly increased treadmill exercise capacity (WT = 6.6 ± 3 min, Tg = 71.9 ± 9.5 min; P = 0.0009). SCD1-Tg mice had decreased fasting plasma glucose, glucose transporter (GLUT)1 mRNA, fatty acid oxidation, mitochondrial content, and increased peroxisome proliferator-activated receptor (PPAR)δ and Pgc-1 protein expression in skeletal muscle. In vitro studies in C2C12 myocytes revealed that linoleate (18:2n6) and not oleate (18:1n9) caused a 3-fold increase in PPARδ and a 9-fold increase in CPT-1b with a subsequent increase in fat oxidation. The present model suggests that increasing delta-9 desaturase activity of muscle increases metabolic function, exercise capacity, and lipid oxidation likely through increased PUFA content, which increases PPARδ expression and activity. However, the mechanism of action that results in increased PUFA content of SCD1-Tg mice remains to be elucidated. PMID:23918045

The effect of middle ear cavity and superior canal dehiscence on wideband acoustic immittance in fresh human cadaveric specimens

NASA Astrophysics Data System (ADS)

Masud, Salwa F.; Raufer, Stefan; Neely, Stephen T.; Nakajima, Hideko H.

2018-05-01

Superior canal dehiscence (SCD) is a hole in the bony wall of the superior semicircular canal, which can cause various auditory and/or vestibular symptoms and can result in wrong and/or delayed diagnosis. Wideband acoustic immittance (WAI) can potentially distinguish various mechanical middle-ear pathologies as well as inner-ear pathologies non-invasively. We found that in patients, SCD was commonly associated with a narrow-band decrease in power reflectance (PR, derived from WAI) near 1 kHz. Because clinical data has large variation across individual ears and because we do not know the individual "normal" state prior to SCD, we measured WAI in five fresh temporal bone specimens to determine the effects of SCD with respect to the normal state. In temporal bone, we measured PR to assess mechanical changes before and after SCD, as well as to assess the effect of an open or closed middle-ear cavity. After SCD, PR had a consistent decrease between 0.48 and 0.76 kHz, and a slight increase between 1.04 and 1.4 kHz in the open cavity condition. However, in several experiments, we observed low PR around 1 kHz in the normal state before SCD, likely due to the specimen's open middle ear cavity (MEC). Because we see effects of both SCD and open MEC around 1 kHz, some of the SCD effect can be masked by the effect of the MEC in the temporal bone specimens. To compensate for this MEC effect, we estimated the effect of SCD in a closed MEC case, but the effect did not differ significantly from the measured open MEC. This study demonstrates the limitation of temporal bone experiments with open MEC when studying inner-ear lesions with WAI.

Significant prevalence of sickle cell disease in Southwest Germany: results from a birth cohort study indicate the necessity for newborn screening.

PubMed

Kunz, Joachim B; Awad, Saida; Happich, Margit; Muckenthaler, Lena; Lindner, Martin; Gramer, Gwendolyn; Okun, Jürgen G; Hoffmann, Georg F; Bruckner, Thomas; Muckenthaler, Martina U; Kulozik, Andreas E

2016-02-01

Children with sickle cell disease (SCD) benefit from newborn screening, because life-threatening complications can be prevented by pre-symptomatic diagnosis. In Germany, the immigration of people from endemic countries is steadily growing. Comprehensive data about the epidemiology and prevalence of SCD in Germany are however lacking, and SCD is not included in the national newborn screening program. We provide data on the prevalence of SCD in a population from both urban and rural areas in Southwest Germany. Anonymized dried blood spots from 37,838 unselected newborns were analyzed by allele-specific PCR for the HbS mutation. Samples tested positive were subjected to Sanger sequencing of the entire β-globin coding sequence firstly to validate the screening and secondly to identify compound heterozygous SCD patients with other mutations of the β-globin gene. We identified 83 carriers of the sickle cell trait, three compound heterozygous SCD patients (two with sickle cell-β-thalassemia, one with sickle cell-Hb Tianshui) but no homozygous SCD patients. The novel molecular method and strategy for newborn screening for SCD presented here compares favorably in terms of sensitivity (1.0 for homozygous HbS, 0.996 for heterozygous HbS), specificity (0.996), practicability, and costs with conventional biochemical screening. Our results demonstrate a significant prevalence of SCD of approximately 1:12,000 in an unselected urban and rural population in Southwest Germany. Together with previously published even higher results from exclusively urban populations in Berlin and Hamburg, our data provide the basis for the decision on a newborn screening program for SCD in Germany.

Enhanced levels of soluble CD40 ligand exacerbate platelet aggregation and thrombus formation through a CD40-dependent tumor necrosis factor receptor-associated factor-2/Rac1/p38 mitogen-activated protein kinase signaling pathway.

PubMed

Yacoub, Daniel; Hachem, Ahmed; Théorêt, Jean-François; Gillis, Marc-Antoine; Mourad, Walid; Merhi, Yahye

2010-12-01

CD40 ligand is a thromboinflammatory molecule that predicts cardiovascular events. Platelets constitute the major source of soluble CD40 ligand (sCD40L), which has been shown to influence platelet activation, although its exact functional impact on platelets and the underlying mechanisms remain undefined. We aimed to determine the impact and the signaling mechanisms of sCD40L on platelets. sCD40L strongly enhances platelet activation and aggregation. Human platelets treated with a mutated form of sCD40L that does not bind CD40, and CD40(-/-) mouse platelets failed to elicit such responses. Furthermore, sCD40L stimulation induces the association of the tumor necrosis factor receptor-associated factor-2 with platelet CD40. Notably, sCD40L primes platelets through activation of the small GTPase Rac1 and its downstream target p38 mitogen-activated protein kinase, which leads to platelet shape change and actin polymerization. Moreover, sCD40L exacerbates thrombus formation and leukocyte infiltration in wild-type mice but not in CD40(-/-) mice. sCD40L enhances agonist-induced platelet activation and aggregation through a CD40-dependent tumor necrosis factor receptor-associated factor-2/Rac1/p38 mitogen-activated protein kinase signaling pathway. Thus, sCD40L is an important platelet primer predisposing platelets to enhanced thrombus formation in response to vascular injury. This may explain the link between circulating levels of sCD40L and cardiovascular diseases.

SCD-HeFT: Use of RR Interval Statistics for Long-term Risk Stratification for Arrhythmic Sudden Cardiac Death

PubMed Central

Au-yeung, Wan-tai M.; Reinhall, Per; Poole, Jeanne E.; Anderson, Jill; Johnson, George; Fletcher, Ross D.; Moore, Hans J.; Mark, Daniel B.; Lee, Kerry L.; Bardy, Gust H.

2015-01-01

Background In the SCD-HeFT a significant fraction of the congestive heart failure (CHF) patients ultimately did not die suddenly from arrhythmic causes. CHF patients will benefit from better tools to identify if ICD therapy is needed. Objective To identify predictor variables from baseline SCD-HeFT patients’ RR intervals that correlate to arrhythmic sudden cardiac death (SCD) and mortality and to design an ICD therapy screening test. Methods Ten predictor variables were extracted from pre-randomization Holter data from 475 patients enrolled in the SCD-HeFT ICD arm using novel and traditional heart rate variability methods. All variables were correlated to SCD using Mann Whitney-Wilcoxon test and receiver operating characteristic analysis. ICD therapy screening tests were designed by minimizing the cost of false classifications. Survival analysis, including log-rank test and Cox models, was also performed. Results α1 and α2 from detrended fluctuation analysis, the ratio of low to high frequency power, the number of PVCs per hour and heart rate turbulence slope are all statistically significant for predicting the occurrences of SCD (p<0.001) and survival (log-rank p<0.01). The most powerful multivariate predictor tool using the Cox Proportional Hazards was α2 with a hazard ratio of 0.0465 (95% CI: 0.00528 – 0.409, p<0.01). Conclusion Predictor variables from RR intervals correlate to the occurrences of SCD and distinguish survival among SCD-HeFT ICD patients. We believe SCD prediction models should incorporate Holter based RR interval analysis to refine ICD patient selection especially in removing patients who are unlikely to benefit from ICD therapy. PMID:26096609

Substance P is increased in patients with sickle cell disease and associated with haemolysis and hydroxycarbamide use

PubMed Central

Brandow, Amanda M.; Wandersee, Nancy J.; Dasgupta, Mahua; Hoffmann, Raymond G.; Hillery, Cheryl A.; Stucky, Cheryl L.; Panepinto, Julie A.

2016-01-01

Summary Sickle cell disease (SCD) pain transitions from acute to chronic for unknown reasons. Chronic elevation of the pain neurotransmitter substance P (SP) sensitizes pain nociceptors. We evaluated SP levels in controls and SCD patients during baseline and acute pain and investigated associations between SP and age, gender, pain history, haemolysis and hydroxycarbamide (also termed hydroxyurea) use. Plasma SP levels were measured using enzyme-linked immunosorbent assay. Independent samples t-test compared SP levels between: 1) SCD baseline and controls and 2) SCD baseline and acute pain. Multivariate linear regression determined associations between SP and age, gender, pain history and hydroxycarbamide use. Spearman correlation determined an association between SP and haemolysis. We enrolled 35 African American controls, 25 SCD baseline and 12 SCD pain patients. SCD patients were 7-19 years old. Mean±standard deviation SP level (pg/ml) in SCD baseline was higher than controls (32.4±11.6 vs. 22.9±7.6, P=0.0009). SP in SCD pain was higher than baseline (78.1±43.4 vs. 32.4±11.6, P=0.004). Haemolysis correlated with increased SP: Hb (r=−0.7, P=0.0002), reticulocyte count (r=0.61, P=0.0016), bilirubin (r=0.68, P=0.0216), LDH (r=0.62, P=0.0332), aspartate aminotransferase (r=0.68, P=0.003). Patients taking hydroxycarbamide had increased SP (β=29.2, P=0.007). SP could be a mediator of or marker for pain sensitization in SCD and a biomarker and/or target for novel pain treatment. PMID:27539682

Perspectives in Genetics and Sickle Cell Disease Prevention in Africa: Beyond the Preliminary Data from Cameroon.

PubMed

Wonkam, Ambroise; Ngo Bitoungui, Valentina Josiane; Ngogang, Jeanne

2015-01-01

Management of sickle cell disease (SCD) in Africa needs to be accompanied by various preventive strategies, including early detection via prenatal genetic diagnosis (PND). Contrary to Cameroonian doctors who considered termination of an affected pregnancy (TAP) for SCD in 36.1%, the majority of parents (62.5%) with affected children accepted TAP in principle. In practice, most women opted for TAP (90%), justified by a huge psycho-social burden. The ethical and legal challenges of PND prompted the need to explore the use of genetics for secondary prevention of SCD. In 610 Cameroonian SCD patients, the genomic variations in two principal foetal haemoglobin-promoting loci were significantly associated with foetal haemoglobin levels. In addition, the co-inheritance of a 3.7-kb α-globin gene deletion and SCD was associated with a late disease onset and possibly improved survival: there was a much higher allele frequency of the 3.7-kb α-globin gene deletion in SCD patients (∼ 40%) than in haemoglobin AA controls (∼ 10%). The data indicate the urgent need to develop and implement policy actions in sub-Saharan Africa on at least four levels: (1) the implementation of SCD screening practices and early neonatal follow-up; (2) the development and incorporating of socio-economic support to alleviate the burden of SCD on affected families; (3) the exploration of the appropriateness of the medical abortion laws for SCD, and (4) the development of national plans for genetic medicine, including research on genomic variants that affect the phenotypes of SCD, in order to potentially use them for anticipatory guidance. © 2015 S. Karger AG, Basel.

The role of the arginine metabolome in pain: implications for sickle cell disease.

PubMed

Bakshi, Nitya; Morris, Claudia R

2016-01-01

Sickle cell disease (SCD) is the most common hemoglobinopathy in the US, affecting approximately 100,000 individuals in the US and millions worldwide. Pain is the hallmark of SCD, and a subset of patients experience pain virtually all of the time. Of interest, the arginine metabolome is associated with several pain mechanisms highlighted in this review. Since SCD is an arginine deficiency syndrome, the contribution of the arginine metabolome to acute and chronic pain in SCD is a topic in need of further attention. Normal arginine metabolism is impaired in SCD through various mechanisms that contribute to endothelial dysfunction, vaso-occlusion, pulmonary complications, risk of leg ulcers, and early mortality. Arginine is a semiessential amino acid that serves as a substrate for protein synthesis and is the precursor to nitric oxide (NO), polyamines, proline, glutamate, creatine, and agmatine. Since arginine is involved in multiple metabolic processes, a deficiency of this amino acid has the potential to disrupt many cellular and organ functions. NO is a potent vasodilator that is depleted in SCD and may contribute to vaso-occlusive pain. As the obligate substrate for NO production, arginine also plays a mechanistic role in SCD-related pain, although its contribution to pain pathways likely extends beyond NO. Low global arginine bioavailability is associated with pain severity in both adults and children with SCD as well as other non-SCD pain syndromes. Preliminary clinical studies of arginine therapy in SCD demonstrate efficacy in treating acute vaso-occlusive pain, as well as leg ulcers and pulmonary hypertension. Restoration of arginine bioavailability through exogenous supplementation of arginine is, therefore, a promising therapeutic target. Phase II clinical trials of arginine therapy for sickle-related pain are underway and a Phase III randomized controlled trial is anticipated in the near future.

Sequential compression devices in postoperative urologic patients: an observational trial and survey study on the influence of patient and hospital factors on compliance

PubMed Central

2013-01-01

Background Sequential compression devices (SCDs) are commonly used for thromboprophylaxis in postoperative patients but compliance is often poor. We investigated causes for noncompliance, examining both hospital and patient related factors. Methods 100 patients undergoing inpatient urologic surgery were enrolled. All patient had SCD sleeves placed preoperatively. Postoperative observations determined SCD compliance and reasons for non-compliance. Patient demographics, length of stay, inpatient unit type, and surgery type were recorded. At discharge, a patient survey gauged knowledge and attitudes regarding SCDs and bother with SCDs. Statistical analysis was performed to correlate SCD compliance with patient demographics; patient knowledge and attitudes regarding SCDs; and patient self-reported bother with SCDs. Results Observed overall compliance was 78.6%. The most commonly observed reasons for non-compliance were SCD machines not being initially available on the ward (71% of non-compliant observations on post-operative day 1) and SCD use not being restarted promptly after return to bed (50% of non-compliant observations for entire hospital stay). Mean self-reported bother scores related to SCDs were low, ranging from 1–3 out of 10 for all 12 categories of bother assessed. Patient demographics, knowledge, attitudes and bother with SCD devices were not significantly associated with non-compliance. Conclusions Patient self-reported bother with SCD devices was low. Hospital factors, including SCD machine availability and timely restarting of devices by nursing staff when a patient returns to bed, played a greater role in SCD non-compliance than patient factors. Identifying and addressing hospital related causes for poor SCD compliance may improve postoperative urologic patient safety. PMID:23578129

Pre- and post-transplant monitoring of soluble CD30 levels as predictor of acute renal allograft rejection.

PubMed

Wang, Dong; Wu, Guo-Jun; Wu, Wei-Zhen; Yang, Shun-Liang; Chen, Jin-Hua; Wang, He; Lin, Wen-Hong; Wang, Qing-Hua; Zeng, Zhang-Xin; Tan, Jian-Ming

2007-06-01

Identification of renal graft candidates at high risk of impending acute rejection (AR) and graft loss may be helpful for patient-tailored immunosuppressive regimens and renal graft survival. To investigate the feasibility with soluble CD30 (sCD30) as predictor of AR, sCD30 levels of 70 patients were detected on day 0 pre-transplant and day 1, 3, 5, 7, 10, 14, 21, and 30 post-transplant. AR episodes in 6 months were recorded and then patients were divided into Group AR (n=11) and Group UC (n=59). Results showed that the patients had higher pre-transplant sCD30 levels than healthy people. A significant decrease of sCD30 was observed on the first day post-transplant and continued until day 14 post-transplant. Soluble CD30 presented a stable level from day 14 to 30 post-transplant. Pre-transplant sCD30 levels of Group AR were much higher than those of Group UC (P<0.001). Patients of Group AR also had higher sCD30 levels than those of Group UC on day 1, 3, 5, 7, 10 and 14 (P<0.001). The sCD30 level presented a significantly delayed decrease in the patients of Group AR. Statistical results showed that the highest value of area under ROC curve (0.95) was obtained on day 5 post-transplant, suggesting that sCD30 levels on day 5 are of high predictive value. Therefore, sCD30 level may be a good marker of increased alloreactivity and of significant predictive value. It's necessary to monitor the variation of sCD30 in the early period post-transplant.

Remotely operable compact instruments for measuring atmospheric CO2 and CH4 column densities at surface monitoring sites

NASA Astrophysics Data System (ADS)

Kobayashi, N.; Inoue, G.; Kawasaki, M.; Yoshioka, H.; Minomura, M.; Murata, I.; Nagahama, T.; Matsumi, Y.; Tanaka, T.; Morino, I.; Ibuki, T.

2010-08-01

Remotely operable compact instruments for measuring atmospheric CO2 and CH4 column densities were developed in two independent systems: one utilizing a grating-based desktop optical spectrum analyzer (OSA) with a resolution enough to resolve rotational lines of CO2 and CH4 in the regions of 1565-1585 and 1674-1682 nm, respectively; the other is an application of an optical fiber Fabry-Perot interferometer (FFPI) to obtain the CO2 column density. Direct sunlight was collimated via a small telescope installed on a portable sun tracker and then transmitted through an optical fiber into the OSA or the FFPI for optical analysis. The near infrared spectra of the OSA were retrieved by a least squares spectral fitting algorithm. The CO2 and CH4 column densities deduced were in excellent agreement with those measured by a Fourier transform spectrometer with high resolution. The rovibronic lines in the wavelength region of 1570-1575 nm were analyzed by the FFPI. The I0 and I values in the Beer-Lambert law equation to obtain CO2 column density were deduced by modulating temperature of the FFPI, which offered column CO2 with the statistical error less than 0.2% for six hours measurement.

Understanding star formation in molecular clouds. II. Signatures of gravitational collapse of IRDCs

NASA Astrophysics Data System (ADS)

Schneider, N.; Csengeri, T.; Klessen, R. S.; Tremblin, P.; Ossenkopf, V.; Peretto, N.; Simon, R.; Bontemps, S.; Federrath, C.

2015-06-01

We analyse column density and temperature maps derived from Herschel dust continuum observations of a sample of prominent, massive infrared dark clouds (IRDCs) i.e. G11.11-0.12, G18.82-0.28, G28.37+0.07, and G28.53-0.25. We disentangle the velocity structure of the clouds using 13CO 1→0 and 12CO 3→2 data, showing that these IRDCs are the densest regions in massive giant molecular clouds (GMCs) and not isolated features. The probability distribution function (PDF) of column densities for all clouds have a power-law distribution over all (high) column densities, regardless of the evolutionary stage of the cloud: G11.11-0.12, G18.82-0.28, and G28.37+0.07 contain (proto)-stars, while G28.53-0.25 shows no signs of star formation. This is in contrast to the purely log-normal PDFs reported for near and/or mid-IR extinction maps. We only find a log-normal distribution for lower column densities, if we perform PDFs of the column density maps of the whole GMC in which the IRDCs are embedded. By comparing the PDF slope and the radial column density profile of three of our clouds, we attribute the power law to the effect of large-scale gravitational collapse and to local free-fall collapse of pre- and protostellar cores for the highest column densities. A significant impact on the cloud properties from radiative feedback is unlikely because the clouds are mostly devoid of star formation. Independent from the PDF analysis, we find infall signatures in the spectral profiles of 12CO for G28.37+0.07 and G11.11-0.12, supporting the scenario of gravitational collapse. Our results are in line with earlier interpretations that see massive IRDCs as the densest regions within GMCs, which may be the progenitors of massive stars or clusters. At least some of the IRDCs are probably the same features as ridges (high column density regions with N> 1023 cm-2 over small areas), which were defined for nearby IR-bright GMCs. Because IRDCs are only confined to the densest (gravity dominated) cloud regions, the PDF constructed from this kind of a clipped image does not represent the (turbulence dominated) low column density regime of the cloud. The column density maps (FITS files) are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/578/A29

Existence of a soluble form of CD50 (intercellular adhesion molecule-3) produced upon human lymphocyte activation. Present in normal human serum and levels are increased in the serum of systemic lupus erythematosus patients.

PubMed

Pino-Otín, M R; Viñas, O; de la Fuente, M A; Juan, M; Font, J; Torradeflot, M; Pallarés, L; Lozano, F; Alberola-Ila, J; Martorell, J

1995-03-15

CD50 (ICAM-3) is a leukocyte differentiation Ag expressed almost exclusively on hemopoietic cells, with a key role in the first steps of immune response. To develop a specific sandwich ELISA to detect a soluble CD50 form (sCD50), two different mAbs (140-11 and 101-1D2) recognizing non-overlapping epitopes were used. sCD50 was detected in the supernatant of stimulated PBMCs, with the highest levels after CD3 triggering. Simultaneously, the CD50 surface expression diminished during the first 24 h. sCD50 isolated from culture supernatant and analyzed by immunoblotting showed an apparent m.w. of 95 kDa, slightly smaller than the membrane form. These data, together with Northern blot kinetics analysis, suggest that sCD50 is cleaved from cell membrane. Furthermore, we detect sCD50 in normal human sera and higher levels in sera of systemic lupus erythematosus (SLE) patients, especially in those in active phase. The sCD50 levels showed a positive correlation with sCD27 levels (r = 0.4213; p = 0.0026). Detection of sCD50, both after in vitro CD3 triggering of PBMCs and increased in SLE sera, suggests that sCD50 could be used as a marker of lymphocyte stimulation.

Metformin plus oral contraceptive may decrease plasma sCD40 ligand in women with PCOS patients.

PubMed

Kebapcilar, Levent; Kebapcilar, Ayse Gul; Bilgir, Oktay; Taner, Cuneyt Eftal; Bozkaya, Giray; Yildiz, Yasar; Sari, Ismail

2011-02-01

To evaluate sCD40L levels in women with polycystic ovary syndrome (PCOS) who use combination therapy with metformin and oral contraceptives. Total of 60 patients with PCOS was studied to evaluate and compare with a non-PCOS group consisting of 30 subjects. A low-dose oral contraceptive containing ethinyl oestradiol-cyproterone acetate (EE/CA) and metformin (M; 850 mg metformin twice a day) were given for three cycles. Plasma sCD40L was measured before and after the treatment of 3 months. At baseline, the sCD40L levels of the patients with PCOS was significantly higher than those of control subjects (3.1 ± 2.0 vs. 2.05 ± 1.0, respectively; p=0.002). An average of 3 months of EE/CA-M therapy induced a significant decrease of sCD40L levels in the PCOS group (3.1 ± 2.0 vs. 2.5 ± 1.0; p=0.026). After having treated patients with PCOS, the sCD40L level was not completely normalised when compared to the healthy controls (2.5 ± 1.0 vs. 2.05 ± 1.0; p=0.039). PCOS is associated with elevated levels of sCD40L. Adding metformin therapy to EE/CA may decrease sCD40L levels in women PCOS. However, after the treatment for PCOS subjects, the sCD40L was not completely normalised when compared patients to healthy controls.

A Review of the Literature on the Multiple Dimensions of Chronic Pain in Adults with Sickle Cell Disease

PubMed Central

Taylor, Lou Ella V.; Stotts, Nancy A.; Humphreys, Janice; Treadwell, Marsha J.; Miaskowski, Christine

2010-01-01

Sickle cell disease (SCD) is a major healthcare and societal problem that affects millions of people worldwide. In Nigeria, 45,000 to 90,000 babies are born each year with SCD. In the United States, SCD is the most common genetic disorder, affecting more than 80,000 people, the majority of whom are African American. Sickle cell pain is the hallmark feature of SCD. Most of the research on pain from SCD has focused on children with acute pain associated with sickle cell crisis. Consequently, very little is known about the occurrence and characteristics of chronic pain, especially in adults with SCD. Individuals with SCD who experience chronic pain are often underserved and their pain is under-treated. This under-treatment may result in millions of dollars per year spent on emergency room visits, hospitalizations, and lost work productivity. The primary purpose of this literature review was to summarize the findings from studies that evaluated the characteristics of chronic pain in adults with SCD. Each of the studies included in this review was evaluated to determine if it provided data on the following multidimensional characteristics of chronic pain: occurrence, number of pain episodes, duration, pattern, quality, location, intensity, aggravating factors, relieving factors, and impact of pain on function. A secondary purpose was to identify gaps in knowledge and directions for future research on the multiple dimensions of chronic pain in adults with SCD. PMID:20656451

Measurement of soluble CD59 in CSF in demyelinating disease: Evidence for an intrathecal source of soluble CD59.

PubMed

Zelek, Wioleta M; Watkins, Lewis M; Howell, Owain W; Evans, Rhian; Loveless, Sam; Robertson, Neil P; Beenes, Marijke; Willems, Loek; Brandwijk, Ricardo; Morgan, B Paul

2018-02-01

CD59, a broadly expressed glycosylphosphatidylinositol-anchored protein, is the principal cell inhibitor of complement membrane attack on cells. In the demyelinating disorders, multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD), elevated complement protein levels, including soluble CD59 (sCD59), were reported in cerebrospinal fluid (CSF). We compared sCD59 levels in CSF and matched plasma in controls and patients with MS, NMOSD and clinically isolated syndrome (CIS) and investigated the source of CSF sCD59 and whether it was microparticle associated. sCD59 was quantified using enzyme-linked immunosorbent assay (ELISA; Hycult; HK374-02). Patient and control CSF was subjected to western blotting to characterise anti-CD59-reactive materials. CD59 was localised by immunostaining and in situ hybridisation. CSF sCD59 levels were double those in plasma (CSF, 30.2 ng/mL; plasma, 16.3 ng/mL). Plasma but not CSF sCD59 levels differentiated MS from NMOSD, MS from CIS and NMOSD/CIS from controls. Elimination of microparticles confirmed that CSF sCD59 was not membrane anchored. CSF levels of sCD59 are not a biomarker of demyelinating diseases. High levels of sCD59 in CSF relative to plasma suggest an intrathecal source; CD59 expression in brain parenchyma was low, but expression was strong on choroid plexus (CP) epithelium, immediately adjacent the CSF, suggesting that this is the likely source.

Aircraft measurements of BrO, IO, glyoxal, NO 2, H 2O, O 2–O 2 and aerosol extinction profiles in the tropics: comparison with aircraft-/ship-based in situ and lidar measurements

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

Volkamer, Rainer; Baidar, S.; Campos, T. L.

Here, tropospheric chemistry of halogens and organic carbon over tropical oceans modifies ozone and atmospheric aerosols, yet atmospheric models remain largely untested for lack of vertically resolved measurements of bromine monoxide (BrO), iodine monoxide (IO) and small oxygenated hydrocarbons like glyoxal (CHOCHO) in the tropical troposphere. BrO, IO, glyoxal, nitrogen dioxide (NO 2), water vapor (H 2O) and O 2–O 2 collision complexes (O 4) were measured by the University of Colorado Airborne Multi-AXis Differential Optical Absorption Spectroscopy (CU AMAX-DOAS) instrument, aerosol extinction by high spectral resolution lidar (HSRL), in situ aerosol size distributions by an ultra high sensitivity aerosolmore » spectrometer (UHSAS) and in situ H 2O by vertical-cavity surface-emitting laser (VCSEL) hygrometer. Data are presented from two research flights (RF12, RF17) aboard the National Science Foundation/National Center for Atmospheric Research Gulfstream V aircraft over the tropical Eastern Pacific Ocean (tEPO) as part of the "Tropical Ocean tRoposphere Exchange of Reactive halogens and Oxygenated hydrocarbons" (TORERO) project (January/February 2012). We assess the accuracy of O 4 slant column density (SCD) measurements in the presence and absence of aerosols. Our O 4-inferred aerosol extinction profiles at 477 nm agree within 6% with HSRL in the boundary layer and closely resemble the renormalized profile shape of Mie calculations constrained by UHSAS at low (sub-Rayleigh) aerosol extinction in the free troposphere. CU AMAX-DOAS provides a flexible choice of geometry, which we exploit to minimize the SCD in the reference spectrum (SCD REF, maximize signal-to-noise ratio) and to test the robustness of BrO, IO and glyoxal differential SCDs. The RF12 case study was conducted in pristine marine and free tropospheric air. The RF17 case study was conducted above the NOAA RV Ka'imimoana (TORERO cruise, KA-12-01) and provides independent validation data from ship-based in situ cavity-enhanced DOAS and MAX-DOAS. Inside the marine boundary layer (MBL) no BrO was detected (smaller than 0.5 pptv), and 0.2–0.55 pptv IO and 32–36 pptv glyoxal were observed. The near-surface concentrations agree within 30% (IO) and 10% (glyoxal) between ship and aircraft. The BrO concentration strongly increased with altitude to 3.0 pptv at 14.5 km (RF12, 9.1 to 8.6° N; 101.2 to 97.4° W). At 14.5 km, 5–10 pptv NO 2 agree with model predictions and demonstrate good control over separating tropospheric from stratospheric absorbers (NO 2 and BrO). Our profile retrievals have 12–20 degrees of freedom (DoF) and up to 500 m vertical resolution. The tropospheric BrO vertical column density (VCD) was 1.5 × 10 13 molec cm –2 (RF12) and at least 0.5 × 10 13 molec cm –2 (RF17, 0–10 km, lower limit). Tropospheric IO VCDs correspond to 2.1 × 10 12 molec cm –2 (RF12) and 2.5 × 10 12 molec cm –2 (RF17) and glyoxal VCDs of 2.6 × 10 14 molec cm –2 (RF12) and 2.7 × 10 14 molec cm –2 (RF17). Surprisingly, essentially all BrO as well as the dominant IO and glyoxal VCD fraction was located above 2 km (IO: 58 ± 5%, 0.1–0.2 pptv; glyoxal: 52 ± 5%, 3–20 pptv). To our knowledge there are no previous vertically resolved measurements of BrO and glyoxal from aircraft in the tropical free troposphere. The atmospheric implications are briefly discussed. Future studies are necessary to better understand the sources and impacts of free tropospheric halogens and oxygenated hydrocarbons on tropospheric ozone, aerosols, mercury oxidation and the oxidation capacity of the atmosphere.« less

[Evaluation of bone mineral density in children with sickle cell disease].

PubMed

Garrido Colino, C; Beléndez Bieler, C; Pérez Díaz, M; Cela de Julián, E

2015-04-01

To evaluate bone mineral density (BMD) in children with sickle cell disease (SCD) in the Community of Madrid. The BMD was estimated in 40 children with SCD, and with an age range between 3 and 16 years, using densitometry (DXA), as recommended by the International Society for Clinical Densitometry (ISCD). The mean age at the time of the study was 7.97±3.95 years, the mean value of the DXA expressed in Z -score was -0.91±1.46 with a range of minimum values - 5.30 and 2.30 maximum. More than half (57.5%) of all the children had normal BMD (Z>-1), 25% had low BMD (Z between -1 and -2), and 17.5% showed an abnormal Z -score values of osteoporosis (Z -score<-2). The Pearson linear correlation was statistically significant between Z -score value and the haemoglobin level (r=0.368, p=.019), finding no correlation with the levels of 25 (OH) vitamin D. Prospective studies are needed with a larger number of patients to understand the future implications of bone densitometry changes and associated risk factors. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

Attention Deficit Hyperactivity Disorder in Children With Sickle Cell Disease Referred for an Evaluation.

PubMed

Acquazzino, Melissa A; Miller, Meghan; Myrvik, Matthew; Newby, Robert; Scott, John Paul

2017-07-01

Neuropsychological deficits, including difficulties with attention, are well described in children with sickle cell disease (SCD). Very little is known about attention deficit hyperactivity disorder (ADHD) in children with SCD. The objective of this study was to determine the proportion of ADHD in children with SCD referred for neuropsychological evaluation. This prospective, cross-sectional study included patients (age, 4 to 18 y) with SCD and completion of a neuropsychological evaluation between December 2013 and March 2016. Patients were referred for neuropsychological evaluation because of concern regarding school performance, development, and/or behavior. The diagnosis of ADHD was made by a neuropsychologist on the basis of the diagnostic criteria in the Diagnostic Statistical Manual-Fourth or Fifth Editions. ADHD medication usage rate was obtained by medical record review. Of the 89 patients with SCD referred for neuropsychological evaluation, 25% (95% confidence interval, 16%-35%) met diagnostic criteria for ADHD. Only 21% of the patients with SCD and ADHD were prescribed an ADHD medication. Our study supports routine ADHD screening in children with SCD who have poor school performance or behavioral concerns. Despite the benefits of pharmacologic treatment, the majority of patients with SCD and ADHD did not receive a medication for management of their ADHD.

Coping and coping assistance among children with sickle cell disease and their parents

PubMed Central

Barakat, Lamia P.; Alderfer, Melissa A.; Marsac, Meghan L.

2014-01-01

The ways in which a family copes with the physical and psychosocial burdens of sickle cell disease (SCD) can influence child and family functioning. However, few studies have examined SCD-related stressors beyond pain or how children and parents cope with these stressors. This study aimed to describe child coping and parent attempts to help their children cope (i.e., coping assistance) with a range of SCD stressors by using a triangulated mixed methods design. We also explored convergence between findings from qualitative interviews and quantitative coping inventories. Fifteen children (aged 6 – 14) with SCD and their parents (N = 15) completed semi-structured interviews and self-report measures to assess SCD-related stressors, coping, and coping assistance strategies. Findings indicate that children experience numerous stressors related to SCD and its treatment, including but not limited to pain. To manage these stressors, families employ a range of approach- and avoidance-oriented coping strategies. Quantitative and qualitative assessments provided complementary and unique contributions to understanding coping processes among children with SCD and their parents. Examining a broad range of stressors and integrating multiple assessment methods helps improve our understanding of coping with pediatric SCD, which may inform clinical practice and family-focused intervention development. PMID:24327131

Epidemiology and treatment of relative anemia in children with sickle cell disease in sub-Saharan Africa.

PubMed

Bello-Manga, Halima; DeBaun, Michael R; Kassim, Adetola A

2016-11-01

Sickle cell disease (SCD) is the most common inherited hemoglobinopathy in the world, with the majority of cases in sub-Saharan Africa. Concomitant nutritional deficiencies, infections or exposure to environmental toxins exacerbate chronic anemia in children with SCD. The resulting relative anemia is associated with increased risk of strokes, poor cognitive function and impaired growth. It may also attenuate optimal response to hydroxyurea therapy, the only effective and practical treatment option for SCD in sub-Saharan Africa. This review will focus on the epidemiology, clinical sequelae, and treatment of relative anemia in children with SCD living in low and middle-income countries in sub-Saharan Africa. Areas covered: The causes and treatment of relative anemia in children with SCD in sub-Saharan Africa. The MEDLINE database was searched using medical subject headings (MeSH) and keywords for articles regarding relative anemia in children with SCD in sub-Saharan Africa. Expert commentary: Anemia due to nutritional deficiencies and infectious diseases such as helminthiasis and malaria are prevalent in sub-Saharan Africa. Their co-existence in children with SCD increases morbidity and mortality. Therefore, preventing, diagnosing and treating the underlying cause of this relative anemia will improve SCD-related outcomes in children in sub-Saharan Africa.

CDC Grand Rounds: Improving the Lives of Persons with Sickle Cell Disease.

PubMed

Hulihan, Mary; Hassell, Kathryn L; Raphael, Jean L; Smith-Whitley, Kim; Thorpe, Phoebe

2017-11-24

Approximately 100,000 Americans have sickle cell disease (SCD), a group of recessively inherited red blood cell disorders characterized by abnormal hemoglobin, called hemoglobin S or sickle hemoglobin, in the red blood cells. Persons with hemoglobin SS or hemoglobin Sß 0 thalassemia, also known as sickle cell anemia (SCA), have the most severe form of SCD. Hemoglobin SC disease and hemoglobin Sß + thalassemia are other common forms of SCD. Red blood cells that contain sickle hemoglobin are inflexible and can stick to vessel walls, causing a blockage that slows or stops blood flow. When this happens, oxygen cannot reach nearby tissues, leading to attacks of sudden, severe pain, called pain crises, which are the clinical hallmark of SCD. The red cell sickling and poor oxygen delivery can also cause damage to the brain, spleen, eyes, lungs, liver, and multiple other organs and organ systems. These chronic complications can lead to increased morbidity, early mortality, or both. Tremendous strides in treating and preventing the complications of SCD have extended life expectancy. Now, nearly 95% of persons born with SCD in the United States reach age 18 years (1); however, adults with the most severe forms of SCD have a life span that is 20-30 years shorter than that of persons without SCD (2).

Development of a subjective cognitive decline questionnaire using item response theory: a pilot study.

PubMed

Gifford, Katherine A; Liu, Dandan; Romano, Raymond; Jones, Richard N; Jefferson, Angela L

2015-12-01

Subjective cognitive decline (SCD) may indicate unhealthy cognitive changes, but no standardized SCD measurement exists. This pilot study aims to identify reliable SCD questions. 112 cognitively normal (NC, 76±8 years, 63% female), 43 mild cognitive impairment (MCI; 77±7 years, 51% female), and 33 diagnostically ambiguous participants (79±9 years, 58% female) were recruited from a research registry and completed 57 self-report SCD questions. Psychometric methods were used for item-reduction. Factor analytic models assessed unidimensionality of the latent trait (SCD); 19 items were removed with extreme response distribution or trait-fit. Item response theory (IRT) provided information about question utility; 17 items with low information were dropped. Post-hoc simulation using computerized adaptive test (CAT) modeling selected the most commonly used items (n=9 of 21 items) that represented the latent trait well (r=0.94) and differentiated NC from MCI participants (F(1,146)=8.9, p=0.003). Item response theory and computerized adaptive test modeling identified nine reliable SCD items. This pilot study is a first step toward refining SCD assessment in older adults. Replication of these findings and validation with Alzheimer's disease biomarkers will be an important next step for the creation of a SCD screener.

Cognitive behavioral therapy in patients with sickle cell disease.

PubMed

Daniels, Sheena

2015-01-01

Sickle cell disease (SCD) is an inherited autosomal recessive disorder. In the United States, most individuals with SCD are African Americans, withan incidence of 1 in 400 to 1 in 500 live births. SCD is a lifelong disorder with no known cure. SCD causes anemia, frequent painful episodes, and reduced life ex- pectancy. The most disturbing clinical problem associated with SCD is severe pain episodes, the most common reason for hospitalization. Pharmacological interventions have been the mainstream for treatment; however, psychological interventions such as cognitive behavioral therapy (CBT) may complement current medical treatment, lead- ing to better coping and overall improved quality of life. In a quasi-experimental one-group pretest-posttest study, 9 African American individuals with SCD completed 3 weekly educational sessions learning CBT methods. Participants demonstrated increased frequency of use of CBT methods post-intervention, including diverting attention, coping self-statements, and behavioral activities, leading to better pain control. However, quality of life and role limitation did not show significant improvement. CBT may be beneficial to those suffering from SCD when combined with conventional treatment options; however, there are still barriers to incorporating psychological interventions into practice. CBT shows promise for individuals with chronic conditions such as SCD, but more investigation into its efficacy is needed with larger sample sizes over longer periods of time.

Caregiver Perspectives of Stigma Associated With Sickle Cell Disease in Adolescents.

PubMed

Wesley, Kimberly M; Zhao, Mimi; Carroll, Yvonne; Porter, Jerlym S

2016-01-01

Patients and families affected by various medical conditions report experiencing health-related stigma, which contributes to detrimental physical, psychological, and social outcomes. Sickle cell disease (SCD) is a genetic disorder that affects 89,000 individuals in the United States and is often associated with negative stereotypes and incorrect assumptions. The present study explored the perception of stigma as reported by caregivers of adolescents with SCD. Focus groups were conducted with 20 caregivers of patients with SCD. Focus groups were audio recorded and transcribed. The data were coded independently by two authors, and then reviewed conjointly until consensus was reached. Caregivers reported the perception of stigma in academic, medical, community, and family settings. They also reported internalized stigma including negative feelings toward having a child with SCD, feeling upset with others, and seeing negative emotions in their child due to SCD. Caregivers reported a general lack of knowledge about SCD across settings. These results demonstrated that stigma may affect individuals with SCD across multiple settings. These results also highlighted areas for intervention, with a focus on increasing communication and education toward medical providers, schools, and communities. Interventions can utilize technology, social media, and advertisement campaigns. Additionally, support groups for patients with SCD may help decrease stigma and validate patients' experiences. Copyright © 2016 Elsevier Inc. All rights reserved.

Assessing Error Awareness as a Mediator of the Relationship between Subjective Concerns and Cognitive Performance in Older Adults

PubMed Central

Buckley, Rachel F.; Laming, Gemma; Chen, Li Peng Evelyn; Crole, Alice; Hester, Robert

2016-01-01

Objectives Subjective concerns of cognitive decline (SCD) often manifest in older adults who exhibit objectively normal cognitive functioning. This subjective-objective discrepancy is counter-intuitive when mounting evidence suggests that subjective concerns relate to future clinical progression to Alzheimer’s disease, and so possess the potential to be a sensitive early behavioural marker of disease. In the current study, we aimed to determine whether individual variability in conscious awareness of errors in daily life might mediate this subjective-objective relationship. Methods 67 cognitively-normal older adults underwent cognitive, SCD and mood tests, and an error awareness task. Results Poorer error awareness was not found to mediate a relationship between SCD and objective performance. Furthermore, non-clinical levels of depressive symptomatology were a primary driving factor of SCD and error awareness, and significantly mediated a relationship between the two. Discussion We were unable to show that poorer error awareness mediates SCD and cognitive performance in older adults. Our study does suggest, however, that underlying depressive symptoms influence both poorer error awareness and greater SCD severity. Error awareness is thus not recommended as a proxy for SCD, as reduced levels of error awareness do not seem to be reflected by greater SCD. PMID:27832173

Determination of carotenoids in spear shrimp shells (Parapenaeopsis hardwickii) by liquid chromatography.

PubMed

Lin, Wan-Chin; Chien, John-Tung; Chen, Bing-Huei

2005-06-29

The objectives of this study were to develop a high-performance liquid chromatography method for analysis of carotenoids in spear shrimp shells (Parapenaeopsis hardwickii) and to compare the extraction efficiency of carotenoids by supercritical carbon dioxide (SCD) and solvents. Results showed that the most appropriate HPLC method was accomplished by employing a Cosmosil 5C18-AR-II column and a mobile phase of methanol-dichloromethane-acetonitrile (90:5:5, v/v/v) (A) and water (100%) (B) with the following gradient elution: 92% A and 8% B in the beginning, decreased to 4% B in 9.5 min, 1% B in 26 min, 0% B in 35 min, maintained for 25 min, and returned to 92% A and 8% B in 61 min. All-trans-astaxanthin and its two cis isomers, as well as five astaxanthin monoesters and 11 diesters were resolved within 60 min with a flow rate at 2 mL/min and detection at 480 nm. Astaxanthin diesters were found to contain 12 fatty acids, of which palmitic acid and stearic acid constituted a large portion, whereas astaxanthin monoesters were found to contain 10 fatty acids with arachidonic acid dominating. Solvent extraction could generate a higher content of trans-astaxanthin and astaxanthin esters, while SCD extraction could produce greater levels of 9-cis-astaxanthin and 13-cis-astaxanthin.

Saccharomyces cerevisiae-derived virus-like particle parvovirus B19 vaccine elicits binding and neutralizing antibodies in a mouse model for sickle cell disease.

PubMed

Penkert, Rhiannon R; Young, Neal S; Surman, Sherri L; Sealy, Robert E; Rosch, Jason; Dormitzer, Philip R; Settembre, Ethan C; Chandramouli, Sumana; Wong, Susan; Hankins, Jane S; Hurwitz, Julia L

2017-06-22

Parvovirus B19 infections are typically mild in healthy individuals, but can be life threatening in individuals with sickle cell disease (SCD). A Saccharomyces cerevisiae-derived B19 VLP vaccine, now in pre-clinical development, is immunogenic in wild type mice when administered with the adjuvant MF59. Because SCD alters the immune response, we evaluated the efficacy of this vaccine in a mouse model for SCD. Vaccinated mice with SCD demonstrated similar binding and neutralizing antibody responses to those of heterozygous littermate controls following a prime-boost-boost regimen. Due to the lack of a mouse parvovirus B19 challenge model, we employed a natural mouse pathogen, Sendai virus, to evaluate SCD respiratory tract responses to infection. Normal mucosal and systemic antibody responses were observed in these mice. Results demonstrate that mice with SCD can respond to a VLP vaccine and to a respiratory virus challenge, encouraging rapid development of the B19 vaccine for patients with SCD. Copyright © 2017 Elsevier Ltd. All rights reserved.

Hydroxyurea in Pediatric Patients With Sickle Cell Disease: What Nurses Need to Know.

PubMed

Rees, Allison L

2016-09-01

Sickle cell disease (SCD) is an inherited disorder in which sickled red blood cells occlude the small vessels of the body, reducing oxygen delivery to tissues and ultimately negatively affecting many of the body's major organs. Hydroxyurea has proven beneficial in the treatment of SCD and prevention of disease-related complications. The 2014 guidelines put forth by the National Heart, Lung, and Blood Institute recommend hydroxyurea treatment in infants 9 months and older, children, and adolescents with SCD-SS or SCD-Sβ(0) thalassemia regardless of clinical severity. This is a change from the 2002 guidelines in which hydroxyurea was recommended for adolescents and children with SCD-SS or SCD-Sβ(0) thalassemia with frequent episodes of pain, a history of acute chest syndrome, severe and symptomatic anemia or other severe vaso-occlusive events. Nurses play a critical role in working with patients and families to provide education, guidance, and support to improve compliance to mitigate the long-term effects of SCD. © 2015 by Association of Pediatric Hematology/Oncology Nurses.

Strong human leukocyte antigen matching effect in nonsensitized kidney recipients with high pretransplant soluble CD30.

PubMed

Süsal, Caner; Pelzl, Steffen; Opelz, Gerhard

2003-10-27

The influence of human leukocyte antigen (HLA) matching on graft survival is greater in patients with preformed lymphocytotoxic antibodies than in nonsensitized patients. Pretransplant serum soluble CD30 (sCD30) affects graft outcome independently of presensitization status. The impact of HLA compatibility on kidney transplant survival was analyzed in 3980 nonsensitized first cadaveric kidney recipients in relation to the pretransplant serum sCD30 content. Although HLA compatibility influenced graft outcome only marginally in nonsensitized recipients with low sCD30 (at 3 years: P=0.0095; at 5 years: P=0.1033), a strong HLA matching effect was observed in nonsensitized recipients with high sCD30 (at 3 years: P<0.0001; at 5 years: P=0.0001). Nonsensitized patients with high pretransplant sCD30 benefit from an HLA well-matched kidney. Patients should be tested for sCD30 while on the waiting list for a kidney transplant, and HLA well-matched kidneys should be allocated to patients with high sCD30.

Evaluation of serum sCD30 in renal transplantation patients with and without acute rejection.

PubMed

Cervelli, C; Fontecchio, G; Scimitarra, M; Azzarone, R; Famulari, A; Pisani, F; Battistoni, C; Di Iulio, B; Fracassi, D; Scarnecchia, M A; Papola, F

2009-05-01

Despite new immunosuppressive approaches, acute rejection episodes (ARE) are still a major cause of early kidney dysfunction with a negative impact on long-term allograft survival. Noninvasive markers able to identify renal ARE earlier than creatinine measurement include sCD30. We sought to establish whether circulating levels of sCD30 in pretransplantation and posttransplantation periods were of clinical relevance to avoid graft damage. Quantitative detection of serum sCD30 was performed using an enzyme-linked immunosorbent assay. Our results demonstrated that the mean concentrations of sCD30 were significantly higher in the sera of renal transplant recipients with ARE (30.04 U/mL) and in uremic patients on the waiting list (37.7 U/mL) compared with healthy controls (HC; 9.44 U/mL), but not nonrejecting patients (12.01 U/mL). Statistical analysis revealed a strong association between high sCD30 levels in posttransplantation sera and ARE risk. This study suggested that sCD30 levels were a reliable predictor of ARE among deceased-donor kidney recipients.

MAX-DOAS measurements of HONO slant column densities during the MAD-CAT campaign: inter-comparison, sensitivity studies on spectral analysis settings, and error budget

NASA Astrophysics Data System (ADS)

Wang, Yang; Beirle, Steffen; Hendrick, Francois; Hilboll, Andreas; Jin, Junli; Kyuberis, Aleksandra A.; Lampel, Johannes; Li, Ang; Luo, Yuhan; Lodi, Lorenzo; Ma, Jianzhong; Navarro, Monica; Ortega, Ivan; Peters, Enno; Polyansky, Oleg L.; Remmers, Julia; Richter, Andreas; Puentedura, Olga; Van Roozendael, Michel; Seyler, André; Tennyson, Jonathan; Volkamer, Rainer; Xie, Pinhua; Zobov, Nikolai F.; Wagner, Thomas

2017-10-01

In order to promote the development of the passive DOAS technique the Multi Axis DOAS - Comparison campaign for Aerosols and Trace gases (MAD-CAT) was held at the Max Planck Institute for Chemistry in Mainz, Germany, from June to October 2013. Here, we systematically compare the differential slant column densities (dSCDs) of nitrous acid (HONO) derived from measurements of seven different instruments. We also compare the tropospheric difference of SCDs (delta SCD) of HONO, namely the difference of the SCDs for the non-zenith observations and the zenith observation of the same elevation sequence. Different research groups analysed the spectra from their own instruments using their individual fit software. All the fit errors of HONO dSCDs from the instruments with cooled large-size detectors are mostly in the range of 0.1 to 0.3 × 1015 molecules cm-2 for an integration time of 1 min. The fit error for the mini MAX-DOAS is around 0.7 × 1015 molecules cm-2. Although the HONO delta SCDs are normally smaller than 6 × 1015 molecules cm-2, consistent time series of HONO delta SCDs are retrieved from the measurements of different instruments. Both fits with a sequential Fraunhofer reference spectrum (FRS) and a daily noon FRS lead to similar consistency. Apart from the mini-MAX-DOAS, the systematic absolute differences of HONO delta SCDs between the instruments are smaller than 0.63 × 1015 molecules cm-2. The correlation coefficients are higher than 0.7 and the slopes of linear regressions deviate from unity by less than 16 % for the elevation angle of 1°. The correlations decrease with an increase in elevation angle. All the participants also analysed synthetic spectra using the same baseline DOAS settings to evaluate the systematic errors of HONO results from their respective fit programs. In general the errors are smaller than 0.3 × 1015 molecules cm-2, which is about half of the systematic difference between the real measurements.The differences of HONO delta SCDs retrieved in the selected three spectral ranges 335-361, 335-373 and 335-390 nm are considerable (up to 0.57 × 1015 molecules cm-2) for both real measurements and synthetic spectra. We performed sensitivity studies to quantify the dominant systematic error sources and to find a recommended DOAS setting in the three spectral ranges. The results show that water vapour absorption, temperature and wavelength dependence of O4 absorption, temperature dependence of Ring spectrum, and polynomial and intensity offset correction all together dominate the systematic errors. We recommend a fit range of 335-373 nm for HONO retrievals. In such fit range the overall systematic uncertainty is about 0.87 × 1015 molecules cm-2, much smaller than those in the other two ranges. The typical random uncertainty is estimated to be about 0.16 × 1015 molecules cm-2, which is only 25 % of the total systematic uncertainty for most of the instruments in the MAD-CAT campaign. In summary for most of the MAX-DOAS instruments for elevation angle below 5°, half daytime measurements (usually in the morning) of HONO delta SCD can be over the detection limit of 0.2 × 1015 molecules cm-2 with an uncertainty of ˜ 0.9 × 1015 molecules cm-2.

Aerosols correction of the OMI tropospheric NO2 retrievals over cloud-free scenes: Different methodologies based on the O2-O2 477 nm band

NASA Astrophysics Data System (ADS)

Chimot, Julien; Vlemmix, Tim; Veefkind, Pepijn; Levelt, Pieternel

2016-04-01

Numerous studies have drawn attention to the complexities related to the retrievals of tropospheric NO2 columns derived from satellite UltraViolet-Visible (UV-Vis) measurements in the presence of aerosols. Correction for aerosol effects will remain a challenge for the next generation of air quality satellite instruments such as TROPOMI on Sentinel-5 Precursor, Sentinel-4 and Sentinel-5. The Ozone Monitoring Instrument (OMI) instrument has provided daily global measurements of tropospheric NO2 for more than a decade. However, aerosols are not explicitly taken into account in the current operational OMI tropospheric NO2 retrieval chain (DOMINO v2 [Boersma et al., 2011]). Our study analyses 2 approaches for an operational aerosol correction, based on the use of the O2-O2 477 nm band. The 1st approach is the cloud-model based aerosol correction, also named "implicit aerosol correction", and already used in the operational chain. The OMI O2-O2 cloud retrieval algorithm, based on the Differential Optical Absorption Spectroscopy (DOAS) approach, is applied both to cloudy and to cloud-free scenes with aerosols present. Perturbation of the OMI cloud retrievals over scenes dominated by aerosols has been observed in recent studies led by [Castellanos et al., 2015; Lin et al., 2015; Lin et al., 2014]. We investigated the causes of these perturbations by: (1) confronting the OMI tropospheric NO2, clouds and MODIS AQUA aerosol products; (2) characterizing the key drivers of the aerosol net effects, compared to a signal from clouds, in the UV-Vis spectra. This study has focused on large industrialised areas like East-China, over cloud-free scenes. One of the key findings is the limitation due to the coarse sampling of the employed cloud Look-Up Table (LUT) to convert the results of the applied DOAS fit into effective cloud fraction and pressure. This leads to an underestimation of tropospheric NO2 amount in cases of particles located at elevated altitude. A higher sampling of the variation of O2-O2 SCD and continuum reflectance as a function of effective cloud parameters in case of low effective cloud fraction values is requested for applying an aerosol correction. The updates of the OMI O2-O2 cloud algorithm, based on the scheduled new OMI cloud LUT, will be presented in terms of impacts of the effective cloud retrievals and reduced biases of tropospheric NO2 columns over cloud-free scenes dominated by aerosols in China. A 2nd approach is investigated, assuming a more explicit aerosol correction. Previous analyses pointed out that the O2-O2 spectra contain information about aerosols: the continuum reflectance is primarily constrained by the Aerosol Optical thickness (AOT) while the O2-O2 Slant Column Density (SCD) mostly results from the combination of AOT and aerosols altitude. We have developed a first prototype algorithm allowing to retrieve information about AOT and aerosol altitude from the O2-O2 DOAS fit. We will discuss preliminary sensitivities and the potential accuracy of the associated explicit aerosol correction, without the use of effective cloud parameters.

[Neuromuscular blocking and respiratory depressing actions of sodium ammonium dimethyl-2-(propano-1,3-dithiosulfate) monohydrate].

PubMed

Cao, B J; Chen, Z K; Chi, Z Q

1990-05-01

The neuromuscular blocking and respiratory depressing actions of the new insecticide sodium ammonium dimethyl-2-(propano-1,3-dithiosulfate) monohydrate (SCD) were investigated. In peroneal-tibialis anterior nerve-muscle preparations of urethane anesthetized rabbit, SCD 6.5 mg/kg iv completely depressed the indirectly elicited twitch tension but not the directly elicited one. This compound also caused initial potentiation of the indirectly elicited twitch tension. In the partially paralyzed preparations, potentiation of contractions occurred following a brief period of indirectly tetanic stimulation. Nereistoxin but not SCD blocked the indirectly elicited twitch tension of isolated rat diaphragm. The neuromuscular blockade induced by SCD and nereistoxin was antagonized by neostigmine and 4-aminopyridine. SCD and nereistoxin had little or no effect on arterial blood pressure and phrenic nerve discharge of rabbits. The results indicated that SCD-poisoned rabbits died of respiratory paralysis following the neuromuscular blockade.

Prognostic values of soluble CD30 and CD30 gene polymorphisms in heart transplantation.

PubMed

Frisaldi, Elisa; Conca, Raffaele; Magistroni, Paola; Fasano, Maria Edvige; Mazzola, Gina; Patanè, Francesco; Zingarelli, Edoardo; Dall'omo, Anna M; Brusco, Alfredo; Amoroso, Antonio

2006-04-27

Pretransplant soluble CD30 (sCD30) is a predictor of kidney graft outcome. Its status as a predictor of heart transplant (HT) outcome has not been established. We have studied this question by assessing sCD30 levels and the number of (CCAT)n repeats of the microsatellite in the CD30 promoter region, which is able alone to repress gene transcription, in the sera of 83 HT patients and 77 of their donors. sCD30 was non-significantly increased in the patients, whereas there were no differences in the CD30 microsatellite allele frequencies. A negative correlation between the number of (CCAT)n and sCD30 levels was evident in the donors. Patients with pretransplant sCD30

Arginine methylation promotes translation repression activity of eIF4G-binding protein, Scd6.

PubMed

Poornima, Gopalakrishna; Shah, Shanaya; Vignesh, Venkadasubramanian; Parker, Roy; Rajyaguru, Purusharth I

2016-11-02

Regulation of translation plays a critical role in determining mRNA fate. A new role was recently reported for a subset of RGG-motif proteins in repressing translation initiation by binding eIF4G1. However the signaling mechanism(s) that leads to spatial and temporal regulation of repression activity of RGG-motif proteins remains unknown. Here we report the role of arginine methylation in regulation of repression activity of Scd6, a conserved RGG-motif protein. We demonstrate that Scd6 gets arginine methylated at its RGG-motif and Hmt1 plays an important role in its methylation. We identify specific methylated arginine residues in the Scd6 RGG-motif in vivo We provide evidence that methylation augments Scd6 repression activity. Arginine methylation defective (AMD) mutant of Scd6 rescues the growth defect caused by overexpression of Scd6, a feature of translation repressors in general. Live-cell imaging of the AMD mutant revealed that it is defective in inducing formation of stress granules. Live-cell imaging and pull-down results indicate that it fails to bind eIF4G1 efficiently. Consistent with these results, a strain lacking Hmt1 is also defective in Scd6-eIF4G1 interaction. Our results establish that arginine methylation augments Scd6 repression activity by promoting eIF4G1-binding. We propose that arginine methylation of translation repressors with RGG-motif could be a general modulator of their repression activity. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Evolving Evidence for the Value of Neuroimaging Methods and Biological Markers in Subjects Categorized with Subjective Cognitive Decline.

PubMed

Lista, Simone; Molinuevo, Jose L; Cavedo, Enrica; Rami, Lorena; Amouyel, Philippe; Teipel, Stefan J; Garaci, Francesco; Toschi, Nicola; Habert, Marie-Odile; Blennow, Kaj; Zetterberg, Henrik; O'Bryant, Sid E; Johnson, Leigh; Galluzzi, Samantha; Bokde, Arun L W; Broich, Karl; Herholz, Karl; Bakardjian, Hovagim; Dubois, Bruno; Jessen, Frank; Carrillo, Maria C; Aisen, Paul S; Hampel, Harald

2015-09-24

There is evolving evidence that individuals categorized with subjective cognitive decline (SCD) are potentially at higher risk for developing objective and progressive cognitive impairment compared to cognitively healthy individuals without apparent subjective complaints. Interestingly, SCD, during advancing preclinical Alzheimer's disease (AD), may denote very early, subtle cognitive decline that cannot be identified using established standardized tests of cognitive performance. The substantial heterogeneity of existing SCD-related research data has led the Subjective Cognitive Decline Initiative (SCD-I) to accomplish an international consensus on the definition of a conceptual research framework on SCD in preclinical AD. In the area of biological markers, the cerebrospinal fluid signature of AD has been reported to be more prevalent in subjects with SCD compared to healthy controls; moreover, there is a pronounced atrophy, as demonstrated by magnetic resonance imaging, and an increased hypometabolism, as revealed by positron emission tomography, in characteristic brain regions affected by AD. In addition, SCD individuals carrying an apolipoprotein ɛ4 allele are more likely to display AD-phenotypic alterations. The urgent requirement to detect and diagnose AD as early as possible has led to the critical examination of the diagnostic power of biological markers, neurophysiology, and neuroimaging methods for AD-related risk and clinical progression in individuals defined with SCD. Observational studies on the predictive value of SCD for developing AD may potentially be of practical value, and an evidence-based, validated, qualified, and fully operationalized concept may inform clinical diagnostic practice and guide earlier designs in future therapy trials.

The Fucosylation Inhibitor, 2-Fluorofucose, Inhibits Vaso-Occlusion, Leukocyte-Endothelium Interactions and NF-ĸB Activation in Transgenic Sickle Mice

PubMed Central

Belcher, John D.; Chen, Chunsheng; Nguyen, Julia; Abdulla, Fuad; Nguyen, Phong; Nguyen, Minh; Okeley, Nicole M.; Benjamin, Dennis R.; Senter, Peter D.; Vercellotti, Gregory M.

2015-01-01

2-Fluorofucose (2FF) blocks the fucosylation and the tethering of sialyl-Lewisx tetrasaccharide and structural variants on leukocytes and red blood cells to P- and E-selectins on activated endothelial cell surfaces. Because P- and E-selectin are required for vaso-occlusion in murine sickle cell disease (SCD), we investigated whether 2FF would inhibit vaso-occlusion in SCD mice. Microvascular stasis was measured in subcutaneous venules in NY1DD and HbSS-Townes SCD mice with dorsal skin-fold chambers after infusion of hemoglobin or exposure to hypoxia/reoxygenation. 2FF in drinking water or administered by gavage inhibited stasis in sickle mice in a dose-responsive manner. Significant inhibitory effects on stasis were seen 1 day post-treatment. 2FF treatment of SCD mice also significantly reduced leukocyte rolling and adhesion along the vessel walls of SCD mice and the static adhesion of neutrophils and sickle red blood cells isolated from 2FF-treated SCD mice to resting and activated endothelial cells. Total white blood cell counts increased in response to 2FF. NF-ĸB activation and VCAM-1 and E-selectin expression were inhibited in the livers of SCD mice consistent with an overall decrease in vascular inflammation and ischemia-reperfusion physiology. Pretreatment with 2FF completely eliminated heme-induced lethality in HbSS-Townes mice, consistent with the observed anti-inflammatory and anti-adhesive properties of 2FF in SCD mice. These data suggest that 2FF may be beneficial for preventing or treating vaso-occlusive crises in SCD patients. PMID:25706118

Absence of stearoyl-CoA desaturase-1 does not promote DSS-induced acute colitis.

PubMed

Macdonald, Marcia L E; Bissada, Nagat; Vallance, Bruce A; Hayden, Michael R

2009-12-01

Absence of stearoyl-CoA desaturase-1 (SCD1) in mice leads to chronic inflammation of the skin and increased susceptibility to atherosclerosis, while also increasing plasma inflammatory markers. A recent report suggested that SCD1 deficiency also increases disease severity in a mouse model of inflammatory bowel disease, induced by dextran sulfate sodium (DSS). However, SCD1-deficient mice are known to consume increased amounts of water, which would also be expected to increase the intake of DSS-treated water. The aim of this study was to determine the effect of SCD1 deficiency on DSS-induced acute colitis with DSS dosing adjusted to account for genotype differences in fluid consumption. Wild-type controls were treated with 3.5% DSS for 5 days to induce moderately severe colitis, while the concentration of DSS given to SCD1-deficient mice was lowered to 2.5% to control for increased fluid consumption. Colonic inflammation was assessed by clinical and histological scoring. Although SCD1-deficient mice consumed a total intake of DSS that was greater than that of wild-type controls, colonic inflammation, colon length and fecal blood were not altered by SCD1-deficiency in DSS-induced colitis, while diarrhea and total weight loss were modestly improved. Despite SCD1 deficiency leading to chronic inflammation of the skin and increased susceptibility to atherosclerosis, it does not accelerate inflammation in the DSS-induced model of acute colitis when DSS intake is controlled. These observations suggest that SCD1 deficiency does not play a significant role in colonic inflammation in this model.

Quantitative intravital two-photon excitation microscopy reveals absence of pulmonary vaso-occlusion in unchallenged Sickle Cell Disease mice

PubMed Central

Bennewitz, Margaret F; Watkins, Simon C; Sundd, Prithu

2014-01-01

Sickle cell disease (SCD) is a genetic disorder that leads to red blood cell (RBC) sickling, hemolysis and the upregulation of adhesion molecules on sickle RBCs. Chronic hemolysis in SCD results in a hyper-inflammatory state characterized by activation of circulating leukocytes, platelets and endothelial cells even in the absence of a crisis. A crisis in SCD is often triggered by an inflammatory stimulus and can lead to the acute chest syndrome (ACS), which is a type of lung injury and a leading cause of mortality among SCD patients. Although it is believed that pulmonary vaso-occlusion could be the phenomenon contributing to the development of ACS, the role of vaso-occlusion in ACS remains elusive. Intravital imaging of the cremaster microcirculation in SCD mice has been instrumental in establishing the role of neutrophil-RBC-endothelium interactions in systemic vaso-occlusion; however, such studies, although warranted, have never been done in the pulmonary microcirculation of SCD mice. Here, we show that two-photon excitation fluorescence microscopy can be used to perform quantitative analysis of neutrophil and RBC trafficking in the pulmonary microcirculation of SCD mice. We provide the experimental approach that enables microscopic observations under physiological conditions and use it to show that RBC and neutrophil trafficking is comparable in SCD and control mice in the absence of an inflammatory stimulus. The intravital imaging scheme proposed in this study can be useful in elucidating the cellular and molecular mechanism of pulmonary vaso-occlusion in SCD mice following an inflammatory stimulus. PMID:25995970

Sudden cardiac death rates in an Australian population: a data linkage study.

PubMed

Feng, Jia-Li; Hickling, Siobhan; Nedkoff, Lee; Knuiman, Matthew; Semsarian, Christopher; Ingles, Jodie; Briffa, Tom G

2015-11-01

The aim of the present study was to develop criteria to identify sudden cardiac death (SCD) and estimate population rates of SCD using administrative mortality and hospital morbidity records in Western Australia. Four criteria were developed using place, death within 24 h, principal and secondary diagnoses, underlying and associated cause of death, and/or occurrence of a post mortem to identify SCD. Average crude, age-standardised and age-specific rates of SCD were estimated using population person-linked administrative data. In all, 9567 probable SCDs were identified between 1997 and 2010, with one-third aged ≥ 35 years having no prior admission for cardiovascular disease. SCD was more frequent in men (62.1%). The estimated average annual crude SCD rate for the period was 34.6 per 100 000 person-years with an average annual age-standardised rate of 37.8 per 100 000 person-years. Age-specific standardised rates were 1.1 per 100 000 person-years and 70.7 per 100 000 person-years in people aged 1-34 and ≥ 35 years, respectively. Ischaemic heart disease (IHD) was recorded as the underlying cause of death in approximately 80% of patients aged ≥ 35 years, followed by valvular heart disease and heart failure. IHD was the most common cause of death in those aged 1-34 years, followed by unspecified cardiomyopathy and dysrhythmias. Administrative morbidity and mortality data can be used to estimate rates of SCD and therefore provide a suitable methodology for monitoring SCD over time. The findings highlight the magnitude of SCD and its potential for public health prevention.

Religious coping and the use of prayer in children with sickle cell disease.

PubMed

Cotton, Sian; Grossoehme, Daniel; McGrady, Meghan E

2012-02-01

While adolescents and adults with sickle cell disease (SCD) have reported using religion to cope with SCD, there is no data examining religious coping in young children with SCD. The purpose of this qualitative study was to: (1) describe the types of religious coping used by children with SCD; (2) describe the content and frequency of prayer used in relation to SCD; and (3) examine how children viewed God/Higher Power in relation to their SCD. Children with SCD participated in a semi-structured interview and an art drawing exercise focused on the use of general coping and religious coping. Interviews were coded, organized, and analyzed using a template organizational style of interpretation and NVivo 8.0 qualitative software. Of the 19 participants, the average age was 8.05 years (SD ±1.81); 11 were female (58%); all (100%) were African-American and 9 (47%) were Protestant. Children used religion to gain control, make meaning, and find comfort. Most children reported praying to get well, to keep from getting sick, and to get out of the hospital. Children described a functional God who made them take their medicine or took them to the hospital and an emotional God who made them happy and comforted them when they were sad or scared. These children with SCD reported using religion to help cope with the illness. Providers should be aware of the importance of religion to many of these children and integrate religion, as appropriate, into discussions about coping with SCD. Copyright © 2011 Wiley Periodicals, Inc.

What Is the Most Representative Parameter for Describing the Size of the Atlas? CT Morphometric Analysis of the Atlas with Special Reference to Atlas Hypoplasia.

PubMed

Yamahata, Hitoshi; Hirano, Hirofumi; Yamaguchi, Satoshi; Mori, Masanao; Niiro, Tadaaki; Tokimura, Hiroshi; Arita, Kazunori

2017-09-15

The spinal canal diameter (SCD) is one of the most studied factors for the assessment of cervical spinal canal stenosis. The inner anteroposterior diameter (IAP), the SCD, and the cross-sectional area (CSA) of the atlas have been used for the evaluation of the size of the atlas in patients with atlas hypoplasia, a rare form of developmental spinal canal stenosis, however, there is little information on their relationship. The aim of this study was to identify the most useful parameter for depicting the size of the atlas. The CSA, the IAP, and the SCD were measured on computed tomography (CT) images at the C1 level of 213 patients and compared in this retrospective study. These three parameters increased with increasing patient height and weight. There was a strong correlation between IAP and SCD (r = 0.853) or CSA (r = 0.822), while correlation between SCD and CSA (r = 0.695) was weaker than between IAP and CSA. Partial correlation analysis showed that IAP was positively correlated with SCD (r = 0.687) and CSA (r = 0.612) when CSA or SCD were controlled. SCD was negatively correlated with CSA when IAP was controlled (r = -0.21). The IAP can serve as the CSA for the evaluation of the size of the atlas ring, while the SCD does not correlate with the CSA. As the patient height and weight affect the size of the atlas, analysis of the spinal canal at the C1 level should take into account physiologic patient data.

Public health burden of sudden cardiac death in the United States.

PubMed

Stecker, Eric C; Reinier, Kyndaron; Marijon, Eloi; Narayanan, Kumar; Teodorescu, Carmen; Uy-Evanado, Audrey; Gunson, Karen; Jui, Jonathan; Chugh, Sumeet S

2014-04-01

Sudden cardiac death (SCD) is a leading cause of death in the United States, but the relative public health burden is unknown. We estimated the burden of premature death from SCD and compared it with other diseases. Analyses were based on the following data sources (using most recent sources that provided appropriately stratified data): (1) leading causes of death among men and women from 2009 US death certificate reporting; (2) individual cancer mortality rates from 2008 death certificate reporting from the Centers for Disease Control and Prevention's National Program of Cancer Registries; (3) county, state, and national population data for 2009 from the US Census Bureau; and (4) SCD rates from the Oregon Sudden Unexpected Death Study (SUDS) population-based surveillance study of SCD between 2002 and 2004. Cases were identified from multiple sources in a prospectively designed surveillance program. Incidence, counts, and years of potential life lost for SCD and other major diseases were compared. The age-adjusted national incidence of SCD was 60 per 100 000 population (95% confidence interval, 54-66 per 100,000). The burden of premature death for men (2.04 million years of potential life lost; 95% uncertainty interval, 1.86-2.23 million) and women (1.29 million years of potential life lost; 95% uncertainty interval, 1.13-1.45 million) was greater for SCD than for all individual cancers and most other leading causes of death. The societal burden of SCD is high relative to other major causes of death. Accordingly, improved national surveillance with the goal of optimizing and monitoring SCD prevention and treatment should be a high priority.

Improved Guideline Adherence With Integrated Sickle Cell Disease and Asthma Care.

PubMed

McClain, Brandi L; Ivy, Zalaya K; Bryant, Valencia; Rodeghier, Mark; DeBaun, Michael R

2016-07-01

In children with sickle cell disease (SCD), concomitant asthma is associated with increased morbidity and mortality when compared with children with SCD without asthma. Despite the well-established burden of asthma in children with SCD, no paradigm of care exists for the co-management of these two diseases. To address this gap, an integrated SCD and asthma clinic was created in a community health center that included (1) a dual respiratory therapist/asthma case manager; (2) an SCD nurse practitioner with asthma educator certification; (3) an onsite pulmonary function test laboratory; (4) a pediatric hematologist with expertise in managing SCD and asthma; and (5) application of the National Asthma Education and Prevention Program guidelines. A before (2010-2012) and after (2013-2014) study design was used to assess for improved quality of care with implementation of an integrative care model among 61 children with SCD and asthma followed from 2010 to 2014. Asthma action plan utilization after initial diagnosis increased with the integrative care model (n=16, 56% before, 100% after, p=0.003), as did the use of spirometry in children aged ≥5 years (n=41, 65% before, 95% after, p<0.001) and correction of lower airway obstruction (n=10, 30% before, 80% after, p=0.03). Although the use of an integrative care model for SCD and asthma improved evidence-based asthma care, longer follow-up and evaluation will be needed to determine the impact on SCD-related morbidity. Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Relationship between Surgically Treated Superior Canal Dehiscence Syndrome and Body Mass Index.

PubMed

Jan, Taha A; Cheng, Yew Song; Landegger, Lukas D; Lin, Brian M; Srikanth, Priya; Niesten, Marlien E F; Lee, Daniel J

2017-04-01

Objective Examine the association between body mass index (BMI) and superior canal dehiscence (SCD) among patients who have undergone surgical repair for superior canal dehiscence. Study Design Retrospective comparison study. Setting Neurotology tertiary care center. Subjects and Methods Retrospective review of consecutive adult patients evaluated at our institution for SCD syndrome between November 2006 and August 2015. A control group who underwent imaging within the same period for reasons other than SCD was also included. Patient demographics, weight, and height were examined. We performed multiple subgroup analyses to investigate the relationship of BMI, surgery vs no surgery, and correlation between patient BMI and SCD size. Results Of the 268 patients with SCD, 99 underwent surgery; 96 of these patients had complete medical records and were eligible for inclusion. Eighty-eight patients were noted to have arcuate eminence defects, and the mean BMI of this surgical cohort was 28.09 ± 5.26 kg/m 2 . Nonsurgically treated patients with SCD with available data (n = 94) had a mean BMI of 27.97 ± 6.95 kg/m 2 . A control group of 204 patients who underwent computed tomography for non-SCD-related causes was analyzed, of whom 155 had available data with a mean BMI of 27.91 ± 6.38 kg/m 2 . Conclusion We demonstrate that adult patients who undergo surgery for SCD are not obese (mean BMI <30), and size of dehiscence poorly correlates with BMI. Our observations call into question the proposed theory that patient weight is a risk factor for the development of symptomatic SCD involving the arcuate eminence.

Sensitivity of alternative measures of functioning and wellbeing for adults with sickle cell disease: comparison of PROMIS® to ASCQ-Me℠.

PubMed

Keller, San; Yang, Manshu; Treadwell, Marsha J; Hassell, Kathryn L

2017-06-02

Sickle Cell Disease (SCD) causes profound suffering and decrements in daily functioning. Demand is growing for valid and reliable measures to systematically document these effects, particularly in adults. The Adult Sickle Cell Quality of Life Measurement System, ASCQ-Me℠, was developed for this purpose. ASCQ-Me℠ is one of four measurement systems housed within the Person-Centered Assessment Resource (PCAR), funded by the National Institutes of Health, to support clinical research. To help users select the best of these measures for adults with SCD, we evaluated and compared two PCAR systems: one designed to be "universally applicable" (the Patient-Reported Outcome Measurement Information System, PROMIS®) and one designed specifically for SCD (ASCQ-Me℠). Respondents to PROMIS and ASCQ-Me questions were 490 adults with SCD from seven geographically-disbursed clinics within the US. Data were collected for six ASCQ-Me measures (Emotional Impact, Sleep Impact, Social Impact, Stiffness Impact, Pain Impact, SCD Pain Episode Frequency and Severity) and ten PROMIS measures (Pain Impact, Pain Behavior, Physical Functioning, Anxiety, Depression, Fatigue, Satisfaction with Discretionary Social Activities, Satisfaction with Social Roles, Sleep Disturbance, and Sleep-Related Impairment). Statistical analyses, including analysis of variance and multiple linear regression, were conducted to determine the sensitivity of measures to SCD severity. SCD severity was assessed via a checklist of associated treatments and conditions. For those with the most severe SCD, PROMIS scores showed worse health compared to the general population for nine of ten health domains: the magnitude of the difference ranged 0.5 to 1.1 standard deviation units. The PROMIS domains most severely affected were Physical Functioning and Pain (Impact and Behavior). Significant differences by tertile of the SCD-MHC were shown for most PROMIS short forms and all ASCQ-Me short and fixed forms. In most models, ASCQ-Me measures explained statistically significant unique variance in SCD-MHC scores complementary to that explained by corresponding PROMIS measures. Study results supported the validity of both PROMIS and ASCQ-Me measures for use in adults with SCD. Compared to comparable PROMIS scores, most ASCQ-Me scores were better predictors of SCD disease severity, as measured by a medical history checklist. The clinical implications of these results require further investigation.

Sickle cell disease in children.

PubMed

Meier, Emily Riehm; Miller, Jeffery L

2012-05-07

Early identification of infants with sickle cell disease (SCD) by newborn screening, now universal in all 50 states in the US, has improved survival, mainly by preventing overwhelming sepsis with the early use of prophylactic penicillin. Routine transcranial Doppler screening with the institution of chronic transfusion decreases the risk of stroke from 10% to 1% in paediatric SCD patients. Hydroxyurea decreases the number and frequency of painful crises, acute chest syndromes and number of blood transfusions in children with SCD. Genetic research continues to be driven toward the prevention and ultimate cure of SCD before adulthood. This review focuses on clinical manifestations and therapeutic strategies for paediatric SCD as well as the evolving topic of gene-focused prevention and therapy.

Working Memory in Children With Neurocognitive Effects From Sickle Cell Disease: Contributions of the Central Executive and Processing Speed

PubMed Central

Smith, Kelsey E.; Schatz, Jeffrey

2017-01-01

Children with sickle cell disease (SCD) are at risk for working memory deficits due to multiple disease processes. We assessed working memory abilities and related functions in 32 school-age children with SCD and 85 matched comparison children using Baddeley’s working memory model as a framework. Children with SCD performed worse than controls for working memory, central executive function, and processing/rehearsal speed. Central executive function was found to mediate the relationship between SCD status and working memory, but processing speed did not. Cognitive remediation strategies that focus on central executive processes may be important for remediating working memory deficits in SCD. PMID:27759435

Stearoyl-CoA desaturase activity is elevated by the suppression of its degradation by clofibric acid in the liver of rats.

PubMed

Toyama, Tomoaki; Kudo, Naomi; Mitsumoto, Atsushi; Hibino, Yasuhide; Tsuda, Tadashi; Kawashima, Yoichi

2007-04-01

A mechanism by which fibrates control stearoyl-CoA desaturase (SCD) in the liver was studied. Treatment of rats with 2-(4-chlorophenoxy)-2-methylpropionic acid (clofibric acid) or feeding of a fat-free diet markedly elevated hepatic activity of SCD. Both the treatment with clofibric acid and the feeding of the fat-free diet caused an increase in the steady-state level of SCD1 mRNA and enhanced transcriptional rate. The half-lives of SCD for control rats, rats treated with clofibric acid rats, and rats fed the fat-free diet were estimated to be 2.0, 3.9, and 1.9 h, respectively. Activity of palmitoyl-CoA chain elongase (PCE) was increased by both clofibric acid treatment and feeding of the fat-free diet as was observed with SCD. Steady-state level of rat fatty acid elongase 2 mRNA was increased by the treatment with clofibric acid or feeding of fat-free diet, although the transcriptional rate was not altered. Different from SCD, PCE was highly stable and its half-life was not changed by either clofibric acid or fat-free diet. These results strongly suggest that the decreased degradation of SCD is responsible for the increase in its activity in addition to increased transcription of SCD1 in the rats treated with clofibric acid.

The Role of Soluble CD40L Ligand in Human Carcinogenesis.

PubMed

Angelou, Anastasios; Antoniou, Efstathios; Garmpis, Nikolaos; Damaskos, Christos; Theocharis, Stamatios; Margonis, Georgios-Antonios

2018-05-01

The role of CD40/CD40L in carcinogenesis is widely examined. The mechanisms linking the CD40/CD40L system and the soluble form of CD40 ligand (sCD40L) with neoplasia are nowadays a topic of intensive research. CD40L and sCD40L belong to the TNF superfamily and are molecules with a proinflammatory role. A variety of cells express CD40L such as the immune system cells, the endothelial cells and activated platelets. Although many medications such as statins have been shown to reduce sCD40L, it is still debated whether specific treatments targeting the CD40/CD40L system will prove to be effective against carcinogenesis in the near future. A comprehensive search of the Pubmed Database was conducted for English-language studies using a list of key words. At diagnosis, serum samples of patients with neoplasia contained higher levels of sCD40L than healthy controls, suggesting that sCD40L may play a predictive role in human carcinogenesis. Patients with neoplasia had higher circulating sCD40L levels and it is likely that sCD40L may have a predictive role. It is still unclear whether sCD40L can be used as a therapeutic target. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Ingested soluble CD14 from milk is transferred intact into the blood of newborn rats.

PubMed

Ward, Tonya L; Spencer, William J; Davis, Laura D R; Harrold, Joann; Mack, David R; Altosaar, Illimar

2014-02-01

Milk acts as an edible immune system that is transferred from mother to newborn. Soluble Cluster of Differentiation 14 (sCD14) is a protein found in significant quantities in human milk (~8-29 µg/ml). At a 10-fold lower concentration in the blood (~3 µg/ml), the most notable role of sCD14 is to sequester lipopolysaccharides of Gram-negative bacteria from immune cells. To explore the pharmacodynamics of this milk protein and its biological fate, the biodistribution of radiolabeled sCD14 ((14)C, (125)I) was monitored in 10-d-old rat pups. Up to 3.4 ± 2.2% of the radiolabeled sCD14 administered was observed, intact, in the pup blood for up to 8 h post-ingestion. Additionally, 30.3 ± 13.0% of the radiolabeled sCD14 administered was observed degraded in the stomach at 8 h post-ingestion. A reservoir of intact, administered sCD14 (3.2 ± 0.3%), however, remained in the stomach at 8 h post-ingestion. Intact sCD14 was observed in the small intestine at 5.5 ± 1.6% of the dose fed at 8 h post-ingestion. The presence of intact sCD14 in the blood and the gastrointestinal tract of newborns post-ingestion has implications in the development of allergies, obesity, and other inflammation-related pathogeneses later in life.

Peritransplant Soluble CD30 as a Risk Factor for Slow Kidney Allograft Function, Early Acute Rejection, Worse Long-Term Allograft Function, and Patients' Survival.

PubMed

Trailin, Andriy V; Ostapenko, Tetyana I; Nykonenko, Tamara N; Nesterenko, Svitlana N; Nykonenko, Olexandr S

2017-01-01

We aimed to determine whether serum soluble CD30 (sCD30) could identify recipients at high risk for unfavorable early and late kidney transplant outcomes. Serum sCD30 was measured on the day of kidney transplantation and on the 4th day posttransplant. We assessed the value of these measurements in predicting delayed graft function, slow graft function (SGF), acute rejection (AR), pyelonephritis, decline of allograft function after 6 months, and graft and patient survival during 5 years of follow-up in 45 recipients. We found the association between low pretransplant serum levels of sCD30 and SGF. The absence of significant decrease of sCD30 on the 4th day posttransplant was characteristic for SGF, early AR (the 8th day-6 months), late AR (>6 months), and early pyelonephritis (the 8th day-2 months). Lower pretransplant and posttransplant sCD30 predicted worse allograft function at 6 months and 2 years, respectively. Higher pretransplant sCD30 was associated with higher frequency of early AR, and worse patients' survival, but only in the recipients of deceased-donor graft. Pretransplant sCD30 also allowed to differentiate patients with early pyelonephritis and early AR. Peritransplant sCD30 is useful in identifying patients at risk for unfavorable early and late transplant outcomes.

Rationale and design of the Pan-African Sudden Cardiac Death survey: the Pan-African SCD study.

PubMed

Bonny, Aimé; Ngantcha, Marcus; Amougou, Sylvie Ndongo; Kane, Adama; Marrakchi, Sonia; Okello, Emmy; Taty, Georges; Gehani, Abdulrrazzak; Diakite, Mamadou; Talle, Mohammed A; Lambiase, Pier D; Houenassi, Martin; Chin, Ashley; Otieno, Harun; Temu, Gloria; Owusu, Isaac Koffi; Karaye, Kamilu M; Awad, Abdalla A M; Winkel, Bo Gregers; Priori, Silvia G

2014-01-01

The estimated rate of sudden cardiac death (SCD) in Western countries ranges from 300,000 to 400,000 annually, which represents 0.36 to 1.28 per 1 000 inhabitants in Europe and the United States. The burden of SCD in Africa is unknown. Our aim is to assess the epidemiology of SCD in Africa. The Pan-Africa SCD study is a prospective, multicentre, community-based registry monitoring all cases of cardiac arrest occurring in victims over 15 years old. We will use the definition of SCD as 'witnessed natural death occurring within one hour of the onset of symptoms' or 'unwitnessed natural death within 24 hours of the onset of symptoms'. After approval from institutional boards, we will record demographic, clinical, electrocardiographic and biological variables of SCD victims (including survivors of cardiac arrest) in several African cities. All deaths occurring in residents of districts of interest will be checked for past medical history, circumstances of death, and autopsy report (if possible). We will also analyse the employment of resuscitation attempts during the time frame of sudden cardiac arrest (SCA) in various patient populations throughout African countries. This study will provide comprehensive, contemporary data on the epidemiology of SCD in Africa and will help in the development of strategies to prevent and manage cardiac arrest in this region of the world.

Cutaneous CD30+ cells in children with atopic dermatitis.

PubMed

Cavagni, G; Caffarelli, C; Facchetti, F; Brugnoni, D; Notarangelo, L D; Tosoni, C; Altobelli, R

2000-03-01

CD30 expression can be considered a marker of Th2 cells. We investigated the presence of CD30+ cells in the lesional skin of children with atopic dermatitis (AD). We also analyzed the possible relationship between CD30+ cells and serum soluble CD 30 (sCD30) levels, and IgE, soluble interleukin-2 (IL-2) receptor (sIL-2R) or soluble CD23 (sCD23) levels in the blood, and clinical score. Ten eczematous children (4 males, 6 females; median age: 4 years and 5 months; range: 11 months to 14 years), 9 sex- and age-matched control children and an adult control group were studied. A clinical score (SCORAD index), was given to eczematous lesions. Blood was taken for the determination of IgE, sCD30, sIL-2R and sCD23 levels. Punch biopsies of lesional skin were stained with hematoxylin and eosin or incubated with anti-CD30 monoclonal antibodies. Skin prick tests (SPTs) were also performed. In the biopsy specimens, CD30 expression was observed in high proportions of infiltrating cells. In children with AD, total serum IgE, sCD30, sIL-2R, sCD23 and eosinophils were significantly elevated compared to controls. CD30+ cells were not associated with serum IgE, sCD30, sIL-2R, sCD23, or SPT results, score of inflammatory cells in lesional skin or clinical score. Children with AD who had high total IgE and specific IgE antibodies did not differ from those with normal total IgE and negative specific IgE in respect of age, clinical score, number of CD30+ cells, sCD30, sIL-2R and sCD23 levels, score of inflammatory cells in skin or clinical score. Our results showed remarkable numbers of CD30+ cells in the lesional skin and high sCD30 in the serum of children with AD. CD30+ cells did not correlate with systemic markers of IgE reaction. Copyright 2000 S. Karger AG, Basel

A common SCN5A variant is associated with PR interval and atrial fibrillation among African Americans.

PubMed

Ilkhanoff, Leonard; Arking, Dan E; Lemaitre, Rozenn N; Alonso, Alvaro; Chen, Lin Y; Durda, Peter; Hesselson, Stephanie E; Kerr, Kathleen F; Magnani, Jared W; Marcus, Gregory M; Schnabel, Renate B; Smith, J Gustav; Soliman, Elsayed Z; Reiner, Alexander P; Sotoodehnia, Nona

2014-11-01

We examined the association of rs7626962 (S1103Y) or rs7629265, a variant in high linkage disequilibrium with S1103Y (r(2) = 0.87 - 1), with sudden cardiac death (SCD) and atrial fibrillation (AF) among African Americans. The SCN5A missense variant S1103Y has been associated with SCD among African Americans in small case-control studies, but larger population-based studies are needed to validate these findings. The association of this variant with AF has not been fully explored. Using genotyping data on over 7,000 African Americans from 5 cohorts (Atherosclerosis Risk in Communities [ARIC], Cleveland Family Study [CFS], Jackson Heart Study [JHS], Multi-Ethnic Study of Atherosclerosis [MESA], Cardiovascular Health Study [CHS]), we examined the association of rs7629265 with electrocardiographic PR, QRS, and QT intervals, and with incident AF and SCD. We examined association of S1103Y (rs7626962) with SCD using a population-based case-control study of SCD Cardiac Arrest Blood Study (CABS). Meta-analyses across 5 cohorts demonstrated that rs7629265 was significantly associated with PR duration (β = -4.1 milliseconds; P = 2.2×10(-6) ), but not significantly associated with QRS or QT intervals. In meta-analyses of prospectively followed ARIC and CHS participants (n = 3,656), rs7629265 was associated with increased AF risk (n = 299 AF cases; HR = 1.74, P = 1.9 × 10(-4) ). By contrast, rs7629265 was not significantly associated with SCD risk in ARIC (n = 83 SCD cases; P = 0.30) or CHS (n = 54 SCD cases; P = 0.47). Similarly, S1103Y was not significantly associated with SCD risk in CABS (n = 225 SCD cases; P = 0.29). The common SCN5A variant, rs7629265, is associated with increased AF risk and shorter PR interval among African Americans. In contrast to prior reports, we found no evidence of association of rs7629265 or rs7626962 (S1103Y) with SCD risk in the general population. © 2014 Wiley Periodicals, Inc.

Hydrodynamic flow in capillary-channel fiber columns for liquid chromatography.

PubMed

Stanelle, Rayman D; Sander, Lane C; Marcus, R Kenneth

2005-12-23

The flow characteristics of capillary-channel polymer (C-CP) fiber liquid chromatographic (LC) columns have been investigated. The C-CP fibers are manufactured with eight longitudinal grooves (capillary channels) extending the length of the fibers. Three C-CP fiber examples were studied, with fiber dimensions ranging from approximately 35 microm to 65 microm, and capillary-channel dimensions ranging from approximately 6 microm to 35 microm. The influence of fiber packing density and column inner diameter on peak asymmetry, peak width, and run-to-run reproducibility have been studied for stainless steel LC columns packed with polyester (PET) and polypropylene (PP) C-CP fibers. The van Deemter A-term was evaluated as a function of fiber packing density (approximately 0.3 g/cm(3)-0.75 g/cm(3)) for columns of 4.6 mm inner diameter (i.d.) and at constant packing densities for 1.5 mm, 3.2 mm, 4.6 mm, and 7.7 mm i.d. columns. Although column diameter had little influence on the eluting peak widths, peak asymmetry increased with increasing column diameter. The A-terms for the C-CP fiber packed columns are somewhat larger than current commercial, microparticulate-packed columns, and means for improvement are discussed. Applications in the area of protein (macromolecule) separations appear the most promising at this stage of the system development.

Association between serum soluble CD40 ligand levels and mortality in patients with severe sepsis.

PubMed

Lorente, Leonardo; Martín, María M; Varo, Nerea; Borreguero-León, Juan María; Solé-Violán, Jordi; Blanquer, José; Labarta, Lorenzo; Díaz, César; Jiménez, Alejandro; Pastor, Eduardo; Belmonte, Felipe; Orbe, Josune; Rodríguez, José A; Gómez-Melini, Eduardo; Ferrer-Agüero, José M; Ferreres, José; Llimiñana, María C; Páramo, José A

2011-03-15

CD40 Ligand (CD40L) and its soluble counterpart (sCD40L) are proteins that exhibit prothrombotic and proinflammatory properties on binding to their cell surface receptor CD40. The results of small clinical studies suggest that sCD40L levels could play a role in sepsis; however, there are no data on the association between sCD40L levels and mortality of septic patients. Thus, the aim of this study was to determine whether circulating sCD40L levels could be a marker of adverse outcome in a large cohort of patients with severe sepsis. This was a multicenter, observational and prospective study carried out in six Spanish intensive care units. Serum levels of sCD40L, tumour necrosis factor-alpha and interleukin-10, and plasma levels of tissue factor were measured in 186 patients with severe sepsis at the time of diagnosis. Serum sCD40L was also measured in 50 age- and sex-matched controls. Survival at 30 days was used as the endpoint. Circulating sCD40L levels were significantly higher in septic patients than in controls (P = 0.01), and in non-survivors (n = 62) compared to survivors (n = 124) (P = 0.04). However, the levels of CD40L were not different regarding sepsis severity. Logistic regression analysis showed that sCD40L levels >3.5 ng/mL were associated with higher mortality at 30 days (odds ratio = 2.89; 95% confidence interval = 1.37 to 6.07; P = 0.005). The area under the curve of sCD40L levels >3.5 ng/mL as predictor of mortality at 30 days was 0.58 (95% CI = 0.51 to 0.65; P = 0.03). In conclusion, circulating sCD40L levels are increased in septic patients and are independently associated with mortality in these patients; thus, its modulation could represent an attractive therapeutic target.

Population-based studies of antithyroid drugs and sudden cardiac death

PubMed Central

van Noord, Charlotte; Sturkenboom, Miriam C J M; Straus, Sabine M J M; Hofman, Albert; Witteman, Jacqueline C M; Stricker, Bruno H Ch

2009-01-01

AIM Thyroid free T4 is associated with QTc-interval prolongation, which is a risk factor for sudden cardiac death (SCD). Hyperthyroidism has been associated with SCD in case reports, but there are no population-based studies confirming this. The aim was to investigate whether use of antithyroid drugs (as a direct cause or as an indicator of poorly controlled hyperthyroidism) is associated with an increased risk of SCD. METHODS We studied the occurrence of SCD in a two-step procedure in two different Dutch populations. First, the prospective population-based Rotterdam Study including 7898 participants (≥55 years old). Second, we used the Integrated Primary Care Information (IPCI) database, which is a longitudinal general practice research database to see whether we could replicate results from the first study. Drug use at the index date was assessed with prescription information from automated pharmacies (Rotterdam Study) or drug prescriptions from general practices (IPCI). We used a Cox proportional hazards model in a cohort analysis, adjusted for age, gender and use of QTc prolonging drugs (Rotterdam Study) and conditional logistic regression analysis in a case–control analysis, matched for age, gender, practice and calendar time and adjusted for arrhythmia and cerebrovascular ischaemia (IPCI). RESULTS In the Rotterdam Study, 375 participants developed SCD during follow-up. Current use of antithyroid drugs was associated with SCD [adjusted hazard ratio 3.9; 95% confidence interval (CI) 1.7, 8.7]. IPCI included 1424 cases with SCD and 14 443 controls. Also in IPCI, current use of antithyroid drugs was associated with SCD (adjusted odds ratio 2.9; 95% CI 1.1, 7.4). CONCLUSIONS Use of antithyroid drugs was associated with a threefold increased risk of SCD. Although this might be directly caused by antithyroid drug use, it might be more readily explained by underlying poorly controlled hyperthyroidism, since treated patients who developed SCD still had low thyroid-stimulating hormone levels shortly before death. PMID:19740403

Subjective Cognitive Decline Is Associated With Altered Default Mode Network Connectivity in Individuals With a Family History of Alzheimer's Disease.

PubMed

Verfaillie, Sander C J; Pichet Binette, Alexa; Vachon-Presseau, Etienne; Tabrizi, Shirin; Savard, Mélissa; Bellec, Pierre; Ossenkoppele, Rik; Scheltens, Philip; van der Flier, Wiesje M; Breitner, John C S; Villeneuve, Sylvia

2018-05-01

Both subjective cognitive decline (SCD) and a family history of Alzheimer's disease (AD) portend risk of brain abnormalities and progression to dementia. Posterior default mode network (pDMN) connectivity is altered early in the course of AD. It is unclear whether SCD predicts similar outcomes in cognitively normal individuals with a family history of AD. We studied 124 asymptomatic individuals with a family history of AD (age 64 ± 5 years). Participants were categorized as having SCD if they reported that their memory was becoming worse (SCD + ). We used extensive neuropsychological assessment to investigate five different cognitive domain performances at baseline (n = 124) and 1 year later (n = 59). We assessed interconnectivity among three a priori defined ROIs: pDMN, anterior ventral DMN, medial temporal memory system (MTMS), and the connectivity of each with the rest of brain. Sixty-eight (55%) participants reported SCD. Baseline cognitive performance was comparable between groups (all false discovery rate-adjusted p values > .05). At follow-up, immediate and delayed memory improved across groups, but the improvement in immediate memory was reduced in SCD + compared with SCD - (all false discovery rate-adjusted p values < .05). When compared with SCD - , SCD + subjects showed increased pDMN-MTMS connectivity (false discovery rate-adjusted p < .05). Higher connectivity between the MTMS and the rest of the brain was associated with better baseline immediate memory, attention, and global cognition, whereas higher MTMS and pDMN-MTMS connectivity were associated with lower immediate memory over time (all false discovery rate-adjusted p values < .05). SCD in cognitively normal individuals is associated with diminished immediate memory practice effects and a brain connectivity pattern that mirrors early AD-related connectivity failure. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

The effect of hypnosis on pain and peripheral blood flow in sickle-cell disease: a pilot study

PubMed Central

Bhatt, Ravi R; Martin, Sarah R; Evans, Subhadra; Lung, Kirsten; Coates, Thomas D; Zeltzer, Lonnie K; Tsao, Jennie C

2017-01-01

Background Vaso-occlusive pain crises (VOCs) are the “hallmark” of sickle-cell disease (SCD) and can lead to sympathetic nervous system dysfunction. Increased sympathetic nervous system activation during VOCs and/or pain can result in vasoconstriction, which may increase the risk for subsequent VOCs and pain. Hypnosis is a neuromodulatory intervention that may attenuate vascular and pain responsiveness. Due to the lack of laboratory-controlled pain studies in patients with SCD and healthy controls, the specific effects of hypnosis on acute pain-associated vascular responses are unknown. The current study assessed the effects of hypnosis on peripheral blood flow, pain threshold, tolerance, and intensity in adults with and without SCD. Subjects and methods Fourteen patients with SCD and 14 healthy controls were included. Participants underwent three laboratory pain tasks before and during a 30-minute hypnosis session. Peripheral blood flow, pain threshold, tolerance, and intensity before and during hypnosis were examined. Results A single 30-minute hypnosis session decreased pain intensity by a moderate amount in patients with SCD. Pain threshold and tolerance increased following hypnosis in the control group, but not in patients with SCD. Patients with SCD exhibited lower baseline peripheral blood flow and a greater increase in blood flow following hypnosis than controls. Conclusion Given that peripheral vasoconstriction plays a role in the development of VOC, current findings provide support for further laboratory and clinical investigations of the effects of cognitive–behavioral neuromodulatory interventions on pain responses and peripheral vascular flow in patients with SCD. Current results suggest that hypnosis may increase peripheral vasodilation during both the anticipation and experience of pain in patients with SCD. These findings indicate a need for further examination of the effects of hypnosis on pain and vascular responses utilizing a randomized controlled trial design. Further evidence may help determine unique effects of hypnosis and potential benefits of integrating cognitive–behavioral neuromodulatory interventions into SCD treatment. PMID:28769584

Sudden cardiac death associated with physical exertion in the US military, 2005-2010.

PubMed

Smallman, Darlene P; Webber, Bryant J; Mazuchowski, Edward L; Scher, Ann I; Jones, Sam O; Cantrell, Joyce A

2016-01-01

Sudden cardiac death associated with physical exertion (SCD/E) is a complicated pathophysiological event. This study aims to calculate the incidence rate of SCD/E in the US military population from 2005 to 2010, to characterise the demographic and cardiovascular risk profiles of decedents, and to evaluate aetiologies of and circumstances surrounding the deaths. Perimortem and other relevant data were collected from the Armed Forces Medical Examiners Tracking System, Armed Forces Health Longitudinal Technology Application, and Defense Medical Epidemiology Database for decedents meeting SCD/E case definition. Incidence rates were calculated and compared using negative binomial regression. The incidence of SCD/E in the Active Component (ie, full-time active duty) US military from 2005 to 2010 was 1.63 per 100 000 person-years (py): 0.98 and 3.84 per 100 000 py in those aged <35 and ≥35 years, respectively. Atherosclerotic cardiovascular disease was the leading cause of death overall (55%) and in the ≥35-year age group (78%), whereas the leading cause of death in the <35-year age group (31%) could not be precisely determined and was termed idiopathic SCD/E (iSCD/E). SCD/E was more common in males than females (incidence rate ratio (IRR) = 5.28, 95% CI 2.16 to 12.93) and more common in blacks than whites (IRR=2.60, 95% CI 1.81 to 3.72). All female cases were black. From 2005 to 2010, the incidence of SCD/E in US military members aged <35 years was similar to most reported corresponding civilian SCD rates. However, the leading cause of death was iSCD/E and not cardiomyopathy. Improved surveillance and age-based prevention strategies may reduce these rates. 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/

Serum sCD30: A promising biomarker for predicting the risk of bacterial infection after kidney transplantation.

PubMed

Fernández-Ruiz, Mario; Parra, Patricia; López-Medrano, Francisco; Ruiz-Merlo, Tamara; González, Esther; Polanco, Natalia; Origüen, Julia; San Juan, Rafael; Andrés, Amado; Aguado, José María

2017-04-01

The transmembrane glycoprotein CD30 contributes to regulate the balance between Th 1 and Th 2 responses. Previous studies have reported conflicting results on the utility of its soluble form (sCD30) to predict post-transplant infection. Serum sCD30 was measured by a commercial ELISA assay at baseline and post-transplant months 1, 3, and 6 in 100 kidney transplant (KT) recipients (279 monitoring points). The impact of sCD30 levels on the incidence of overall, bacterial and opportunistic infection during the first 12 months after transplantation was assessed by Cox regression. There were no differences in serum sCD30 according to the occurrence of overall or opportunistic infection. However, sCD30 levels were higher in patients with bacterial infection compared to those without at baseline (P=.038) and months 1 (P<.0001), 3 (P=.043), and 6 after transplantation (P=.006). Patients with baseline sCD30 levels ≥13.5 ng/mL had lower 12-month bacterial infection-free survival (35.0% vs 80.0%; P<.0001). After adjusting for potential confounders, baseline sCD30 levels ≥13.5 ng/mL remained as an independent risk factor for bacterial infection (adjusted hazard ratio [aHR]: 4.65; 95% confidence interval [CI]: 2.05-10.53; <.001). Analogously, sCD30 levels ≥6.0 ng/mL at month 1 acted as a risk factor for subsequent bacterial infection (aHR: 5.29; 95% CI: 1.11-25.14; P=.036). Higher serum sCD30 levels were associated with an increased risk of bacterial infection after KT. We hypothesize that this biomarker reflects a Th 2 -polarized T-cell response, which exerts a detrimental effect on the immunity against bacterial pathogens. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Soluble CD26 levels and its association to epidemiologic parameters in a sample population.

PubMed

De Chiara, Loretta; Rodríguez-Piñeiro, Ana M; Cordero, Oscar J; Rodríguez-Berrocal, Francisco J; Ayude, Daniel; Rivas-Hervada And, Francisco J; de la Cadena, María Páez

2009-01-01

Previous studies have suggested the use of soluble CD26 (sCD26) as a tumour marker for the detection of colorectal cancer (CRC) and advanced adenomas. The aim of this study was to assess the sCD26 concentration in a large cohort to evaluate its association to epidemiologic parameters and CRC-related symptoms/pathologies. Serum samples were collected from 2,754 putatively healthy individuals with ages ranging from 30-65 years, and with personal or familial history of polyps, CRC and/or CR symptoms. sCD26 levels were measured by ELISA. No association was found between the sCD26 concentration and age (< 50 and 50), the personal or familial history of polyps or CRC, rectal bleeding, haemorrhoids or diverticula. However, sCD26 was related to non-inflammatory benign pathologies (excluding rectal bleeding, changes in bowel habits, haemorrhoids, diverticula) and to inflammatory benign pathologies. Our results confirm that the sCD26 can be easily offered and evaluated in a large cohort. Additionally, the validation of sCD26 as a tumour marker for screening and case-finding purposes requires a further comparison with an established non-invasive test like the faecal occult blood.

Prasugrel hydrochloride for the treatment of sickle cell disease.

PubMed

Conran, Nicola; Rees, David C

2017-07-01

Therapeutic options for sickle cell disease (SCD) are limited and, currently, only one drug (hydroxyurea) has FDA approval for the treatment of adult SCD. While this genetic disease is caused by hemoglobin polymerization, subsequent downstream events trigger platelet activation, vaso-occlusion and the disease's complex pathophysiology. Areas covered: The oral thienopyridine, prasugrel hydrochloride, irreversibly inhibits the P2Y12 receptors, inhibiting ADP-dependent platelet activation. We discuss recent clinical trials evaluating the pharmokinetics of prasugrel and its potential for use in SCD. Expert opinion: Prasugrel administration in SCD appears to be well tolerated and safe. However, although this drug modestly inhibits platelet activity in these patients, administration of prasugrel to a large group of children and adolescents for up to 24 months failed to convincingly reduce vaso-occlusive complications. Speculatively, prasugrel may be of occasional use for off-license purposes in patients unable or unwilling to take hydroxyurea (particularly in 12-17-year olds). Although there is currently no prospect of prasugrel being licensed for use in SCD, the success of on-going trials of other antiplatelet agents in SCD might lead to further trials of prasugrel in SCD.

Identification of a Sudden Cardiac Death Susceptibility Locus at 2q24.2 through Genome-Wide Association in European Ancestry Individuals

PubMed Central

Reinier, Kyndaron; Teodorescu, Carmen; Uy-Evanado, Audrey; Carter-Monroe, Naima; Kaikkonen, Kari S.; Kortelainen, Marja-Leena; Boucher, Gabrielle; Lagacé, Caroline; Moes, Anna; Zhao, XiaoQing; Kolodgie, Frank; Rivadeneira, Fernando; Hofman, Albert; Witteman, Jacqueline C. M.; Uitterlinden, André G.; Marsman, Roos F.; Pazoki, Raha; Bardai, Abdennasser; Koster, Rudolph W.; Dehghan, Abbas; Hwang, Shih-Jen; Bhatnagar, Pallav; Post, Wendy; Hilton, Gina; Prineas, Ronald J.; Li, Man; Köttgen, Anna; Ehret, Georg; Boerwinkle, Eric; Coresh, Josef; Kao, W. H. Linda; Psaty, Bruce M.; Tomaselli, Gordon F.; Sotoodehnia, Nona; Siscovick, David S.; Burke, Greg L.; Marbán, Eduardo; Spooner, Peter M.; Cupples, L. Adrienne; Jui, Jonathan; Gunson, Karen; Kesäniemi, Y. Antero; Wilde, Arthur A. M.; Tardif, Jean-Claude; O'Donnell, Christopher J.; Bezzina, Connie R.; Virmani, Renu; Stricker, Bruno H. C. h.; Tan, Hanno L.; Albert, Christine M.; Chakravarti, Aravinda; Rioux, John D.; Huikuri, Heikki V.; Chugh, Sumeet S.

2011-01-01

Sudden cardiac death (SCD) continues to be one of the leading causes of mortality worldwide, with an annual incidence estimated at 250,000–300,000 in the United States and with the vast majority occurring in the setting of coronary disease. We performed a genome-wide association meta-analysis in 1,283 SCD cases and >20,000 control individuals of European ancestry from 5 studies, with follow-up genotyping in up to 3,119 SCD cases and 11,146 controls from 11 European ancestry studies, and identify the BAZ2B locus as associated with SCD (P = 1.8×10−10). The risk allele, while ancestral, has a frequency of ∼1.4%, suggesting strong negative selection and increases risk for SCD by 1.92–fold per allele (95% CI 1.57–2.34). We also tested the role of 49 SNPs previously implicated in modulating electrocardiographic traits (QRS, QT, and RR intervals). Consistent with epidemiological studies showing increased risk of SCD with prolonged QRS/QT intervals, the interval-prolonging alleles are in aggregate associated with increased risk for SCD (P = 0.006). PMID:21738491

Identification of the hot-spot areas for sickle cell disease using cord blood screening at a district hospital: an Indian perspective.

PubMed

Dixit, Sujata; Sahu, Pushpansu; Kar, Shantanu Kumar; Negi, Sapna

2015-10-01

Sickle cell disease (SCD), a genetic disorder often reported late, can be identified early in life, and hot-spot areas may be identified to conduct genetic epidemiology studies. This study was undertaken to estimate prevalence and to identify hot spot area for SCD in Kalahandi district, by screening cord blood of neonates delivered at the district hospital as first-hand information. Kalahandi District Hospital selected for the study is predominated by tribal population with higher prevalence of SCD as compared to other parts of Odisha. Cord blood screening of SCD was carried out on 761 newborn samples of which 13 were screened to be homozygous for SCD. Information on area of parent's residence was also collected. Madanpur Rampur area was found to be with the highest prevalence of SCD (10.52 %) and the gene distribution did not follow Hardy-Weinberg Equation indicating un-natural selection. The approach of conducting neonatal screening in a district hospital for identification of SCD is feasible and appropriate for prioritizing area for the implementation of large-scale screening and planning control measures thereof.

Separation of carbon nanotubes into chirally enriched fractions

DOEpatents

Doorn, Stephen K [Los Alamos, NM; Niyogi, Sandip [Los Alamos, NM

2012-04-10

A mixture of single-walled carbon nanotubes ("SWNTs") is separated into fractions of enriched chirality by preparing an aqueous suspension of a mixture of SWNTs and a surfactant, injecting a portion of the suspension on a column of separation medium having a density gradient, and centrifuging the column. In some embodiments, salt is added prior to centrifugation. In other embodiments, the centrifugation is performed at a temperature below room temperature. Fractions separate as colored bands in the column. The diameter of the separated SWNTs decreases with increasing density along the gradient of the column. The colored bands can be withdrawn separately from the column.

Interstellar C IV and Si IV column densities toward early-type stars

NASA Technical Reports Server (NTRS)

Bruhweiler, F. C.; Kondo, Y.; Mccluskey, G. E.

1980-01-01

Equivalent widths and deduced column densities of Si IV and C IV are examined for 18 early-type close binaries, and physical processes responsible for the origin of these ions in the interstellar medium are investigated. The available C IV/Si IV column density ratios typically lie within a narrow range from 0.8 to 4.5, and there is evidence that the column density of C IV is higher than that of N V along most lines of sight, suggesting that C IV is not formed in the same hot region as O VI. In addition, the existence of regions with a narrowly defined new temperature range around 50,000 deg K is indicated. The detection of the semitorrid gas of Bruhweiler, Kondo, and McCluskey (1978, 1979) is substantiated, and the relation of this gas to the observations of coronal gas in the galactic halo is discussed.

Gestational dietary betaine supplementation suppresses hepatic expression of lipogenic genes in neonatal piglets through epigenetic and glucocorticoid receptor-dependent mechanisms.

PubMed

Cai, Demin; Wang, Junjian; Jia, Yimin; Liu, Haoyu; Yuan, Mengjie; Dong, Haibo; Zhao, Ruqian

2016-01-01

Methyl donors play critical roles in nutritional programming through epigenetic regulation of gene expression. Here we fed gestational sows with control or betaine-supplemented diets (3g/kg) throughout the pregnancy to explore the effects of maternal methyl-donor nutrient on neonatal expression of hepatic lipogenic genes. Betaine-exposed piglets demonstrated significantly lower liver triglyceride content associated with down-regulated hepatic expression of lipogenic genes acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), stearoyl-CoA desaturase (SCD) and sterol regulatory element-binding protein-1c. Moreover, s-adenosyl methionine to s-adenosyl homocysteine ratio was elevated in the liver of betaine-exposed piglets, which was accompanied by DNA hypermethylation on FAS and SCD gene promoters and more enriched repression histone mark H3K27me3 on SCD gene promoter. Furthermore, glucocorticoid receptor (GR) binding to SCD gene promoter was diminished along with reduced serum cortisol and liver GR protein content in betaine-exposed piglets. GR-mediated SCD gene regulation was confirmed in HepG2 cells in vitro. Dexamethasone (Dex) drastically increased the luciferase activity of porcine SCD promoter, while the deletion of GR response element on SCD promoter significantly attenuated Dex-mediated SCD transactivation. In addition, miR-let-7e, miR-1285 and miR-124a, which respectively target porcine SCD, ACC and GR, were significantly up-regulated in the liver of betaine-exposed piglets, being in accordance with decreased protein content of these three genes. Taken together, our results suggest that maternal dietary betaine supplementation during gestation attenuates hepatic lipogenesis in neonatal piglets via epigenetic and GR-mediated mechanisms. Copyright © 2015 Elsevier B.V. All rights reserved.

Altered fatty acid metabolism and reduced stearoyl-coenzyme a desaturase activity in asthma.

PubMed

Rodriguez-Perez, N; Schiavi, E; Frei, R; Ferstl, R; Wawrzyniak, P; Smolinska, S; Sokolowska, M; Sievi, N A; Kohler, M; Schmid-Grendelmeier, P; Michalovich, D; Simpson, K D; Hessel, E M; Jutel, M; Martin-Fontecha, M; Palomares, O; Akdis, C A; O'Mahony, L

2017-11-01

Fatty acids and lipid mediator signaling play an important role in the pathogenesis of asthma, yet this area remains largely underexplored. The aims of this study were (i) to examine fatty acid levels and their metabolism in obese and nonobese asthma patients and (ii) to determine the functional effects of altered fatty acid metabolism in experimental models. Medium- and long-chain fatty acid levels were quantified in serum from 161 human volunteers by LC/MS. Changes in stearoyl-coenzyme A desaturase (SCD) expression and activity were evaluated in the ovalbumin (OVA) and house dust mite (HDM) murine models. Primary human bronchial epithelial cells from asthma patients and controls were evaluated for SCD expression and activity. The serum desaturation index (an indirect measure of SCD) was significantly reduced in nonobese asthma patients and in the OVA murine model. SCD1 gene expression was significantly reduced within the lungs following OVA or HDM challenge. Inhibition of SCD in mice promoted airway hyper-responsiveness. SCD1 expression was suppressed in bronchial epithelial cells from asthma patients. IL-4 and IL-13 reduced epithelial cell SCD1 expression. Inhibition of SCD reduced surfactant protein C expression and suppressed rhinovirus-induced IP-10 secretion, which was associated with increased viral titers. This is the first study to demonstrate decreased fatty acid desaturase activity in humans with asthma. Experimental models in mice and human epithelial cells suggest that inhibition of desaturase activity leads to airway hyper-responsiveness and reduced antiviral defense. SCD may represent a new target for therapeutic intervention in asthma patients. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Subjective memory and concentration deficits in medication-free, non-elderly Asians with major depressive disorder: prevalence and their correlates.

PubMed

Srisurapanont, Manit; Bautista, Dianne; Chen, Chia-Hui; Wang, Gang; Udomratn, Pichet; Eurviriyanukul, Kanokkwan

2015-01-15

Subjective cognitive impairment (SCI) in major depressive disorder (MDD) is prevalent and correlated with disability. This study aimed to examine the prevalence rates and correlates of subjective memory deficit (SMD) and subjective concentration deficit (SCD) in medication-free, non-elderly Asians with MDD. The SMD and SCD were assessed by using two items of the Symptom Checklist-90-Revised (SCL-90-R). Other measurements of interest included the Montgomery-Asberg Depression Rating Scale (MADRS), the Fatigue Severity Scale (FSS), the Sheehan Disability Scale (SDS), and the Short Form Health Survey (SF-36). Adjusted odds ratios with 95% confidence intervals were calculated. Of 515 participants from China, Korea, Malaysia, Singapore, Taiwan, and Thailand, 347 (67.4%) and 377 (73.2%) had SMD and SCD, respectively. In total, 420 participants (81.6%) had SMD alone, SCD alone, and both deficits. Severe depression and poor mental health were significant correlates of SMD. Severe depression, clinically significant disability, poor physical health, and poor mental health were significantly independent correlates of SCD. Compared with young adults (18-34 years), older adults aged 50-65 years had a significantly lower risk of SCD (OR=.33, 95% CI: .19-.57). Only two SCL-90-R items were used to assess the SMD and SCD. The exclusion of MDD patients treated with psychotropic medications eliminated many patients commonly seen in typical clinic settings. SMD and SCD are prevalent in medication-free, non-elderly Asians with MDD. Both deficits are correlated with depression and mental health status. The independent correlation between SCD and disability underscores the crucial role of SCI in MDD. Copyright © 2014 Elsevier B.V. All rights reserved.

Incidence of sudden cardiac death in Germany: results from an emergency medical service registry in Lower Saxony

PubMed Central

Martens, Eimo; Sinner, Moritz F.; Siebermair, Johannes; Raufhake, Carsten; Beckmann, Britt M.; Veith, Stefan; Düvel, Dieter; Steinbeck, Gerhard; Kääb, Stefan

2014-01-01

Aims Sudden cardiac death (SCD) is among the most common causes of death in western countries including Germany. Whereas risk stratification and primary prevention is still insufficient, we also lack accurate incidence estimates. Current estimates vary widely (18.6–128/100 000/year), but data on SCD incidence in Germany are missing. Depending on SCD definitions, death needs to occur between 1 and 24 h after the onset of symptoms. Methods and results In the district of Aurich (190 000 inhabitants, Lower Saxony, Germany), emergency medical service (EMS) is provided by a district government operated single carrier and two hospitals. To evaluate all EMS calls in this district from 2002 to 2009, we obtained EMS protocols, medical records, and death certificates for data analysis and adjudication of SCD. We defined SCD according to the definition of the World Health Organization, considering patients with cardiac arrest within ≤1 h after the onset of symptoms. We also required cardiopulmonary resuscitation being performed by EMS personnel. The overall mortality rate in the district of Aurich (1060/100 000/year) corresponded well with the average mortality rate in Germany (1030/100 000/year). During the observation period, we adjudicated 1212 SCD cases, equivalent to an annual rate of 151 SCD cases (81 cases/100 000/year). Rates remained remarkably stable over time, and affected a considerable number of individuals of working age (32/100 000/year). Conclusion Consistent with prior reports, the SCD incidence in a district of Germany is substantial. Despite an elaborate EMS system and advanced medical care, SCD rates remain stable and necessitate improved, individualized risk stratification. PMID:25061228

Incidence of sudden cardiac death in Germany: results from an emergency medical service registry in Lower Saxony.

PubMed

Martens, Eimo; Sinner, Moritz F; Siebermair, Johannes; Raufhake, Carsten; Beckmann, Britt M; Veith, Stefan; Düvel, Dieter; Steinbeck, Gerhard; Kääb, Stefan

2014-12-01

Sudden cardiac death (SCD) is among the most common causes of death in western countries including Germany. Whereas risk stratification and primary prevention is still insufficient, we also lack accurate incidence estimates. Current estimates vary widely (18.6-128/100,000/year), but data on SCD incidence in Germany are missing. Depending on SCD definitions, death needs to occur between 1 and 24 h after the onset of symptoms. In the district of Aurich (190,000 inhabitants, Lower Saxony, Germany), emergency medical service (EMS) is provided by a district government operated single carrier and two hospitals. To evaluate all EMS calls in this district from 2002 to 2009, we obtained EMS protocols, medical records, and death certificates for data analysis and adjudication of SCD. We defined SCD according to the definition of the World Health Organization, considering patients with cardiac arrest within ≤1 h after the onset of symptoms. We also required cardiopulmonary resuscitation being performed by EMS personnel. The overall mortality rate in the district of Aurich (1060/100,000/year) corresponded well with the average mortality rate in Germany (1030/100,000/year). During the observation period, we adjudicated 1212 SCD cases, equivalent to an annual rate of 151 SCD cases (81 cases/100,000/year). Rates remained remarkably stable over time, and affected a considerable number of individuals of working age (32/100,000/year). Consistent with prior reports, the SCD incidence in a district of Germany is substantial. Despite an elaborate EMS system and advanced medical care, SCD rates remain stable and necessitate improved, individualized risk stratification. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Cardiology.

Inducing effect of clofibric acid on stearoyl-CoA desaturase in intestinal mucosa of rats.

PubMed

Yamazaki, Tohru; Kadokura, Makiko; Mutoh, Yuki; Sakamoto, Takeshi; Okazaki, Mari; Mitsumoto, Atsushi; Kawashima, Yoichi; Kudo, Naomi

2014-12-01

Fibrates have been reported to elevate the hepatic proportion of oleic acid (18:1n-9) through inducing stearoyl-CoA desaturase (SCD). Despite abundant studies on the regulation of SCD in the liver, little is known about this issue in the small intestine. The present study aimed to investigate the effect of clofibric acid on the fatty acid profile, particularly monounsaturated fatty acids (MUFA), and the SCD expression in intestinal mucosa. Treatment of rats with a diet containing 0.5% (w/w) clofibric acid for 7 days changed the MUFA profile of total lipids in intestinal mucosa; the proportion of 18:1n-9 was significantly increased, whereas those of palmitoleic (16:1n-7) and cis-vaccenic (18:1n-7) acids were not changed. Upon the treatment with clofibric acid, SCD was induced and the gene expression of SCD1, SCD2, and fatty acid elongase (Elovl) 6 was up-regulated, but that of Elovl5 was unaffected. Fat-free diet feeding for 28 days increased the proportions of 16:1n-7 and 18:1n-7, but did not effectively change that of 18:1n-9, in intestinal mucosa. Fat-free diet feeding up-regulated the gene expression of SCD1, but not that of SCD2, Elovl6, or Elovl5. These results indicate that intestinal mucosa significantly changes its MUFA profile in response to challenges by clofibric acid and a fat-free diet and suggest that up-regulation of the gene expression of SCD along with Elovl6 is indispensable to elevate the proportion of 18:1n-9 in intestinal mucosa.

Increased iron export by ferroportin induces restriction of HIV-1 infection in sickle cell disease.

PubMed

Kumari, Namita; Ammosova, Tatiana; Diaz, Sharmin; Lin, Xionghao; Niu, Xiaomei; Ivanov, Andrey; Jerebtsova, Marina; Dhawan, Subhash; Oneal, Patricia; Nekhai, Sergei

2016-12-27

The low incidence of HIV-1 infection in patients with sickle cell disease (SCD) and inhibition of HIV-1 replication in vitro under the conditions of low intracellular iron or heme treatment suggests a potential restriction of HIV-1 infection in SCD. We investigated HIV-1 ex vivo infection of SCD peripheral blood mononuclear cells (PBMCs) and found that HIV-1 replication was inhibited at the level of reverse transcription (RT) and transcription. We observed increased expression of heme and iron-regulated genes, previously shown to inhibit HIV-1, including ferroportin, IKBα, HO-1, p21, and SAM domain and HD domain-containing protein 1 (SAMHD1). HIV-1 inhibition was less pronounced in hepcidin-treated SCD PBMCs and more pronounced in the iron or iron chelators treated, suggesting a key role of iron metabolism. In SCD PBMCs, labile iron levels were reduced and protein levels of ferroportin, HIF-1α, IKBα, and HO-1 were increased. Hemin treatment induced ferroportin expression and inhibited HIV-1 in THP-1 cells, mimicking the HIV-1 inhibition in SCD PBMCs, especially as hepcidin similarly prevented HIV-1 inhibition. In THP-1 cells with knocked down ferroportin, IKBα, or HO-1 genes but not HIF-1α or p21, HIV-1 was not inhibited by hemin. Activity of SAMHD1-regulatory CDK2 was decreased, and SAMHD1 phosphorylation was reduced in SCD PBMCs and hemin-treated THP-1 cells, suggesting SAMHD1-mediated HIV-1 restriction in SCD. Our findings point to ferroportin as a trigger of HIV-1 restriction in SCD settings, linking reduced intracellular iron levels to the inhibition of CDK2 activity, reduction of SAMHD1 phosphorylation, increased IKBα expression, and inhibition of HIV-1 RT and transcription.

Autonomic responses to cold face stimulation in sickle cell disease: a time-varying model analysis.

PubMed

Chalacheva, Patjanaporn; Kato, Roberta M; Sangkatumvong, Suvimol; Detterich, Jon; Bush, Adam; Wood, John C; Meiselman, Herbert; Coates, Thomas D; Khoo, Michael C K

2015-07-14

Sickle cell disease (SCD) is characterized by sudden onset of painful vaso-occlusive crises (VOC), which occur on top of the underlying chronic blood disorder. The mechanisms that trigger VOC remain elusive, but recent work suggests that autonomic dysfunction may be an important predisposing factor. Heart-rate variability has been employed in previous studies, but the derived indices have provided only limited univariate information about autonomic cardiovascular control in SCD. To circumvent this limitation, a time-varying modeling approach was applied to investigate the functional mechanisms relating blood pressure (BP) and respiration to heart rate and peripheral vascular resistance in healthy controls, untreated SCD subjects and SCD subjects undergoing chronic transfusion therapy. Measurements of respiration, heart rate, continuous noninvasive BP and peripheral vascular resistance were made before, during and after the application of cold face stimulation (CFS), which perturbs both the parasympathetic and sympathetic nervous systems. Cardiac baroreflex sensitivity estimated from the model was found to be impaired in nontransfused SCD subjects, but partially restored in SCD subjects undergoing transfusion therapy. Respiratory-cardiac coupling gain was decreased in SCD and remained unchanged by chronic transfusion. These results are consistent with autonomic dysfunction in the form of impaired parasympathetic control and sympathetic overactivity. As well, CFS led to a significant reduction in vascular resistance baroreflex sensitivity in the nontransfused SCD subjects but not in the other groups. This blunting of the baroreflex control of peripheral vascular resistance during elevated sympathetic drive could be a potential factor contributing to the triggering of VOC in SCD. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Increased iron export by ferroportin induces restriction of HIV-1 infection in sickle cell disease

PubMed Central

Kumari, Namita; Ammosova, Tatiana; Diaz, Sharmin; Lin, Xionghao; Niu, Xiaomei; Ivanov, Andrey; Jerebtsova, Marina; Dhawan, Subhash; Oneal, Patricia

2016-01-01

The low incidence of HIV-1 infection in patients with sickle cell disease (SCD) and inhibition of HIV-1 replication in vitro under the conditions of low intracellular iron or heme treatment suggests a potential restriction of HIV-1 infection in SCD. We investigated HIV-1 ex vivo infection of SCD peripheral blood mononuclear cells (PBMCs) and found that HIV-1 replication was inhibited at the level of reverse transcription (RT) and transcription. We observed increased expression of heme and iron-regulated genes, previously shown to inhibit HIV-1, including ferroportin, IKBα, HO-1, p21, and SAM domain and HD domain-containing protein 1 (SAMHD1). HIV-1 inhibition was less pronounced in hepcidin-treated SCD PBMCs and more pronounced in the iron or iron chelators treated, suggesting a key role of iron metabolism. In SCD PBMCs, labile iron levels were reduced and protein levels of ferroportin, HIF-1α, IKBα, and HO-1 were increased. Hemin treatment induced ferroportin expression and inhibited HIV-1 in THP-1 cells, mimicking the HIV-1 inhibition in SCD PBMCs, especially as hepcidin similarly prevented HIV-1 inhibition. In THP-1 cells with knocked down ferroportin, IKBα, or HO-1 genes but not HIF-1α or p21, HIV-1 was not inhibited by hemin. Activity of SAMHD1-regulatory CDK2 was decreased, and SAMHD1 phosphorylation was reduced in SCD PBMCs and hemin-treated THP-1 cells, suggesting SAMHD1-mediated HIV-1 restriction in SCD. Our findings point to ferroportin as a trigger of HIV-1 restriction in SCD settings, linking reduced intracellular iron levels to the inhibition of CDK2 activity, reduction of SAMHD1 phosphorylation, increased IKBα expression, and inhibition of HIV-1 RT and transcription. PMID:28203649

Development of a comprehensive survey of sexuality issues including a self-report version of the International Spinal Cord Injury sexual function basic data sets.

PubMed

New, P W; Currie, K E

2016-08-01

Questionnaire development, validation and completion. Develop comprehensive survey of sexuality issues including validated self-report versions of the International Spinal Cord Injury male sexual function and female sexual and reproductive function basic data sets (SR-iSCI-sexual function). People with spinal cord damage (SCD) living in the community, Australia from August 2013 to June 2014. An iterative process involving rehabilitation medicine clinicians, a nurse specialising in sexuality issues in SCD and people with SCD who developed a comprehensive survey that included the SR-iSCI-sexual function. Participants recruitment through spinal rehabilitation review clinic and community organisations that support people with SCD. Surveys completed by 154 people. Most were male (n=101, 65.6%). Respondents' median age was 50 years (interquartile range (IQR) 38-58), and they were a median of 10 years (IQR 4-20) after the onset of SCD. Sexual problems unrelated to SCD were reported by 12 (8%) respondents, and 114 (n=75.5%) reported sexual problems because of SCD. Orgasms were much less likely (χ(2)=13.1, P=0.006) to be normal in males (n=5, 5%) compared with females (n=11, 22%). Males had significantly worse (χ(2)=26.0, P=0.001) psychogenic genital functioning (normal n=9, 9%) than females (normal n=13, 26%) and worse (χ(2)=10.8, P=0.013) reflex genital functioning. Normal ejaculation was reported in only three (3%) men. Most (n=26, 52%) women reported reduced or absent menstruation pattern since SCD. The SR-iSCI-sexual function provides a useful tool for researchers and clinicians to collect information regarding patient-reported sexual functioning after SCD and to facilitate comparative studies.

Autonomic Nervous System Reactivity: Children With and Without Sickle Cell Disease

PubMed Central

Treadwell, Marsha J.; Alkon, Abbey; Styles, Lori; Boyce, W. Thomas

2011-01-01

Background Previous studies of healthy children have demonstrated a link between autonomic nervous system (ANS) reactivity and health outcomes, but there is limited research on whether ANS reactivity is similar for children with chronic conditions. Objective To determine if ANS reactivity differs for children with sickle cell disease (SCD) compared to a community sample of children without SCD. Method In two cross-sectional, descriptive studies, 32 public school children without chronic health problems were compared with 33 children with SCD. The children were 5-8 years old and they completed standardized protocols measuring ANS responses (respiratory sinus arrhythmia and pre-ejection period) during rest and challenge conditions in social, cognitive, sensory, and emotion domains. Reactivity was calculated as the difference between challenge response minus rest for each domain and overall. Results There were differences in the distributions of the samples in parent education and child age, so these variables were adjusted for in subsequent analyses. The community sample showed parasympathetic withdrawal (low respiratory sinus arrhythmia scores) and greater parasympathetic reactivity (low respiratory sinus arrhythmia difference scores and percentage of negative scores) compared with the children with SCD in the social (p < .05) and sensory domains (p < .05). The children with SCD showed greater sympathetic reactivity (low preejection period difference scores) compared with the community children in the cognitive domain (p < .05) and a greater percentage of children with SCD versus the community children showed negative pre-ejection period difference scores (sympathetic reactivity) in the social domain (p < .05). The community sample, but not the children with SCD, showed changes in respiratory sinus arrhythmia across domains (p < .05). Discussion Children with SCD may display a different pattern of ANS responses to laboratory challenges compared with children without SCD from the same community. PMID:21532352

Self-Reported Chemotherapy-Related Cognitive Impairment Compared with Cognitive Complaints following Menopause.

PubMed

Vega, Jennifer N; Dumas, Julie; Newhouse, Paul

2018-06-15

Cancer-related cognitive impairment (CRCI) is commonly reported following the administration of cancer treatment. Current longitudinal studies, primarily in women with breast cancer, suggest that up to 35%-60% of patients exhibit persistent CRCI (pCRCI) following completion of chemotherapy. Complaints of subjective cognitive decline (SCD) are also commonly reported by women during and following the menopause transition in non-cancer patients. Although the majority of evidence for cognitive difficulties in cancer patients and survivors is attributed to chemotherapy, there is growing evidence to suggest that menopausal status can also influence cognitive function in cancer patients. Given that menopausal status may be contributing to pCRCI, we compared a group of primarily post-menopausal women with pCRCI to two groups of post-menopausal women: women who endorse menopause-associated SCD (maSCD+) and women who do not (maSCD-) to explore the similarities/differences between maSCD and pCRCI and the potential role of menopause in pCRCI. pCRCI participants report more severe SCD symptoms than women after natural menopause, despite being on average 2.5-years post-chemotherapy, supporting previous findings that CRCI can persist for months to years after completing treatment. pCRCI participants not only endorsed greater SCD, but also exhibited objective performance differences. In addition, pCRCI participants endorsed significantly greater menopausal symptoms compared to either maSCD group. Results were not related to menopausal status prior to chemotherapy or current endocrine therapy use. These results suggest that while menopausal symptoms may contribute to SCD experienced by cancer patients after chemotherapy, they do not fully account for pCRCI. This article is protected by copyright. All rights reserved.

Genetic diminution of circulating prothrombin ameliorates multiorgan pathologies in sickle cell disease mice.

PubMed

Arumugam, Paritha I; Mullins, Eric S; Shanmukhappa, Shiva Kumar; Monia, Brett P; Loberg, Anastacia; Shaw, Maureen A; Rizvi, Tilat; Wansapura, Janaka; Degen, Jay L; Malik, Punam

2015-10-08

Sickle cell disease (SCD) results in vascular occlusions, chronic hemolytic anemia, and cumulative organ damage. A conspicuous feature of SCD is chronic inflammation and coagulation system activation. Thrombin (factor IIa [FIIa]) is both a central protease in hemostasis and a key modifier of inflammatory processes. To explore the hypothesis that reduced prothrombin (factor II [FII]) levels in SCD will limit vaso-occlusion, vasculopathy, and inflammation, we used 2 strategies to suppress FII in SCD mice. Weekly administration of FII antisense oligonucleotide "gapmer" to Berkeley SCD mice to selectively reduce circulating FII levels to ∼10% of normal for 15 weeks significantly diminished early mortality. More comprehensive, long-term comparative studies were done using mice with genetic diminution of circulating FII. Here, cohorts of FII(lox/-) mice (constitutively carrying ∼10% normal FII) and FII(WT) mice were tracked in parallel for a year following the imposition of SCD via hematopoietic stem cell transplantation. This genetically imposed suppression of FII levels resulted in an impressive reduction in inflammation (reduction in leukocytosis, thrombocytosis, and circulating interleukin-6 levels), reduced endothelial cell dysfunction (reduced endothelial activation and circulating soluble vascular cell adhesion molecule), and a significant improvement in SCD-associated end-organ damage (nephropathy, pulmonary hypertension, pulmonary inflammation, liver function, inflammatory infiltration, and microinfarctions). Notably, all of these benefits were achieved with a relatively modest 1.25-fold increase in prothrombin times, and in the absence of hemorrhagic complications. Taken together, these data establish that prothrombin is a powerful modifier of SCD-induced end-organ damage, and present a novel therapeutic target to ameliorate SCD pathologies. © 2015 by The American Society of Hematology.

Modeling the Offensive-Defensive Interaction and Resulting Outcomes in Basketball.

PubMed

Lamas, Leonardo; Santana, Felipe; Heiner, Matthew; Ugrinowitsch, Carlos; Fellingham, Gilbert

2015-01-01

We analyzed the interaction between offensive (i.e. space creation dynamics--SCDs) and defensive (i.e. space protection dynamics--SPDs) actions in six play outcomes (free shot, contested shot, new SCD, reset, foul, and turnover) in Spanish professional basketball games. Data consisted of 1548 SCD-SPD-outcome triples obtained from six play-off games. We used Bayesian methods to compute marginal probabilities of six outcomes following five different SCDs. We also computed probabilities of the six outcomes following the 16 most frequent SCD-SPD combinations. The pick action (e.g. pick and roll, pop and pop) was the most prevalent SCD (33%). However, this SCD did not produce the highest probability of a free shot (0.235). The highest probability of a free shot followed the SCD without ball (0.409). The pick was performed not only to attempt scoring but also to initiate offenses, as it produced the highest probability leading to a new SCD (0.403). Additionally, the SPD performed influenced the outcome of the SCD. This reinforces the notion that the opposition (offensive-defensive interaction) should be considered. To the best of our knowledge, in team sports, this is the first study to successfully model the tactical features involved in offense-defense interactions. Our analyses revealed that the high frequency of occurrence of some SCDs may be justified not only by an associated high probability of free shots but also by the possibility of progressively create more space in the defense (i.e. a new SCD as outcome). In the second case, it evidences offensive strategic features of progressive disruption of the defensive system through the concatenation of subsequent offensive actions.

DNA vaccines expressing soluble CD4-envelope proteins fused to C3d elicit cross-reactive neutralizing antibodies to HIV-1.

PubMed

Bower, Joseph F; Green, Thomas D; Ross, Ted M

2004-10-25

DNA vaccines expressing the envelope (Env) of the human immunodeficiency virus type 1 (HIV-1) have been relatively ineffective at generating high-titer, long-lasting, neutralizing antibodies in a variety of animal models. In this study, DNA vaccines were constructed to express a fusion protein of the soluble human CD4 (sCD4) and the gp120 subunit of the HIV-1 envelope. To enhance the immunogenicity of the expressed fusion protein, three copies of the murine C3d (mC3d3) were added to the carboxyl terminus of the complex. Monoclonal antibodies that recognize CD4-induced epitopes on gp120 efficiently bound to sCD4-gp120 or sCD4-gp120-mC3d3. In addition, both sCD4-gp120 and sCD4-gp120-mC3d3 bound to cells expressing appropriate coreceptors in the absence of cell surface hCD4. Mice (BALB/c) vaccinated with DNA vaccines expressing either gp120-mC3d3 or sCD4-gp120-mC3d3 elicited antibodies that neutralized homologous virus infection. However, the use of sCD4-gp120-mC3d3-DNA elicited the highest titers of neutralizing antibodies that persisted after depletion of anti-hCD4 antibodies. Interestingly, only mice vaccinated with DNA expressing sCD4-gp120-mC3d3 had antibodies that elicited cross-protective neutralizing antibodies. The fusion of sCD4 to the HIV-1 envelope exposes neutralizing epitopes that elicit broad protective immunity when the fusion complex is coupled with the molecular adjuvant, C3d.

Levels of human platelet-derived soluble CD40 ligand depend on haplotypes of CD40LG-CD40-ITGA2

PubMed Central

Aloui, Chaker; Prigent, Antoine; Tariket, Sofiane; Sut, Caroline; Fagan, Jocelyne; Cognasse, Fabrice; Chakroun, Tahar; Garraud, Olivier; Laradi, Sandrine

2016-01-01

Increased circulating soluble CD40 ligand (sCD40L) is commonly associated with inflammatory disorders. We aimed to investigate whether gene polymorphisms in CD40LG, CD40 and ITGA2 are associated with a propensity to secrete sCD40L; thus, we examined this issue at the level of human platelets, the principal source of sCD40L. We performed single polymorphism and haplotype analyses to test for the effect of twelve polymorphisms across the CD40LG, CD40 and ITGA2 genes in blood donors. ITGA2 presented a positive association with rs1126643, with a significant modification in sCD40L secretion (carriers of C allele, P = 0.02), unlike the investigated CD40LG and CD40 polymorphisms. One CD40LG haplotype (TGGC) showing rs975379 (C/T), rs3092952 (A/G), rs3092933 (A/G) and rs3092929 (A/C) was associated with increased sCD40L levels (1.906 μg/L (95% CI: 1.060 to 2.751); P = 0.000009). The sCD40L level was associated with the inter-chromosomal CD40LG/CD40/ITGA2 haplotype (ATC), displaying rs3092952 (A/G), rs1883832 (C/T) and rs1126643 (C/T), with increased sCD40L levels (P = 0.0135). Our results help to decipher the genetic role of CD40LG, CD40 and ITGA2 with regard to sCD40L levels found in platelet components. Given the crucial role of sCD40L, this haplotype study in a transfusion model may be helpful to further determine the role of haplotypes in inflammatory clinical settings. PMID:27094978

Modeling the Offensive-Defensive Interaction and Resulting Outcomes in Basketball

PubMed Central

Lamas, Leonardo; Santana, Felipe; Heiner, Matthew; Ugrinowitsch, Carlos; Fellingham, Gilbert

2015-01-01

Purpose We analyzed the interaction between offensive (i.e. space creation dynamics -SCDs) and defensive (i.e. space protection dynamics—SPDs) actions in six play outcomes (free shot, contested shot, new SCD, reset, foul, and turnover) in Spanish professional basketball games. Method Data consisted of 1548 SCD-SPD-outcome triples obtained from six play-off games. We used Bayesian methods to compute marginal probabilities of six outcomes following five different SCDs. We also computed probabilities of the six outcomes following the 16 most frequent SCD-SPD combinations. Results The pick action (e.g. pick and roll, pop and pop) was the most prevalent SCD (33%). However, this SCD did not produce the highest probability of a free shot (0.235). The highest probability of a free shot followed the SCD without ball (0.409). The pick was performed not only to attempt scoring but also to initiate offenses, as it produced the highest probability leading to a new SCD (0.403). Additionally, the SPD performed influenced the outcome of the SCD. This reinforces the notion that the opposition (offensive-defensive interaction) should be considered. To the best of our knowledge, in team sports, this is the first study to successfully model the tactical features involved in offense-defense interactions. Our analyses revealed that the high frequency of occurrence of some SCDs may be justified not only by an associated high probability of free shots but also by the possibility of progressively create more space in the defense (i.e. a new SCD as outcome). In the second case, it evidences offensive strategic features of progressive disruption of the defensive system through the concatenation of subsequent offensive actions. PMID:26659134

One-night sleep deprivation induces changes in the DNA methylation and serum activity indices of stearoyl-CoA desaturase in young healthy men.

PubMed

Skuladottir, Gudrun Valgerdur; Nilsson, Emil Karl; Mwinyi, Jessica; Schiöth, Helgi Birgir

2016-08-26

Sleep deprivation has been associated with obesity among adults, and accumulating data suggests that stearoyl-CoA desaturase 1 (SCD1) expression has a relevant impact on fatty acid (FA) composition of lipid pools and obesity. The aim of this study was to investigate the effect of one-night total sleep deprivation (TSD) on DNA methylation in the 5'-prime region of SCD1, and whether detected changes in DNA methylation are associated with SCD activity indices (product to precursor FA ratios; 16:1n-7/16:0 and 18:1n-9/18:0) derived from serum phospholipids (PL). Sixteen young, normal-weight, healthy men completed two study sessions, one with one-night TSD and one with one-night normal sleep (NS). Sleep quality and length was assessed by polysomnography, and consisted of electroencephalography, electrooculography, and electromyography. Fasting whole blood samples were collected on the subsequent morning for analysis of DNA methylation and FAs in serum PL. Linear regression analyses were performed to assess the association between changes in DNA methylation and SCD activity indices. Three CpG sites close to the transcription start site (TSS) of SCD1 (cg00954566, cg24503796, cg14089512) were significantly differentially methylated in dependency of sleep duration (-log10 P-value > 1.3). Both SCD-16 and SCD-18 activity indices were significantly elevated (P < 0.05) following one-night TSD, and significantly associated with DNA methylation changes of the three mentioned probes in the 5' region of SCD1. Our results suggest a relevant link between TSD, hepatic SCD1 expression and de-novo fatty acid synthesis via epigenetically driven regulatory mechanisms.

Integrating Fat Embolism Syndrome Scoring Indices in Sickle Cell Disease: A Practice Management Review.

PubMed

Bailey, Keneisha; Wesley, Jagila; Adeyinka, Adebayo; Pierre, Louisdon

2017-01-01

Fat embolism syndrome (FES) has been described in the literature as a rare complication of sickle cell disease (SCD). A review article published in 2005 reported 24 cases of FES associated with SCD. In many cases, a definitive diagnosis of FES in SCD is made on autopsy because of the lack of early recognition and the paucity of sensitive and specific testing for this syndrome. Patients with FES usually have a fulminant, rapidly deteriorating clinical course with mortality occurring within the first 24 hours. We postulate that FES is not well recognized in SCD and that FES scores are useful diagnostic tools in patients with SCD. We queried the electronic medical records with the diagnostic codes for SCD with acute chest syndrome (ACS), pulmonary embolism, or acute respiratory distress syndrome admitted to our hospital from 2008 to 2016 to identify patients suspected of having FES. In addition, we performed an extensive literature review to evaluate the management practice of pediatric patients with FES and SCD from 1966 to 2016. Six patients met our selection criteria from the hospital records, and 4 case reports from the literature search were also included. We applied the Gurd and Wilson criteria and the Schonfeld Fat Embolism Index to identify patients who met the criteria for FES. Nine patients fulfilled Gurd and Wilson criteria, and 9 patients who were evaluable met the Schonfeld criteria for FES. A rapidly deteriorating clinical course in a patient with SCD presenting with ACS or severe vaso-occlusive crisis should trigger a high index of suspicion for FES. Gurd and Wilson criteria or the Schonfeld Fat Embolism Index are useful diagnostic tools for FES in SCD.

Pretransplant soluble CD30 is a better predictor of posttransplant development of donor-specific antibodies and acute vascular rejection than panel reactive antibodies.

PubMed

Vaidya, Smita; Partlow, David; Barnes, Titus; Gugliuzza, Kristine

2006-12-27

This study tests a hypothesis that pretransplant concentration of soluble CD30 (sCD30) is a better predictor of posttransplant development of donor-specific HLA antibodies (DSA) and acute vascular rejection (AVR) than panel reactive HLA antibodies (PRA). Pretransplant sera from 115 patients were evaluated for their PRA and sCD30 concentrations. All patients received calcineurin-inhibitor based immunosuppressive therapy. Objective measurements for rejection were biopsy-proven AVR episodes within first 6 months of the transplant. Posttransplant sera of patients with or without AVR were tested for the presence of DSA. AVR rate was 16% (18/115). Patients positive for PRA and sCD30 tests were at significantly higher risk for AVR compared to those patients negative for both tests (36% versus 5%, p = 0.01). Among negative PRA patients risk for AR was significantly elevated if they were also tested positive for sCD30 concentrations (21% versus 5%, p = 0.04). Of the 18 patients with AVR, 14 were positive for sCD30, and 13 of them (93%) developed DSA posttransplant (p = 0.001) Nineteen patients without AVR were tested for DSA and sCD30 concentrations. Only two of these 19 patients were positive for sCD30 and DSA. AVR was strongly associated with the patients tested positive for both the tests: DSA and sCD30 (p = 0.00007). Furthermore, patients with AVR are more likely to produce DSA than those without AVR (p = 0.02). These data support our hypothesis that patients positive for sCD30 contents are at high risk the development of DSA and AVR posttransplant regardless of their pretransplant PRA.

High serum soluble CD30 does not predict acute rejection in liver transplant patients.

PubMed

Matinlauri, I; Höckerstedt, K; Isoniemi, H

2006-12-01

Increased pre- and posttransplantation values of soluble CD30 (sCD30) have been shown to be associated with acute kidney transplant rejection. We sought to study whether high sCD30 could predict rejection early after liver transplantation. The study population included 54 consecutive liver transplant patients, whose samples were collected before liver transplantation and at discharge, which was at a mean time of 3 weeks after transplantation. During the first 6 months posttransplantation, 22 patients experienced an acute rejection episode. Serum sCD30 concentrations were measured by an enzyme-linked immunoassay; changes in serum sCD30 levels posttransplantation were also expressed as relative values compared with pretransplantation results. Liver patients before transplantation displayed higher serum sCD30 values compared with healthy controls: mean values +/- SD were 93 +/- 58 IU/mL vs 17 +/- 8 IU/mL, respectively. At 3 weeks after transplantation the mean sCD30 concentration in liver transplant patients decreased to 59 +/- 42 IU/mL (P = .005). The mean pretransplantation serum sCD30 value was slightly lower among rejecting vs nonrejecting patients: 78 +/- 43 IU/mL vs 104 +/- 65 IU/mL (P = NS). Posttransplantation values in both groups decreased significantly: 47 +/- 34 IU/mL in patients with rejection (P = .014) vs 69 +/- 45 IU/mL in patients without rejection (P = .012). The relative value at 3 weeks posttransplantation decreased slightly more among patients with vs without rejection (70% vs 88%; NS). No correlation was found between serum sCD30 and anti-HLA class I antibodies or crossmatch positivity. In conclusion, neither pre- nor posttransplantation sCD30 levels were associated with acute rejection in liver transplant patients.

[Evaluation of immune status of kidney transplant recipients by combined HLA-G5 and sCD30].

PubMed

JIN, Zhan-kui; TIAN, Pu-xun; XUE, Wu-jun; DING, Xiao-ming; PAN, Xiao-ming; DING, Chen-guang; JIA, Li-ning; GE, Guan-qun; HAO, Jun-jun

2010-09-28

to study the relationship between the expression of serum human leucocyte antigen-G5 (HLA-G5)/soluble CD30 (sCD30) and the function of renal graft in kidney transplant recipients and investigate the immune status of recipients with combined HLA-G5 and sCD30. from January 2002 to November 2008, a total of 66 kidney transplant recipients in our centre were selected as subjects and divided into three groups: stable function of renal graft (n = 38), acute rejection (n = 15) and chronic rejection (n = 13). The expressions of serum HLA-G5 and sCD30 were detected. There were two different immune conditions with acute/chronic allograft rejection and normal renal graft in kidney transplant recipients as evaluated by combined HLA-G5 and sCD30. The sensitivity, specificity and critical value of the method were analyzed by the curve of receiver operating characteristic. the levels of HLA-G5 and sCD30 were significantly correlated with serum creatinine (r = -0.493, 0.691, both P < 0.01). Within the first year post-transplantation, the sensitivity was 78.6% and the specificity 85.7% when HLA-G5 critical value 82 microg/L and sCD30 critical value 12.2 microg/L. After one year post-transplantation: the sensitivity was 92.3% and the specificity 84.6% when HLA-G5 critical value 141 microg/L and sCD30 critical value 10.3 microg/L. the immune state of recipients are evaluated by combine HLA-G5 and sCD30 which may be a simple and valid method.

Serial soluble CD30 measurements as a predictor of kidney graft outcome.

PubMed

Halim, M A; Al-Otaibi, T; Al-Muzairai, I; Mansour, M; Tawab, K A; Awadain, W H; Balaha, M A; Said, T; Nair, P; Nampoory, M R N

2010-04-01

High levels of soluble CD30 (sCD30), a marker for T-helper 2-type cytokine-producing T cells, pre or post-renal transplantation serves as a useful predictor of acute rejection episodes. Over the course of 1-year, we evaluated the accuracy of serial sCD30 tests to predict acute rejection episodes versus other pathologies that affect graft outcomes. Fifty renal transplant recipients were randomly selected to examine sCD30 on days 0, 3, 5, 7, 14, and 21 followed by 1, 3, 6, and 12 months. The results were analyzed for development of an acute rejection episode, acute tubular necrosis (ATN), or other pathology as well as the graft outcome at 1 year. Compared with pretransplantation sCD30, there was a significant reduction in the average sCD30 immediately posttransplantation from day 3 onward (P<.0001). Patients were divided into four groups: (1) uncomplicated courses (56%); (2) acute rejection episodes (18%); (3) ATN (16%); and (4) other diagnoses (10%). There was a significant reduction in sCD30 immediately posttransplantation for groups 1, 2, and 3 (P<.0001, .004, and .002 respectively) unlike group 4 (P=.387). Patients who developed an acute rejection episode after 1 month showed higher pretransplantation sCD30 values than these who displayed rejection before 1 month (P=.019). All groups experienced significant improvement in graft function over 1-year follow-up without any significant differences. Though a significant drop of sCD30 posttransplantation was recorded, serial measurements of sCD30 did not show a difference among subjects who displayed acute rejection episodes, ATN, or other diagnoses. Copyright (c) 2010 Elsevier Inc. All rights reserved.

A Common Missense Variant in the Neuregulin1 Gene is associated with Both Schizophrenia and Sudden Cardiac Death

PubMed Central

Huertas-Vazquez, Adriana; Teodorescu, Carmen; Reinier, Kyndaron; Uy-Evanado, Audrey; Chugh, Harpriya; Jerger, Katherine; Ayala, Jo; Gunson, Karen; Jui, Jonathan; Newton-Cheh, Christopher; Albert, Christine M.; Chugh, Sumeet S.

2013-01-01

Background Both schizophrenia and epilepsy have been linked to increased risk of sudden cardiac death (SCD). We hypothesized that DNA variants within genes previously associated with schizophrenia and epilepsy may contribute to an increased risk of SCD. Objective To investigate the contribution to SCD susceptibility of DNA variants previously implicated in schizophrenia and epilepsy. Methods From the ongoing Oregon Sudden Unexpected Death Study, comparisons were performed among 340 SCD cases presenting with ventricular fibrillation and 342 controls. We tested for association between 17 SNPs mapped to 14 loci previously implicated in schizophrenia and epilepsy using logistic regression, assuming additive, dominant and recessive genetic models. Results The minor allele of the non-synonymous SNP rs10503929 within the Neuregulin 1 gene (NRG1) was associated with SCD under all three investigated models, with the strongest association for the recessive genetic model (recessive P=4.01×10−5, OR= 4.04; additive P=2.84×10−7, OR= 1.9 and dominant P=9.01×10−6, OR= 2.06). To validate our findings, we further explored the association of this variant in the Harvard Cohort SCD study. The SNP rs10503929 was associated with an increased risk of SCD under the recessive genetic model (P=0.0005, OR= 2.7). This missense variation causes a methionine to threonine change and functional effects are currently unknown. Conclusions The observed association between a schizophrenia-related NRG1 variant and SCD may represent the first evidence of coexisting genetic susceptibility between two conditions that have an established clinical overlap. Further investigation is warranted to explore the molecular mechanisms of this variant in the pathogenesis of SCD. PMID:23524320

Risk factors for sudden cardiac death among patients with schizophrenia.

PubMed

Hou, Ping-Yi; Hung, Galen Chin-Lun; Jhong, Jia-Rong; Tsai, Shang-Ying; Chen, Chiao-Chicy; Kuo, Chian-Jue

2015-10-01

Patients with schizophrenia suffer from excessive premature mortality, and sudden cardiac death (SCD) is receiving growing attention as a potential cause. The present study investigated the incidence of SCD and its risk factors in a large schizophrenia cohort. We enrolled a consecutive series of 8264 patients diagnosed with schizophrenia (according to DSM-III-R and DSM-IV criteria) who were admitted to a psychiatric center in northern Taiwan from January 1, 1985 through December 31, 2008. By linking with national mortality database, 64 cases of SCD were identified. The standardized mortality ratio (SMR) for SCD was estimated. The cases were matched with controls randomly selected using risk-set sampling in a 1:2 ratio. A standardized chart review process was used to collect socio-demographic and clinical characteristics and the prescribed drugs for each study subject. Multivariate conditional logistic regression analysis was used to identify correlates of SCD at the index admission and the latest admission. The SMR for SCD was 4.5. For the clinical profiles at the index admission, physical disease (adjusted risk ratio [aRR]=2.91, P<.01) and aggressive behaviors (aRR=3.99, P<.01) were associated with the risk of SCD. Regarding the latest admission, electrocardiographic abnormalities (aRR=5.46, P<.05) and administration of first-generation antipsychotics (aRR=5.13, P<.01) elevated the risk for SCD. Consistently, aggressive behaviors (aRR=3.26, P<.05) were associated with increased risk as well. Apart from cardiovascular profiles and antipsychotics, physical aggression is a crucial risk factor that deserves ongoing work for clarifying the mechanisms mediating SCD in schizophrenia. Copyright © 2015 Elsevier B.V. All rights reserved.

Sudden Cardiac Death After Non-ST-Segment Elevation Acute Coronary Syndrome.

PubMed

Hess, Paul L; Wojdyla, Daniel M; Al-Khatib, Sana M; Lokhnygina, Yuliya; Wallentin, Lars; Armstrong, Paul W; Roe, Matthew T; Ohman, E Magnus; Harrington, Robert A; Alexander, John H; White, Harvey D; Van de Werf, Frans; Piccini, Jonathan P; Held, Claes; Aylward, Philip E; Moliterno, David J; Mahaffey, Kenneth W; Tricoci, Pierluigi

2016-04-01

In the current therapeutic era, the risk for sudden cardiac death (SCD) after non-ST-segment elevation acute coronary syndrome (NSTE ACS) has not been characterized completely. To determine the cumulative incidence of SCD during long-term follow-up after NSTE ACS, to develop a risk model and risk score for SCD after NSTE ACS, and to assess the association between recurrent events after the initial ACS presentation and the risk for SCD. This pooled cohort analysis merged individual data from 48 286 participants in 4 trials: the Apixaban for Prevention of Acute Ischemic Events 2 (APPRAISE-2), Study of Platelet Inhibition and Patient Outcomes (PLATO), Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER), and Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes (TRILOGY ACS) trials. The cumulative incidence of SCD and cardiovascular death was examined according to time after NSTE ACS. Using competing risk and Cox proportional hazards models, clinical factors at baseline and after the index event that were associated with SCD after NSTE ACS were identified. Baseline factors were used to develop a risk model. Data were analyzed from January 2, 2014, to December 11, 2015. Sudden cardiac death. Of the initial 48 286 patients, 37 555 patients were enrolled after NSTE ACS (67.4% men; 32.6% women; median [interquartile range] age, 65 [57-72] years). Among these, 2109 deaths occurred after a median follow-up of 12.1 months. Of 1640 cardiovascular deaths, 513 (31.3%) were SCD. At 6, 18, and 30 months, the cumulative incidence estimates of SCD were 0.79%, 1.65%, and 2.37%, respectively. Reduced left ventricular ejection fraction, older age, diabetes mellitus, lower estimated glomerular filtration rate, higher heart rate, prior myocardial infarction, peripheral artery disease, Asian race, male sex, and high Killip class were significantly associated with SCD. A model developed to calculate the risk for SCD in trials with systematic collection of left ventricular ejection fraction had a C index of 0.77. An integer-based score was developed from this model and yielded a calculated SCD probability ranging from 0.1% to 56.7% (C statistic, 0.75). In a multivariable model that included time-dependent clinical events occurring after the index hospitalization for ACS, SCD was associated with recurrent myocardial infarction (hazard ratio [HR], 2.95; 95% CI, 2.29-3.80; P < .001) and any hospitalization (HR, 2.45; 95% CI, 1.98-3.03; P < .001), whereas coronary revascularization had a negative relationship with SCD (HR, 0.75; 95% CI, 0.58-0.98; P = .03). In the current therapeutic era, SCD accounts for about one-third of cardiovascular deaths after NSTE ACS. Risk stratification can be performed with good accuracy using commonly collected clinical variables. Clinical events occurring after the index hospitalization are underappreciated but important risk factors.

Scavenger receptor function of mouse Fcγ receptor III contributes to progression of atherosclerosis in apolipoprotein E hyperlipidemic mice.

PubMed

Zhu, Xinmei; Ng, Hang Pong; Lai, Yen-Chun; Craigo, Jodi K; Nagilla, Pruthvi S; Raghani, Pooja; Nagarajan, Shanmugam

2014-09-01

Recent studies showed loss of CD36 or scavenger receptor-AI/II (SR-A) does not ameliorate atherosclerosis in a hyperlipidemic mouse model, suggesting receptors other than CD36 and SR-A may also contribute to atherosclerosis. In this report, we show that apolipoprotein E (apoE)-CD16 double knockout (DKO; apoE-CD16 DKO) mice have reduced atherosclerotic lesions compared with apoE knockout mice. In vivo and in vitro foam cell analyses showed apoE-CD16 DKO macrophages accumulated less neutral lipids. Reduced foam cell formation in apoE-CD16 DKO mice is not due to change in expression of CD36, SR-A, and LOX-1. This led to a hypothesis that CD16 may have scavenger receptor activity. We presented evidence that a soluble form of recombinant mouse CD16 (sCD16) bound to malondialdehyde-modified low-density lipoprotein (MDALDL), and this binding is blocked by molar excess of MDA- modified BSA and anti-MDA mAbs, suggesting CD16 specifically recognizes MDA epitopes. Interestingly, sCD16 inhibited MDALDL binding to macrophage cell line, as well as soluble forms of recombinant mouse CD36, SR-A, and LOX-1, indicating CD16 can cross-block MDALDL binding to other scavenger receptors. Anti-CD16 mAb inhibited immune complex binding to sCD16, whereas it partially inhibited MDALDL binding to sCD16, suggesting MDALDL binding site may be in close proximity to the immune complex binding site in CD16. Loss of CD16 expression resulted in reduced levels of MDALDL-induced proinflammatory cytokine expression. Finally, CD16-deficient macrophages showed reduced MDALDL-induced Syk phosphorylation. Collectively, our findings suggest scavenger receptor activity of CD16 may, in part, contribute to the progression of atherosclerosis. Copyright © 2014 by The American Association of Immunologists, Inc.

CAREST—Multilingual Regional Integration for Health Promotion and Research on Sickle Cell Disease and Thalassemia

PubMed Central

Knight-Madden, Jennifer; Romana, Marc; Villaescusa, Rinaldo; Reid, Marvin; Etienne-Julan, Maryse; Boutin, Laurence; Elana, Gisèle; Elenga, Narcisse; Wheeler, Gillian; Lee, Ketty; Nieves, Rosa; Jones Lecointe, Althea; Lalanne-Mistrih, Marie-Laure; Loko, Gylna; Keclard-Christophe, Lisiane

2016-01-01

Sickle cell disease (SCD) is a significant problem in the Caribbean, where many individuals have African and Asian forebears. However, reliable prevalence data and specific health care programs for SCD are often missing in this region. Closer collaboration between Caribbean territories initiated in 2006 to set up strategies to promote better equity in the health care system for SCD patients led to the formation of CAREST: the Caribbean Network of Researchers on Sickle Cell Disease and Thalassemia. We present the effectiveness of collaborations established by CAREST to promote SCD newborn screening programs and early childhood care, to facilitate health worker training and approaches for prevention and treatment of SCD complications, and to carry out inter-Caribbean research studies. PMID:26999505

Sudden cardiac death in the young

PubMed Central

Ackerman, Michael; Atkins, Dianne L; Triedman, John K

2016-01-01

Although the occurrence of sudden cardiac death (SCD) in a young person is a rare event, it is traumatic and often widely publicized. In recent years, SCD in this population has been increasingly seen as a public health and safety issue. This review presents current knowledge relevant to the epidemiology of SCD and to strategies for prevention, resuscitation and identification of those at greatest risk. Areas of active research and controversy include the development of best practices in screening, risk stratification approaches and post-mortem evaluation, and identification of modifiable barriers to providing better outcomes after resuscitation of young SCD victims. Institution of a national registry of SCD in the young will provide data that will help to answer these questions. PMID:26951821

Three-Dimensional Printed Prosthesis for Repair of Superior Canal Dehiscence.

PubMed

Kozin, Elliott D; Remenschneider, Aaron K; Cheng, Song; Nakajima, Hideko Heidi; Lee, Daniel J

2015-10-01

Outcomes following repair of superior canal dehiscence (SCD) are variable, and surgery carries a risk of persistent or recurrent SCD symptoms, as well as a risk of hearing loss and vestibulopathy. Poor outcomes may occur from inadequate repair of the SCD or mechanical insult to the membranous labyrinth. Repair of SCD using a customized, fixed-length prosthesis may address current operative limitations and improve surgical outcomes. We aim to 3-dimensionally print customized prostheses to resurface or occlude bony SCD defects. Dehiscences were created along the arcuate eminence of superior semicircular canals in cadaveric temporal bones. Prostheses were designed and created using computed tomography and a 3-dimensional printer. The prostheses occupied the superior semicircular canal defect, reflected in postrepair computed tomography scans. This novel approach to SCD repair could have advantages over current techniques. Refinement of prosthesis design and materials will be important if this approach is translated into clinical use. © American Academy of Otolaryngology-Head and Neck Surgery Foundation 2015.

Sickle cell disease in Africa: an overview of the integrated approach to health, research, education and advocacy in Tanzania, 2004–2016

PubMed Central

Tluway, Furahini; Makani, Julie

2017-01-01

Summary Sickle cell disease (SCD) is the single most important genetic cause of childhood mortality globally. Tanzania has one of the highest annual births of SCD individuals in the world, estimated to reach 11 000 births a year. Without intervention, 50–90% of children will die in childhood. However, cost-effective interventions have the potential to reduce childhood mortality by up to 70%. The effects of SCD are multi-dimensional, ranging from causing high morbidity and mortality, and reducing the quality of life, to imposing a high socio-economic burden on individuals, families and health systems. In the past 12 years, the SCD programme in Tanzania has developed, with local and global partnerships, a systematic framework for comprehensive research that is integrated into providing healthcare, training and advocacy in SCD. This report outlines the approach and achievements of collective initiatives for management and control of SCD in Tanzania. PMID:28295224

When is the optimal time to screen for Chlamydia in adolescents and young adults with sickle cell disease?

PubMed

Bluett-Mills, Gabriella; Kanter, Julie

2015-02-01

Louisiana has a high rate of chlamydia, an easily identifiable and treatable sexually transmitted disease. Patients with chronic diseases, such as sickle cell disease (SCD) often forgo routine primary care visits. We hypothesized that patients with SCD have an increased percentage of asymptomatic chlamydia compared with a matched population. A retrospective cohort study was performed over a 12-month period on eligible patients with SCD (ages 15-30 years). Patients were screened for asymptomatic chlamydia by urine polymerase chain reaction during comprehensive care visits in the SCD clinic. Thirty-four patients underwent testing during the study period, and 4/34 patients (11.8%) tested positive for chlamydia. State data show a rate of 1791/100 000 (1.8%) among a demographically matched cohort. Patients with SCD had a larger percentage of asymptomatic chlamydia than a demographically matched control population. Patients with SCD should be screened by specialists for chlamydia in addition to undergoing routine primary care evaluations. © The Author(s) 2014.

The ethics of a proposed study of hematopoietic stem cell transplant for children with "less severe" sickle cell disease.

PubMed

Nickel, Robert S; Hendrickson, Jeanne E; Haight, Ann E

2014-08-07

Hematopoietic stem cell transplant (HSCT) is the only cure for sickle cell disease (SCD). HSCT using an HLA-identical sibling donor is currently an acceptable treatment option for children with severe SCD, with expected HSCT survival >95% and event-free survival >85%. HSCT for children with less severe SCD (children who have not yet suffered overt disease complications or only had mild problems) is controversial. It is important to consider the ethical issues of a proposed study comparing HLA-identical sibling HSCT to best supportive care for children with less severe SCD. In evaluating the principles of nonmaleficence, respect for individual autonomy, and justice, we conclude that a study of HLA-identical sibling HSCT for all children with SCD, particularly hemoglobin SS and Sβ(0)-thalassemia disease, is ethically sound. Future work should explore the implementation of a large trial to help determine whether HSCT is a beneficial treatment of children with less severe SCD. © 2014 by The American Society of Hematology.

Does Sickle Cell Disease Protect Against Diabetes Mellitus?

PubMed Central

Mohamed, Ali A.; Al-Qurashi, Fathia; Whitford, David L.

2015-01-01

Objectives: The co-existence of diabetes mellitus (DM) and sickle cell disease (SCD) is rare. This study aimed to explore whether SCD patients have the same DM prevalence as the general population in a country with a high prevalence of DM. Methods: This cross-sectional study included all SCD adult patients admitted to Salmaniya Medical Complex, Bahrain, between 2003 and 2010 (n = 2,204). A random sample (n = 520) was taken to establish the prevalence of DM. Laboratory records were examined to determine the presence of DM. Results: There were 376 SCD patients with complete records; of these, 24 (6.4%) had DM. The age- and sex-standardised prevalence of DM was 8.3%. Conclusion: While the prevalence of DM in SCD patients in Bahrain was high, it was lower than expected in this population. SCD may have a protective effect towards DM development. However, the impact of these two conditions on vascular diseases suggest a need for screening and aggressive treatment in this population. PMID:25685370

[Worldwide experience with automated external defibrillators: What have we achieved? What else can we expect?].

PubMed

Trappe, Hans-Joachim

2016-03-01

In Germany approximately 70,000-100,000 SCD patients die from sudden cardiac death (SCD). SCD is not caused by a single factor but is a multifactorial problem. In 50 % of SCD victims, sudden cardiac death is the first manifestation of heart disease. SCD is caused by ventricular tachyarrhythmias in approximately 90 % of patients, whereas SCD is caused by bradyarrhythmias in 5-10 % of the patients. Risk stratification is not possible in the majority of them prior to the fatal event. Early defibrillation is the method of choice to terminate ventricular fibrillation. Therefore, it is mandatory to install automatic external defibrillators (AED) in places with many people. There is general agreement that early defibrillation with automated external defibrillators (AED) is an effective tool to treat patients with ventricular fibrillation and will improve survival. It seems necessary to teach cardiocompression and AED use, also to children and adolescents. AED therapy "at home" did not improve survival in patients with cardiac arrest and can not be recommended.

Knowledge, attitude and practice of premarital counseling for sickle cell disease among youth in Yaba, Nigeria.

PubMed

Oludarei, Gabriel O; Ogili, Matthew C

2013-12-01

Nigeria accounts for 50% of sickle cell disease (SCD) births worldwide and about 2.3% of her population suffers from SCD with 25% of Nigerians being healthy carriers. This study determined the knowledge, attitude and practice of youths in Yaba, Nigeria towards pre-marital genetic counseling. Data was collected using a questionnaire containing both open ended and closed ended questions. The questionnaires (n= 280) were analyzed by frequency counts, percentages and chi-square. The study shows that 80% of youths had knowledge, 86% had positive attitude and 65% had practiced things related to SCD and premarital counseling. There was a significant association between respondents' educational qualification and knowledge, attitude and practices related to SCD and SCD premarital counseling, and between age and attitude and practices related to SCD premarital counseling. In conclusion, public education on the role of premarital genetic counseling should continue and avenues to allow individuals carry out genotype test should still be encouraged.

Highly-ionized metals as probes of the circumburst gas in the natal regions of gamma-ray bursts

NASA Astrophysics Data System (ADS)

Heintz, K. E.; Watson, D.; Jakobsson, P.; Fynbo, J. P. U.; Bolmer, J.; Arabsalmani, M.; Cano, Z.; Covino, S.; D'Elia, V.; Gomboc, A.; Japelj, J.; Kaper, L.; Krogager, J.-K.; Pugliese, G.; Sánchez-Ramírez, R.; Selsing, J.; Sparre, M.; Tanvir, N. R.; Thöne, C. C.; de Ugarte Postigo, A.; Vergani, S. D.

2018-06-01

We present here a survey of high-ionization absorption lines in the afterglow spectra of long-duration gamma-ray bursts (GRBs) obtained with the VLT/X-shooter spectrograph. Our main goal is to investigate the circumburst medium in the natal regions of GRBs. Our primary focus is on the N V λλ 1238,1242 line transitions, but we also discuss other high-ionization lines such as O VI, C IV and Si IV. We find no correlation between the column density of N V and the neutral gas properties such as metallicity, H I column density and dust depletion, however the relative velocity of N V, typically a blueshift with respect to the neutral gas, is found to be correlated with the column density of H I. This may be explained if the N V gas is part of an H II region hosting the GRB, where the region's expansion is confined by dense, neutral gas in the GRB's host galaxy. We find tentative evidence (at 2σ significance) that the X-ray derived column density, NH, X, may be correlated with the column density of N V, which would indicate that both measurements are sensitive to the column density of the gas located in the vicinity of the GRB. We investigate the scenario where N V (and also O VI) is produced by recombination after the corresponding atoms have been stripped entirely of their electrons by the initial prompt emission, in contrast to previous models where highly-ionized gas is produced by photoionization from the GRB afterglow.

The Spectrum of Epidemiology Underlying Sudden Cardiac Death

PubMed Central

Hayashi, Meiso; Shimizu, Wataru; Albert, Christine M.

2015-01-01

Sudden cardiac death (SCD) from cardiac arrest is a major international public health problem accounting for an estimated 15–20% of all deaths. Although resuscitation rates are generally improving throughout the world, the majority of individuals who suffer a sudden cardiac arrest will not survive. SCD most often develops in older adults with acquired structural heart disease, but it also rarely occurs in the young, where it is more commonly due to inherited disorders. Coronary heart disease (CHD) is known to be the most common pathology underlying SCD, followed by cardiomyopathies, inherited arrhythmia syndromes, and valvular heart disease. Over the past three decades, declines in SCD rates have not been as steep as for other causes of CHD deaths, and there is a growing fraction of SCDs not due to CHD and/or ventricular arrhythmias, particularly among certain subsets of the population. The growing heterogeneity of the pathologies and mechanisms underlying SCD present major challenges for SCD prevention, which are magnified further by a frequent lack of recognition of the underlying cardiac condition prior to death. Multifaceted preventative approaches, which address risk factors in seemingly low risk and known high-risk populations will be required to decrease the burden of SCD. In this Compendium, we review the wide-ranging spectrum of epidemiology underlying SCD within both the general population and in high-risk subsets with established cardiac disease placing an emphasis on recent global trends, remaining uncertainties, and potential targeted preventive strategies. PMID:26044246

Adverse neurological outcomes in Nigerian children with sickle cell disease.

PubMed

Lagunju, I A; Brown, B J

2012-12-01

Sickle cell disease (SCD) is reported to be the most common genetic disorder affecting Nigerians. Children with SCD are at a high risk of neurological morbidity. The main objective of this study was to determine the pattern of adverse neurological outcomes among a cohort of Nigerian children with SCD. All children with SCD seen in the Department of Paediatrics, University College Hospital, Ibadan, Nigeria, over a period of 2 years were carefully evaluated for symptoms and signs of neurological complications, defined as clinical outcomes referable to the central nervous system. Of the 214 children evaluated, 187 were diagnosed with Hb SS disease and 27 with Hb SC disease. Neurological complications were identified in 78 (36.4 %) of the cases. The most common complications were headache (17.8 %), seizure (9.3 %) and stroke (8.4 %). Other less frequent complications included bacterial meningitis (2.8 %), spontaneous visual loss (1.4 %), paraplegia (0.9 %) and transient ischaemic attacks (0.9 %). Neurological complications occurred more frequently in children with sickle cell anaemia than in those with Hb SC disease (P = 0.002, 95 % CI 1.450-82.870). Adverse neurological events are common in Nigerian children with SCD, with a significantly higher risk in Hb SS than Hb SC disease. Stroke represents a major underlying cause of symptomatic epilepsy in SCD. Institution of primary preventive measures for stroke in SCD will significantly reduce the burden of stroke and epilepsy associated with SCD in Nigeria.

Peritransplant Soluble CD30 as a Risk Factor for Slow Kidney Allograft Function, Early Acute Rejection, Worse Long-Term Allograft Function, and Patients' Survival

PubMed Central

Ostapenko, Tetyana I.; Nykonenko, Tamara N.; Nesterenko, Svitlana N.; Nykonenko, Olexandr S.

2017-01-01

Background We aimed to determine whether serum soluble CD30 (sCD30) could identify recipients at high risk for unfavorable early and late kidney transplant outcomes. Methods Serum sCD30 was measured on the day of kidney transplantation and on the 4th day posttransplant. We assessed the value of these measurements in predicting delayed graft function, slow graft function (SGF), acute rejection (AR), pyelonephritis, decline of allograft function after 6 months, and graft and patient survival during 5 years of follow-up in 45 recipients. Results We found the association between low pretransplant serum levels of sCD30 and SGF. The absence of significant decrease of sCD30 on the 4th day posttransplant was characteristic for SGF, early AR (the 8th day–6 months), late AR (>6 months), and early pyelonephritis (the 8th day–2 months). Lower pretransplant and posttransplant sCD30 predicted worse allograft function at 6 months and 2 years, respectively. Higher pretransplant sCD30 was associated with higher frequency of early AR, and worse patients' survival, but only in the recipients of deceased-donor graft. Pretransplant sCD30 also allowed to differentiate patients with early pyelonephritis and early AR. Conclusions Peritransplant sCD30 is useful in identifying patients at risk for unfavorable early and late transplant outcomes. PMID:28694560

High pre-transplant soluble CD30 levels are predictive of the grade of rejection.

PubMed

Rajakariar, Ravindra; Jivanji, Naina; Varagunam, Mira; Rafiq, Mohammad; Gupta, Arun; Sheaff, Michael; Sinnott, Paul; Yaqoob, M M

2005-08-01

In renal transplantation, serum soluble CD30 (sCD30) levels in graft recipients are associated with increased rejection and graft loss. We investigated whether pre-transplant sCD30 concentrations are predictive of the grade of rejection. Pre-transplant sera of 51 patients with tubulointerstitial rejection (TIR), 16 patients with vascular rejection (VR) and an age-matched control group of 41 patients with no rejection (NR) were analyzed for sCD30. The transplant biopsies were immunostained for C4d. The median sCD30 level was significantly elevated in the group with VR (248 Units (U)/mL, range: 92-802) when compared with TIR (103 U/mL, range: 36-309, p<0.001) and NR (179 U/mL, range: 70-343, p<0.03). Moreover, patients with TIR had significantly lower sCD30 levels compared to NR. Based on C4d staining, a TH2 driven process, the median sCD30 levels were significantly raised in C4d+ patients compared with C4d- group (177 U/mL vs. 120 U/mL, p<0.05). sCD30 levels measured at time of transplantation correlate with the grade of rejection. High pre-transplant levels are associated with antibody-mediated rejection which carries a poorer prognosis. sCD30 could be another tool to assess immunological risk prior to transplantation and enable a patient centered approach to immunosuppression.

Predicting renal graft failure by sCD30 levels and de novo HLA antibodies at 1year post-transplantation.

PubMed

Wang, Dong; Wu, Guojun; Chen, Jinhua; Yu, Ziqiang; Wu, Weizhen; Yang, Shunliang; Tan, Jianming

2012-06-01

HLA antibodies and sCD30 levels were detected in the serum sampled from 620 renal graft recipients at 1 year post-transplantation, which were followed up for 5 years. Six-year graft and patient survivals were 81.6% and 91.0%. HLA antibodies were detected in 45 recipients (7.3%), of whom there were 14 cases with class I antibodies, 26 cases with class II, and 5 cases with both class I and II. Much more graft loss was record in recipients with HLA antibodies than those without antibodies (60% vs. 15.1%, p<0.001). Significantly higher sCD30 levels were recorded in recipients suffering graft loss than the others (73.9±48.8 U/mL vs. 37.3±14.6 U/mL, p<0.001). Compared with those with high sCD30 levels, recipients with low sCD30 levels (<50 U/mL) had much better 6-year graft survival (92.4% vs. 46.6%, p<0.001). Further statistical analysis showed that detrimental effect of de novo HLA antibodies and high sCD30 on graft survival was not only independent but also additive. Therefore, post-transplantation monitoring of HLA antibodies and sCD30 levels is necessary and recipients with elevated sCD30 level and/or de novo HLA antibody should be paid more attention in order to achieve better graft survival. Copyright © 2012 Elsevier B.V. All rights reserved.

Analysis and meta-analysis of single-case designs: an introduction.

PubMed

Shadish, William R

2014-04-01

The last 10 years have seen great progress in the analysis and meta-analysis of single-case designs (SCDs). This special issue includes five articles that provide an overview of current work on that topic, including standardized mean difference statistics, multilevel models, Bayesian statistics, and generalized additive models. Each article analyzes a common example across articles and presents syntax or macros for how to do them. These articles are followed by commentaries from single-case design researchers and journal editors. This introduction briefly describes each article and then discusses several issues that must be addressed before we can know what analyses will eventually be best to use in SCD research. These issues include modeling trend, modeling error covariances, computing standardized effect size estimates, assessing statistical power, incorporating more accurate models of outcome distributions, exploring whether Bayesian statistics can improve estimation given the small samples common in SCDs, and the need for annotated syntax and graphical user interfaces that make complex statistics accessible to SCD researchers. The article then discusses reasons why SCD researchers are likely to incorporate statistical analyses into their research more often in the future, including changing expectations and contingencies regarding SCD research from outside SCD communities, changes and diversity within SCD communities, corrections of erroneous beliefs about the relationship between SCD research and statistics, and demonstrations of how statistics can help SCD researchers better meet their goals. Copyright © 2013 Society for the Study of School Psychology. Published by Elsevier Ltd. All rights reserved.

Endothelin-1 receptor antagonists regulate cell surface-associated protein disulfide isomerase in sickle cell disease.

PubMed

Prado, Gregory N; Romero, Jose R; Rivera, Alicia

2013-11-01

Increased endothelin-1 (ET-1) levels, disordered thiol protein status, and erythrocyte hydration status play important roles in sickle cell disease (SCD) through unresolved mechanisms. Protein disulfide isomerase (PDI) is an oxidoreductase that mediates thiol/disulfide interchange reactions. We provide evidence that PDI is present in human and mouse erythrocyte membranes and that selective blockade with monoclonal antibodies against PDI leads to reduced Gardos channel activity (1.6±0.03 to 0.56±0.02 mmol·10(13) cell(-1)·min(-1), P<0.001) and density of sickle erythrocytes (D50: 1.115±0.001 to 1.104±0.001 g/ml, P=0.012) with an IC50 of 4 ng/ml. We observed that erythrocyte associated-PDI activity was increased in the presence of ET-1 (3.1±0.2 to 5.6±0.4%, P<0.0001) through a mechanism that includes casein kinase II. Consistent with these results, in vivo treatment of BERK sickle transgenic mice with ET-1 receptor antagonists lowered circulating and erythrocyte associated-PDI activity (7.1±0.3 to 5.2±0.2%, P<0.0001) while improving hematological parameters and Gardos channel activity. Thus, our results suggest that PDI is a novel target in SCD that regulates erythrocyte volume and oxidative stress and may contribute to cellular adhesion and endothelial activation leading to vasoocclusion as observed in SCD.

Determination of the line shapes of atomic nitrogen resonance lines by magnetic scans

NASA Technical Reports Server (NTRS)

Lawrence, G. M.; Stone, E. J.; Kley, D.

1976-01-01

A technique is given for calibrating an atomic nitrogen resonance lamp for use in determining column densities of atoms in specific states. A discharge lamp emitting the NI multiplets at 1200 A and 1493 A is studied by obtaining absorption by atoms in a magnetic field (0-2.5 T). This magnetic scanning technique enables the determination of the absorbing atom column density, and an empirical curve of growth is obtained because the atomic f-value is known. Thus, the calibrated lamp can be used in the determination of atomic column densities.

Large-Scale Structure of the Molecular Gas in Taurus Revealed by High Spatial Dynamic Range Spectral Line Mapping

NASA Technical Reports Server (NTRS)

Goldsmith, Paul F.

2008-01-01

Viewgraph topics include: optical image of Taurus; dust extinction in IR has provided a new tool for probing cloud morphology; observations of the gas can contribute critical information on gas temperature, gas column density and distribution, mass, and kinematics; the Taurus molecular cloud complex; average spectra in each mask region; mas 2 data; dealing with mask 1 data; behavior of mask 1 pixels; distribution of CO column densities; conversion to H2 column density; variable CO/H2 ratio with values much less than 10(exp -4) at low N indicated by UV results; histogram of N(H2) distribution; H2 column density distribution in Taurus; cumulative distribution of mass and area; lower CO fractional abundance in mask 0 and 1 regions greatly increases mass determined in the analysis; masses determined with variable X(CO) and including diffuse regions agrees well with the found from L(CO); distribution of young stars as a function of molecular column density; star formation efficiency; star formation rate and gas depletion; and enlarged images of some of the regions with numerous young stars. Additional slides examine the origin of the Taurus molecular cloud, evolution from HI gas, kinematics as a clue to its origin, and its relationship to star formation.

Antibody-immobilized column for quick cell separation based on cell rolling.

PubMed

Mahara, Atsushi; Yamaoka, Tetsuji

2010-01-01

Cell separation using methodological standards that ensure high purity is a very important step in cell transplantation for regenerative medicine and for stem cell research. A separation protocol using magnetic beads has been widely used for cell separation to isolate negative and positive cells. However, not only the surface marker pattern, e.g., negative or positive, but also the density of a cell depends on its developmental stage and differentiation ability. Rapid and label-free separation procedures based on surface marker density are the focus of our interest. In this study, we have successfully developed an antiCD34 antibody-immobilized cell-rolling column, that can separate cells depending on the CD34 density of the cell surfaces. Various conditions for the cell-rolling column were optimized including graft copolymerization, and adjustment of the column tilt angle, and medium flow rate. Using CD34-positive and -negative cell lines, the cell separation potential of the column was established. We observed a difference in the rolling velocities between CD34-positive and CD34-negative cells on antibody-immobilized microfluidic device. Cell separation was achieved by tilting the surface 20 degrees and the increasing medium flow. Surface marker characteristics of the isolated cells in each fraction were analyzed using a cell-sorting system, and it was found that populations containing high density of CD34 were eluted in the delayed fractions. These results demonstrate that cells with a given surface marker density can be continuously separated using the cell rolling column.

C+/H2 gas in star-forming clouds and galaxies

NASA Astrophysics Data System (ADS)

Nordon, Raanan; Sternberg, Amiel

2016-11-01

We present analytic theory for the total column density of singly ionized carbon (C+) in the optically thick photon dominated regions (PDRs) of far-UV irradiated (star-forming) molecular clouds. We derive a simple formula for the C+ column as a function of the cloud (hydrogen) density, the far-UV field intensity, and metallicity, encompassing the wide range of galaxy conditions. When assuming the typical relation between UV and density in the cold neutral medium, the C+ column becomes a function of the metallicity alone. We verify our analysis with detailed numerical PDR models. For optically thick gas, most of the C+ column is mixed with hydrogen that is primarily molecular (H2), and this `C+/H2' gas layer accounts for almost all of the `CO-dark' molecular gas in PDRs. The C+/H2 column density is limited by dust shielding and is inversely proportional to the metallicity down to ˜0.1 solar. At lower metallicities, H2 line blocking dominates and the C+/H2 column saturates. Applying our theory to CO surveys in low-redshift spirals, we estimate the fraction of C+/H2 gas out of the total molecular gas to be typically ˜0.4. At redshifts 1 < z < 3 in massive disc galaxies the C+/H2 gas represents a very small fraction of the total molecular gas (≲ 0.16). This small fraction at high redshifts is due to the high gas surface densities when compared to local galaxies.

VizieR Online Data Catalog: Gamma Ray Bursts detected by Swift (2004-2015) (Buchner+, 2017)

NASA Astrophysics Data System (ADS)

Buchner, J.; Schulze, S.; Bauer, F.

2016-04-01

Gamma Ray Bursts (GRB) typically show intrinsic LOS column densities of 1021-23cm2. We performed a thorough statistical analysis of all available X-ray spectra of Swift-detected GRBs. In the associated paper we use sub-samples to analyse the population properties of LGRB and concluded that the obscuration is due to large-scale gas inside the GRB host galaxy, due to the shape of the column density distribution and its correlation with host stellar mass. This catalogue presents X-ray spectral analysis of all Swift-detected GRBs. It includes information about the GRB (ID, Swift Trigger ID, duration, RA/Dec in J2000, galactic coordinates, Milky Way column density). Those properties are taken from the http://www.swift.ac.uk/ and http://gcn.gsfc.nasa.gov/ websites. We removed prompt emission and flares, leaving only a certain time interval for spectral extraction. We use two models to analyse X-ray spectra: TBABS and SPHERE. Both include updated abundances and cross-sections as compared to previous works. The latter includes the effects of Compton-scattering and FeKa fluorescence relevant at high column densities. Columns list the posterior mean, standard deviation, 10% and 90% quantiles. Note that the column densities are converted to hydrogen assuming local ISM abundances, but are derived primarily from photo-electric absorption of e.g. Fe and O, and therefore primarily measure metal gas. (2 data files).

School Performance and Disease Interference in Adolescents with Sickle Cell Disease

ERIC Educational Resources Information Center

Crosby, Lori E.; Joffe, Naomi E.; Irwin, Mary Kay; Strong, Heather; Peugh, James; Shook, Lisa; Kalinyak, Karen A.; Mitchell, Monica J.

2015-01-01

Sickle cell disease (SCD) results in neuropsychological complications that place adolescents at higher risk for limited educational achievement. A first step to developing effective educational interventions is to understand the impact of SCD on school performance. The current study assessed perceptions of school performance, SCD interference and…

Academic Attainment Findings in Children with Sickle Cell Disease

ERIC Educational Resources Information Center

Epping, Amanda S.; Myrvik, Matthew P.; Newby, Robert F.; Panepinto, Julie A.; Brandow, Amanda M.; Scott, J. Paul

2013-01-01

Background: Children with sickle cell disease (SCD) demonstrate deficits in cognitive and academic functioning. This study compared the academic attainment of children with SCD relative to national, state, and local school district rates for African American students. Methods: A retrospective chart review of children with SCD was completed and…

Patterns of liver iron accumulation in patients with sickle cell disease and thalassemia with iron overload.

PubMed

Hankins, Jane S; Smeltzer, Matthew P; McCarville, M Beth; Aygun, Banu; Hillenbrand, Claudia M; Ware, Russell E; Onciu, Mihaela

2010-07-01

The rate and pattern of iron deposition and accumulation are important determinants of liver damage in chronically transfused patients. To investigate iron distribution patterns at various tissue iron concentrations, effects of chelation on hepatic iron compartmentalization, and differences between patients with sickle cell disease (SCD) and thalassemia major (TM), we prospectively investigated hepatic histologic and biochemical findings in 44 patients with iron overload (35 SCD and 9 TM). The median hepatic iron content (HIC) in patients with TM and SCD was similar at 12.9 and 10.3 mg Fe/g dry weight, respectively (P = 0.73), but patients with SCD had significantly less hepatic fibrosis and inflammation (P < 0.05), less hepatic injury, and significantly less blood exposure. Patients with SCD had predominantly sinusoidal iron deposition, but hepatocyte iron deposition was observed even at low HIC. Chelated patients had more hepatocyte and portal tract iron than non-chelated ones, but similar sinusoidal iron deposition. These data suggest that iron deposition in patients with SCD generally follows the traditional pattern of transfusional iron overload; however, parenchymal hepatocyte deposition also occurs early and chelation removes iron preferentially from the reticuloendothelium. Pathophysiological and genetic differences affecting iron deposition and accumulation in SCD and TM warrants further investigation.

Lung vaso-occlusion in sickle cell disease mediated by arteriolar neutrophil-platelet microemboli.

PubMed

Bennewitz, Margaret F; Jimenez, Maritza A; Vats, Ravi; Tutuncuoglu, Egemen; Jonassaint, Jude; Kato, Gregory J; Gladwin, Mark T; Sundd, Prithu

2017-01-12

In patients with sickle cell disease (SCD), the polymerization of intraerythrocytic hemoglobin S promotes downstream vaso-occlusive events in the microvasculature. While vaso-occlusion is known to occur in the lung, often in the context of systemic vaso-occlusive crisis and the acute chest syndrome, the pathophysiological mechanisms that incite lung injury are unknown. We used intravital microscopy of the lung in transgenic humanized SCD mice to monitor acute vaso-occlusive events following an acute dose of systemic lipopolysaccharide sufficient to trigger events in SCD but not control mice. We observed cellular microembolism of precapillary pulmonary arteriolar bottlenecks by neutrophil-platelet aggregates. Blood from SCD patients was next studied under flow in an in vitro microfluidic system. Similar to the pulmonary circulation, circulating platelets nucleated around arrested neutrophils, translating to a greater number and duration of neutrophil-platelet interactions compared with normal human blood. Inhibition of platelet P-selectin with function-blocking antibody attenuated the neutrophil-platelet interactions in SCD patient blood in vitro and resolved pulmonary arteriole microembolism in SCD mice in vivo. These results establish the relevance of neutrophil-platelet aggregate formation in lung arterioles in promoting lung vaso-occlusion in SCD and highlight the therapeutic potential of targeting platelet adhesion molecules to prevent acute chest syndrome.

Airway and alveolar nitric oxide production, lung function, and pulmonary blood flow in sickle cell disease.

PubMed

Lunt, Alan; Ahmed, Na'eem; Rafferty, Gerrard F; Dick, Moira; Rees, David; Height, Sue; Thein, Swee Lay; Greenough, Anne

2016-02-01

Children with sickle cell disease (SCD) often have obstructive lung function abnormalities which could be due to asthma or increased pulmonary blood volume; it is important to determine the underlying mechanism to direct appropriate treatment. In asthmatics, exhaled nitric oxide (FeNO) is elevated. FeNO, however, can also be raised due to increased alveolar production. Our aim, therefore, was to determine if airway or alveolar NO production differed between SCD children and ethnic and age-matched controls. Lung function, airway NO flux and alveolar NO production, and effective pulmonary blood flow were assessed in 18 SCD children and 18 ethnic and age-matched controls. The SCD children compared to the controls had a higher respiratory system resistance (P = 0.0008), alveolar NO production (P = 0.0224), and pulmonary blood flow (P < 0.0001), but not airway NO flux. There was no significant correlation between FeNO and respiratory system resistance in either group, but in the SCD children, there were correlations between alveolar NO production (P = 0.0006) and concentration (P < 0.0001) and pulmonary blood flow. Airway NO flux was not elevated in the SCD children nor correlated with airways obstruction, suggesting that airways obstruction, at least in some SCD children, is not due to asthma.

Loss of stearoyl-CoA desaturase 1 rescues cardiac function in obese leptin-deficient mice.

PubMed

Dobrzyn, Pawel; Dobrzyn, Agnieszka; Miyazaki, Makoto; Ntambi, James M

2010-08-01

The heart of leptin-deficient ob/ob mice is characterized by pathologic left ventricular hypertrophy along with elevated triglyceride (TG) content, increased stearoyl-CoA desaturase (SCD) activity, and increased myocyte apoptosis. In the present study, using an ob/ob;SCD1(-/-) mouse model, we tested the hypothesis that lack of SCD1 could improve steatosis and left ventricle (LV) function in leptin deficiency. We show that disruption of the SCD1 gene improves cardiac function in ob/ob mice by correcting systolic and diastolic dysfunction without affecting levels of plasma TG and FFA. The improvement is associated with reduced expression of genes involved in FA transport and lipid synthesis in the heart, as well as reduction in cardiac FFA, diacylglycerol, TG, and ceramide levels. The rate of FA beta-oxidation is also significantly lower in the heart of ob/ob;SCD1(-/-) mice compared with ob/ob controls. Moreover, SCD1 deficiency reduces cardiac apoptosis in ob/ob mice due to increased expression of antiapoptotic factor Bcl-2 and inhibition of inducible nitric oxide synthase and caspase-3 activities. Reduction in myocardial lipid accumulation and inhibition of apoptosis appear to be one of the main mechanisms responsible for improved LV function in ob/ob mice caused by SCD1 deficiency.

Cellular function reinstitution of offspring red blood cells cloned from the sickle cell disease patient blood post CRISPR genome editing.

PubMed

Wen, Jianguo; Tao, Wenjing; Hao, Suyang; Zu, Youli

2017-06-13

Sickle cell disease (SCD) is a disorder of red blood cells (RBCs) expressing abnormal hemoglobin-S (HbS) due to genetic inheritance of homologous HbS gene. However, people with the sickle cell trait (SCT) carry a single allele of HbS and do not usually suffer from SCD symptoms, thus providing a rationale to treat SCD. To validate gene therapy potential, hematopoietic stem cells were isolated from the SCD patient blood and treated with CRISPR/Cas9 approach. To precisely dissect genome-editing effects, erythroid progenitor cells were cloned from single colonies of CRISPR-treated cells and then expanded for simultaneous gene, protein, and cellular function studies. Genotyping and sequencing analysis revealed that the genome-edited erythroid progenitor colonies were converted to SCT genotype from SCD genotype. HPLC protein assays confirmed reinstallation of normal hemoglobin at a similar level with HbS in the cloned genome-edited erythroid progenitor cells. For cell function evaluation, in vitro RBC differentiation of the cloned erythroid progenitor cells was induced. As expected, cell sickling assays indicated function reinstitution of the genome-edited offspring SCD RBCs, which became more resistant to sickling under hypoxia condition. This study is an exploration of genome editing of SCD HSPCs.

A prospective study of nurse and patient education on compliance with sequential compression devices.

PubMed

Stewart, David; Zalamea, Nia; Waxman, Ken; Schuster, Rob; Bozuk, Michael

2006-10-01

Sequential compression devices (SCD) have become the most common form of prophylaxis against the formation of deep venous thrombosis (DVT) among surgical patients. However, compliance with SCD has traditionally been poor. The aim of this study was to assess the affect of patient and nurse education by surgeons on SCD compliance. This was a prospective study involving a single teaching hospital. Compliance was checked twice daily. The main outcomes were compliance rates with SCD use before and after nurse and patient education. Nurses were not aware of the study. Surgical floors had a history of resident and attending interactions regarding SCD, whereas nonsurgical floors did not. A handout that emphasized SCD importance was also given to patients on surgical units. Before education, surgical units had a compliance rate of 61.5 per cent, whereas nonsurgical units had a 48 per cent compliance rate. This difference was significant (P = 0.014). After nursing and patient education on the busiest surgical floor, compliance rates on the surgical ward increased to 65 per cent, a difference that was not of statistical significance (P = 0.515). A nursing unit's daily experience is the most important factor in their compliance rates with SCD use. Focused nursing lectures and patient education may have incremental value.

Soluble CD40L Is a Useful Marker to Predict Future Strokes in Patients With Minor Stroke and Transient Ischemic Attack.

PubMed

Li, Jiejie; Wang, Yilong; Lin, Jinxi; Wang, David; Wang, Anxin; Zhao, Xingquan; Liu, Liping; Wang, Chunxue; Wang, Yongjun

2015-07-01

Elevated soluble CD40 ligand (sCD40L) was shown to be related to cardiovascular events, but the role of sCD40L in predicting recurrent stroke remains unclear. Baseline sCD40L levels were measured in 3044 consecutive patients with acute minor stroke and transient ischemic attack, who had previously been enrolled in the Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events (CHANCE) trial. Cox proportional-hazards model was used to assess the association of sCD40L with recurrent stroke. Patients in the top tertile of sCD40L levels had increased risk of recurrent stroke comparing with those in the bottom tertile, after adjusted for conventional confounding factors (hazard ratio, 1.49; 95% confidence interval, 1.11-2.00; P=0.008). The patients with elevated levels of both sCD40L and high-sensitive C-reactive protein also had increased risk of recurrent stroke (hazard ratio, 1.81; 95% confidence interval, 1.23-2.68; P=0.003). Elevated sCD40L levels independently predict recurrent stroke in patients with minor stroke and transient ischemic attack. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00979589. © 2015 American Heart Association, Inc.

Evolution of HI from Z=5 to the present

NASA Technical Reports Server (NTRS)

Storrie-Lombardi, L. J.

2002-01-01

Studies of damped Lya systems provide us with a good measure of the evolution of the HI column density distribution function and the contribution to the comoving mass density in neutral gas out to redshifts of z = 5 . The column density distribution function at high redshift steepens for the highest column density HI absorbers, though the contribution to the comoving mass density of neutral gas remains fiat from 2 < z < 5 . Results from studies at z < 2 are finding substantial numbers of damped absorbers identified from MgII absorption, compared to previous blind surveys. These results indicate that the contribution to the comoving mass density in neutral gas may be constant from z 0 to z 5. Details of recent work in the redshift range z < 2 work is covered elsewhere in this volume (see D. Nestor). We review here recent results for the redshift range 2 < z < 5.

Association between serum soluble CD40 ligand levels and mortality in patients with severe sepsis

PubMed Central

2011-01-01

Introduction CD40 Ligand (CD40L) and its soluble counterpart (sCD40L) are proteins that exhibit prothrombotic and proinflammatory properties on binding to their cell surface receptor CD40. The results of small clinical studies suggest that sCD40L levels could play a role in sepsis; however, there are no data on the association between sCD40L levels and mortality of septic patients. Thus, the aim of this study was to determine whether circulating sCD40L levels could be a marker of adverse outcome in a large cohort of patients with severe sepsis. Methods This was a multicenter, observational and prospective study carried out in six Spanish intensive care units. Serum levels of sCD40L, tumour necrosis factor-alpha and interleukin-10, and plasma levels of tissue factor were measured in 186 patients with severe sepsis at the time of diagnosis. Serum sCD40L was also measured in 50 age- and sex-matched controls. Survival at 30 days was used as the endpoint. Results Circulating sCD40L levels were significantly higher in septic patients than in controls (P = 0.01), and in non-survivors (n = 62) compared to survivors (n = 124) (P = 0.04). However, the levels of CD40L were not different regarding sepsis severity. Logistic regression analysis showed that sCD40L levels >3.5 ng/mL were associated with higher mortality at 30 days (odds ratio = 2.89; 95% confidence interval = 1.37 to 6.07; P = 0.005). The area under the curve of sCD40L levels >3.5 ng/mL as predictor of mortality at 30 days was 0.58 (95% CI = 0.51 to 0.65; P = 0.03). Conclusions In conclusion, circulating sCD40L levels are increased in septic patients and are independently associated with mortality in these patients; thus, its modulation could represent an attractive therapeutic target. PMID:21406105

High-performance IR detectors at SCD present and future

NASA Astrophysics Data System (ADS)

Nesher, O.; Klipstein, P. C.

2005-09-01

For over 27 years, SCD has been manufacturing and developing a wide range of high performance infra-red detectors, designed to operate in either the mid-wave (MWIR) or the long-wave (LWIR) atmospheric windows. These detectors have been integrated successfully into many different types of system including missile seekers, Time Delay Integration scanning systems, Hand-Held cameras, Missile Warning Systems and many others. SCD's technology for the MWIR wavelength range is based on its well established 2-D arrays of InSb photodiodes. The arrays are flip-chip bonded to SCD's analogue or digital signal processors, all of which have been designed in-house. The 2-D Focal Plane Array (FPA) detectors have a format of 320×256 elements for a 30 μm pitch and 480×384 or 640×512 elements for a 20 μm pitch. Typical operating temperatures are around 77-85K. Five years ago SCD began to develop a new generation of MWIR detectors based on the epitaxial growth of Antimonide Based Compound Semiconductors (ABCS). This ABCS technology allows band-gap engineering of the detection material which enables higher operating temperatures and multi-spectral detection. This year SCD presented its first prototype FPA from this program, an InAlSb based detector operating at a temperature of 100 K. By the end of this year SCD will introduce the first prototype MWIR detector with a 640×512 element format and a pitch of 15 μm. For the LWIR wave-length range SCD manufactures both linear Hg1-xCdxTe (MCT) detectors with a line of 250 elements and Time Delay and Integration (TDI) detectors with formats of 288×4 and 480×6. Recently, SCD has demonstrated its first prototype un-cooled detector which is based on VOx technology and which has a format of 384×288 elements, a pitch of 25 μm and a typical NETD of 50mK at F/1. In this paper we describe the present technologies and products of SCD and the future evolution of our detectors for the MWIR and LWIR detection.

High-performance IR detectors at SCD present and future

NASA Astrophysics Data System (ADS)

Nesher, O.; Klipstein, P. C.

2006-03-01

For over 27 years, SCD has been manufacturing and developing a wide range of high performance infrared detectors, designed to operate in either the mid-wave (MWIR) or the long-wave (LWIR) atmospheric windows. These detectors have been integrated successfully into many different types of system including missile seekers, time delay integration scanning systems, hand-held cameras, missile warning systems and many others. SCD's technology for the MWIR wavelength range is based on its well established 2D arrays of InSb photodiodes. The arrays are flip-chip bonded to SCD's analogue or digital signal processors, all of which have been designed in-house. The 2D focal plane array (FPA) detectors have a format of 320×256 elements for a 30-μm pitch and 480×384 or 640×512 elements for a 20-μm pitch. Typical operating temperatures are around 77-85 K. Five years ago SCD began to develop a new generation of MWIR detectors based on the epitaxial growth of antimonide based compound semiconductors (ABCS). This ABCS technology allows band-gap engineering of the detection material which enables higher operating temperatures and multi-spectral detection. This year SCD presented its first prototype FPA from this program, an InAlSb based detector operating at a temperature of 100 K. By the end of this year SCD will introduce the first prototype MWIR detector with a 640×512 element format and a pitch of 15 μm. For the LWIR wavelength range SCD manufactures both linear Hg1-xCdxTe (MCT) detectors with a line of 250 elements and time delay and integration (TDI) detectors with formats of 288×4 and 480×6. Recently, SCD has demonstrated its first prototype uncooled detector which is based on VOx technology and which has a format of 384×288 elements, a pitch of 25 μm, and a typical NETD of 50 mK at F/1. In this paper, we describe the present technologies and products of SCD and the future evolution of our detectors for the MWIR and LWIR detection.

Targeting NADPH oxidase decreases oxidative stress in the transgenic sickle cell mouse penis.

PubMed

Musicki, Biljana; Liu, Tongyun; Sezen, Sena F; Burnett, Arthur L

2012-08-01

Sickle cell disease (SCD) is a state of chronic vasculopathy characterized by endothelial dysfunction and increased oxidative stress, but the sources and mechanisms responsible for reactive oxygen species (ROS) production in the penis are unknown. We evaluated whether SCD activates NADPH oxidase, induces endothelial nitric oxide synthase (eNOS) uncoupling, and decreases antioxidants in the SCD mouse penis. We further tested the hypothesis that targeting NADPH oxidase decreases oxidative stress in the SCD mouse penis. SCD transgenic (sickle) mice were used as an animal model of SCD. Hemizygous (hemi) mice served as controls. Mice received an NADPH oxidase inhibitor apocynin (10 mM in drinking water) or vehicle. Penes were excised at baseline for molecular studies. Markers of oxidative stress (4-hydroxy-2-nonenal [HNE]), sources of ROS (eNOS uncoupling and NADPH oxidase subunits p67(phox) , p47(phox) , and gp91(phox) ), and enzymatic antioxidants (superoxide dismutase [SOD]1, SOD2, catalase, and glutathione peroxidase-1 [GPx1]) were measured by Western blot in penes. Sources of ROS, oxidative stress, and enzymatic antioxidants in the SCD penis. Relative to hemi mice, SCD increased (P<0.05) protein expression of NADPH oxidase subunits p67(phox) , p47(phox) , and gp91(phox) , 4-HNE-modified proteins, induced eNOS uncoupling, and reduced Gpx1 expression in the penis. Apocynin treatment of sickle mice reversed (P<0.05) the abnormalities in protein expressions of p47(phox) , gp91(phox) (but not p67(phox) ) and 4-HNE, but only slightly (P>0.05) prevented eNOS uncoupling in the penis. Apocynin treatment of hemi mice did not affect any of these parameters. NADPH oxidase and eNOS uncoupling are sources of oxidative stress in the SCD penis; decreased GPx1 further contributes to oxidative stress. Inhibition of NADPH oxidase upregulation decreases oxidative stress, implying a major role for NADPH oxidase as a ROS source and a potential target for improving vascular function in the SCD mouse penis. © 2012 International Society for Sexual Medicine.

Targeting NADPH Oxidase Decreases Oxidative Stress in the Transgenic Sickle Cell Mouse Penis

PubMed Central

Musicki, Biljana; Liu, Tongyun; Sezen, Sena F.; Burnett, Arthur L.

2012-01-01

Introduction Sickle cell disease (SCD) is a state of chronic vasculopathy characterized by endothelial dysfunction and increased oxidative stress, but the sources and mechanisms responsible for reactive oxygen species (ROS) production in the penis are unknown. Aims We evaluated whether SCD activates NADPH oxidase, induces endothelial nitric oxide synthase (eNOS) uncoupling, and decreases antioxidants in the SCD mouse penis. We further tested the hypothesis that targeting NADPH oxidase decreases oxidative stress in the SCD mouse penis. Methods SCD transgenic (sickle) mice were used as an animal model of SCD. Hemizygous (hemi) mice served as controls. Mice received an NADPH oxidase inhibitor apocynin (10 mM in drinking water) or vehicle. Penes were excised at baseline for molecular studies. Markers of oxidative stress (4-hydroxy-2-nonenal [HNE]), sources of ROS (eNOS uncoupling and NADPH oxidase subunits p67phox, p47phox, and gp91phox), and enzymatic antioxidants (superoxide dismutase [SOD]1, SOD2, catalase, and glutathione peroxidase-1 [GPx1]) were measured by Western blot in penes. Main Outcome Measures Sources of ROS, oxidative stress, and enzymatic antioxidants in the SCD penis. Results Relative to hemi mice, SCD increased (P < 0.05) protein expression of NADPH oxidase subunits p67phox, p47phox, and gp91phox, 4-HNE-modified proteins, induced eNOS uncoupling, and reduced Gpx1 expression in the penis. Apocynin treatment of sickle mice reversed (P < 0.05) the abnormalities in protein expressions of p47phox, gp91phox (but not p67phox) and 4-HNE, but only slightly (P > 0.05) prevented eNOS uncoupling in the penis. Apocynin treatment of hemi mice did not affect any of these parameters. Conclusion NADPH oxidase and eNOS uncoupling are sources of oxidative stress in the SCD penis; decreased GPx1 further contributes to oxidative stress. Inhibition of NADPH oxidase upregulation decreases oxidative stress, implying a major role for NADPH oxidase as a ROS source and a potential target for improving vascular function in the SCD mouse penis. PMID:22620981

Organizing national responses for rare blood disorders: the Italian experience with sickle cell disease in childhood

PubMed Central

2013-01-01

Background Sickle cell disease (SCD) is the most frequent hemoglobinopathy worldwide but remains a rare blood disorder in most western countries. Recommendations for standard of care have been produced in the United States, the United Kingdom and France, where this disease is relatively frequent because of earlier immigration from Africa. These recommendations have changed the clinical course of SCD but can be difficult to apply in other contexts. The Italian Association of Pediatric Hematology Oncology (AIEOP) decided to develop a common national response to the rising number of SCD patients in Italy with the following objectives: 1) to create a national working group focused on pediatric SCD, and 2) to develop tailored guidelines for the management of SCD that could be accessed and practiced by those involved in the care of children with SCD in Italy. Methods Guidelines, adapted to the Italian social context and health system, were developed by 22 pediatric hematologists representing 54 AIEOP centers across Italy. The group met five times for a total of 128 hours in 22 months; documents and opinions were circulated via web. Results Recommendations regarding the prevention and treatment of the most relevant complications of SCD in childhood adapted to the Italian context and health system were produced. For each topic, a pathway of diagnosis and care is detailed, and a selection of health management issues crucial to Italy or different from other countries is described (i.e., use of alternatives for infection prophylaxis because of the lack of oral penicillin in Italy). Conclusions Creating a network of physicians involved in the day-to-day care of children with SCD is feasible in a country where it remains rare. Providing hematologists, primary and secondary care physicians, and caregivers across the country with web-based guidelines for the management of SCD tailored to the Italian context is the first step in building a sustainable response to a rare but emerging childhood blood disorder and in implementing the World Health Organization’s suggestion “to design (and) implement … comprehensive national integrated programs for the prevention and management of SCD". PMID:24139596

Immunological monitoring after organ transplantation: potential role of soluble CD30 blood level measurement.

PubMed

Truong, Dinh Quang; Darwish, Ahmed A; Gras, Jérémie; Wieërs, Grégoire; Cornet, Anne; Robert, Annie; Mourad, Michel; Malaise, Jacques; de Ville de Goyet, Jean; Reding, Raymond; Latinne, Dominique

2007-06-01

Analysing the relevance of soluble CD30 (sCD30) in the bloodstream before and after transplantation may be important for the monitoring of transplant recipients. In this study, 27 patients (15 pediatric liver and 12 adult kidney graft recipients) were investigated. In the liver graft group, the patients who developed acute rejection during the first month (n=9) had a slightly higher sCD30 value on pre-transplantation baseline (day 0) and post-transplantation day 7, when compared to patients with normal graft function (n=6) (day 0: 102(1.6) U/ml versus 118(1.5) U/ml, p=0.52) and (day 7: 69(1.5) U/ml versus 83(1.6) U/ml, p=0.47). Increased serum sCD30 was shown to correlate with increased interleukin-10 circulating levels between day 0 and day 7 (r=0.53; p=0.04), whereas, no correlation could be evidenced between interferon-gamma (IFN-gamma) and sCD30 (r=0.02; p=0.47). Similarly, in the kidney transplantation group, no significant difference was found in sCD30 levels at day 0 in both groups with graft rejection or normal graft function (n=6) (85(1.3) U/ml versus 77(1.6) U/ml, p=0.66), but sCD30 decreased significantly at day 7 post-transplantation from baseline value in the rejection group (n=6) (77(1.6) versus 35(1.4); p=0.02). We conclude that increased serum sCD30 was correlated with increased IL-10 (interleukin-10) circulating levels, but not with IFN-gamma levels in the post-transplantation period. Neither pre-transplantation sCD30 nor sCD30 at day 7 post-transplantation could be correlated with acute rejection in liver graft recipient. The monitoring of sCD30 might constitute a tool to assess the risk of acute rejection in renal transplant but did not appear as a valuable mean for early immunological monitoring in the small group of liver allograft recipients patients analysed in this study.

Seasonal snow cover regime and historical change in Central Asia from 1986 to 2008

NASA Astrophysics Data System (ADS)

Zhou, Hang; Aizen, Elena; Aizen, Vladimir

2017-01-01

A series of statistics describing seasonal Snow Cover Extent and timing in Central Asia (CA) have been derived from AVHRR satellite images for the time period from 1986 to 2008. Analysis of long term mean snow cover statistics shows that the area weighted mean of long term Snow Covering Days (SCD) for the whole CA is 95.2 ± 65.7 days. High elevation mountainous areas above 3000 m in Altai, Tien Shan and Pamir, which account for about 2.8% of total area in CA, have SCD > 240 days. Deserts (Karakorum Desert, Taklamakan Desert, Kumtag Desert) and rain shadow areas of major mountains, accounting for 27.0% of total area in CA, have SCD in the range of 0-30 days. Factors affecting snow cover distribution have been analyzed using simple linear regression and segmented regression. For plain regions and windward regions, the SCD rate is + 5.9 days/100 m, while for leeward regions, the rate jumps from + 0.7 days/100 m to + 10.0 days/100 m at about 2335 m. Latitude affects the SCD, especially in plain regions with insignificant change of elevation, with rates of 9-10 days/degree from south to north. The Mann-Kendal test and the Theil-Sen regression methods have been applied to analyze the spatial heterogeneous trends of change of SCD, Snow Cover Onset Date (SCOD), and Snow Cover Melt Date (SCMD). Area weighed mean SCD in the whole CA does not exhibit significant trend of change from 1986 to 2008. Increase of SCD was observed in the northeastern Kazakh Steppe. Low elevation areas below 2000 m in Central Tien Shan and Eastern Tien Shan, as well as mid-elevation areas from 1000 m to 3000 m in Western Tien Shan, Pamiro-Alai and Western Pamir, also experienced increase of SCD, associated with both earlier SCOD and later SCMD. Decrease of SCD was observed in mountainous areas of Altai, Tien Shan and Pamir, and vast areas in plains surrounding the Aral Sea.

Plasma Soluble CD30 as a Possible Marker of Adult T-cell Leukemia in HTLV-1 Carriers: a Nested Case-Control Study.

PubMed

Takemoto, Shigeki; Iwanaga, Masako; Sagara, Yasuko; Watanabe, Toshiki

2015-01-01

Elevated levels of soluble CD30 (sCD30) are linked with various T-cell neoplasms. However, the relationship between sCD30 levels and the development of adult T-cell leukemia (ATL) in human T-cell leukemia virus type 1 (HTLV-1) carriers remains to be clarified. We here investigated whether plasma sCD30 is associated with risk of ATL in a nested case-control study within a cohort of HTLV-1 carriers. We compared sCD30 levels between 11 cases (i.e., HTLV-1 carriers who later progressed to ATL) and 22 age-, sex- and institution-matched control HTLV-1 carriers (i.e., those with no progression). The sCD30 concentration at baseline was significantly higher in cases than in controls (median 65.8, range 27.2-134.5 U/mL vs. median 22.2, range 8.4-63.1 U/mL, P=0.001). In the univariate logistic regression analysis, a higher sCD30 (≥30.2 U/mL) was significantly associated with ATL development (odds ratio 7.88 and the 95% confidence intervals 1.35-45.8, P = 0.02). Among cases, sCD30 concentration tended to increase at the time of diagnosis of aggressive-type ATL, but the concentration was stable in those developing the smoldering-type. This suggests that sCD30 may serve as a predictive marker for the onset of aggressive-type ATL in HTLV-1 carriers.

Low Cognitive Awareness, but Not Complaint, is a Good Marker of Preclinical Alzheimer's Disease.

PubMed

Cacciamani, Federica; Tandetnik, Caroline; Gagliardi, Geoffroy; Bertin, Hugo; Habert, Marie-Odile; Hampel, Harald; Boukadida, Laurie; Révillon, Marie; Epelbaum, Stéphane; Dubois, Bruno

2017-01-01

Subjective cognitive decline (SCD) may result from many conditions, including Alzheimer's disease (AD). In this study, we searched for a specific pattern of SCD in asymptomatic individuals at risk for AD. Cognitively normal older adults (N = 318) reporting SCD and their informants were enrolled in the INSIGHT-PreAD cohort. We examined the relationship between six SCD measures and both cognitive scores and AD neuroimaging markers (amyloid burden, hippocampal atrophy and brain hypometabolism). An awareness of cognitive decline index (ACDI) has been introduced based on the subject-informant discrepancy in a questionnaire of SCD and participants with low versus high awareness were compared. Scores in the INSIGHT-PreAD SCD questionnaires did not correlate with AD neuroimaging markers. As well, no correlation has been found between SCD measures and cognitive scores. Comparing subjects with a low (n = 19) and high (n = 86) level of awareness, no significant difference in terms of demography, neuropsychiatric symptoms, autonomy, quality of life, cognition, and hippocampal volume was found. However, the "low awareness" group showed greater amyloid burden and lower cortical metabolism, compared to the "high awareness" group. This study provided additional evidence that reporting SCD by itself is not a specific symptom of preclinical AD. Conversely, a low cognitive awareness (namely, when subjects report fewer difficulties than their relatives do) may represent a very early form of anosognosia and serve as a specific indicator of preclinical AD. This finding is of key importance as an enrichment factor to consider in both clinical practice and research trials.

[Nebulized budesonide in the treatment of exacerbations of chronic obstructive pulmonary disease: Efficacy, safety, and effects on the serum levels of soluble differentiation molecules].

PubMed

Makarova, E V; Varvarina, G N; Menkov, N V; Czapaeva, M Yu; Lazareva, E S; Kazatskaya, Zh A; Novikov, V V; Karaulov, A V

2016-01-01

To investigate the efficacy and safety of nebulized budesonide and systemic glucocorticosteroids (GCS) (SGCS) in the treatment of an exacerbation of chronic obstructive pulmonary disease (COPD) and their effects on the serum concentration of soluble leukocyte differentiation antigens. Seventy-eight hospitalized patients with an acute exacerbation of COPD were randomized into two groups: 1) 37 patients took nebulized budesonide 4 mg/day; 2) 41 patients received intravenous prednisolone. The symptoms of COPD, forced expiratory volume in one second (FEV1) and other spirometric indicators, peripheral blood oxygen saturation (SpO2), and adverse events were studied. The serum levels of the soluble adhesion molecules CD50 (sCD50) and CD54 (sCD54) and the lymphocyte activation molecules CD38 (sCD38) and CD25 (sCD25) were investigated by an enzyme immunoassay. There was a significant resolution of the symptoms of COPD, FEV1, and SpO2 in both groups after treatment. The incidence of hyperglycemia episodes was lower in the budesonide group than in the sGCS group. GCSs caused a decrease in the serum level of soluble interleukin-2 receptor (sCD25) in both groups. A prednisolone cycle, unlike a budesonide one, was found to reduce the concentrations of sCD54, sCD50, and sCD38. Nebulized budesonide is an effective and safe alternative to SGCS in treating an exacerbation of COPD. Inhaled GCSs, unlike SGCSs, exhibit anti-inflammatory activity, but exert no immunosuppressive activity.

Cognitive and behavior deficits in sickle cell mice are associated with profound neuropathologic changes in hippocampus and cerebellum

PubMed Central

Wang, Li; Almeida, Luis E.F.; de Souza Batista, Celia M.; Khaibullina, Alfia; Xu, Nuo; Albani, Sarah; Guth, Kira A.; Seo, Ji Sung; Quezado, Martha; Quezado, Zenaide M.N.

2015-01-01

Strokes are perhaps the most serious complications of sickle cell disease (SCD) and by the fifth decade occur in approximately 25% of patients. While most patients do not develop strokes, mounting evidence indicates that even without brain abnormalities on imaging studies, SCD patients can present profound neurocognitive dysfunction. We sought to evaluate the neurocognitive behavior profile of humanized SCD mice (Townes, BERK) and to identify hematologic and neuropathologic abnormalities associated with the behavioral alterations observed in these mice. Heterozygous and homozygous Townes mice displayed severe cognitive deficits shown by significant delays in spatial learning compared to controls. Homozygous Townes also had increased depression- and anxiety-like behaviors as well as reduced performance on voluntary wheel running compared to controls. Behavior deficits observed in Townes were also seen in BERKs. Interestingly, most deficits in homozygotes were observed in older mice and were associated with worsening anemia. Further, neuropathologic abnormalities including the presence of large bands of dark/pyknotic (shrunken) neurons in CA1 and CA3 fields of hippocampus and evidence of neuronal dropout in cerebellum were present in homozygotes but not control Townes. These observations suggest that cognitive and behavioral deficits in SCD mice mirror those described in SCD patients and that aging, anemia, and profound neuropathologic changes in hippocampus and cerebellum are possible biologic correlates of those deficits. These findings support using SCD mice for studies of cognitive deficits in SCD and point to vulnerable brain areas with susceptibility to neuronal injury in SCD and to mechanisms that potentially underlie those deficits. PMID:26462816

Soluble CD30 does not predict late acute rejection or safe tapering of immunosuppression in renal transplantation.

PubMed

Valke, Lars L F G; van Cranenbroek, Bram; Hilbrands, Luuk B; Joosten, Irma

2015-01-01

Previous reports revealed the potential value of the soluble CD30 level (sCD30) as biomarker for the risk of acute rejection and graft failure after renal transplantation, here we examined its use for the prediction of safe tapering of calcineurin inhibitors as well as late acute rejection. In a cohort of renal transplant patients receiving triple immunosuppressive therapy we examined whether sCD30 can be used as a marker for safe (rejection-free) discontinuation of tacrolimus at six months after transplantation (TDS cohort: 24 rejectors and 44 non-rejecting controls). Also, in a second cohort of patients (n=22, rejectors n=11 and non-rejectors n=11), participating in a clinical trial of rituximab as induction therapy after renal transplantation (RITS cohort), we examined whether sCD30 could predict the occurrence of late (>3months post-transplant) acute rejection episodes. sCD30 was measured by ELISA in serum taken before and at several time points after transplantation. Overall, in the TDS cohort sCD30 decreased after transplantation. No difference in sCD30 was observed between rejectors and non-rejecting controls at any of the time points measured. In addition, in the RITS cohort, sCD30 measured at three months after transplantation were not indicative for the occurrence of late acute rejection. In two prospectively followed cohorts of renal transplant patients we found no association between sCD30 and the occurrence of either late acute rejection or acute rejection after reduction of immunosuppression. Copyright © 2014 Elsevier B.V. All rights reserved.

Sinking velocities of phytoplankton measured on a stable density gradient by laser scanning

PubMed Central

Walsby, Anthony E; Holland, Daryl P

2005-01-01

Two particular difficulties in measuring the sinking velocities of phytoplankton cells are preventing convection within the sedimenting medium and determining the changing depth of the cells. These problems are overcome by using a density-stabilized sedimentation column scanned by a laser. For freshwater species, a suspension of phytoplankton is layered over a vertical density gradient of Percoll solution; as the cells sink down the column their relative concentration is measured by the forward scattering of light from a laser beam that repeatedly scans up and down the column. The Percoll gradient stabilizes the column, preventing vertical mixing by convection, radiation or perturbation of density by the descending cells. Measurements were made on suspensions of 15 μm polystyrene microspheres with a density of 1050 kg m−3; the mean velocity was 6.28 μm s−1, within 1.5% of that calculated by the Stokes equation, 6.36 μm s−1. Measurements made on the filamentous cyanobacterium Planktothrix rubescens gave mean velocities within the theoretical range of values based on the range of size, shape, orientation and density of the particles in a modified Stokes equation. Measurements on marine phytoplankton may require density gradients prepared with other substances. PMID:16849271

HIDEEP - an extragalactic blind survey for very low column-density neutral hydrogen

NASA Astrophysics Data System (ADS)

Minchin, R. F.; Disney, M. J.; Boyce, P. J.; de Blok, W. J. G.; Parker, Q. A.; Banks, G. D.; Freeman, K. C.; Garcia, D. A.; Gibson, B. K.; Grossi, M.; Haynes, R. F.; Knezek, P. M.; Lang, R. H.; Malin, D. F.; Price, R. M.; Stewart, I. M.; Wright, A. E.

2003-12-01

We have carried out an extremely long integration time (9000 s beam-1) 21-cm blind survey of 60 deg2 in Centaurus using the Parkes multibeam system. We find that the noise continues to fall as throughout, enabling us to reach an HI column-density limit of 4.2 × 1018 cm-2 for galaxies with a velocity width of 200 km s-1 in the central 32 deg2 region, making this the deepest survey to date in terms of column density sensitivity. The HI data are complemented by very deep optical observations from digital stacking of multi-exposure UK Schmidt Telescope R-band films, which reach an isophotal level of 26.5 R mag arcsec-2 (~=27.5 B mag arcsec-2). 173 HI sources have been found, 96 of which have been uniquely identified with optical counterparts in the overlap area. There is not a single source without an optical counterpart. Although we have not measured the column densities directly, we have inferred them from the optical sizes of their counterparts. All appear to have a column density of NHI= 1020.65+/-0.38. This is at least an order of magnitude above our sensitivity limit, with a scatter only marginally larger than the errors on NHI. This needs explaining. If confirmed it means that HI surveys will only find low surface brightness (LSB) galaxies with high MHI/LB. Gas-rich LSB galaxies with lower HI mass to light ratios do not exist. The paucity of low column-density galaxies also implies that no significant population will be missed by the all-sky HI surveys being carried out at Parkes and Jodrell Bank.

Sudden Cardiac Death in Children and Adolescents: Can We Prevent It?

ERIC Educational Resources Information Center

Berger, Stuart

2001-01-01

Sudden cardiac death (SCD) can occur at any age in apparently healthy people. Early identification and intervention are essential. This article examines SCD in children and adolescents, explaining: who is at risk; the importance of training school personnel for SCD emergencies and having automated external defibrillators (AED) within the schools;…

Soluble CD26/CD30 levels in visceral leishmaniasis: markers of disease activity

PubMed Central

Ajdary, S; Riazi-Rad, F; Jafari-Shakib, R; Mohebbali, M

2006-01-01

Leishmania infantum is the causative agent of zoonotic visceral leishmaniasis (VL). If untreated the disease could be fatal; however, in some cases the infection can run a subclinical course. In subclinical infections a Th1-response predominates, while Th2-responses and/or probably Treg cells are related to unfavourable outcome of the disease in active VL. In the present study we determined the levels of soluble (s) CD26 and CD30 co-stimulatory molecules in sera from patients with active VL, asymptomatic individuals and healthy volunteers. Results showed a significant difference in both sCD26 and sCD30 between infected cases and normal individuals (P ≤ 0·001). However, there was no significant difference in sCD26 levels between asymptomatic cases and patients, although the difference was not significant. sCD30 levels were significantly higher in VL patients than asymptomatic cases (P ≤ 0·001). These findings suggest a possible association between sCD26 and sCD30 levels and the clinical manifestation of L. infantum infection. PMID:16792672

A survey of publication practices of single-case design researchers when treatments have small or large effects.

PubMed

Shadish, William R; Zelinsky, Nicole A M; Vevea, Jack L; Kratochwill, Thomas R

2016-09-01

The published literature often underrepresents studies that do not find evidence for a treatment effect; this is often called publication bias. Literature reviews that fail to include such studies may overestimate the size of an effect. Only a few studies have examined publication bias in single-case design (SCD) research, but those studies suggest that publication bias may occur. This study surveyed SCD researchers about publication preferences in response to simulated SCD results that show a range of small to large effects. Results suggest that SCD researchers are more likely to submit manuscripts that show large effects for publication and are more likely to recommend acceptance of manuscripts that show large effects when they act as a reviewer. A nontrivial minority of SCD researchers (4% to 15%) would drop 1 or 2 cases from the study if the effect size is small and then submit for publication. This article ends with a discussion of implications for publication practices in SCD research. © 2016 Society for the Experimental Analysis of Behavior.

Reactivity to Daily Stressors in Adulthood: The Importance of Stressor Type in Characterizing Risk Factors

PubMed Central

Hay, Elizabeth L.; Diehl, Manfred

2010-01-01

This study examined daily stressors in adults aged 18 to 89 years (M = 49.6 years) over 30 days. We examined the role of individual factors (i.e., age, self-concept differentiation, perceived control) in physical and psychological reactivity to interpersonal, network, home, and health stressors. Findings were consistent with the perspective that adults were less reactive to stress on days they felt in control and that younger adults and adults with high self-concept differentiation (SCD) were more vulnerable to stress. Age, SCD, and daily perceived control, however, interacted with one another and findings varied by stressor type. For example, age differences in reactivity were moderated by SCD whereby older adults with low SCD were particularly resilient to home stressors. Also, whether perceived control buffered adults' reactivity to daily stress varied by age and SCD. For example, only adults with high SCD were psychologically reactive to network stressors and only on days they reported having low control. The findings emphasize the importance of considering how individual characteristics interact in varying ways to influence stress reactivity to different types of stressors. PMID:20230133

Detrimental effects of adenosine signaling in sickle cell disease

PubMed Central

Zhang, Yujin; Dai, Yingbo; Wen, Jiaming; Zhang, Weiru; Grenz, Almut; Sun, Hong; Tao, Lijian; Lu, Guangxiu; Alexander, Danny C; Milburn, Michael V; Carter-Dawson, Louvenia; Lewis, Dorothy E; Zhang, Wenzheng; Eltzschig, Holger K; Kellems, Rodney E; Blackburn, Michael R; Juneja, Harinder S; Xia, Yang

2016-01-01

Hypoxia can act as an initial trigger to induce erythrocyte sickling and eventual end organ damage in sickle cell disease (SCD). Many factors and metabolites are altered in response to hypoxia and may contribute to the pathogenesis of the disease. Using metabolomic profiling, we found that the steady-state concentration of adenosine in the blood was elevated in a transgenic mouse model of SCD. Adenosine concentrations were similarly elevated in the blood of humans with SCD. Increased adenosine levels promoted sickling, hemolysis and damage to multiple tissues in SCD transgenic mice and promoted sickling of human erythrocytes. Using biochemical, genetic and pharmacological approaches, we showed that adenosine A2B receptor (A2BR)-mediated induction of 2,3-diphosphoglycerate, an erythrocyte-specific metabolite that decreases the oxygen binding affinity of hemoglobin, underlies the induction of erythrocyte sickling by excess adenosine both in cultured human red blood cells and in SCD transgenic mice. Thus, excessive adenosine signaling through the A2BR has a pathological role in SCD. These findings may provide new therapeutic possibilities for this disease. PMID:21170046

Psychosocial and pharmacological management of pain in pediatric sickle cell disease.

PubMed

Hildenbrand, Aimee K; Nicholls, Elizabeth G; Daly, Brian P; Marsac, Meghan L; Tarazi, Reem; Deepti, Raybagkar

2014-03-01

For children with sickle cell disease (SCD), pain is associated with significant current and future morbidity and mortality. Unfortunately, few evidence-based guidelines exist for the management of pain episodes in children with SCD. To inform empirically based treatment strategies for pain management in pediatric SCD, this review integrates and evaluates the extant literature on psychosocial and pharmacological approaches to the management of pain. Findings reveal a paucity of rigorous investigations of psychosocial and pharmacological pain management interventions in children with SCD. Psychosocial interventions included were primarily cognitive-behavioral in nature, whereas pharmacological approaches targeted non-opioid analgesics (ie, nonsteroidal anti-inflammatory drugs and corticosteroids) and opioid medications (ie, morphine and oxycodone). However, to date there is not a "gold standard" for pain management among children with SCD. Because psychosocial and physiological processes each play a role in the etiology and experience of pain, effective pain management requires multidimensional, comprehensive treatment approaches. Considering the significant impact of pain on functional outcomes and quality of life among children with SCD, additional clinical trials are warranted to ensure that interventions are safe and efficacious.

Detrimental effects of adenosine signaling in sickle cell disease.

PubMed

Zhang, Yujin; Dai, Yingbo; Wen, Jiaming; Zhang, Weiru; Grenz, Almut; Sun, Hong; Tao, Lijian; Lu, Guangxiu; Alexander, Danny C; Milburn, Michael V; Carter-Dawson, Louvenia; Lewis, Dorothy E; Zhang, Wenzheng; Eltzschig, Holger K; Kellems, Rodney E; Blackburn, Michael R; Juneja, Harinder S; Xia, Yang

2011-01-01

Hypoxia can act as an initial trigger to induce erythrocyte sickling and eventual end organ damage in sickle cell disease (SCD). Many factors and metabolites are altered in response to hypoxia and may contribute to the pathogenesis of the disease. Using metabolomic profiling, we found that the steady-state concentration of adenosine in the blood was elevated in a transgenic mouse model of SCD. Adenosine concentrations were similarly elevated in the blood of humans with SCD. Increased adenosine levels promoted sickling, hemolysis and damage to multiple tissues in SCD transgenic mice and promoted sickling of human erythrocytes. Using biochemical, genetic and pharmacological approaches, we showed that adenosine A(2B) receptor (A(2B)R)-mediated induction of 2,3-diphosphoglycerate, an erythrocyte-specific metabolite that decreases the oxygen binding affinity of hemoglobin, underlies the induction of erythrocyte sickling by excess adenosine both in cultured human red blood cells and in SCD transgenic mice. Thus, excessive adenosine signaling through the A(2B)R has a pathological role in SCD. These findings may provide new therapeutic possibilities for this disease.

The differential effect of genetic variation on soluble CD14 levels in human plasma and milk.

PubMed

Guerra, Stefano; Carla Lohman, I; LeVan, Tricia D; Wright, Anne L; Martinez, Fernando D; Halonen, Marilyn

2004-09-01

The protein CD14 is a pattern recognition receptor for bacterial lipopolysaccharide (LPS). Whether genetic variation has the same influence on soluble CD14 (sCD14) levels in human plasma and milk remains to be determined. We measured sCD14 levels in plasma during pregnancy (n = 196) and in milk in the postpartum (n = 152) for women genotyped for the single nucleotide polymorphisms (SNPs) at positions -1619, -550, and -159 from the transcription start site of the CD14 gene. Plasma- and milk-sCD14 levels differed significantly both by CD14/-1619 and CD14/-550 genotypes and by haplotypes. Most interestingly, sCD14 levels were regulated differentially by the same genetic variants in plasma and milk, with the CD14/-550T allele and the corresponding are ATC haplotype associated with high sCD14 in milk but low sCD14 in plasma. A correlation between sCD14 levels in plasma and milk was absent (r = 0.091, P = NS). Our findings suggest the existence of cell-specific regulation mechanisms of CD14 gene expression.

Applicability of the SMART Model of Transition Readiness for Sickle-Cell Disease

PubMed Central

Valenzuela, Jessica M.; Crosby, Lori E.; Diaz Pow Sang, Claudia

2016-01-01

Objectives This study aimed to examine the applicability of the Social-ecological Model of Adolescent and Young Adult Readiness to Transition (SMART) model for adolescents and young adults (AYA) with sickle-cell disease (SCD). Methods 14 AYA with SCD (14–24 years old) and 10 clinical experts (6–20 years of experience) completed semi-structured interviews. AYA completed brief questionnaires. Interviews were coded for themes, which were reviewed to determine their fit within the SMART model. Results Overall, most themes were consistent with the model (e.g., sociodemographics/culture, neurocognition/IQ, etc.). Factors related to race/culture, pain management, health-care navigation skills, societal stigma, and lack of awareness about SCD were salient for AYA with SCD. Conclusions Findings suggest the SMART model may be appropriate in SCD with the consideration of disease-related stigma. This study is a step toward developing a disease-specific model of transition readiness for SCD. Future directions include the development of a measure of transition readiness for this population. PMID:26717957

The Effect of Superior Semicircular Canal Dehiscence on Intracochlear Sound Pressures

NASA Astrophysics Data System (ADS)

Nakajima, Hideko Heidi; Pisano, Dominic V.; Merchant, Saumil N.; Rosowski, John J.

2011-11-01

Semicircular canal dehiscence (SCD) is a pathological opening in the bony wall of the inner ear that can result in conductive hearing loss. The hearing loss is variable across patients, and the precise mechanism and source of variability is not fully understood. We use intracochlear sound pressure measurements in cadaveric preparations to study the effects of SCD size. Simultaneous measurement of basal intracochlear sound pressures in scala vestibuli (SV) and scala tympani (ST) quantifies the complex differential pressure across the cochlear partition, the stimulus that excites the partition. Sound-induced pressures in SV and ST, as well as stapes velocity and ear-canal pressure are measured simultaneously for various sizes of SCD followed by SCD patching. At low frequencies (<600 Hz) our results show that SCD decreases the pressure in both SV and ST, as well as differential pressure, and these effects become more pronounced as dehiscence size is increased. For frequencies above 1 kHz, the smallest pinpoint dehiscence can have the larger effect on the differential pressure in some ears. These effects due to SCD are reversible by patching the dehiscence.

Can sudden cardiac death in the young be predicted and prevented? Lessons from autopsy for the emergency physician.

PubMed

White, Jennifer L; Chang, Anna Marie; Cesar, Sergi; Sarquella-Brugada, Georgia

2018-06-01

Sudden unexpected death in the young, though rare, is devastating for both the family and the community. Although only 1.3 to 8.5 cases of sudden cardiac death (SCD) occur per 100 000 young people, autopsy is often inconclusive. Many causes of SCD are related to autosomal dominant inherited risk, however; therefore, answers are important for survivors. Causes of autopsy-positive SCD in young patients include hypertrophic cardiomyopathy and arrhythmogenic right ventricular dysplasia. Autopsy-negative SCD has been related to inherited arrhythmogenic causes such as long QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, Wolff- Parkinson-White syndrome, and idiopathic ventricular fibrillation. The important question for the emergency physician is how SCD can be predicted and prevented in the young so that there is no need for an autopsy.

Duty-related risk of sudden cardiac death among young US firefighters.

PubMed

Farioli, A; Yang, J; Teehan, D; Baur, D M; Smith, D L; Kales, S N

2014-09-01

Little is known regarding duty-related risks for sudden cardiac death (SCD) among young firefighters. To investigate duty-related SCD among US firefighters aged 45 or younger. We collected data on duty-related SCD from the US Fire Administration (USFA) and the US National Institute for Occupational Safety and Health (NIOSH). Two physicians independently reviewed each record. The proportions of time spent by firefighters performing specific duties were estimated from a municipal department, 17 large metropolitan departments and a national database. We estimated the duty-specific relative risks (RRs) and 95% confidence intervals (95% CI) of SCD relative to non-emergency duties based on the observed deaths and the expected average proportions of time per duty. The USFA recorded 205 age-eligible on-duty SCDs between 1996 and 2012; 86 (42%) of these deaths and one additional SCD were investigated by NIOSH (total n = 206). NIOSH was more likely (P < 0.001) to report on SCD associated with physical training (69% of cases were investigated) and fire suppression (57%). Compared with non-emergency duties, the risk of SCD was increased for fire suppression (RR 22.1, 95% CI 14.8-32.9), alarm response (RR 2.6, 95% CI 1.5-4.6), alarm return (RR 4.1, 95% CI 2.7-6.2) and physical training (RR 4.8, 95% CI 3.2-7.2). RRs for SCD were higher among firefighters with a pre-existing history of a cardiac condition. All 16 SCDs associated with alarm response occurred among volunteer firefighters. The performance of strenuous emergency duties is strongly associated with an increased risk of SCD among young firefighters, particularly among those with a history of cardiovascular disease. © The Author 2014. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Serum neopterin and soluble CD163 as markers of macrophage activation in paracetamol (acetaminophen)-induced human acute liver injury.

PubMed

Craig, D G; Lee, P; Pryde, E A; Hayes, P C; Simpson, K J

2013-12-01

Macrophage activation is implicated in the pathogenesis of the systemic inflammatory response syndrome (SIRS) following paracetamol (acetaminophen) overdose (POD). Neopterin is synthesised from macrophages and reflects the intensity of monocyte/macrophage activation. Soluble CD163 (sCD163) is a marker of alternatively activated M2 macrophages. To examine neopterin and sCD163 levels in a cohort of acute liver injury patients. Consecutive patients (n = 41, (18 (43.9%) male) with acute liver injury were enrolled. Neopterin and sCD163 levels were measured by ELISA. A total of 24/33 (72.7%) POD patients developed hepatic encephalopathy (HE), and therefore acute liver failure. Both neopterin and sCD163 levels were significantly higher in PODs compared with chronic liver disease (neopterin P < 0.001, sCD163 P = 0.038) and healthy (both P < 0.001) controls. Admission neopterin levels were significantly higher in PODs: with HE (P = 0.001); with the SIRS (P = 0.005); who required renal replacement therapy (P = 0.003); who died or required liver transplantation (P = 0.006; AUROC 78.6% (95% CI 62.2-94.9%). Serum sCD163 levels were significantly higher in those PODs with the SIRS (P = 0.033) on admission, and were higher in those PODs who died or required OLT (P = 0.024). Both admission neopterin and sCD163 levels in PODs correlated with organ failure scores but not with serum ALT. There was no significant correlation between neopterin and sCD163 values. Both serum neopterin and sCD163 levels are significantly elevated following paracetamol overdose, and reflect the degree of macrophage activation in this condition. Serum neopterin in particular may have value as an early proxy marker of macrophage activation following paracetamol overdose. © 2013 John Wiley & Sons Ltd.

Serum sCD163 Levels Are Associated with Type 2 Diabetes Mellitus and Are Influenced by Coffee and Wine Consumption: Results of the Di@bet.es Study

PubMed Central

Rojo-Martínez, Gemma; Maymó-Masip, Elsa; Rodríguez, M. Mar; Solano, Esther; Goday, Albert; Soriguer, Federico; Valdés, Sergio; Chaves, Felipe Javier; Delgado, Elías; Colomo, Natalia; Hernández, Pilar

2014-01-01

Objective Serum levels of soluble TNF-like weak inducer of apoptosis (sTWEAK) and its scavenger receptor CD163 (sCD163) have been linked to insulin resistance. We analysed the usefulness of these cytokines as biomarkers of type 2 diabetes in a Spanish cohort, together with their relationship to food consumption in the setting of the Di@bet.es study. Research Design and Methods This is a cross-sectional, matched case-control study of 514 type 2 diabetes subjects and 517 controls with a Normal Oral Glucose Tolerance Test (NOGTT), using data from the Di@bet.es study. Study variables included clinical and demographic structured survey, food frequency questionnaire and physical examination. Serum concentrations of sTWEAK and sCD163 were measured by ELISA. Linear regression analysis determined which variables were related to sTWEAK and sCD163 levels. Logistic regression analysis was used to estimate odd ratios of presenting type 2 diabetes. Results sCD163 concentrations and sCD163/sTWEAK ratio were 11.0% and 15.0% higher, respectively, (P<0.001) in type 2 diabetes than in controls. Following adjustment for various confounders, the OR for presenting type 2 diabetes in subjects in the highest vs the lowest tertile of sCD163 was [(OR), 2,01 (95%CI, 1,46–2,97); P for trend <0.001]. Coffee and red wine consumption was negatively associated with serum levels of sCD163 (P = 0.0001 and; P = 0.002 for coffee and red wine intake, respectively). Conclusions High circulating levels of sCD163 are associated with type 2 diabetes in the Spanish population. The association between coffee and red wine intake and these biomarkers deserves further study to confirm its potential role in type 2 diabetes. PMID:24978196

Rehabilitation outcomes after infection-related spinal cord disease: a retrospective analysis.

PubMed

McKinley, William; Merrell, Christopher; Meade, Michelle; Brooke, Karen; DiNicola, Anthony

2008-04-01

To compare injury characteristics, demographics, and functional outcomes of patients with infection-related spinal cord disease (IR-SCD) vs. those with traumatic spinal cord injury (SCI). A 10-yr retrospective review of 34 consecutive patients with IR-SCD admitted to an SCI rehabilitation unit at a Level 1 tertiary university medical center. Outcome measures included length of stay (LOS), FIM motor scores, and home discharge rates. The cause of IR-SCD was most often spinal epidural abscess secondary to Staphylococcus aureus (74%). Weakness (90%) and neck/back pain (84%) were the most frequent initial admitting symptoms. Identifiable risk factors included history of recent infection (42%), diabetes mellitus (32%), and intravenous drug abuse (26%). SCD-related complications most commonly included pain (81%), urinary tract infection (52%), and spasticity (45%). When compared with traumatic SCI (n = 560), patients with IR-SCD comprised significantly less of the SCI/D rehabilitation admissions (3% vs. 61%), were older (53 vs. 40 yrs), and more often female (35% vs. 16%). Injuries were more commonly located in the thoracic region (48% vs. 38%). Patients with IR-SCD more often had incomplete injuries (94% vs. 57%). Thirty-two percent of IR-SCD patients had improvements in AIS impairment scale classification. LOS was longer on acute care (25 vs. 16 days), but similar on rehabilitation (36 vs. 34 days), and with lower FIM motor changes (16.2 vs. 22.8) during rehabilitation. Patients with IR-SCD were less often discharged to home (56% vs. 75%). Patients with infection-related SCD comprise a significant subset of SCI/D rehabilitation admissions and have differing demographic and injury characteristics compared with traumatic SCI. Despite less-severe injury characteristics and similar rehabilitation LOS, they achieve lower functional improvements and are less often discharged home, underscoring the importance of patient/family education and discharge planning.

Increased soluble CD36 is linked to advanced steatosis in nonalcoholic fatty liver disease.

PubMed

García-Monzón, Carmelo; Lo Iacono, Oreste; Crespo, Javier; Romero-Gómez, Manuel; García-Samaniego, Javier; Fernández-Bermejo, Miguel; Domínguez-Díez, Agustín; Rodríguez de Cía, Javier; Sáez, Alicia; Porrero, José Luís; Vargas-Castrillón, Javier; Chávez-Jiménez, Enrique; Soto-Fernández, Susana; Díaz, Ainhoa; Gallego-Durán, Rocío; Madejón, Antonio; Miquilena-Colina, María Eugenia

2014-01-01

Soluble CD36 (sCD36) clusters with insulin resistance, but no evidence exists on its relationship with hepatic fat content. We determined sCD36 to assess its link to steatosis in nonalcoholic fatty liver disease (NAFLD) and chronic hepatitis C (CHC) patients. Two hundred and twenty-seven NAFLD, eighty-seven CHC, and eighty-five patients with histologically normal liver (NL) were studied. Steatosis was graded by Kleiner's histological scoring system. Serum sCD36 and hepatic CD36 expression was assessed by immunoassay and immunohistochemistry, respectively. In NAFLD, serum sCD36 levels were significantly higher in simple steatosis than in NL (361.4 ± 286.4 vs. 173.9 ± 137.4 pg/mL, respectively; P < 0.001), but not in steatohepatitis (229.6 ± 202.5 pg/mL; P = 0.153). In CHC, serum sCD36 levels were similar regardless of the absence (428.7 ± 260.3 pg/mL) or presence of steatosis (387.2 ± 283.6 pg/mL; P = 0.173). A progressive increase in serum sCD36 values was found in NAFLD depending on the histological grade of steatosis (P < 0.001), but not in CHC (P = 0.151). Serum sCD36 concentrations were independently associated with advanced steatosis in NAFLD when adjusted by demographic and anthropometric features [odds ratio (OR), 1.001; 95% confidence interval (CI), 1.000 to 1.002; P = 0.021] and by metabolic variables (OR, 1.002; 95% CI, 1.000 to 1.003; P = 0.001). Interestingly, a significant correlation was observed between hepatic CD36 and serum sCD36 (ρ = 0.499, P < 0.001). Increased serum sCD36 is an independent factor associated with advanced steatosis in NAFLD. © 2013 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.

Serum sCD163 levels are associated with type 2 diabetes mellitus and are influenced by coffee and wine consumption: results of the Di@bet.es study.

PubMed

Rojo-Martínez, Gemma; Maymó-Masip, Elsa; Rodríguez, M Mar; Solano, Esther; Goday, Albert; Soriguer, Federico; Valdés, Sergio; Chaves, Felipe Javier; Delgado, Elías; Colomo, Natalia; Hernández, Pilar; Vendrell, Joan; Chacón, Matilde R

2014-01-01

Serum levels of soluble TNF-like weak inducer of apoptosis (sTWEAK) and its scavenger receptor CD163 (sCD163) have been linked to insulin resistance. We analysed the usefulness of these cytokines as biomarkers of type 2 diabetes in a Spanish cohort, together with their relationship to food consumption in the setting of the Di@bet.es study. This is a cross-sectional, matched case-control study of 514 type 2 diabetes subjects and 517 controls with a Normal Oral Glucose Tolerance Test (NOGTT), using data from the Di@bet.es study. Study variables included clinical and demographic structured survey, food frequency questionnaire and physical examination. Serum concentrations of sTWEAK and sCD163 were measured by ELISA. Linear regression analysis determined which variables were related to sTWEAK and sCD163 levels. Logistic regression analysis was used to estimate odd ratios of presenting type 2 diabetes. sCD163 concentrations and sCD163/sTWEAK ratio were 11.0% and 15.0% higher, respectively, (P<0.001) in type 2 diabetes than in controls. Following adjustment for various confounders, the OR for presenting type 2 diabetes in subjects in the highest vs the lowest tertile of sCD163 was [(OR), 2,01 (95%CI, 1,46-2,97); P for trend <0.001]. Coffee and red wine consumption was negatively associated with serum levels of sCD163 (P = 0.0001 and; P = 0.002 for coffee and red wine intake, respectively). High circulating levels of sCD163 are associated with type 2 diabetes in the Spanish population. The association between coffee and red wine intake and these biomarkers deserves further study to confirm its potential role in type 2 diabetes.

Factor V Leiden G1691A and prothrombin G20210A mutations among Palestinian patients with sickle cell disease.

PubMed

Samarah, Fekri; Srour, Mahmoud A

2018-01-01

Vascular thrombosis is an important pathophysiological aspect of sickle cell disease (SCD). This study aimed to investigate the prevalence and clinical impact of factor V Leiden G1691A (FVL) and prothrombin G20210A mutations among Palestinian sickle cell disease (SCD) patients. A total of 117 SCD patients, including 59 patients with sickle cell anemia (SS), 33 patients with sickle β-thalassemia and 25 individuals with sickle cell trait (AS) were studied. The control group consisted of 118 healthy individuals. FVL and prothrombin G20210A mutations were determined by RFLP PCR. Analysis of the clinical history of SCD patients revealed that seven patients have had vascular complications such as ischemic stroke or deep vein thrombosis. In SCD patients, the inheritance of the FVL mutation showed a significantly higher incidence of pain in joints, chest and abdomen as well as regular dependence on blood transfusion compared to SCD with the wild type. Age- and sex-adjusted logistic regression analysis revealed a significant association between FVL and sickle cell anemia with an odds ratio (OR) of 5.6 (95% confidence intervals [CI] of 1.91-39.4, P  = 0.039) in SS patients. However, increased prevalence of the FVL in AS subjects and sickle β-thalassemia patients was not statistically significant compared to controls (OR 3.97, 95% CI 0.51-28.6, P  = 0.17 and OR 3.59, 95% CI 0.35-41.6, P  = 0.26, respectively). The distribution of prothrombin G20210A mutation among SCD patients compared to controls was not significantly different, thus our findings do not support an association of this mutation with SCD. FVL was more prevalent among SS patients compared to controls and it was associated with higher incidence of disease complications among SCD patients.

DNA vaccines expressing soluble CD4-envelope proteins fused to C3d elicit cross-reactive neutralizing antibodies to HIV-1

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

Bower, Joseph F.; Green, Thomas D.; Ross, Ted M.

2004-10-25

DNA vaccines expressing the envelope (Env) of the human immunodeficiency virus type 1 (HIV-1) have been relatively ineffective at generating high-titer, long-lasting, neutralizing antibodies in a variety of animal models. In this study, DNA vaccines were constructed to express a fusion protein of the soluble human CD4 (sCD4) and the gp120 subunit of the HIV-1 envelope. To enhance the immunogenicity of the expressed fusion protein, three copies of the murine C3d (mC3d{sub 3}) were added to the carboxyl terminus of the complex. Monoclonal antibodies that recognize CD4-induced epitopes on gp120 efficiently bound to sCD4-gp120 or sCD4-gp120-mC3d{sub 3}. In addition, bothmore » sCD4-gp120 and sCD4-gp120-mC3d{sub 3} bound to cells expressing appropriate coreceptors in the absence of cell surface hCD4. Mice (BALB/c) vaccinated with DNA vaccines expressing either gp120-mC3d{sub 3} or sCD4-gp120-mC3d{sub 3} elicited antibodies that neutralized homologous virus infection. However, the use of sCD4-gp120-mC3d{sub 3}-DNA elicited the highest titers of neutralizing antibodies that persisted after depletion of anti-hCD4 antibodies. Interestingly, only mice vaccinated with DNA expressing sCD4-gp120-mC3d{sub 3} had antibodies that elicited cross-protective neutralizing antibodies. The fusion of sCD4 to the HIV-1 envelope exposes neutralizing epitopes that elicit broad protective immunity when the fusion complex is coupled with the molecular adjuvant, C3d.« less

Predictors of Sudden Cardiac Death in Doberman Pinschers with Dilated Cardiomyopathy.

PubMed

Klüser, L; Holler, P J; Simak, J; Tater, G; Smets, P; Rügamer, D; Küchenhoff, H; Wess, G

2016-05-01

Doberman Pinschers with dilated cardiomyopathy (DCM) are at high risk of sudden cardiac death (SCD). Risk factors for SCD are poorly defined. To assess cardiac biomarkers, Holter-ECG, echocardiographic variables and canine characteristics in a group of Doberman Pinschers with DCM dying of SCD and in a DCM control group to identify factors predicting SCD. A longitudinal prospective study was performed in 95 Doberman Pinschers with DCM. Forty-one dogs died within 3 months after the last cardiac examination (SCD-group) and were compared to 54 Doberman Pinschers with DCM surviving 1 year after inclusion. Holter-ECG, echocardiography, measurement of N-terminal prohormone of brain-natriuretic peptide (NT-proBNP), and cardiac Troponin I (cTnI) concentrations were recorded for all dogs. Volume overload of the left ventricle (left ventricular end-diastolic volume (LVEDV/BSA) > 91.3 mL/m²) was the single best variable to predict SCD. The probability of SCD increases 8.5-fold (CI0.95  = 0.8-35.3) for every 50 mL/m²-unit increment in LVEDV/BSA. Ejection fraction (EF), left ventricular end-systolic volume (LVESV/BSA) and NT-proBNP were highly correlated with LVEDV/BSA (r = -0.63, 0.96, 0.86, respectively). Generated conditional inference trees (CTREEs) revealed that the presence of ventricular tachycardia (VT), increased concentration of cTnI, and the fastest rate (FR) of ventricular premature complexes (VPC) ≥260 beats per minute (bpm) are additional important variables to predict SCD. Conditional inference trees provided in this study might be useful for risk assessment of SCD in Doberman Pinschers with DCM. Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Plasma soluble cluster of differentiation 147 levels are increased in breast cancer patients and associated with lymph node metastasis and chemoresistance.

PubMed

Kuang, Y H; Liu, Y J; Tang, L L; Wang, S M; Yan, G J; Liao, L Q

2018-05-25

Cluster of differentiation 147 (CD147) contributes to breast cancer invasion, metastasis, and multidrug resistance. Recent studies have shown that peripheral soluble CD147 (sCD147) is increased in hepatocellular tumour and multiple myeloma patients and correlated with disease severity. The primary aim of our study was to assess the level, as well as the biological and clinical significance of sCD147 in breast cancer. We tested plasma sCD147 levels in 308 breast cancer patients by enzyme-linked immunosorbent assay between February 2014 and February 2017. A subset of 165 cases of benign breast diseases was included as a control group at the same period. We analysed the clinical significance of plasma sCD147 with relevance to clinicopathological factors of breast cancer patients. Plasma sCD147 levels were significantly higher in patients with primary breast cancer than those with benign breast diseases (P=0.001), in patients with locally advanced breast cancer (T3-T4 tumour) than those in early breast cancer (T1-T2 tumour; P=0.001), in patients with lymph node metastasis than in those without (P<0.001), and in patients with high recurrence risk than those with medium recurrence risk (P<0.001). Plasma sCD147 levels were also significantly higher in the chemotherapy-resistant group than in the chemotherapy-sensitive group (P=0.040). Plasma sCD147 was an independent predictor for lymph node metastasis in breast cancer patients (P=0.001). This is the first study to demonstrate that plasma sCD147 levels are elevated in breast cancer patients. Soluble CD147 is also associated with tumour size, lymph node metastasis, high recurrent risk, and chemoresistance. Our findings support that plasma sCD147 is an independent predictive factor for lymph node metastasis.

Molecular Analysis of Erection Regulatory Factors in Sickle Cell Disease-Associated Priapism in Human Penis

PubMed Central

Lagoda, Gwen; Sezen, Sena F.; Cabrini, Marcelo R.; Musicki, Biljana; Burnett, Arthur L.

2015-01-01

Purpose Priapism is a vasculopathy occurring in approximately 40% of patients with SCD. Mouse models have suggested that dysregulated NOS and RhoA/ROCK signaling as well as increased oxidative stress may contribute to mechanisms of SCD-associated priapism. We examined changes in protein expressions of NOS and ROCK signaling pathways and a source of oxidative stress, NADPH oxidase, in penile erectile tissue from patients with priapism histories, etiologically related and unrelated to SCD. Materials and Methods Human penile erectile tissue was obtained from patients with SCD-associated priapism (SCD, n=5) and priapism of other etiologies (non-SCD, n=6) during non-emergent penile prosthesis surgery for ED or priapism management and urethroplasty, and from control patients without priapism histories (Control, n=5) during penectomy for penile cancer. Samples were collected, immediately placed in cold buffer and then frozen in liquid nitrogen. Expressions of PDE5, eNOS, nNOS, iNOS, RhoA, ROCK1, ROCK2, p47phox, p67phox, gp91phox and β-actin were determined by Western blot analysis and NO amount was measured using the Griess reaction. Results In the SCD group, PDE5 (p<0.05), eNOS (p<0.01) and RhoA (p<0.01) expressions were significantly decreased while gp91phox (p<0.05) expression was significantly increased compared to Control group values. In the non-SCD group, eNOS (p<0.05), ROCK1 (p<0.05) and p47phox (p<0.05) expressions were significantly decreased compared to Control group values. Total NO levels were not significantly different across study groups. Conclusions The mechanisms of SCD-associated priapism in the human penis may involve dysfunctional NOS and ROCK signaling and increased oxidative stress associated with NADPH oxidase-mediated signaling. PMID:22982429

Soluble CD30 in patients with antibody-mediated rejection of the kidney allograft.

PubMed

Slavcev, Antonij; Honsova, Eva; Lodererova, Alena; Pavlova, Yelena; Sajdlova, Helena; Vitko, Stefan; Skibova, Jelena; Striz, Ilja; Viklicky, Ondrej

2007-07-01

The aim of our retrospective study was to evaluate the clinical significance of measurement of the soluble CD30 (sCD30) molecule for the prediction of antibody-mediated (humoral) rejection (HR). Sixty-two kidney transplant recipients (thirty-one C4d-positive and thirty-one C4d-negative patients) were included into the study. Soluble CD30 levels were evaluated before transplantation and during periods of graft function deterioration. The median concentrations of the sCD30 molecule were identical in C4d-positive and C4d-negative patients before and after transplantation (65.5 vs. 65.0 and 28.2 vs. 36.0 U/ml, respectively). C4d+ patients who developed DSA de novo had a tendency to have higher sCD30 levels before transplantation (80.7+/-53.6 U/ml, n=8) compared with C4d-negative patients (65.0+/-33.4 U/ml, n=15). Soluble CD30 levels were evaluated as positive and negative (>or=100 U/ml and <100 U/ml respectively) and the sensitivity, specificity and accuracy of sCD30 estimation with regard to finding C4d deposits in peritubular capillaries were determined. The sensitivity of sCD30+ testing was generally below 40%, while the specificity of the test, i.e. the likelihood that if sCD30 testing is negative, C4d deposits would be absent, was 82%. C4d+ patients who developed DSA de novo were evaluated separately; the specificity of sCD30 testing for the incidence of HR in this cohort was 86%. We could not confirm in our study that high sCD30 levels (>or=100 U/ml) might be predictive for the incidence of HR. Negative sCD30 values might be however helpful for identifying patients with a low risk for development of DSA and antibody-mediated rejection.

Post-transplant monitoring of soluble CD30 level as predictor of graft outcome: a single center experience from China.

PubMed

Wang, Dong; Wu, Weizhen; Yang, Shunliang; Wang, Qinghua; Tan, Jianming

2012-12-01

There are no reliable parameters for post-transplantation immunological monitoring, which might enable recipient-tailored immunosuppressive therapy. 250 renal graft recipients were enrolled and detected for sCD30 level pre-transplantation, and on days 5 and 14, and on months 1, 3, 6, 12, 24, 36, 48 and 60 post-transplantation. Analysis was performed on correlation between sCD30 level and acute rejection, lung infection, or graft loss respectively. sCD30 levels descended to a nadir with a mean of 10.2 ± 3.8 U/mL on day 30 post-transplantation, then rose gradually, and approached 21.8 ± 10.1 U/mL on month 3, 34.2 ± 16.5 U/mL on month 6, and 42.9 ± 29.5 U/mL on month 12, then presented a stable level. Recipients with AR had significantly higher sCD30 levels than those without AR on days 5 and 14 post-transplantation. Recipients with pneumonia had significantly lower sCD30 levels within 3 months post-transplantation than those without pneumonia. Significantly higher sCD30 levels were recorded in recipients who suffered graft loss than those with normal graft function on days 5 and 14, and on months 6, 12, and 24. High sCD30 level (≥ 48.3 U/mL) at month 12 post-transplantation has an obvious detrimental effect on renal graft survival (p=0.000, HR=9.075). Serum sCD30 level might reflect immune state of renal graft recipients. Post-transplantation sequential monitoring of sCD30 level is necessary, which might not only identify recipients at the risk of acute rejection and graft loss, but also chosen as an independent predictor of pneumonia in renal transplant recipients. Copyright © 2012 Elsevier B.V. All rights reserved.

Occupation and risk of sudden death in a United States community: a case-control analysis.

PubMed

Zhang, Lin; Narayanan, Kumar; Suryadevara, Vallabh; Teodorescu, Carmen; Reinier, Kyndaron; Uy-Evanado, Audrey; Chugh, Harpriya; Zheng, Zhi-Jie; Gunson, Karen; Jui, Jonathan; Chugh, Sumeet S

2015-12-18

Work environment is said to influence cardiovascular risk. We assessed whether nature of occupation affects risk of sudden cardiac death (SCD) in the general population. In the ongoing, prospective Oregon Sudden Unexpected Death Study (catchment population 1 million), working-age SCD cases (18-65 years) were compared with controls who died from any cause. Usual occupation obtained from death certificates was classified using the US Census Bureau standard occupational classification descriptions and categorised as white collar, blue collar or homemaker. Odds ratio (OR) for SCD by occupation category was obtained and clinical profile of SCD cases was compared by occupation type. Among SCD cases (n=646; 74% male) compared to controls (n=622; 73.6% male), the proportion of white collar workers was higher among male SCD cases (52.7% vs 43.7%; p=0.01); the difference in females was smaller (59.5% vs 55%; p=0.62). Adjusting for race and smoking status, male white collar workers had a higher risk of SCD compared to blue collar workers (OR=1.67, (1.26 to 2.23), p<0.001). A similar, non-significant trend was observed among females (OR 1.49 (0.81 to 2.75); p=0.20). White collar SCD cases were less likely to be current smokers (34.7% vs 45.3%, p=0.008), drug misusers (13.1% vs 18.5%) or have diabetes (21.4% vs 28.2%, both p=0.07) compared to blue collar workers. Other cardiac risk factors were similar. A white collar occupation was associated with increased risk of SCD, when compared to blue collar occupations. Since differences in conventional risk factors did not explain this elevated risk, work-related behavioural and psychosocial stressors warrant a closer evaluation. 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/

Occupation and risk of sudden death in a United States community: a case–control analysis

PubMed Central

Zhang, Lin; Narayanan, Kumar; Suryadevara, Vallabh; Teodorescu, Carmen; Reinier, Kyndaron; Uy-Evanado, Audrey; Chugh, Harpriya; Zheng, Zhi-Jie; Gunson, Karen; Jui, Jonathan; Chugh, Sumeet S

2015-01-01

Objective Work environment is said to influence cardiovascular risk. We assessed whether nature of occupation affects risk of sudden cardiac death (SCD) in the general population. Methods In the ongoing, prospective Oregon Sudden Unexpected Death Study (catchment population 1 million), working-age SCD cases (18–65 years) were compared with controls who died from any cause. Usual occupation obtained from death certificates was classified using the US Census Bureau standard occupational classification descriptions and categorised as white collar, blue collar or homemaker. Odds ratio (OR) for SCD by occupation category was obtained and clinical profile of SCD cases was compared by occupation type. Results Among SCD cases (n=646; 74% male) compared to controls (n=622; 73.6% male), the proportion of white collar workers was higher among male SCD cases (52.7% vs 43.7%; p=0.01); the difference in females was smaller (59.5% vs 55%; p=0.62). Adjusting for race and smoking status, male white collar workers had a higher risk of SCD compared to blue collar workers (OR=1.67, (1.26 to 2.23), p<0.001). A similar, non-significant trend was observed among females (OR 1.49 (0.81 to 2.75); p=0.20). White collar SCD cases were less likely to be current smokers (34.7% vs 45.3%, p=0.008), drug misusers (13.1% vs 18.5%) or have diabetes (21.4% vs 28.2%, both p=0.07) compared to blue collar workers. Other cardiac risk factors were similar. Conclusions A white collar occupation was associated with increased risk of SCD, when compared to blue collar occupations. Since differences in conventional risk factors did not explain this elevated risk, work-related behavioural and psychosocial stressors warrant a closer evaluation. PMID:26685031

UBIAD1 Mutation Alters a Mitochondrial Prenyltransferase to Cause Schnyder Corneal Dystrophy

PubMed Central

Nickerson, Michael L.; Kostiha, Brittany N.; Brandt, Wolfgang; Fredericks, William; Xu, Ke-Ping; Yu, Fu-Shin; Gold, Bert; Chodosh, James; Goldberg, Marc; Lu, Da Wen; Yamada, Masakazu; Tervo, Timo M.; Grutzmacher, Richard; Croasdale, Chris; Hoeltzenbein, Maria; Sutphin, John; Malkowicz, S. Bruce; Wessjohann, Ludger; Kruth, Howard S.; Dean, Michael; Weiss, Jayne S.

2010-01-01

Background Mutations in a novel gene, UBIAD1, were recently found to cause the autosomal dominant eye disease Schnyder corneal dystrophy (SCD). SCD is characterized by an abnormal deposition of cholesterol and phospholipids in the cornea resulting in progressive corneal opacification and visual loss. We characterized lesions in the UBIAD1 gene in new SCD families and examined protein homology, localization, and structure. Methodology/Principal Findings We characterized five novel mutations in the UBIAD1 gene in ten SCD families, including a first SCD family of Native American ethnicity. Examination of protein homology revealed that SCD altered amino acids which were highly conserved across species. Cell lines were established from patients including keratocytes obtained after corneal transplant surgery and lymphoblastoid cell lines from Epstein-Barr virus immortalized peripheral blood mononuclear cells. These were used to determine the subcellular localization of mutant and wild type protein, and to examine cholesterol metabolite ratios. Immunohistochemistry using antibodies specific for UBIAD1 protein in keratocytes revealed that both wild type and N102S protein were localized sub-cellularly to mitochondria. Analysis of cholesterol metabolites in patient cell line extracts showed no significant alteration in the presence of mutant protein indicating a potentially novel function of the UBIAD1 protein in cholesterol biochemistry. Molecular modeling was used to develop a model of human UBIAD1 protein in a membrane and revealed potentially critical roles for amino acids mutated in SCD. Potential primary and secondary substrate binding sites were identified and docking simulations indicated likely substrates including prenyl and phenolic molecules. Conclusions/Significance Accumulating evidence from the SCD familial mutation spectrum, protein homology across species, and molecular modeling suggest that protein function is likely down-regulated by SCD mutations. Mitochondrial UBIAD1 protein appears to have a highly conserved function that, at least in humans, is involved in cholesterol metabolism in a novel manner. PMID:20505825

Beneficial Effect of the Nitric Oxide Donor Compound 3-(1,3-Dioxoisoindolin-2-yl)Benzyl Nitrate on Dysregulated Phosphodiesterase 5, NADPH Oxidase, and Nitrosative Stress in the Sickle Cell Mouse Penis: Implication for Priapism Treatment.

PubMed

Silva, Fábio H; Karakus, Serkan; Musicki, Biljana; Matsui, Hotaka; Bivalacqua, Trinity J; Dos Santos, Jean L; Costa, Fernando F; Burnett, Arthur L

2016-11-01

Patients with sickle cell disease (SCD) display priapism, and dysregulated nitric oxide (NO) pathway may contribute to this condition. However, current therapies offered for the prevention of priapism in SCD are few. The 3-(1,3-dioxoisoindolin-2-yl)benzyl nitrate (compound 4C) was synthesized through molecular hybridization of hydroxyurea and thalidomide, which displays an NO-donor property. This study aimed to evaluate the effects of compound 4C on functional and molecular alterations of erectile function in murine models that display low NO bioavailability, SCD transgenic mice, and endothelial NO synthase and neuronal NO synthase double gene-deficient (dNOS -/ ) mice, focusing on the dysregulated NO-cGMP- phosphodiesterase type 5 (PDE5) pathway and oxidative stress in erectile tissue. Wild-type, SCD, and dNOS -/- mice were treated with compound 4C (100 μmol/kg/d, 3 weeks). Intracavernosal pressure in anesthetized mice was evaluated. Corpus cavernosum tissue was dissected free and mounted in organ baths. SCD and dNOS -/- mice displayed a priapism phenotype, which was reversed by compound 4C treatment. Increased corpus cavernosum relaxant responses to acetylcholine and electrical-field stimulation were reduced by 4C in SCD mice. Likewise, increased sodium nitroprusside-induced relaxant responses were reduced by 4C in cavernosal tissue from SCD and dNOS -/- mice. Compound 4C reversed PDE5 protein expression and reduced protein expressions of reactive oxygen species markers, NADPH oxidase subunit gp91 phox , and 3-nitrotyrosine in penises from SCD and dNOS -/- mice. In conclusion, 3-week therapy with the NO donor 4C reversed the priapism in murine models that display lower NO bioavailability. NO donor compounds may constitute an additional strategy to prevent priapism in SCD. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Fine structure of Galactic foreground ISM towards high-redshift AGN - utilizing Herschel PACS and SPIRE data

NASA Astrophysics Data System (ADS)

Perger, K.; Pinter, S.; Frey, S.; Tóth, L. V.

2018-05-01

One of the most certain ways to determine star formation rate in galaxies is based on far infrared (FIR) measurements. To decide the origin of the observed FIR emission, subtracting the Galactic foreground is a crucial step. We utilized Herschel photometric data to determine the hydrogen column densities in three galactic latitude regions, at b = 27°, 50° and -80°. We applied a pixel-by-pixel fit to the spectral energy distribution (SED) for the images aquired from parallel PACS-SPIRE observations in all three sky areas. We determined the column densities with resolutions 45'' and 6', and compared the results with values estimated from the IRAS dust maps. Column densities at 27° and 50° galactic latitudes determined from the Herschel data are in a good agreement with the literature values. However, at the highest galactic latitude we found that the column densities from the Herschel data exceed those derived from the IRAS dust map.

Serum soluble CD30 in early arthritis: a sign of inflammation but not a predictor of outcome.

PubMed

Savolainen, E; Matinlauri, I; Kautiainen, H; Luosujärvi, R; Kaipiainen-Seppänen, O

2008-01-01

To evaluate serum soluble CD30 levels (sCD30) in an early arthritis series and assess their ability to predict the outcome in patients with rheumatoid arthritis (RA) and undifferentiated arthritis (UA) at one year follow-up. Serum sCD30 levels were measured by ELISA from 92 adult patients with RA and UA at baseline and from 60 adult controls. The patients were followed up for one year in the Kuopio 2000 Arthritis Survey. Receiver operating characteristic (ROC) curves were constructed to determine cut off points of sCD30 in RA and UA that select the inflammatory disease from controls. Sensitivity, specificity and positive likelihood ratio, and their 95 % CIs were calculated for sCD30 levels in RA and UA. Median serum sCD30 levels were higher in RA 25.1 (IQ range 16.3-38.6) IU/ml (p<0.001) and in UA 23.4 (15.4-35.6) IU/ml (p<0.001) than in controls 15.1 (10.7-20.8) IU/ml. No differences were recorded between RA and UA (p=0.840). Serum sCD30 levels at baseline did not predict remission at one year follow-up. Serum sCD30 levels were higher in RA and UA than in controls at baseline but they did not predict remission at one year follow-up in this series.

Changes in SCD gene DNA methylation after bariatric surgery in morbidly obese patients are associated with free fatty acids

PubMed Central

Morcillo, Sonsoles; Martín-Núñez, Gracia Mª; García-Serrano, Sara; Gutierrez-Repiso, Carolina; Rodriguez-Pacheco, Francisca; Valdes, Sergio; Gonzalo, Montserrat; Rojo-Martinez, Gemma; Moreno-Ruiz, Francisco J.; Rodriguez-Cañete, Alberto; Tinahones, Francisco; García-Fuentes, Eduardo

2017-01-01

Stearoyl CoA Desaturase-1 (SCD) is considered as playing an important role in the explanation of obesity. The aim of this study was to evaluate whether the DNA methylation SCD gene promoter is associated with the metabolic improvement in morbidly obese patients after bariatric surgery. The study included 120 subjects with morbid obesity who underwent a laparoscopic Roux-en Y gastric by-pass (RYGB) and a control group of 30 obese subjects with a similar body mass index (BMI) to that found in morbidly obese subjects six months after RYGB. Fasting blood samples were obtained before and at six months after RYGB. DNA methylation was measured by pyrosequencing technology. DNA methylation levels of the SCD gene promoter were lower in morbidly obese subjects before bariatric surgery but increased after RYGB to levels similar to those found in the control group. Changes of DNA methylation SCD gene were associated with the changes of free fatty acids levels (r = −0.442, p = 0.006) and HOMA-IR (r = −0.249, p = 0.035) after surgery. RYGB produces an increase in the low SCD methylation promoter levels found in morbidly obese subjects. This change of SCD methylation levels is associated with changes in FFA and HOMA-IR. PMID:28393901

Distinguishing spinocerebellar ataxia with pure cerebellar manifestation from multiple system atrophy (MSA-C) through saccade profiles.

PubMed

Terao, Yasuo; Fukuda, Hideki; Tokushige, Shin-Ichi; Inomata-Terada, Satomi; Yugeta, Akihiro; Hamada, Masashi; Ugawa, Yoshikazu

2017-01-01

Patients with spinocerebellar ataxia with pure cerebellar presentation (SCD) and multiple system atrophy (MSA-C) show similar symptoms at early stages, although cerebellofugal pathology predominates in SCD, and cerebellopetal pathology in MSA-C. We studied whether saccade velocity profiles, which reflect the accelerating and braking functions of the cerebellum, can differentiate these two disorders. We recorded visually guided (VGS) and memory guided saccades (MGS) in 29 MSA-C patients, 12 SCD patients, and 92 age-matched normal subjects, and compared their amplitude, peak velocity and duration (accelerating and decelerating phases). Hypometria predominated in VGS and MGS of MSA-C, whereas hypometria was less marked in SCD, with hypermetria frequently noted in MGS. Peak velocity was reduced, and deteriorated with advancing disease both in SCD and MSA-C groups at smaller target eccentricities. The deceleration phase was prolonged in SCD compared to MSA-C and normal groups at larger target eccentricities, which deteriorated with advancing disease. Saccades in MSA-C were characterized by a more prominent acceleration deficit and those in SCD by a more prominent braking defect, possibly caused by the cerebellopetal and cerebellofugal pathologies, respectively. Saccade profiles provide important information regarding the accelerating and braking signals of the cerebellum in spinocerebellar ataxia. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Elevated urinary leukotriene E4 levels are associated with hospitalization for pain in children with sickle cell disease.

PubMed

Jennings, Jeanine E; Ramkumar, Thiruvamoor; Mao, Jingnan; Boyd, Jessica; Castro, Mario; Field, Joshua J; Strunk, Robert C; DeBaun, Michael R

2008-08-01

Cysteinyl leukotrienes (CsyLTs) are inflammatory mediators produced by white blood cells. Leukotriene LTE(4) is the stable metabolite of CsyLTs, which can be measured in urine. We tested two hypotheses among children with sickle cell disease (SCD): (1) baseline urinary LTE(4) levels are elevated in children with SCD when compared with controls; and (2) baseline LTE(4) levels are associated with an increased incidence rate of hospitalization for SCD-related pain. Baseline LTE(4) levels were measured in children with SCD (cases) and children without SCD matched for age and ethnicity (controls). Medical records of cases were reviewed to assess the frequency of hospitalization for pain within 3 years of study entry. LTE(4) levels were obtained in 71 cases and 22 controls. LTE(4) levels were higher in cases compared with controls (median LTE(4): 100 vs. 57 pg/mg creatinine, P < 0.001). After adjustment for age and asthma diagnosis, a greater incidence rate of hospitalization for pain was observed among children with SCD in the highest LTE(4) tertile when compared with the lowest (114 vs. 52 episodes per 100 patient-years, P = 0.038). LTE(4) levels are elevated in children with SCD when compared with controls. LTE(4) levels are associated with an increased rate of hospitalizations for pain. Copyright 2008 Wiley-Liss, Inc.

Evaluation of pre- and posttransplantation serum interferon-gamma and soluble CD30 for predicting liver allograft rejection.

PubMed

Kim, K H; Oh, E-J; Jung, E-S; Park, Y-J; Choi, J Y; Kim, D-G; Lee, K Y; Kang, C S

2006-06-01

The aim of the present study was to identify whether the serum interferon-gamma (IFNgamma), a Th1 cytokine, or soluble CD30 (sCD30), a marker for activation of Th2 cytokine-producing T cells, predict acute cellular rejection episodes among liver graft patients. Pretransplant and posttransplant sera from 32 living donor liver transplant recipients obtained on days 1, 3, and 7 after surgery were tested for serum IFNgamma and sCD30 concentrations using commercial enzyme-linked immunosorbent assay kits. Recipients with an acute rejection episode (ARE) (n=14) displayed significantly higher IFNgamma concentrations pretransplant than did the patients with no ARE (n=18) (P<.05). The pretransplant serum levels of sCD30 were not different between the non-ARE and ARE groups. However, in comparison with the non-ARE group, who showed steadily decreasing serum sCD30 levels after transplantation, 12 among the 14 patients in the ARE group showed increasing sCD30 levels from day 1 to day 3 after transplantation (P<.05). These results suggest that the sCD30 increment during the early period after liver transplantation affects the immune response of rejection. This observation emphasizes the clinical relevance of serum sCD30, in addition to serum IFNgamma, as predictive markers for acute liver graft rejection.

Association between serum soluble CD30 and serum creatinine before and after renal transplantation.

PubMed

López-Hoyos, M; San Segundo, D; Benito, M J; Fernández-Fresnedo, G; Ruiz, J C; Rodrigo, E; Gómez-Alamillo, C; Benito, A; Arias, M

2008-11-01

There is increasing evidence that circulating levels of soluble CD30 (sCD30) may represent a biomarker for outcome in kidney transplantation. The aim of this study was to measure the pre- and posttransplantation serum levels of sCD30 in cadaveric kidney transplant recipients and correlate them with serum creatinine. Serum sCD30 was measured by a commercial enzyme-linked immunosorbent assay (ELISA) from prospective samples of 38 kidney allograft recipients serially transplanted at our center. Samples were collected at day 0 pretransplantation and at months 6, 12, 18, and 24 posttransplantation. We also studied sera from 29 patients with chronic kidney disease (CKD) at different stages of the K/DOQI guidelines, as a control group. Serum levels of sCD30 decreased significantly in samples posttransplantation compared with pretransplantation. The significant decrease after transplantation may be related to the improvement in renal function since we observed a significant correlation between serum levels of sCD30 and creatinine (sCr) at all times of the study. In addition, the patients with chronic renal failure showed a significant association between serum sCD30 and sCr (r = .454; P = .013). Our results did not suggest that the measurement of sCD30 may be used as a valuable biomarker in renal transplantation. Increased levels may be related to a decrease in its renal elimination.

Risk factors for vitamin D deficiency in sickle cell disease.

PubMed

Han, Jin; Zhang, Xu; Saraf, Santosh L; Gowhari, Michel; Molokie, Robert E; Hassan, Johara; Jain, Shivi; Shah, Binal N; Abbasi, Taimur; Machado, Roberto F; Gordeuk, Victor R

2018-05-16

Vitamin D deficiency (VDD), 25-OHD levels <20 ng/ml, is prevalent among patients with sickle cell disease (SCD) and is linked to acute and chronic pain and bone fracture in this population. There is limited literature regarding VDD-associated risk factors for SCD. We examined potential clinical and genomic parameters associated with VDD in 335 adults with SCD in a cross-sectional study. VDD was present in 65% of adult SCD patients, and 25-OHD levels independently and positively correlated with older age (P < 0·001) and vitamin D supplementation (P < 0·001). 25-OHD levels were higher in SCD patients over 40 years of age compared to the general African-American population. Both lower 25-OHD levels and increased pain frequency were associated with increased expression of SLC6A5 encoding glycine transporter-2 (GlyT2), a protein involved in neuronal pain pathways. Lower 25-OHD levels were also associated with increased expression of CYP3A4, and with decreased expression of GC (also termed DBP) and VDR, three genes involved in vitamin D metabolism. We conclude that vitamin D supplementation should be an almost universal feature of the care of young adults with SCD, and that further research is warranted into genomic factors that regulate vitamin D metabolism in SCD. © 2018 John Wiley & Sons Ltd.

African American Adolescents with Sickle Cell Disease: Support Groups and Psychological Well-Being.

ERIC Educational Resources Information Center

Gardner, Marilyn M.; Telfair, Joseph

1999-01-01

Studied the impact of support groups on the psychological well-being of adolescents with sickle cell disease (SCD). Response of 79 adolescent SCD group members show that psychological well-being was best predicted by fewer physical symptoms and greater satisfaction with the group. Findings suggest the beneficial effects of SCD support groups. (SLD)

Peer Relationships and Emotional Well-Being of Youngsters with Sickle Cell Disease.

ERIC Educational Resources Information Center

Noll, Robert B; And Others

1996-01-01

Compared measures of peer relationships and emotional well-being of children with sickle cell disease (SCD) to those of same-classroom peers. Found that, compared to nondiseased subjects, SCD females were perceived as less sociable and less well accepted; SCD males were perceived as less aggressive. No other differences were identified for…

Correlations in the three-dimensional Lyman-alpha forest contaminated by high column density absorbers

NASA Astrophysics Data System (ADS)

Rogers, Keir K.; Bird, Simeon; Peiris, Hiranya V.; Pontzen, Andrew; Font-Ribera, Andreu; Leistedt, Boris

2018-05-01

Correlations measured in three dimensions in the Lyman-alpha forest are contaminated by the presence of the damping wings of high column density (HCD) absorbing systems of neutral hydrogen (H I; having column densities N(H I) > 1.6 × 10^{17} atoms cm^{-2}), which extend significantly beyond the redshift-space location of the absorber. We measure this effect as a function of the column density of the HCD absorbers and redshift by measuring three-dimensional (3D) flux power spectra in cosmological hydrodynamical simulations from the Illustris project. Survey pipelines exclude regions containing the largest damping wings. We find that, even after this procedure, there is a scale-dependent correction to the 3D Lyman-alpha forest flux power spectrum from residual contamination. We model this residual using a simple physical model of the HCD absorbers as linearly biased tracers of the matter density distribution, convolved with their Voigt profiles and integrated over the column density distribution function. We recommend the use of this model over existing models used in data analysis, which approximate the damping wings as top-hats and so miss shape information in the extended wings. The simple `linear Voigt model' is statistically consistent with our simulation results for a mock residual contamination up to small scales (|k| < 1 h Mpc^{-1}). It does not account for the effect of the highest column density absorbers on the smallest scales (e.g. |k| > 0.4 h Mpc^{-1} for small damped Lyman-alpha absorbers; HCD absorbers with N(H I) ˜ 10^{21} atoms cm^{-2}). However, these systems are in any case preferentially removed from survey data. Our model is appropriate for an accurate analysis of the baryon acoustic oscillations feature. It is additionally essential for reconstructing the full shape of the 3D flux power spectrum.

Reproductive health choices for young adults with sickle cell disease or trait: randomized controlled trial immediate posttest effects.

PubMed

Wilkie, Diana J; Gallo, Agatha M; Yao, Yingwei; Molokie, Robert E; Stahl, Christine; Hershberger, Patricia E; Zhao, Zhongsheng; Suarez, Marie L; Labotka, Robert J; Johnson, Bonnye; Angulo, Rigo; Angulo, Veronica; Carrasco, Jesus; Shuey, David; Pelligra, Stephanie; Wang, Edward; Rogers, Dennie T; Thompson, Alexis A

2013-01-01

People with sickle cell disease (SCD) or sickle cell trait (SCT) may not have information about genetic inheritance needed for making informed reproductive health decisions. CHOICES is a Web-based, multimedia educational intervention that provides information about reproductive options and consequences to help those with SCD or SCT identify and implement an informed parenting plan. Efficacy of CHOICES compared with usual care must be evaluated. The purpose was to compare immediate posttest effects of CHOICES versus an attention-control usual care intervention (e-Book) on SCD-/SCT-related reproductive health knowledge, intention, and behavior. In a randomized controlled study, we recruited subjects with SCD/SCT from clinics, community settings, and online networks with data collected at sites convenient to the 234 subjects with SCD (n = 136) or SCT (n = 98). Their ages ranged from 18 to 35 years; 65% were women, and 94% were African American. Subjects completed a measure of sickle cell reproductive knowledge, intention, and behavior before and immediately after the intervention. Compared with the e-Book group, the CHOICES group had significantly higher average knowledge scores and probability of reporting a parenting plan to avoid SCD or SCD and SCT when pretest scores were controlled. Effects on intention and planned behavior were not significant. The CHOICES group showed significant change in their intention and planned behavior, whereas the e-Book group did not show significant change in their intention, but their planned behavior differed significantly. Initial efficacy findings are encouraging but warrant planned booster sessions and outcome follow-ups to determine sustained intervention efficacy on reproductive health knowledge, intention, and actual behavior of persons with SCD/SCT.

An Expert Review of Pharmacogenomics of Sickle Cell Disease Therapeutics: Not Yet Ready for Global Precision Medicine

PubMed Central

Mnika, Khuthala; Pule, Gift D.; Dandara, Collet

2016-01-01

Abstract Sickle cell disease (SCD) is a blood disease caused by a single nucleotide substitution (T > A) in the beta globin gene on chromosome 11. The single point mutation (Glu6Val) promotes polymerization of hemoglobin S (HbS) and causes sickling of erythrocytes. Vaso-occlusive painful crises are associated with recurrent and long-term use of analgesics/opioids and hydroxyurea (HU) by people living with SCD. The present analysis offers a state-of-the-art expert review of the effectiveness of pharmacogenomics/genetics of pain management in SCD, with specific focus on HU and opioids. The literature search used the following keywords: SCD, pharmacogenomics, pharmacogenetics, pain, antalgics, opioids, morphine, and HU. The literature was scanned until March 2016, with specific inclusion of targeted landmark and background articles on SCD. Surprisingly, our review identified only a limited number of studies that addressed the genetic/genomic basis of variable responses to pain (e.g., variants in OPRM1, HMOX-1, GCH1, VEGFA COMT genes), and pharmacogenomics of antalgics and opioids (e.g., variants in OPRM1, STAT6, ABCB1, and COMT genes) in SCD. There has been greater progress made toward identifying the key genomic variants, mainly in BCL11A, HBS1L-MYB, or SAR1, which contribute to response to HU treatment. However, the complete picture on pharmacogenomic determinants of the above therapeutic phenotypes remains elusive. Strikingly, no study has been conducted in sub-Saharan Africa where majority of the patients with SCD live. This alerts the broader global life sciences community toward the existing disparities in optimal and ethical targeting of research and innovation investments for SCD specifically and precision medicine and pharmacology research broadly. PMID:27636225

Managing serious clinical deterioration in a tertiary hospital in Hong Kong: from indicators development to multiple measures in reducing the rates.

PubMed

Ho, Jasperine Ka Yee; Lee, Quinnie; Lam, Jaden Chun Ho; Tang, Kam Shing

2017-06-01

Timely detection and management of acutely deteriorating patients can save lives. Tuen Mun Hospital (TMH), a 1800-bed acute tertiary hospital serving more than 1.06 million populations in Hong Kong, is exploring to quantitatively monitor serious clinical deterioration (SCD) and uses it to guide patient care improvement initiatives. Literature review on definition and measurement of SCD was conducted. Monthly SCD rates of TMH were first calculated according to the published methodology and benchmarked against those of international centres. A refined composite clinical indicator good for local use was compiled. In the second phase, p-control charts of SCD have been plotted based on cumulative data. TMH's performance was comparable with that of international centres. SCD on p-control charts has been plotting since January 2013. There were peaks in all 4 SCD rates during the winter surge period in 2013-2014. In the third phase, multiple measures have been taking to reduce the SCD rates including targeting the 3 main factors of winter surge situation. We are delighted to observe that the pattern did not repeat in the rate of cardiac arrest without do not attempt cardiopulmonary resuscitation (DNACPR) and rate of death without DNACPR in the same period in 2014-2015. SCD becomes a clinical governance tool to monitor the performance of clinical teams in treating acutely deteriorating patients in TMH. Any abnormal patterns or indications of special cause variations in the control charts would alert leaders to look for root causes of special cause variations and manage accordingly. We hope that this project will extend to corporate level and become a sustainable clinical indicator to guide audits, quality improvement initiatives and strategic planning. © 2016 John Wiley & Sons, Ltd.

Characterization of Stearoyl-CoA Desaturases from a Psychrophilic Antarctic Copepod, Tigriopus kingsejongensis.

PubMed

Jung, Woongsic; Kim, Eun Jae; Han, Se Jong; Choi, Han-Gu; Kim, Sanghee

2016-10-01

Stearoyl-CoA desaturase is a key regulator in fatty acid metabolism that catalyzes the desaturation of stearic acid to oleic acid and controls the intracellular levels of monounsaturated fatty acids (MUFAs). Two stearoyl-CoA desaturases (SCD, Δ9 desaturases) genes were identified in an Antarctic copepod, Tigriopus kingsejongensis, that was collected in a tidal pool near the King Sejong Station, King George Island, Antarctica. Full-length complementary DNA (cDNA) sequences of two T. kingsejongensis SCDs (TkSCDs) were obtained from next-generation sequencing and isolated by reverse transcription PCR. DNA sequence lengths of the open reading frames of TkSCD-1 and TkSCD-2 were determined to be 1110 and 681 bp, respectively. The molecular weights deduced from the corresponding genes were estimated to be 43.1 kDa (TkSCD-1) and 26.1 kDa (TkSCD-2). The amino acid sequences were compared with those of fatty acid desaturases and sterol desaturases from various organisms and used to analyze the relationships among TkSCDs. As assessed by heterologous expression of recombinant proteins in Escherichia coli, the enzymatic functions of both stearoyl-CoA desaturases revealed that the amount of C16:1 and C18:1 fatty acids increased by greater than 3-fold after induction with isopropyl β-D-thiogalactopyranoside. In particular, C18:1 fatty acid production increased greater than 10-fold in E. coli expressing TkSCD-1 and TkSCD-2. The results of this study suggest that both SCD genes from an Antarctic marine copepod encode a functional desaturase that is capable of increasing the amounts of palmitoleic acid and oleic acid in a prokaryotic expression system.

Positive feedback loop and synergistic effects between hypoxia-inducible factor-2α and stearoyl-CoA desaturase-1 promote tumorigenesis in clear cell renal cell carcinoma.

PubMed

Zhang, Yujian; Wang, Hui; Zhang, Jin; Lv, Jianwei; Huang, Yiran

2013-04-01

Adapting to hypoxic stress is pivotal in tumor progression and determining tumor malignancy. The transcriptional factor hypoxia-inducible factor (HIF) is crucial in modulating tumorous hypoxic responses through altering cell energy metabolism, which includes the modification of glucose and lipid metabolism-associated gene expression. Stearoyl-CoA desaturase-1 (SCD1) is the main isoform of SCDs, the rate-limiting enzymes in the biosynthesis of monounsaturated fatty acids from saturated fatty acids, which is extensively activated in cancer progression. In this study, we found that SCD1 and HIF-2α were overexpressed in human clear cell renal cell carcinoma (ccRCC) tissues and ccRCC cell lines, and were upregulated in the 786-0 ccRCC cell line under hypoxia. Knockdown of SCD1 or HIF-2α impacted the other's expression. Enhancing SCD1 resulted in HIF-2α upregulation, which could be blocked by inhibiting the PI3K/Akt pathway. Deficiency of SCD1 or HIF-2α in 768-0 cells led to apoptosis, less colony formation ability, and decreased cell migration. More obvious effects were observed in 786-0 cells with double SCD1 and HIF-2α knockdown. These results indicate a PI3K/Akt-mediated loop between SCD1 and HIF-2α that mutually enhances their protein levels. Both SCD1 and HIF-2α are critical to promoting tumorigenesis by synergistically acting on maintaining cell survival, triggering cell migration, and enhancing the colony formation ability of cancer cells. © 2013 Japanese Cancer Association.

Biophysical markers of the peripheral vasoconstriction response to pain in sickle cell disease

PubMed Central

Khaleel, Maha; Sunwoo, John; Shah, Payal; Detterich, Jon A.; Kato, Roberta M.; Thuptimdang, Wanwara; Meiselman, Herbert J.; Sposto, Richard; Tsao, Jennie; Wood, John C.; Zeltzer, Lonnie; Coates, Thomas D.; Khoo, Michael C. K.

2017-01-01

Painful vaso-occlusive crisis (VOC), a complication of sickle cell disease (SCD), occurs when sickled red blood cells obstruct flow in the microvasculature. We postulated that exaggerated sympathetically mediated vasoconstriction, endothelial dysfunction and the synergistic interaction between these two factors act together to reduce microvascular flow, promoting regional vaso-occlusions, setting the stage for VOC. We previously found that SCD subjects had stronger vasoconstriction response to pulses of heat-induced pain compared to controls but the relative degrees to which autonomic dysregulation, peripheral vascular dysfunction and their interaction are present in SCD remain unknown. In the present study, we employed a mathematical model to decompose the total vasoconstriction response to pain into: 1) the neurogenic component, 2) the vascular response to blood pressure, 3) respiratory coupling and 4) neurogenic-vascular interaction. The model allowed us to quantify the contribution of each component to the total vasoconstriction response. The most salient features of the components were extracted to represent biophysical markers of autonomic and vascular impairment in SCD and controls. These markers provide a means of phenotyping severity of disease in sickle-cell anemia that is based more on underlying physiology than on genotype. The marker of the vascular component (BMv) showed stronger contribution to vasoconstriction in SCD than controls (p = 0.0409), suggesting a dominant myogenic response in the SCD subjects as a consequence of endothelial dysfunction. The marker of neurogenic-vascular interaction (BMn-v) revealed that the interaction reinforced vasoconstriction in SCD but produced vasodilatory response in controls (p = 0.0167). This marked difference in BMn-v suggests that it is the most sensitive marker for quantifying combined alterations in autonomic and vascular function in SCD in response to heat-induced pain. PMID:28542469

PedsQL™ Multidimensional Fatigue Scale in sickle cell disease: feasibility, reliability, and validity.

PubMed

Panepinto, Julie A; Torres, Sylvia; Bendo, Cristiane B; McCavit, Timothy L; Dinu, Bogdan; Sherman-Bien, Sandra; Bemrich-Stolz, Christy; Varni, James W

2014-01-01

Sickle cell disease (SCD) is an inherited blood disorder characterized by a chronic hemolytic anemia that can contribute to fatigue and global cognitive impairment in patients. The study objective was to report on the feasibility, reliability, and validity of the PedsQL™ Multidimensional Fatigue Scale in SCD for pediatric patient self-report ages 5-18 years and parent proxy-report for ages 2-18 years. This was a cross-sectional multi-site study whereby 240 pediatric patients with SCD and 303 parents completed the 18-item PedsQL™ Multidimensional Fatigue Scale. Participants also completed the PedsQL™ 4.0 Generic Core Scales. The PedsQL™ Multidimensional Fatigue Scale evidenced excellent feasibility, excellent reliability for the Total Scale Scores (patient self-report α = 0.90; parent proxy-report α = 0.95), and acceptable reliability for the three individual scales (patient self-report α = 0.77-0.84; parent proxy-report α = 0.90-0.97). Intercorrelations of the PedsQL™ Multidimensional Fatigue Scale with the PedsQL™ Generic Core Scales were predominantly in the large (≥0.50) range, supporting construct validity. PedsQL™ Multidimensional Fatigue Scale Scores were significantly worse with large effects sizes (≥0.80) for patients with SCD than for a comparison sample of healthy children, supporting known-groups discriminant validity. Confirmatory factor analysis demonstrated an acceptable to excellent model fit in SCD. The PedsQL™ Multidimensional Fatigue Scale demonstrated acceptable to excellent measurement properties in SCD. The results demonstrate the relative severity of fatigue symptoms in pediatric patients with SCD, indicating the potential clinical utility of multidimensional assessment of fatigue in patients with SCD in clinical research and practice. © 2013 Wiley Periodicals, Inc.

PedsQL™ Multidimensional Fatigue Scale in Sickle Cell Disease: Feasibility, Reliability and Validity

PubMed Central

Panepinto, Julie A.; Torres, Sylvia; Bendo, Cristiane B.; McCavit, Timothy L.; Dinu, Bogdan; Sherman-Bien, Sandra; Bemrich-Stolz, Christy; Varni, James W.

2013-01-01

Background Sickle cell disease (SCD) is an inherited blood disorder characterized by a chronic hemolytic anemia that can contribute to fatigue and global cognitive impairment in patients. The study objective was to report on the feasibility, reliability, and validity of the PedsQL™ Multidimensional Fatigue Scale in SCD for pediatric patient self-report ages 5–18 years and parent proxy-report for ages 2–18 years. Procedure This was a cross-sectional multi-site study whereby 240 pediatric patients with SCD and 303 parents completed the 18-item PedsQL™ Multidimensional Fatigue Scale. Participants also completed the PedsQL™ 4.0 Generic Core Scales. Results The PedsQL™ Multidimensional Fatigue Scale evidenced excellent feasibility, excellent reliability for the Total Scale Scores (patient self-report α = 0.90; parent proxy-report α = 0.95), and acceptable reliability for the three individual scales (patient self-report α = 0.77–0.84; parent proxy-report α = 0.90–0.97). Intercorrelations of the PedsQL™ Multidimensional Fatigue Scale with the PedsQL™ Generic Core Scales were predominantly in the large (≥ 0.50) range, supporting construct validity. PedsQL™ Multidimensional Fatigue Scale Scores were significantly worse with large effects sizes (≥0.80) for patients with SCD than for a comparison sample of healthy children, supporting known-groups discriminant validity. Confirmatory factor analysis demonstrated an acceptable to excellent model fit in SCD. Conclusions The PedsQL™ Multidimensional Fatigue Scale demonstrated acceptable to excellent measurement properties in SCD. The results demonstrate the relative severity of fatigue symptoms in pediatric patients with SCD, indicating the potential clinical utility of multidimensional assessment of fatigue in patients with SCD in clinical research and practice. PMID:24038960

Incidence of Sudden Cardiac Death in a Young Active Population

PubMed Central

Farioli, Andrea; Christophi, Costas A; Quarta, Candida Cristina; Kales, Stefanos N

2015-01-01

Background Little is known about the burden of sudden cardiac death (SCD) among active, presumably healthy persons. We investigated the incidence of SCD among US male career firefighters. Methods and Results All on-duty SCDs among US male career firefighters between 1998 and 2012 were identified from the US Fire Administration and the US National Institute for Occupational Safety and Health databases. Age-specific incidence rates (IRs) of SCD with 95% CIs were computed. A joinpoint model was fitted to analyze the trend in IR and to help estimate the annual percentage change of SCD rates over the years. The effects of seasonality were assessed through a Poisson regression model. We identified 182 SCDs; based on 99 available autopsy reports, the leading underlying cause of death was coronary heart disease (79%). The overall IR was 18.1 SCDs per 100 000 person-years. The age-specific IRs of SCD ranged between 3.8 (for those aged 18 to 24 years) and 45.2 (for those aged 55 to 64 years) per 100 000 person-years. The annual rate of SCD steadily declined over time (annual percentage change −3.9%, 95% CI −5.8 to −2.0). SCD events were more frequent during January (peak-to-low ratio 1.70; 95% CI 1.09 to 2.65). In addition, the IR was 3 times higher during high-risk duties compared with low-risk duties. IRs among firefighters were lower than those observed among the US general population and US military personnel. Conclusions SCD risk in this active working population is overestimated using statistics from the general population. To address public health questions among these subpopulations, more specific studies of active adults should be conducted. PMID:26066031

Splenic morphological changes are accompanied by altered baseline immunity in a mouse model of sickle-cell disease.

PubMed

Szczepanek, Steven M; McNamara, Jeffrey T; Secor, Eric R; Natarajan, Prabitha; Guernsey, Linda A; Miller, Lauren A; Ballesteros, Enrique; Jellison, Evan; Thrall, Roger S; Andemariam, Biree

2012-11-01

Although functional asplenia from infarctions may be a major contributor to increased infectious mortality in sickle-cell disease (SCD), this relationship has not been fully defined. We used the transgenic Berkeley SCD mouse to define blood and splenic immunophenotypic differences in this model compared with C57BL/6 and hemizygous controls. In the serum of SCD mice, we found increased IgG2a and suppressed IgM, IgG2b, and IgA levels. Serum IL-6 levels in SCD mice were elevated, whereas IL-1α, CXCL10, and CCL5 levels were decreased. The blood of SCD mice had higher white blood cell counts, with an increased percentage of lymphocytes and decreases in other leukocytes. Immunophenotyping of lymphocytes revealed higher percentages of CD8(+) and T-regulatory cells and lower percentages of B cells. SCD mouse spleens exhibited histological disorganization, with reduction of defined lymphoid follicles and expansion of red pulp, a greater than fourfold increase in splenic mononuclear cells, marked expansion of the nucleated red blood cell fraction, and B-cell and CD8(+) T-cell lymphopenia. Within the splenic B-cell population, there was a significant decrease in B-1a B cells, with a corresponding decrease in IgA secreting plasma cells in the gut. Confocal microscopy of spleens demonstrated complete disruption of the normal lymphofollicular structure in the white pulp of SCD mice without distinct B, T, and marginal zones. Our findings suggest that altered SCD splenic morphological characteristics result in an impaired systemic immune response. Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Increased concentrations of soluble CD40 ligand platelet in patients with primary antiphospholipidic syndrome.

PubMed

Galicia López, Aida; Olguín Ortega, Lourdes; Saavedra, Miguel A; Méndez Cruz, René; Jimenez Flores, Rafael; García de la Peña, Maximiliano

2013-01-01

To determine the concentrations of sCD40L in patients with PAPS, and establish its association with the number of thrombosis. We included patients with PAPS and healthy controls of the same age and sex. For analysis, patients with PAPS were divided into 2 groups: 1) patients with 1 thrombosis, and 2) patients with >1 thrombosis. Soluble CD40L concentrations were determined by ELISA method. sCD40L concentrations were significantly higher in patients with PAPS compared with the controls (9.72 ng ± 11.23 ng/ml vs. 4.69 ± 4.04 ng/ml) (P=.04) There was no association between serum levels of sCD40L and the number of thrombosis (1 thrombosis: 9.81 ± 9.87 ng/ml vs 9.63 ± 12.75 ng/ml in ≥ 1thrombosis (P=.13). In women with pregnancy and abortions, (13 patients) concentrations of sCD40L were higher than in those patients without a history of abortion (26 patients) but without statically significant difference (12.11 ± 16.46 ng/ml vs. 8.80 ± 8.61 ng/ml) (P=.33). There was no correlation between levels of sCD40L and the total number of thrombosis. Patients with PAPS have higher concentrations of sCD40L compared with healthy subjects, although this is not associated with a greater number of thrombosis. Among patients with PAPS, there is a tendency to higher concentrations of sCD40L in women with pregnancy and history of abortion. Since the platelet is the main cellular source of sCD40L, is possible that this pathway plays a pathogenic role in patients with PAPS. Copyright © 2012 Elsevier España, S.L. All rights reserved.

QT prolongation and sudden cardiac death risk in hypertrophic cardiomyopathy.

PubMed

Patel, Salma I; Ackerman, Michael J; Shamoun, Fadi E; Geske, Jeffrey B; Ommen, Steve R; Love, William T; Cha, Stephen S; Bos, Johan M; Lester, Steven J

2018-03-07

Risk assessment for sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM) remains complex. The goal of this study was to assess electrocardiogram (ECG)-derived risk factors on SCD in a large HCM population Methods: Retrospective review of adults with HCM evaluated at Mayo Clinic, Rochester, MN from 1 December 2002 to 31 December 2012 was performed. Data inclusive of ECG and 24-hour ambulatory Holter monitor were assessed. SCD events were documented by ventricular fibrillation (VF) noted on implantable cardioverter defibrillator (ICD), or appropriate VT or VF-terminating ICD shock. Overall, 1615 patients (mean age 53.7 ± 15.2 years; 943 males, 58.4%) were assessed, with mean follow-up 2.46 years and 110 SCD events. Via logistic regression (n = 820), the odds of SCD increased with increasing number of conventional risk factors. With one risk factor the OR was 4.88 (p < .0001; CI 2.22-10.74), two risk factors the OR was 6.922 (p < .0001; CI 2.94-16.28) and three or more risk factors, the OR was 13.997 (p < .0001; CI 5.649-34.68). Adding QTc > 450 to this logistic regression model had OR 1.722 (p = .04, CI 1.01-2.937) to predict SCD. QTc ≥ 450 was a significant predictor for death (HR 1.88, p = .021, CI 1.10-3.20). There was no correlation between sinus bradycardia, sinus tachycardia, first degree AV block, atrial fibrillation, left bundle branch block, right bundle branch block, premature atrial complexes, premature ventricular complexes, supraventricular tachycardia, PR interval, QRS interval and SCD. Prolonged QTc was a risk factor for SCD and death even when controlling for typical risk factors.

An Expert Review of Pharmacogenomics of Sickle Cell Disease Therapeutics: Not Yet Ready for Global Precision Medicine.

PubMed

Mnika, Khuthala; Pule, Gift D; Dandara, Collet; Wonkam, Ambroise

2016-10-01

Sickle cell disease (SCD) is a blood disease caused by a single nucleotide substitution (T > A) in the beta globin gene on chromosome 11. The single point mutation (Glu6Val) promotes polymerization of hemoglobin S (HbS) and causes sickling of erythrocytes. Vaso-occlusive painful crises are associated with recurrent and long-term use of analgesics/opioids and hydroxyurea (HU) by people living with SCD. The present analysis offers a state-of-the-art expert review of the effectiveness of pharmacogenomics/genetics of pain management in SCD, with specific focus on HU and opioids. The literature search used the following keywords: SCD, pharmacogenomics, pharmacogenetics, pain, antalgics, opioids, morphine, and HU. The literature was scanned until March 2016, with specific inclusion of targeted landmark and background articles on SCD. Surprisingly, our review identified only a limited number of studies that addressed the genetic/genomic basis of variable responses to pain (e.g., variants in OPRM1, HMOX-1, GCH1, VEGFA COMT genes), and pharmacogenomics of antalgics and opioids (e.g., variants in OPRM1, STAT6, ABCB1, and COMT genes) in SCD. There has been greater progress made toward identifying the key genomic variants, mainly in BCL11A, HBS1L-MYB, or SAR1, which contribute to response to HU treatment. However, the complete picture on pharmacogenomic determinants of the above therapeutic phenotypes remains elusive. Strikingly, no study has been conducted in sub-Saharan Africa where majority of the patients with SCD live. This alerts the broader global life sciences community toward the existing disparities in optimal and ethical targeting of research and innovation investments for SCD specifically and precision medicine and pharmacology research broadly.

Reproductive Health CHOICES for Young Adults with Sickle Cell Disease or Trait: Randomized Controlled Trial Immediate Posttest Effects

PubMed Central

Wilkie, Diana J; Gallo, Agatha M.; Yao, Yingwei; Molokie, Robert E.; Stahl, Christine; Hershberger, Patricia E.; Zhao, Zhongsheng; Suarez, Marie L.; Labotka, Robert J.; Johnson, Bonnye; Angulo, Rigo; Angulo, Veronica; Carrasco, Jesus; Shuey, David; Pelligra, Stephanie; Wang, Edward; Rogers, Dennie T.; Thompson, Alexis A.

2013-01-01

Background People with sickle cell disease (SCD) or sickle cell trait (SCT) may not have information about genetic inheritance needed for making informed reproductive health decisions. CHOICES is a web-based, multimedia educational intervention that provides information about reproductive options and consequences to help those with SCD or SCT identify and implement an informed parenting plan. Efficacy of CHOICES compared with usual care must be evaluated. Objective The purpose was to compare immediate posttest effects of CHOICES versus an attention control usual care intervention (e-Book) on SCD/SCT-related reproductive health knowledge, intention, and behavior. Methods In a randomized controlled study, we recruited subjects with SCD/SCT from clinics, community settings, and online networks with data collected at sites convenient to the 234 subjects with SCD (n = 136) or SCT (n = 98) (age ranged from18-35 years, 65% were female, and 94% were African American). Subjects completed a measure of sickle cell reproductive knowledge, intention, and behavior before and immediately after the intervention. Results Compared to the e-Book group, the CHOICES group had significantly higher average knowledge scores and probability of reporting a parenting plan to avoid SCD or SCD and SCT when pretest scores were controlled. Effects on intention and planned behavior were not significant. The CHOICES group showed significant change in their intention and planned behavior; the e-Book group did not show significant change in their intention, but their planned behavior differed significantly. Discussion Initial efficacy findings are encouraging but warrant planned booster sessions and outcome follow-ups to determine sustained intervention efficacy on reproductive health knowledge, intention, and actual behavior of persons with SCD/SCT. PMID:23995469

Vitamin D, Parathyroid Hormone and Sudden Cardiac Death: Results from the Cardiovascular Health Study

PubMed Central

Deo, Rajat; Katz, Ronit; Shlipak, Michael G.; Sotoodehnia, Nona; Psaty, Bruce M.; Sarnak, Mark J.; Fried, Linda F.; Chonchol, Michel; de Boer, Ian H.; Enquobahrie, Daniel; Siscovick, David; Kestenbaum, Bryan

2012-01-01

Recent studies have demonstrated greater risks of cardiovascular events and mortality among persons who have lower 25-hydroxyvitamin D (25-OHD) and higher parathyroid hormone (PTH) levels. We sought to evaluate the association between markers of mineral metabolism and sudden cardiac death (SCD) among the 2,312 participants from the Cardiovascular Health Study who were free of clinical cardiovascular disease at baseline. We estimated associations of baseline 25-OHD and PTH concentrations individually and in combination with SCD using Cox proportional hazards models after adjustment for demographics, cardiovascular risk factors, and kidney function. During a median follow-up of 14 years, there were 73 adjudicated SCD events. The annual incidence of SCD was greater among subjects who had lower 25-OHD concentrations: 2 events per 10,000 for 25-OHD ≥ 20 ng/ml and 4 events per 10,000 for 25-OHD < 20 ng/ml. Similarly, SCD incidence was greater among subjects who had higher PTH concentrations: 2 events per 10,000 for PTH ≤ 65 pg/ml and 4 events per 10,000 for PTH > 65 pg/ml. Multivariate adjustment attenuated associations of 25-OHD and PTH with SCD. Finally, 267 participants (11.7% of the cohort) had high PTH and low 25-OHD concentrations. This combination was associated with a more than 2-fold risk of SCD after adjustment (hazard ratio 2.19, 95% confidence interval 1.17, 4.10, p=0.017) compared to participants with normal levels of PTH and 25-OHD. The combination of lower 25-OHD and higher PTH concentrations appears to be associated independently with SCD risk among older adults without cardiovascular disease. PMID:22068871

Soluble CD30 and Hepatocyte growth factor as predictive markers of antibody-mediated rejection of the kidney allograft.

PubMed

Pavlova, Yelena; Viklicky, Ondrej; Slatinska, Janka; Bürgelova, Marcela; Süsal, Caner; Skibova, Jelena; Honsová, Eva; Striz, Ilja; Kolesar, Libor; Slavcev, Antonij

2011-07-01

Our retrospective study was aimed to assess the relevance of pre- and post-transplant measurements of serum concentrations of the soluble CD30 molecule (soluble CD30, sCD30) and the cytokine Hepatocyte growth factor (HGF) for prediction of the risk for development of antibody-mediated rejection (AMR) in kidney transplant patients. Evaluation of sCD30, HGF levels and the presence of HLA-specific antibodies in a cohort of 205 patients was performed before, 2weeks and 6months after transplantation. Patients were followed up for kidney graft function and survival for two years. We found a tendency of higher incidence of AMR in retransplanted patients with elevated pre-transplant sCD30 (≥100U/ml) (p=0.051), however no such correlation was observed in first-transplant patients. Kidney recipients with simultaneously high sCD30 and HLA-specific antibodies (sCD30+/Ab+) before transplantation had significantly lower AMR-free survival compared to the other patient groups (p<0.001). HGF concentrations were not associated with the incidence of AMR at any time point of measurement, nevertheless, the combined analysis HGF and sCD30 showed increased incidence of AMR in recipients with elevated pretransplant sCD30 and low HGF levels. the predictive value of pretransplant sCD30 for the development of antibody-mediated rejection after transplantation is significantly potentiated by the co-presence of HLA specific antibodies. The role of HGF as a rejection-protective factor in patients with high pretransplant HGF levels would need further investigation. Copyright © 2011 Elsevier B.V. All rights reserved.

[Combined assay of soluble CD30 and hepatocyte growth factor for diagnosis of acute renal allograft rejection].

PubMed

Li, Chuan-jiang; Yu, Li-xin; Xu, Jian; Fu, Shao-jie; Deng, Wen-feng; Du, Chuan-fu; Wang, Yi-bin

2008-02-01

To study the value of detection of both preoperative soluble CD30 (sCD30) and hepatocyte growth factor (HGF) level 5 days after transplantation in the diagnosis of acute rejection of renal allograft. Preoperative serum sCD30 levels and HGF level 5 days after transplantation were determined in 65 renal-transplant recipients using enzyme-linked immunosorbent assay. The recipients were divided according to the sCD30 levels positivity. Receiver operating characteristic (ROC) curves were used to assess the value of HGF level on day 5 posttransplantation for diagnosis of acute renal allograft rejection, and the value of combined assay of the sCD30 and HGF levels was also estimated. After transplantation, 26 recipients developed graft rejection and 39 had uneventful recovery without rejection. With the cut-off value of sCD30 of 120 U/ml, the positivity rate of sCD30 was significantly higher in recipients with graft rejection than in those without (61.5% vs 17.9%, P<0.05). Recipients with acute rejection showed also significantly higher HGF levels on day 5 posttransplantation than those without rejection (P<0.05). ROC curve analysis indicated that HGF levels on day 5 posttransplantation was a good marker for diagnosis of acute renal allograft rejection, and at the cut-off value of 90 ug/L, the diagnostic sensitivity was 84.6% and specificity 76.9%. Evaluation of both the sCD30 and HGF levels significantly enhanced the diagnostic accuracy of acute graft rejection. Combined assay of serum sCD30 and HGF levels offers a useful means for diagnosis of acute renal allograft rejection.

Technology Access and Smartphone App Preferences for Medication Adherence in Adolescents and Young Adults With Sickle Cell Disease.

PubMed

Badawy, Sherif M; Thompson, Alexis A; Liem, Robert I

2016-05-01

Hydroxyurea is the only Food and Drug Administration approved medication for sickle cell disease (SCD) with short- and long-term benefits for both morbidity and mortality. However, hydroxyurea underutilization and adherence remain challenges for patients with SCD. The objectives of this study were to determine access to technology among adolescents and young adults (AYA) with SCD and to identify their preferred technology-based strategies for improving medication adherence. A cross-sectional survey was administered in a variety of clinical settings from October 2014 through May 2015 to AYA (12-22 years) with SCD (all genotypes) followed in a Comprehensive Sickle Cell Program. Eighty of 107 eligible participants completed the survey for a 75% response rate. Participants (51% female, 94% Black) had a mean age of 15.3 ± 2.8 years. Most participants (75%) were on a daily medication with about half on hydroxyurea. Forgetfulness (67%) was the most common barrier to medication adherence. The majority of participants (85%) owned smartphones and either owned or had access to electronic tablets (83%), laptops (72%), or desktops (70%). Of the proposed smartphone app features, daily medication reminders were ranked first most frequently, followed by education about SCD, adherence text prompts, education about SCD medications, and medication log. The majority of our AYA with SCD owned smartphones and had access to other electronic devices. Our survey results provided valuable insight into the preferred app features and optimal strategies for developing technology-based interventions, such as a multicomponent app, to increase medication adherence for AYA with SCD or other chronic conditions. © 2016 Wiley Periodicals, Inc.

Coagulation Abnormalities of Sickle Cell Disease: Relationship with Clinical Outcomes and the Effect of Disease Modifying Therapies

PubMed Central

Noubouossie, Denis; Key, Nigel S.; Ataga, Kenneth I.

2015-01-01

Sickle cell disease (SCD) is a hypercoagulable state. Patients exhibit increased platelet activation, high plasma levels of markers of thrombin generation, depletion of natural anticoagulant proteins, abnormal activation of the fibrinolytic system, and increased tissue factor expression, even in the non-crisis “steady state.” Furthermore, SCD is characterized by an increased risk of thrombotic complications. The pathogenesis of coagulation activation in SCD appears to be multi-factorial, with contributions from ischemia-reperfusion injury and inflammation, hemolysis and nitric oxide deficiency, and increased sickle RBC phosphatidylserine expression. Recent studies in animal models suggest that activation of coagulation may contribute to the pathogenesis of SCD, but the data on the contribution of coagulation and platelet activation to SCD-related complications in humans are limited. Clinical trials of new generations of anticoagulants and antiplatelet agents, using a variety of clinical endpoints are warranted. PMID:26776344

[Study of oculomotor disorders in spinocerebellar ataxia genotype].

PubMed

Oda, Rie; Takemoto, Tsuyoshi; Kawai, Motoharu; Yamashita, Hiroshi

2006-01-01

Spinocerebellar degeneration (SCD) exhibits a variety of spinal and cerebullar symptoms and progress. The recent advent of molecular genetics has revealed triplet repeat mutation in the gene of SCD patients. Due to the underlying genetic defects, hereditary SCD is referred to as different spinocerebellar ataxia (SCA) genotypes. We conducted vestibular functional tests in 33 SCD patients, including 3 with SCA3 and 2 with SCA6. We compared the degree of lower extremity ataxia with the degree of oculomotor disorder by using eye tracking tests (ETT) and optokinetic pattern tests (OKP). Both SCA3 and SCA6 show high ETT score and low mean slowest phase velocity in OKP. This means that SCA3 and SCA6 tend to have oculomotor disorder precedes extremity ataxia. Oculomotor examination should thus prove to be a useful, senstive indicator in screening SCD patients from early disease onset, and in evaluating the disease progression and the effectiveness of treatment.

Use of Cardiac Injury Markers in the Postmortem Diagnosis of Sudden Cardiac Death.

PubMed

Carvajal-Zarrabal, Octavio; Hayward-Jones, Patricia M; Nolasco-Hipolito, Cirilo; Barradas-Dermitz, Dulce Ma; Calderón-Garcidueñas, Ana Laura; López-Amador, Noé

2017-09-01

In the daily practice of forensic pathology, sudden cardiac death (SCD) is a diagnostic challenge. Our aim was to determine the usefulness of blood biomarkers [creatine kinase CK-MB, myoglobin, troponins I and T (cTn-I and T), and lactate dehydrogenase] measured by immunoassay technique, in the postmortem diagnosis of SCD. Two groups were compared, 20 corpses with SCD and 8 controls. Statistical significance was determined by variance analysis procedures, with a post hoc Tukey multiple range test for comparison of means (p < 0.05). SCD cases showed significantly higher levels (p < 0.05) of cTn-T and cTn-I compared to the control group. Although only cases within the first 8 h of postmortem interval were included, and the control group consisted mainly of violent death cases, our results suggest that blood troponin levels may be useful to support a diagnosis of SCD. © 2017 American Academy of Forensic Sciences.

Sickle cell disease and HIV: a case highlighting management challenges for children in a resource-limited setting.

PubMed

Odera, Esther Brenda; Kwobah, Charles; Stone, Geren; Some, Faraj; Vreeman, Rachel Christine

2014-01-01

Sickle cell disease (SCD) is a genetic disorder resulting from a mutation in the hemoglobin (Hb) gene. Sickle cell disease results in chronic anemia and a variety of acute and chronic complications that can lead to early mortality. A child with both SCD and HIV presents a management challenge, particularly in a resource-limited setting. In this case report, we describe the case of an 18-month-old Kenyan girl with SCD and HIV who developed a severe hypersensitivity reaction to first-line antiretroviral therapy (ART). Selecting an appropriate drug substitute for a child with SCD and HIV presents a management dilemma when the available options have problematic side effect profiles or are inaccessible or inappropriate according to national guidelines. The challenges in choosing an appropriate ART regimen for a child with SCD and HIV highlight the lack of data and scarcity of treatment options for pediatric patients.

Single-Case Design Research: Building the Evidence-Base in the Field of Education of Deaf and Hard of Hearing Students.

PubMed

Cannon, Joanna E; Guardino, Caroline; Antia, Shirin D; Luckner, John L

2016-01-01

The field of education of deaf and hard of hearing (DHH) students has a paucity of evidence-based practices (EBPs) to guide instruction. The authors discussed how the research methodology of single-case design (SCD) can be used to build EBPs through direct and systematic replication of studies. An overview of SCD research methods is presented, including an explanation of how internal and external validity issues are addressed, and why SCD is appropriate for intervention research with DHH children. The authors then examine the SCD research in the field according to quality indicators (QIs; at the individual level and as a body of evidence) to determine the existing evidence base. Finally, future replication areas are recommended to fill the gaps in SCD research with students who are DHH in order to add to the evidence base in the field.

Cloudy Skies over AGN: Observations with Simbol-X

NASA Astrophysics Data System (ADS)

Salvati, M.; Risaliti, G.

2009-05-01

Recent time-resolved spectroscopic X-ray studies of bright obscured AGN show that column density variability on time scales of hours/days may be common, at least for sources with NH>1023 cm-2. This opens new oppurtunities in the analysis of the structure of the circumnuclear medium and of the X-ray source: resolving the variations due to single clouds covering/uncovering the X-ray source provides tight constraints on the source size, the clouds' size and distance, and their average number, density and column density. We show how Simbol-X will provide a breakthrough in this field, thanks to its broad band coverage, allowing (a) to precisely disentangle the continuum and NH variations, and (2) to extend the NH variability analysis to column densities >1023 cm-2.

Psychiatric Disorders in a Sample of Saudi Arabian Adolescents with Sickle Cell Disease

ERIC Educational Resources Information Center

Amr, Mostafa Abdel-Monhem; Amin, Tarek Tawfik; Hablas, Hatem Refaat

2010-01-01

The objectives of this study were to determine the magnitude of psychiatric disorders and to define socio-demographic and disease-related risk factors in a sample of adolescents with SCD in Al-Hassa, Saudi Arabia. The sample consisted of 110 adolescents with SCD and a convenient sample of 202 adolescents without SCD as controls. Psychiatric…

A Sickle Cell Disease Patient with Severe Tricuspid Regurgitation and Early Developed Pulmonary Hypertension.

PubMed

Vaidya, Gaurang; Sarwar, Muhammad; Sun, Zongxia; Wei, Tiemin; Liu, Kan

2015-01-01

Pulmonary hypertension (PH) worsens the mortality of the patients with sickle cell disease (SCD). The exact mechanism of PH development/progression in SCD, including the role of tricuspid regurgitation (TR), remains unclear. We herein report an unusual SCD case, complicated by chronic thromboembolic disorder, who developed severe TR and an accelerated progression of PH. Tricuspid valve surgery significantly ameliorated the patient's symptoms and reduced hospital readmission. The early detection and management of the reversible disorder accelerating the PH development in SCD patients may alter the clinical course, improve the quality of life, and potentially affect the long-term outcome.

Oxidative stress in sickle cell disease; pathophysiology and potential implications for disease management.

PubMed

Nur, Erfan; Biemond, Bart J; Otten, Hans-Martin; Brandjes, Dees P; Schnog, John-John B

2011-06-01

Sickle cell disease (SCD) is a hemoglobinopathy characterized by hemolytic anemia, increased susceptibility to infections and vaso-occlusion leading to a reduced quality of life and life expectancy. Oxidative stress is an important feature of SCD and plays a significant role in the pathophysiology of hemolysis, vaso-occlusion and ensuing organ damage in sickle cell patients. Reactive oxygen species (ROS) and the (end-)products of their oxidative reactions are potential markers of disease severity and could be targets for antioxidant therapies. This review will summarize the role of ROS in SCD and their potential implication for SCD management. Copyright © 2011 Wiley-Liss, Inc.

Rare association of spondylo costal dysostosis with split cord malformations type II: A case report and a brief review of literature

PubMed Central

Srinivas, Bhavanam Hanuma; Puligopu, Aneel Kumar; Sukhla, Dinesh; Ranganath, Prajnya

2014-01-01

Spondylo costal dysostosis (SCD) is a genetic skeletal disorder characterized by a variety of costo-vertebral malformations. SCD with type I split cord malformation (SCM) have been reported in the literature. We report an unusual association of SCD with type II SCM. Imaging studies revealed multiple vertebral segmentations, rib malformations, spina bifida and low lying cord with type II SCM at the D12-L3 level. She underwent detethering of the cord. To the best of our knowledge, this is the first report of the association of SCD with type II SCM. PMID:25250070

Sickle Cell Vaso-occlusive Crisis Induces the Release of Circulating Serum Heat Shock Protein-70

PubMed Central

Adewoye, Adeboye H.; Klings, Elizabeth S.; Farber, Harrison W.; Palaima, Elizabeth; Bausero, Maria A.; McMahon, Lillian; Odhiambo, Adam; Surinder, Safaya; Yoder, Mark; Steinberg, Martin H.; Asea, Alexzander

2006-01-01

Inflammation may play an important role in the pathophysiology of sickle cell disease (SCD), and recent studies have identified the 70-kDa heat shock protein (Hsp70) as an important mediator of inflammatory responses. Here we demonstrate a significant increase in circulating serum Hsp70 level in SCD during vaso-occlusive crisis (VOC) as compared with baseline steady-state levels (P < 0.05) and a significant increase in Hsp70 levels in SCD at baseline compared with normal controls (P < 0.05). Taken together, these results indicate that circulating serum Hsp70 might be a marker for VOC in SCD. PMID:15726596

Sickle cell vaso-occlusive crisis induces the release of circulating serum heat shock protein-70.

PubMed

Adewoye, Adeboye H; Klings, Elizabeth S; Farber, Harrison W; Palaima, Elizabeth; Bausero, Maria A; McMahon, Lillian; Odhiambo, Adam; Surinder, Safaya; Yoder, Mark; Steinberg, Martin H; Asea, Alexzander

2005-03-01

Inflammation may play an important role in the pathophysiology of sickle cell disease (SCD), and recent studies have identified the 70-kDa heat shock protein (Hsp70) as an important mediator of inflammatory responses. Here we demonstrate a significant increase in circulating serum Hsp70 level in SCD during vaso-occlusive crisis (VOC) as compared with baseline steady-state levels (P <0.05) and a significant increase in Hsp70 levels in SCD at baseline compared with normal controls (P <0.05). Taken together, these results indicate that circulating serum Hsp70 might be a marker for VOC in SCD.

Soluble CD30 serum levels before and after treatment with alpha-interferon in patients with chronic hepatitis C.

PubMed

Di Cesare, Enrico; Spadaro, Aldo; Ajello, Antonino; Ferraù, Oscar; Alessi, Nunziata; Luigiano, Carmelo; Melluso, Rossana; Freni, Maria A

2005-01-01

It has been suggested that soluble CD30 (sCD30) serum levels in chronic hepatitis C are correlated with the activity of the disease and with the outcome of interferon (IFN) treatment. In this study, sCD30 serum levels in 25 patients with chronic hepatitis C, before and after treatment with IFN-2alpha, were measured. A total of 20 healthy subjects were used as controls. High sCD30 levels in serum were found in 36% of patients and in 5% of controls. In patients with sCD30 levels above or within the normal range, no significant differences in age, gender, serum transaminases and histology activity index were found. In relation to IFN treatment, only responder patients had serum sCD30 higher than controls, although the difference between responders and non-responders was not significant. No changes from baseline values were observed after treatment. Although high, sCD30 serum levels in chronic hepatitis C are not correlated with the disease activity, are not affected by IFN treatment and are not predictors of response to IFN treatment.

Fertility challenges for women with sickle cell disease.

PubMed

Ghafuri, Djamila L; Stimpson, Sarah-Jo; Day, Melissa E; James, Andra; DeBaun, Michael R; Sharma, Deva

2017-10-01

Sickle cell disease (SCD) represents one of the most common monogenic blood disorders worldwide, with an incidence of over 300,000 newborns affected per year. Reproductive challenges for men and women with SCD have been previously reviewed; however, evidence-based strategies to prevent and manage infertility and increase fecundity are lacking in women with SCD, which is one of the most important factors for quality of life. Areas covered: This review article summarizes the known risk factors for infertility, low fecundity, and premature menopause related to SCD. Expert commentary: Women with SCD have unique risk factors that may impact their ability to conceive, including chronic inflammation, oxidative stress, transfusion-related hemochromatosis, and ovarian sickling, causing ischemia and reperfusion injury to the ovary. Contraception is strongly recommended while on hydroxyurea therapy during reproductive years and discontinuing hydroxyurea for family planning and during pregnancy based on teratogenicity in animal studies. Hematopoietic stem cell transplantation (HSCT), the only curative therapy, sometimes involves conditioning regimens containing alkylating agents and total body irradiation that contribute to infertility and premature ovarian failure. Prior to HSCT or gene therapy, we strongly recommend referral to a reproductive endocrinologist to discuss fertility preservation and surrogacy options for all women with SCD.

Kcne2 Deletion Creates a Multisystem Syndrome Predisposing to Sudden Cardiac Death

PubMed Central

Hu, Zhaoyang; Kant, Ritu; Anand, Marie; King, Elizabeth C.; Krogh-Madsen, Trine; Christini, David J.; Abbott, Geoffrey W.

2014-01-01

Background Sudden cardiac death (SCD) is the leading global cause of mortality, exhibiting increased incidence in diabetics. Ion channel gene perturbations provide a well-established ventricular arrhythmogenic substrate for SCD. However, most arrhythmia susceptibility genes - including the KCNE2 K+ channel β subunit - are expressed in multiple tissues, suggesting potential multiplex SCD substrates. Methods and Results Using “whole transcript” transcriptomics, we uncovered cardiac angiotensinogen upregulation and remodeling of cardiac angiotensinogen interaction networks in P21 Kcne2−/− mouse pups, and adrenal remodeling consistent with metabolic syndrome in adult Kcne2−/− mice. This led to the discovery that Kcne2 disruption causes multiple acknowledged SCD substrates of extracardiac origin: diabetes, hypercholesterolemia, hyperkalemia, anemia and elevated angiotensin II. Kcne2 deletion was also prerequisite for aging-dependent QT prolongation, ventricular fibrillation and SCD immediately following transient ischemia, and fasting-dependent hypoglycemia, myocardial ischemia and atrioventricular block. Conclusions Disruption of a single, widely expressed arrhythmia susceptibility gene can generate a multisystem syndrome comprising manifold electrical and systemic substrates and triggers of SCD. This paradigm is expected to apply to other arrhythmia susceptibility genes, the majority of which encode ubiquitously expressed ion channel subunits or regulatory proteins. PMID:24403551

Orbital and attitude evolution of SCD-1 and SCD-2 Brazilian satellites

NASA Astrophysics Data System (ADS)

Murcia, J. O.; Carrara, V.; Kuga, H. K.

2017-10-01

The SCD-1 and SCD-2 satellites were launched in 1993 and 1998, respectively, with use of the Launcher “Pegasus” of the OSC (Orbital Sciences Corporation). 21 and 16 years later, the satellites are still in orbit around the Earth and providing data for users. Mission and Operational data from Satellite Tracking Center Network are stored in mission files in the Satellite Control Center (SCC) and made available to the users. The SCC also stores history files of the satellite orbit and attitude ephemeris, besides the on-board telemetry, temperatures, equipment status, etc. This work will present some analysis of the orbit ephemeris evolution based upon the Two-Line Elements sets (TLE’s) obtained from NORAD (North American Aerospace Defense Command). Attitude evolution along time is also presented for both satellites from SCC data. The orbit decay will be explained as resulting mainly due to the solar activity during the satellite lifetime. This work aims to report the history of more than 20 years of continuous operation of SCD-1 and SCD-2. At the end, an estimation of the orbital decay is forecast with the use of NASA’s DAS software.

Emerging Point-of-Care Technologies for Sickle Cell Disease Screening and Monitoring

PubMed Central

Alapan, Yunus; Fraiwan, Arwa; Kucukal, Erdem; Hasan, M. Noman; Ung, Ryan; Kim, Myeongseop; Odame, Isaac; Little, Jane A.; Gurkan, Umut A.

2016-01-01

Introduction Sickle Cell Disease (SCD) affects 100,000 Americans and more than 14 million people globally, mostly in economically disadvantaged populations, requires early diagnosis after birth and constant monitoring throughout the life-span of the patient. Areas Covered Early diagnosis of SCD still remains a challenge in preventing childhood mortality in the developing world due to requirements of skilled personnel and high-cost of currently available modalities. On the other hand, SCD monitoring presents insurmountable challenges due to heterogeneities among patient populations, as well as in the same individual longitudinally. Here, we describe emerging point-of-care micro/nano platform technologies for SCD screening and monitoring, and critically discuss current state-of-the-art, potential challenges associated with these technologies, and future directions. Expert Commentary Recently developed microtechnologies offer simple, rapid, and affordable screening of SCD and have the potential to facilitate universal screening in resource-limited settings and developing countries. On the other hand, monitoring of SCD is more complicated compared to diagnosis and requires comprehensive validation of efficacy. Early use of novel microdevices for patient monitoring might come in especially handy in new clinical trial designs of emerging therapies. PMID:27785945

Saturated phosphatidic acids mediate saturated fatty acid-induced vascular calcification and lipotoxicity.

PubMed

Masuda, Masashi; Miyazaki-Anzai, Shinobu; Keenan, Audrey L; Okamura, Kayo; Kendrick, Jessica; Chonchol, Michel; Offermanns, Stefan; Ntambi, James M; Kuro-O, Makoto; Miyazaki, Makoto

2015-10-26

Recent evidence indicates that saturated fatty acid-induced (SFA-induced) lipotoxicity contributes to the pathogenesis of cardiovascular and metabolic diseases; however, the molecular mechanisms that underlie SFA-induced lipotoxicity remain unclear. Here, we have shown that repression of stearoyl-CoA desaturase (SCD) enzymes, which regulate the intracellular balance of SFAs and unsaturated FAs, and the subsequent accumulation of SFAs in vascular smooth muscle cells (VSMCs), are characteristic events in the development of vascular calcification. We evaluated whether SMC-specific inhibition of SCD and the resulting SFA accumulation plays a causative role in the pathogenesis of vascular calcification and generated mice with SMC-specific deletion of both Scd1 and Scd2. Mice lacking both SCD1 and SCD2 in SMCs displayed severe vascular calcification with increased ER stress. Moreover, we employed shRNA library screening and radiolabeling approaches, as well as in vitro and in vivo lipidomic analysis, and determined that fully saturated phosphatidic acids such as 1,2-distearoyl-PA (18:0/18:0-PA) mediate SFA-induced lipotoxicity and vascular calcification. Together, these results identify a key lipogenic pathway in SMCs that mediates vascular calcification.

Systemic reduction of soluble complement receptor II/CD21 during pregnancy to levels reminiscent of autoimmune disease.

PubMed

Masilamani, Madhan; Rajasekaran, Narendiran; Singh, Anjana; Low, Hui-Zhi; Albus, Kerstin; Anders, Swantje; Behne, Frank; Eiermann, Peter; König, Katharina; Mindnich, Clarissa; Ribarska, Teodora; Illges, Harald

2008-09-01

Complement receptor type II/CD21 is the functional receptor for complement fragments such as C3d, iC3b and the Epstein Barr Virus. A soluble form of CD21 (sCD21) is shed from lymphocytes surface and is able to bind to its ligands found in the plasma. The amount of sCD21 in serum may modulate immunity as the plasma levels are correlated with autoimmune conditions, such as Systemic Lupus Erythematosus, Rheumatoid Arthritis and Sjoegren's Syndrome. Because of the fact that pregnancy may lead to remission of autoimmune diseases we determined the serum levels of sCD21 during pregnancy and postpartum. The serum sCD21 levels during pregnancy are significantly lower as compared to that of the healthy controls. There were no significant differences in sCD21 levels between the mother and the cord blood also immediately after parturition. Restoration of sCD21 levels to normal values takes between 6 weeks and 1 year after childbirth. Our study indicates that CD21-shedding is affected during pregnancy comparable to that of autoimmunity.

Hydroxyurea therapy in adult Nigerian sickle cell disease: a monocentric survey on pattern of use, clinical effects and patient's compliance.

PubMed

Adewoyin, Ademola Samson; Oghuvwu, Omokiniovo Sunday; Awodu, Omolade Augustina

2017-03-01

The clinical prospects of hydroxyurea therapy in the management of sickle cell disease (SCD) require evaluation in the Nigerian setting to develop indigenous guidelines. This survey examines the pattern of hydroxyurea therapy, its clinico-haematologic benefits and safety profile in Nigerian SCD subjects. A cross sectional pilot survey was carried out among 60 adult SCD subjects over 3 months. Data on clinical phenotypes, relevant haematological parameters and details of hydroxyurea therapy were obtained using a structured questionnaire through an interview process and case file review. The median age was 30 years. Thirty-four (56.7%) of the subjects are aware of hydroxyurea therapy in SCD. Twenty-four (40%) SCD patients had previously used hydroxyurea. Only 4 subjects were fully compliant. Reasons for non-compliance included poor knowledge and lack of funds. In particular, hydroxyurea reduced leucocyte count and increased mean red cell volume (MCV) in compliant subjects. Hydroxyurea use is low among Nigerian SCD subjects despite its proven efficacy/clinical prospects in the developed nations. Large scale multicenter studies and clinical trials are needed to form a basis for developing standard local treatment protocol for its use.

Inflammatory targets of therapy in sickle cell disease

PubMed Central

Owusu-Ansah, Amma; Ihunnah, Chibueze A.; Walker, Aisha L.; Ofori-Acquah, Solomon F.

2015-01-01

Sickle cell disease (SCD) is a monogenic globin disorder characterized by the production of a structurally abnormal hemoglobin (Hb) variant Hb S, which causes severe hemolytic anemia, episodic painful vaso-occlusion and ultimately end-organ damage. The primary disease pathophysiology is intracellular Hb S polymerization and consequent sickling of erythrocytes. It has become evident over several decades that a more complex disease process contributes to the myriad of clinical complications seen in SCD patients with inflammation playing a central role. Drugs targeting specific inflammatory pathways therefore offer an attractive therapeutic strategy to ameliorate many of the clinical events in SCD. In addition they are useful tools to dissecting the molecular and cellular mechanisms that promote individual clinical events, and for developing improved therapeutics to address more challenging clinical dilemmas such as refractoriness to opioids or hyperalgesia. Here, we discuss the prospect of targeting multiple inflammatory pathways implicated in the pathogenesis of SCD with a focus on new therapeutics, striving to link the actions of the anti-inflammatory agents to a defined pathobiology, and specific clinical manifestations of SCD. We also review the anti-inflammatory attributes and the cognate inflammatory targets of hydroxyurea, the only FDA approved drug for SCD. PMID:26226206

Heart rate variability as predictive factor for sudden cardiac death.

PubMed

Sessa, Francesco; Anna, Valenzano; Messina, Giovanni; Cibelli, Giuseppe; Monda, Vincenzo; Marsala, Gabriella; Ruberto, Maria; Biondi, Antonio; Cascio, Orazio; Bertozzi, Giuseppe; Pisanelli, Daniela; Maglietta, Francesca; Messina, Antonietta; Mollica, Maria P; Salerno, Monica

2018-02-23

Sudden cardiac death (SCD) represents about 25% of deaths in clinical cardiology. The identification of risk factors for SCD is the philosopher's stone of cardiology and the identification of non-invasive markers of risk of SCD remains one of the most important goals for the scientific community.The aim of this review is to analyze the state of the art around the heart rate variability (HRV) as a predictor factor for SCD.HRV is probably the most analyzed index in cardiovascular risk stratification technical literature, therefore an important number of models and methods have been developed.Nowadays, low HRV has been shown to be independently predictive of increased mortality in post- myocardial infarction patients, heart failure patients, in contrast with the data of the general population.Contrariwise, the relationship between HRV and SCD has received scarce attention in low-risk cohorts. Furthermore, in general population the attributable risk is modest and the cost/benefit ratio is not always convenient.The HRV evaluation could become an important tool for health status in risks population, even though the use of HRV alone for risk stratification of SCD is limited and further studies are needed.

Shadow cell differentiation in endometrioid carcinomas of the uterus. Its frequent occurrence and beta-catenin expression.

PubMed

Zámečník, Michal; Bartoš, Pavel; Kaščák, Peter

2015-01-01

Shadow cell differentiation (SCD) is typical for pilomatrixoma and related follicular tumors of the skin. However, it has been described rarely in some extra-cutaneous lesions such as gonadal teratoma, craniopharyngioma, odontogenic cyst, and in rare visceral carcinomas (lung, bladder, gallbladder, uterus, ovary, and colon). In our practice, we have noticed that the occurrence of shadow cells is not very rare in endometrioid carcinoma (EC) of the uterus. For exact determination of SCD in these tumors, we reviewed 59 consecutive cases of uterine EC. The series included curettage and hysteroscopic specimens. We have found SCD in 9 (15.3 %) of the tumors. In these cases, the age of the patients and FIGO grade did not differ significantly from other ECs. Immunohistochemically, all ECs with SCD showed nuclear expression of beta-catenin in areas of SCD, indicating a possible role of the Wnt signaling pathway in tumorigenesis as well as a role of nuclear accumulation of beta-catenin by trans-differentiation from glandular toward squamous and shadow cell phenotypes. We have found that the relatively frequent presence of SCD in ECs can assists in the diagnosis of these tumors.

Effect of the feeding system on the fatty acid composition, expression of the Δ9-desaturase, Peroxisome Proliferator-Activated Receptor Alpha, Gamma, and Sterol Regulatory Element Binding Protein 1 genes in the semitendinous muscle of light lambs of the Rasa Aragonesa breed

PubMed Central

2010-01-01

Background Conjugated linoleic acids (CLAs) are receiving increasing attention because of their beneficial effects on human health, with milk and meat products derived from ruminants as important sources of CLA in the human diet. SCD gene is responsible for some of the variation in CLA concentration in adipose tissues, and PPARγ, PPARα and SREBP1 genes are regulator of SCD gene. The aim of this work was to evaluate the effect of the feeding system on fatty acid composition, CLA content and relative gene expression of Δ9-desaturase (SCD), Peroxisome Proliferator-Activated Receptor Gamma (PPARγ), Peroxisome Proliferator-Activated Receptor Alpha, (PPARα) and Sterol Regulatory Element Binding Protein (SREBP1) in Rasa Aragonesa light lambs in semitendinous muscle. Forty-four single-born male lambs were used to evaluate the effect of the feeding system, varying on an intensity gradient according to the use of concentrates: 1. grazing alfalfa, 2. grazing alfalfa with a supplement for lambs, 3. indoor lambs with grazing ewes and 4. drylot. Results Both grazing systems resulted in a higher concentration of vaccenic acid (VA), CLA, CLA/VA acid ratio, and a lower oleic content, oleic acid (C18:1)/stearic acid (C18:0) ratio, PUFA n-6/n-3 ratio and SCD expression compared to other diets. In addition feeding system affected the fatty acid composition and SCD expression, possibly due to CLA concentration or the PUFA n-6/n-3 ratio. Both expression of the SCD gene and the feeding system were important factors affecting CLA concentration in the animal's semitendinous muscle. PPARγ, PPARα and SREBP1 expression seemed to be unaffected by the feeding system. Although no significant results were found, PPARγ, PPARα and SREBP1 showed similar expression pattern as SCD. Moreover, the correlation results between SCD expression and PPARγ (p < 0.01), as well as SREBP1 (p < 0.01) expression, may suggest that these genes were affecting SCD expression in a different way. Conclusions The data indicated that the feeding system is the main factor affecting the fatty acid composition and SCD gene expression, which is also affected by CLA and possibly by n-6/n-3 PUFAs. PMID:20649987

Polymorphisms in genes in the SREBP1 signalling pathway and SCD are associated with milk fatty acid composition in Holstein cattle.

PubMed

Rincon, Gonzalo; Islas-Trejo, Alma; Castillo, Alejandro R; Bauman, Dale E; German, Bruce J; Medrano, Juan F

2012-02-01

Genes in the sterol regulatory element-binding protein-1 (SREBP1) pathway play a central role in regulation of milk fat synthesis, especially the de-novo synthesis of saturated fatty acids. SCD, a SREBP-responsive gene, is the key enzyme in the synthesis of monounsaturated fatty acids in the mammary gland. In the present study, we discovered SNP in candidate genes associated with this signalling pathway and SCD to identify genetic markers that can be used for genetic and metabolically directed selection in cattle. We resequenced six candidate genes in the SREBP1 pathway (SREBP1, SCAP, INSIG1, INSIG2, MBTPS1, MBTPS2) and two genes for SCD (SCD1 and SCD5) and discovered 47 Tag SNP that were used in a marker-trait association study. Milk and blood samples were collected from Holstein cows in their 1st or 2nd parity at 100-150 days of lactation. Individual fatty acids from C4 to C20, saturated fatty acid (SFA) content, monounsaturated fatty acid content, polyunsaturated fatty acid content and desaturase indexes were measured and used to perform the asociation analysis. Polymorphisms in the SCD5 and INSIG2 genes were the most representative markers associated with SFA/unsaturated fatty acid (UFA) ratio in milk. The analysis of desaturation activity determined that markers in the SCD1 and SCD5 genes showed the most significant effects. DGAT1 K232A marker was included in the study to examine the effect of this marker on the variation of milk fatty acids in our Holstein population. The percentage of variance explained by DGAT1 in the analysis was only 6% of SFA/UFA ratio. Milk fat depression was observed in one of the dairy herds and in this particular dairy one SNP in the SREBP1 gene (rs41912290) accounted for 40% of the phenotypic variance. Our results provide detailed SNP information for key genes in the SREBP1 signalling pathway and SCD that can be used to change milk fat composition by marker-assisted breeding to meet consumer demands regarding human health, as well as furthering understanding of technological aspects of cows' milk.

Endothelin-1 receptor antagonists regulate cell surface-associated protein disulfide isomerase in sickle cell disease

PubMed Central

Prado, Gregory N.; Romero, Jose R.; Rivera, Alicia

2013-01-01

Increased endothelin-1 (ET-1) levels, disordered thiol protein status, and erythrocyte hydration status play important roles in sickle cell disease (SCD) through unresolved mechanisms. Protein disulfide isomerase (PDI) is an oxidoreductase that mediates thiol/disulfide interchange reactions. We provide evidence that PDI is present in human and mouse erythrocyte membranes and that selective blockade with monoclonal antibodies against PDI leads to reduced Gardos channel activity (1.6±0.03 to 0.56±0.02 mmol·1013 cell−1·min−1, P<0.001) and density of sickle erythrocytes (D50: 1.115±0.001 to 1.104±0.001 g/ml, P=0.012) with an IC50 of 4 ng/ml. We observed that erythrocyte associated-PDI activity was increased in the presence of ET-1 (3.1±0.2 to 5.6±0.4%, P<0.0001) through a mechanism that includes casein kinase II. Consistent with these results, in vivo treatment of BERK sickle transgenic mice with ET-1 receptor antagonists lowered circulating and erythrocyte associated-PDI activity (7.1±0.3 to 5.2±0.2%, P<0.0001) while improving hematological parameters and Gardos channel activity. Thus, our results suggest that PDI is a novel target in SCD that regulates erythrocyte volume and oxidative stress and may contribute to cellular adhesion and endothelial activation leading to vasoocclusion as observed in SCD.—Prado, G. N., Romero, J. R., Rivera, A. Endothelin-1 receptor antagonists regulate cell surface-associated protein disulfide isomerase in sickle cell disease. PMID:23913858

Development and validation of a fluorescent microsphere immunoassay for soluble CD30 testing.

PubMed

Pavlov, Igor; Martins, Thomas B; Delgado, Julio C

2009-09-01

Testing for soluble CD30 (sCD30), an indicator of Th2 immune response, is a useful prognostic marker in solid organ transplantation, lymphoproliferative disorders, autoimmunity, and various parasitic diseases. In this study we report the development and validation of a fluorescent microsphere immunoassay for the detection of sCD30 in serum, plasma, and culture supernatants. The dynamic range of this assay is 1 to 400 ng/ml, and the rate of recovery of various concentrations of recombinant sCD30 ranges from 97 to 116% (average recovery, 105%). The test showed a high degree of precision in both intra-assay and interassay studies (coefficients of variation, as high as 7% and 8%, respectively), with a sensitivity of 1 ng/ml. The normal reference range calculated for a cohort of 151 healthy individuals was 1 to 29 ng/ml. The clinical usefulness of the sCD30 fluorescent microsphere immunoassay was demonstrated by showing that levels of sCD30 have a positive correlation with specimens containing high titers of anti-double-stranded DNA antibodies and high titers of immunoglobulin G against Leishmania species. Given the multiplexing potential of the sCD30 fluorescent microsphere immunoassay reported in this study, it is expected that testing of sCD30 concentrations along with those of other cytokines will become an important diagnostic tool for selected immunological and inflammatory diseases where Th2-type cytokine responses have been reported.

Development and Validation of a Fluorescent Microsphere Immunoassay for Soluble CD30 Testing▿

PubMed Central

Pavlov, Igor; Martins, Thomas B.; Delgado, Julio C.

2009-01-01

Testing for soluble CD30 (sCD30), an indicator of Th2 immune response, is a useful prognostic marker in solid organ transplantation, lymphoproliferative disorders, autoimmunity, and various parasitic diseases. In this study we report the development and validation of a fluorescent microsphere immunoassay for the detection of sCD30 in serum, plasma, and culture supernatants. The dynamic range of this assay is 1 to 400 ng/ml, and the rate of recovery of various concentrations of recombinant sCD30 ranges from 97 to 116% (average recovery, 105%). The test showed a high degree of precision in both intra-assay and interassay studies (coefficients of variation, as high as 7% and 8%, respectively), with a sensitivity of 1 ng/ml. The normal reference range calculated for a cohort of 151 healthy individuals was 1 to 29 ng/ml. The clinical usefulness of the sCD30 fluorescent microsphere immunoassay was demonstrated by showing that levels of sCD30 have a positive correlation with specimens containing high titers of anti-double-stranded DNA antibodies and high titers of immunoglobulin G against Leishmania species. Given the multiplexing potential of the sCD30 fluorescent microsphere immunoassay reported in this study, it is expected that testing of sCD30 concentrations along with those of other cytokines will become an important diagnostic tool for selected immunological and inflammatory diseases where Th2-type cytokine responses have been reported. PMID:19605595

Very high levels of soluble CD30 recognize the patients with classical Hodgkin's lymphoma retaining a very poor prognosis.

PubMed

Visco, Carlo; Nadali, Gianpaolo; Vassilakopoulos, Theodoros P; Bonfante, Valeria; Viviani, Simonetta; Gianni, Alessandro M; Federico, Massimo; Luminari, Stefano; Peethambaram, Prema; Witzig, Thomas E; Pangalis, Gerassimos; Cabanillas, Fernando; Medeiros, L Jeffrey; Sarris, Andreas H; Pizzolo, Giovanni

2006-11-01

To evaluate the prognostic role of pretreatment serum levels of soluble CD30 (sCD30) in patients with advanced stage classical Hodgkin's lymphoma (cHL) treated with adriamycin, bleomycin, vinblastine, and dacarbazine or equivalent regimens. We identified 321 previously untreated patients with cHL who presented to the participating centers between 1985 and 2002, and had serum samples available for the determination of sCD30 levels. With a median follow-up of 72 months, the actuarial 5-year overall survival was 82%, and failure-free survival (FFS) was 71%. The median serum level of sCD30 was 65 U/mL (range: 1-2230), and was significantly higher (P < 0.0001) when compared with a group of 113 healthy controls (4 U/mL, range: 0-20). Increasing level of sCD30 was associated with a continuous worsening of FFS and OS, and patients with sCD30 >or=200 U/mL had a 5-year FFS of 39%. With multivariate analysis, sCD30, Ann Arbor stage, and lactic acid dehydrogenase were significant independent factors in terms of FFS. The association of the above-mentioned three independent prognostic variables could discriminate 22% of patients with 5-year FFS of 40%. Our data confirm the independent prognostic role of sCD30 in identifying the patients with high risk of treatment failure, and show that its association with other variables can recognize patients with FFS considerably lower than 50%.

Sudden cardiac death in hemodialysis patients: an in-depth review.

PubMed

Green, Darren; Roberts, Paul R; New, David I; Kalra, Philip A

2011-06-01

Sudden cardiac death (SCD) is the leading cause of death in hemodialysis patients, accounting for death in up to one-quarter of this population. Unlike in the general population, coronary artery disease and heart failure often are not the underlying pathologic processes for SCD; accordingly, current risk stratification tools are inadequate when assessing these patients. Factors assuming greater importance in hemodialysis patients may include left ventricular hypertrophy, electrolyte shift, and vascular calcification. Knowledge regarding SCD in hemodialysis patients is insufficient, in part reflecting the lack of an agreed-on definition of SCD in this population, although epidemiologic studies suggest the most common times for SCD to occur are toward the end of the long 72-hour weekend interval between dialysis sessions and in the 12 hours immediately after hemodialysis. Accordingly, it is hypothesized that the dialysis procedure itself may have important implications for SCD. Supporting this is recognition that hemodialysis is associated with both ventricular arrhythmias and dynamic electrocardiographic changes. Importantly, echocardiography and electrocardiography may show changes that are modifiable by alterations to dialysis prescription. The most effective preventative strategy in the general population, implanted cardioverter-defibrillator devices, are less effective in the presence of chronic kidney disease and have not been studied adequately in dialysis patients. Last, many dialysis patients experience SCD despite not fulfilling current criteria for implantation, making appropriate allocation of defibrillators uncertain. Copyright © 2011 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Preventing tomorrow's sudden cardiac death today: part I: Current data on risk stratification for sudden cardiac death.

PubMed

Al-Khatib, Sana M; Sanders, Gillian D; Bigger, J Thomas; Buxton, Alfred E; Califf, Robert M; Carlson, Mark; Curtis, Anne; Curtis, Jeptha; Fain, Eric; Gersh, Bernard J; Gold, Michael R; Haghighi-Mood, Ali; Hammill, Stephen C; Healey, Jeff; Hlatky, Mark; Hohnloser, Stefan; Kim, Raymond J; Lee, Kerry; Mark, Daniel; Mianulli, Marcus; Mitchell, Brent; Prystowsky, Eric N; Smith, Joseph; Steinhaus, David; Zareba, Wojciech

2007-06-01

Accurate and timely prediction of sudden cardiac death (SCD) is a necessary prerequisite for effective prevention and therapy. Although the largest number of SCD events occurs in patients without overt heart disease, there are currently no tests that are of proven predictive value in this population. Efforts in risk stratification for SCD have focused primarily on predicting SCD in patients with known structural heart disease. Despite the ubiquity of tests that have been purported to predict SCD vulnerability in such patients, there is little consensus on which test, in addition to the left ventricular ejection fraction, should be used to determine which patients will benefit from an implantable cardioverter defibrillator. On July 20 and 21, 2006, a group of experts representing clinical cardiology, cardiac electrophysiology, biostatistics, economics, and health policy were joined by representatives of the US Food and Drug administration, Centers for Medicare Services, Agency for Health Research and Quality, the Heart Rhythm Society, and the device and pharmaceutical industry for a round table meeting to review current data on strategies of risk stratification for SCD, to explore methods to translate these strategies into practice and policy, and to identify areas that need to be addressed by future research studies. The meeting was organized by the Duke Center for the Prevention of SCD at the Duke Clinical Research Institute and was funded by industry participants. This article summarizes the presentations and discussions that occurred at that meeting.

Stearoyl-CoA desaturase activity in bovine cumulus cells protects the oocyte against saturated fatty acid stress

PubMed Central

Aardema, Hilde; van Tol, Helena T. A.; Wubbolts, Richard W.; Brouwers, Jos F. H. M.; Gadella, Bart M.; Roelen, Bernard A. J.

2017-01-01

Abstract Metabolic rich and poor conditions are both characterized by elevated free fatty acid levels and have been associated with impaired female fertility. In particular, saturated free fatty acids have a dose-dependent negative impact on oocyte developmental competence, while monounsaturated free fatty acids appear less harmful. Cumulus cells seem to protect the oocyte against free fatty acids, and the aim of this study was to determine the mechanism behind this protection In particular, the role of the enzyme stearoyl-CoA desaturase (SCD) that converts saturated into monounsaturated fatty acids was investigated. SCD gene and protein were abundantly expressed in cumulus cells, but expression was low in oocytes. The level of SCD protein expression in cumulus cells did not change when COCs were exposed to saturated stearic acid during maturation. SCD inhibition in the presence of stearic acid significantly reduced the developmental competence of oocytes and increased the incidence of apoptosis in cumulus cells. The esterified oleic/stearic acid ratio of the neutral lipid fraction in cumulus cells decreased in the presence of SCD inhibitors when COCs were exposed to saturated free fatty acids during maturation, indicating the SCD-specific conversion of saturated fatty acids under noninhibiting conditions. The observation that cumulus cells can desaturate the potentially toxic stearic acid into oleic acid via SCD activity provides a mechanistic insight into how the cumulus cells protect the oocyte against toxicity by saturated fatty acid. PMID:28486699

Soluble CD40 Ligand and Oxidative Response Are Reciprocally Stimulated during Shiga Toxin-Associated Hemolytic Uremic Syndrome

PubMed Central

Abrey Recalde, Maria J.; Alvarez, Romina S.; Alberto, Fabiana; Mejias, Maria P.; Ramos, Maria V.; Fernandez Brando, Romina J.; Bruballa, Andrea C.; Exeni, Ramon A.; Alconcher, Laura; Ibarra, Cristina A.; Amaral, María M.; Palermo, Marina S.

2017-01-01

Shiga toxin (Stx), produced by Escherichia coli, is the main pathogenic factor of diarrhea-associated hemolytic uremic syndrome (HUS), which is characterized by the obstruction of renal microvasculature by platelet-fibrin thrombi. It is well known that the oxidative imbalance generated by Stx induces platelet activation, contributing to thrombus formation. Moreover, activated platelets release soluble CD40 ligand (sCD40L), which in turn contributes to oxidative imbalance, triggering the release of reactive oxidative species (ROS) on various cellular types. The aim of this work was to determine if the interaction between the oxidative response and platelet-derived sCD40L, as consequence of Stx-induced endothelium damage, participates in the pathogenic mechanism during HUS. Activated human glomerular endothelial cells (HGEC) by Stx2 induced platelets to adhere to them. Although platelet adhesion did not contribute to endothelial damage, high levels of sCD40L were released to the medium. The release of sCD40L by activated platelets was inhibited by antioxidant treatment. Furthermore, we found increased levels of sCD40L in plasma from HUS patients, which were also able to trigger the respiratory burst in monocytes in a sCD40L-dependent manner. Thus, we concluded that platelet-derived sCD40L and the oxidative response are reciprocally stimulated during Stx2-associated HUS. This process may contribute to the evolution of glomerular occlusion and the microangiopathic lesions. PMID:29068360

Non-Pharmacologic Interventions for Older Adults with Subjective Cognitive Decline: Systematic Review, Meta-Analysis, and Preliminary Recommendations.

PubMed

Smart, Colette M; Karr, Justin E; Areshenkoff, Corson N; Rabin, Laura A; Hudon, Carol; Gates, Nicola; Ali, Jordan I; Arenaza-Urquijo, Eider M; Buckley, Rachel F; Chetelat, Gael; Hampel, Harald; Jessen, Frank; Marchant, Natalie L; Sikkes, Sietske A M; Tales, Andrea; van der Flier, Wiesje M; Wesselman, Linda

2017-09-01

In subjective cognitive decline (SCD), older adults present with concerns about self-perceived cognitive decline but are found to have clinically normal function. However, a significant proportion of those adults are subsequently found to develop mild cognitive impairment, Alzheimer's dementia or other neurocognitive disorder. In other cases, SCD may be associated with mood, personality, and physical health concerns. Regardless of etiology, adults with SCD may benefit from interventions that could enhance current function or slow incipient cognitive decline. The objective of this systematic review and meta-analysis, conducted in accordance with the PRISMA guidelines, is to examine the benefits of non-pharmacologic intervention (NPI) in persons with SCD. Inclusion criteria were studies of adults aged 55 + with SCD defined using published criteria, receiving NPI or any control condition, with cognitive, behavioural, or psychological outcomes in controlled trails. Published empirical studies were obtained through a standardized search of CINAHL Complete, Cochrane Central Register of Controlled Trials, MEDLINE with Full Text, PsycINFO, and PsycARTICLES, supplemented by a manual retrieval of relevant articles. Study quality and bias was determined using PEDro. Nine studies were included in the review and meta-analysis. A wide range of study quality was observed. Overall, a small effect size was found on cognitive outcomes, greater for cognitive versus other intervention types. The available evidence suggests that NPI may benefit current cognitive function in persons with SCD. Recommendations are provided to improve future trials of NPI in SCD.

Genome-Wide Analysis Identifies IL-18 and FUCA2 as Novel Genes Associated with Diastolic Function in African Americans with Sickle Cell Disease

PubMed Central

Sysol, Justin R.; Abbasi, Taimur; Patel, Amit R.; Lang, Roberto M.; Gupta, Akash; Garcia, Joe G. N.; Gordeuk, Victor R.; Machado, Roberto F.

2016-01-01

Background Diastolic dysfunction is common in sickle cell disease (SCD), and is associated with an increased risk of mortality. However, the molecular pathogenesis underlying this development is poorly understood. The aim of this study was to identify a gene expression profile that is associated with diastolic function in SCD, potentially elucidating molecular mechanisms behind diastolic dysfunction development. Methods Diastolic function was measured via echocardiography in 65 patients with SCD from two independent study populations. Gene expression microarray data was compared with diastolic function in both study cohorts. Candidate genes that associated in both analyses were tested for validation in a murine SCD model. Lastly, genotyping array data from the replication cohort was used to derive cis-expression quantitative trait loci (cis-eQTLs) and genetic associations within the candidate gene regions. Results Transcriptome data from both patient cohorts implicated 7 genes associated with diastolic function, and mouse SCD myocardial expression validated 3 of these genes. Genetic associations and eQTLs were detected in 2 of the 3 genes, FUCA2 and IL18. Conclusions FUCA2 and IL18 are associated with diastolic function in SCD patients, and may be involved in the pathogenesis of the disease. Genetic polymorphisms within the FUCA2 and IL18 gene regions are also associated with diastolic function in SCD, likely by affecting expression levels of the genes. PMID:27636371

BK Virus Load Associated with Serum Levels of sCD30 in Renal Transplant Recipients

PubMed Central

Malik, Salma N.; Al-Saffer, Jinan M.; Jawad, Rana S.

2016-01-01

Background. Rejection is the main drawback facing the renal transplant operations. Complicated and overlapping factors, mainly related to the immune system, are responsible for this rejection. Elevated serum levels of sCD30 were frequently recorded as an indicator for renal allograft rejection, while BV virus is considered as one of the most serious consequences for immunosuppressive treatment of renal transplant recipients (RTRs). Aims. This study aimed to determine the association of BK virus load with serum levels of sCD30 in RTRs suffering from nephropathy. Patients and Methods. A total of 50 RTRs with nephropathy and 30 age-matched apparently healthy individuals were recruited for this study. Serum samples were obtained from each participant. Real-time PCR was used to quantify BK virus load in RTRs serum, while ELISA technique was employed to estimate serum levels of sCD30. Results. Twenty-two percent of RTRs had detectable BKV with mean viral load of 1.094E + 06 ± 2.291E + 06. RTRs showed higher mean serum level of sCD30 (20.669 ± 18.713 U/mL) than that of controls (5.517 ± 5.304 U/mL) with significant difference. BK virus load had significant positive correlation with the serum levels of sCD30 in RTRs group. Conclusion. These results suggest that serum levels of sCD30 could be used as an indicator of BK viremia, and accordingly the immunosuppressive regime should be adjusted. PMID:27051424

Post-transplant HLA class II antibodies and high soluble CD30 levels are independently associated with poor kidney graft survival.

PubMed

Langan, L L; Park, L P; Hughes, T L; Irish, A; Luxton, G; Witt, C S; Christiansen, F T

2007-04-01

HLA-specific antibodies (HSA) and soluble CD30 (sCD30) were measured in 208 renal transplant recipients with functioning grafts at least 1 year after transplantation (median 8.2 years) to investigate the predictive value of HSA and sCD30 on subsequent graft outcome. HSA (class I and class II) were detected by both ELISA LAT-M and Luminex LabScreen assays. Data on graft outcome was collected with a median follow-up time of 3.5 years after antibody and sCD30 measurement. Recipients with post-transplant HLA class II antibodies had particularly poor graft outcome with a hazard ratio (HR) of 7.8 (p < 0.0001) when detected by ELISA, and a HR of 6.0 (p < 0.0001) when detected by Luminex. A high post-transplant sCD30 level >or=100 U/mL was associated with increased risk of subsequent graft failure (HR 2.7, p = 0.03). sCD30 and HSA had an independent and additive association with graft outcome. Recipients with HLA class II antibody and high sCD30 had the highest risk of subsequent graft failure (HR 43.4, p < 0.0001 and HR 18.1, p = 0.0008 for ELISA and Luminex, respectively). These data show that detection of HSA and serum sCD30 measured at least 1-year post-transplant provides valuable and predictive information regarding subsequent graft outcome.

Experimental investigation on temperature distribution of foamed concrete filled steel tube column under standard fire

NASA Astrophysics Data System (ADS)

Kado, B.; Mohammad, S.; Lee, Y. H.; Shek, P. N.; Kadir, M. A. A.

2018-04-01

Standard fire test was carried out on 3 hollow steel tube and 6 foamed concrete filled steel tube columns. Temperature distribution on the columns was investigated. 1500 kg/m3 and 1800 kg/m3 foamed concrete density at 15%, 20% and 25% load level are the parameters considered. The columns investigated were 2400 mm long, 139.7 mm outer diameter and 6 mm steel tube thickness. The result shows that foamed concrete filled steel tube columns has the highest fire resistance of 43 minutes at 15% load level and low critical temperature of 671 ºC at 25% load level using 1500 kg/m3 foamed concrete density. Fire resistance of foamed concrete filled column increases with lower foamed concrete strength. Foamed concrete can be used to provide more fire resistance to hollow steel column or to replace normal weight concrete in concrete filled columns. Since filling hollow steel with foamed concrete produce column with high fire resistance than unfilled hollow steel column. Therefore normal weight concrete can be substituted with foamed concrete in concrete filled column, it will reduces the self-weight of the structure because of its light weight at the same time providing the desired fire resistance.

Constraining the H2 column density distribution at z ˜ 3 from composite DLA spectra

NASA Astrophysics Data System (ADS)

Balashev, S. A.; Noterdaeme, P.

2018-07-01

We present the detection of the average H2 absorption signal in the overall population of neutral gas absorption systems at z˜ 3 using composite absorption spectra built from the Sloan Digital Sky Survey-III damped Lyman α catalogue. We present a new technique to directly measure the H2 column density distribution function f_H_2(N) from the average H2 absorption signal. Assuming a power-law column density distribution, we obtain a slope β = -1.29 ± 0.06(stat) ± 0.10 (sys) and an incidence rate of strong H2 absorptions [with N(H2) ≳ 1018 cm-2] to be 4.0 ± 0.5(stat) ± 1.0 (sys) per cent in H I absorption systems with N(H I) ≥1020 cm-2. Assuming the same inflexion point where f_H_2(N) steepens as at z = 0, we estimate that the cosmological density of H2 in the column density range log N(H_2) (cm^{-2})= 18{-}22 is {˜ } 15 per cent of the total. We find one order of magnitude higher H2 incident rate in a sub-sample of extremely strong damped Lyman α absorption systems (DLAs) [log N(H I) (cm^{-2}) ≥ 21.7], which, together with the derived shape of f_H_2(N), suggests that the typical H I-H2 transition column density in DLAs is log N(H)(cm-2) ≳ 22.3 in agreement with theoretical expectations for the average (low) metallicity of DLAs at high-z.

Constraining the H2 column density distribution at z˜3 from composite DLA spectra

NASA Astrophysics Data System (ADS)

Balashev, S. A.; Noterdaeme, P.

2018-04-01

We present the detection of the average H2 absorption signal in the overall population of neutral gas absorption systems at z ˜ 3 using composite absorption spectra built from the Sloan Digital Sky Survey-III damped Lyman-α catalogue. We present a new technique to directly measure the H2 column density distribution function f_H_2(N) from the average H2 absorption signal. Assuming a power-law column density distribution, we obtain a slope β = -1.29 ± 0.06(stat) ± 0.10 (sys) and an incidence rate of strong H2 absorptions (with N(H2) ≳ 1018 cm-2) to be 4.0 ± 0.5(stat) ± 1.0 (sys) % in H I absorption systems with N(H I)≥1020 cm-2. Assuming the same inflexion point where f_H_2(N) steepens as at z = 0, we estimate that the cosmological density of H2 in the column density range log N(H_2) (cm^{-2})= 18-22 is ˜15% of the total. We find one order of magnitude higher H2 incident rate in a sub-sample of extremely strong DLAs (log N(H I) (cm^{-2}) ≥ 21.7), which, together with the the derived shape of f_H_2(N), suggests that the typical H I-H2 transition column density in DLAs is log N(H)(cm-2) ≳ 22.3 in agreement with theoretical expectations for the average (low) metallicity of DLAs at high-z.

Efficiency gain limits of the parallel segmented inlet and outlet flow concept in analytical liquid chromatography columns suffering from radial transcolumn packing density gradients.

PubMed

Broeckhoven, Ken; Desmet, Gert

2012-10-05

The maximal gain in efficiency that can be expected from the use of the segmented column end fittings that were recently introduced to alleviate the effect of transcolumn packing density gradients has been quantified and generalized using numerical computations of the band broadening process. It was found that, for an unretained compound in a column with a parabolic packing density gradient, the use of a segmented inlet or a segmented outlet allows to eliminate about 60-100% of the plate height contribution (H(tc)) originating from a parabolic transcolumn velocity gradient in a d(c)=4.6 mm column. In a d(c)=2.1 mm column, these percentages change from 10 to 100%. Using a combined segmented in- and outlet, H(tc) can be reduced by about 90-100% (d(c)=4.6 mm column) or 20-100% (d(c)=2.1 mm column). The strong variation of these gain percentages is due to fact that they depend very strongly on the column length and the flow rate. Dimensionless graphs have been established that allow to directly quantify the effect for each specific case. It was also found that, in agreement with one's physical intuition, trans-column velocity profiles that are more flat in the central region benefit more from the concept than sharp, parabolic-like profiles. The gain margins furthermore tend to become smaller with increasing retention and increasing diffusion coefficient. Copyright © 2012 Elsevier B.V. All rights reserved.

Pressure, temperature and density drops along supercritical fluid chromatography columns in different thermal environments. III. Mixtures of carbon dioxide and methanol as the mobile phase.

PubMed

Poe, Donald P; Veit, Devon; Ranger, Megan; Kaczmarski, Krzysztof; Tarafder, Abhijit; Guiochon, Georges

2014-01-03

The pressure, temperature and density drops along SFC columns eluted with a CO2/methanol mobile phase were measured and compared with theoretical values. For columns packed with 3- and 5-μm particles the pressure and temperature drops were measured using a mobile phase of 95% CO2 and 5% methanol at a flow rate of 5mL/min, at temperatures from 20 to 100°C, and outlet pressures from 80 to 300bar. The density drop was calculated based on the temperature and pressure at the column inlet and outlet. The columns were suspended in a circulating air bath, either bare or covered with foam insulation. The experimental measurements were compared to theoretical results obtained by numerical simulation. For the convective air condition at outlet pressures above 100bar the average difference between the experimental and calculated temperature drops and pressure drops were 0.1°C and 0.7% for the bare 3-μm column, respectively, and were 0.6°C and 4.1% for the insulated column. The observed temperature drops for the insulated columns are consistent with those predicted by the Joule-Thomson coefficients for isenthalpic expansion. The dependence of the temperature and the pressure drops on the Joule-Thomson coefficient and kinematic viscosity are described for carbon dioxide mobile phases containing up to 20% methanol. Copyright © 2013 Elsevier B.V. All rights reserved.

Galactic cold cores. IX. Column density structures and radiative-transfer modelling

NASA Astrophysics Data System (ADS)

Juvela, M.; Malinen, J.; Montillaud, J.; Pelkonen, V.-M.; Ristorcelli, I.; Tóth, L. V.

2018-06-01

Context. The Galactic Cold Cores (GCC) project has made Herschel photometric observations of interstellar clouds where Planck detected compact sources of cold dust emission. The fields are in different environments and stages of star formation. Aims: Our aim is to characterise the structure of the clumps and their parent clouds, and to study the connections between the environment and the formation of gravitationally bound objects. We also examine the accuracy to which the structure of dense clumps can be determined from sub-millimetre data. Methods: We use standard statistical methods to characterise the GCC fields. Individual clumps are extracted using column density thresholding. Based on sub-millimetre measurements, we construct a three-dimensional radiative transfer (RT) model for each field. These are used to estimate the relative radiation field intensities, to probe the clump stability, and to examine the uncertainty of column density estimates. We examine the structural parameters of the clumps, including their radial column density profiles. Results: In the GCC fields, the structure noise follows the relations previously established at larger scales and in lower-density clouds. The fractal dimension has no significant dependence on column density and the values DP = 1.25 ± 0.07 are only slightly lower than in typical molecular clouds. The column density probability density functions (PDFs) exhibit large variations, for example, in the case of externally compressed clouds. At scales r > 0.1 pc, the radial column density distributions of the clouds follow an average relation of N r-1. In spite of a great variety of clump morphologies (and a typical aspect ratio of 1.5), clumps tend to follow a similar N r-1 relation below r 0.1 pc. RT calculations indicate only factor 2.5 variation in the local radiation field intensity. The fraction of gravitationally bound clumps increases significantly in regions with AV > 5 mag but most bound objects appear to be pressure-confined. Conclusions: The host clouds of the cold clumps in the GCC sample have statistical properties similar to general molecular clouds. The gravitational stability, peak column density, and clump orientation are connected to the cloud background while most other statistical clump properties (e.g. DP and radial profiles) are insensitive to the environment. The study of clump morphology should be continued with a comparison with numerical simulations. Planck (http://www.esa.int/Planck) is a project of the European Space Agency (ESA) with instruments provided by two scientific consortia funded by ESA member states (in particular the lead countries: France and Italy) with contributions from NASA (USA), and telescope reflectors provided in a collaboration between ESA and a scientific consortium led and funded by Denmark.Herschel is an ESA space observatory with science instruments provided by European-led Principal Investigator consortia and with important participation from NASA.

Determination of the best method to estimate glomerular filtration rate from serum creatinine in adult patients with sickle cell disease: a prospective observational cohort study.

PubMed

Arlet, Jean-Benoît; Ribeil, Jean-Antoine; Chatellier, Gilles; Eladari, Dominique; De Seigneux, Sophie; Souberbielle, Jean-Claude; Friedlander, Gérard; de Montalembert, Marianne; Pouchot, Jacques; Prié, Dominique; Courbebaisse, Marie

2012-08-06

Sickle cell disease (SCD) leads to tissue hypoxia resulting in chronic organ dysfunction including SCD associated nephropathy. The goal of our study was to determine the best equation to estimate glomerular filtration rate (GFR) in SCD adult patients. We conducted a prospective observational cohort study. Since 2007, all adult SCD patients in steady state, followed in two medical departments, have had their GFR measured using iohexol plasma clearance (gold standard). The Cockcroft-Gault, MDRD-v4, CKP-EPI and finally, MDRD and CKD-EPI equations without adjustment for ethnicity were tested to estimate GFR from serum creatinine. Estimated GFRs were compared to measured GFRs according to the graphical Bland and Altman method. Sixty-four SCD patients (16 men, median age 27.5 years [range 18.0-67.5], 41 with SS-genotype were studied. They were Sub-Saharan Africa and French West Indies natives and predominantly lean (median body mass index: 22 kg/m2 [16-33]). Hyperfiltration (defined as measured GFR >110 mL/min/1.73 m2) was detected in 53.1% of patients. Urinary albumin/creatinine ratio was higher in patients with hyperfiltration than in patients with normal GFR (4.05 mg/mmol [0.14-60] versus 0.4 mg/mmol [0.7-81], p = 0.01). The CKD-EPI equation without adjustment for ethnicity had both the lowest bias and the greatest precision. Differences between estimated GFRs using the CKP-EPI equation and measured GFRs decreased with increasing GFR values, whereas it increased with the Cockcroft-Gault and MDRD-v4 equations. We confirm that SCD patients have a high rate of glomerular hyperfiltration, which is frequently associated with microalbuminuria or macroalbuminuria. In non-Afro-American SCD patients, the best method for estimating GFR from serum creatinine is the CKD-EPI equation without adjustment for ethnicity. This equation is particularly accurate to estimate high GFR values, including glomerular hyperfiltration, and thus should be recommended to screen SCD adult patients at high risk for SCD nephropathy.

Cardiomyocyte injury assessed by a highly sensitive troponin assay and sudden cardiac death in the community: the Cardiovascular Health Study.

PubMed

Hussein, Ayman A; Gottdiener, John S; Bartz, Traci M; Sotoodehnia, Nona; deFilippi, Christopher; Dickfeld, Timm; Deo, Rajat; Siscovick, David; Stein, Phyllis K; Lloyd-Jones, Donald

2013-12-03

This study sought to determine the association between markers of cardiomyocyte injury in ambulatory subjects and sudden cardiac death (SCD). The pathophysiology of SCD is complex but is believed to be associated with an abnormal cardiac substrate in most cases. The association between biomarkers of cardiomyocyte injury in ambulatory subjects and SCD has not been investigated. Levels of cardiac troponin T, a biomarker of cardiomyocyte injury, were measured by a highly sensitive assay (hsTnT) in 4,431 ambulatory participants in the Cardiovascular Health Study, a longitudinal community-based prospective cohort study. Serial measures were obtained in 3,089 subjects. All deaths, including SCD, were adjudicated by a central events committee. Over a median follow-up of 13.1 years, 246 participants had SCD. Baseline levels of hsTnT were significantly associated with SCD (hazard ratio [HR] for +1 log(hsTnT): 2.04, 95% confidence interval [CI]: 1.78 to 2.34]. This association persisted in covariate-adjusted Cox analyses accounting for baseline risk factors (HR: 1.30, 95% CI: 1.05 to 1.62), as well as for incident heart failure and myocardial infarction (HR: 1.26, 95% CI: 1.01 to 1.57). The population was also categorized into 3 groups based on baseline hsTnT levels and SCD risk [fully adjusted HR: 1.89 vs. 1.55 vs. 1 (reference group) for hsTnT ≥12.10 vs. 5.01 to 12.09 vs. ≤ 5.00 pg/ml, respectively; p trend = 0.005]. On serial measurements, change in hsTnT levels was also associated with SCD risk (fully adjusted HR for +1 pg/ml per year increase from baseline: 1.03, 95% CI: 1.01 to 1.06). The findings suggest an association between cardiomyocyte injury in ambulatory subjects and SCD risk beyond that of traditional risk factors. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Maximizing performance in supercritical fluid chromatography using low-density mobile phases.

PubMed

Gritti, Fabrice; Fogwill, Michael; Gilar, Martin; Jarrell, Joseph A

2016-10-14

The performance of a 3.0mm×150mm column packed with 1.8μm fully porous HSS-SB-C 18 particles was investigated in supercritical fluid chromatography (SFC) with low-density, highly expansible carbon dioxide. These conditions are selected for the analysis of semi-volatile compounds. Elevated temperatures (>100°C) were then combined with low column back pressures (<100bar). In this work, the inlet temperature of pure carbon dioxide was set at 107°C, the active back pressure regulator (ABPR) pressure was fixed at 100bar, and the flow rate was set at 2.1mL/min at 12°C (liquefied carbon dioxide) and at an inlet column pressure close to 300bar. Nine n-alkylbenzenes (from benzene to octadecylbenzene) were injected under linear (no sample overload) conditions. The severe steepness of the temperature gradients across the column diameter were predicted from a simplified heat transfer model. Such conditions dramatically lower the column performance by affecting the symmetry of the peak shape. In order to cope with this problem, three different approaches were experimentally tested. They include (1) the decoupling and the proper selection of the inlet eluent temperature with respect to the oven temperature, (2) the partial thermal insulation of the column using polyethylene aerogel, and (3) the application of a high vacuum (10 -5 Torr provided by a turbo-molecular pump) in a housing chamber surrounding the whole column body. The results reveal that (1) the column efficiency can be maximized by properly selecting the difference between the eluent and the oven temperatures, (2) the mere wrapping of the column with an excellent insulating material is insufficient to fully eliminate heat exchanges by conduction and the undesirable radial density gradients across the column i.d., and (3) the complete thermal insulation of the SFC column under high vacuum allows to maximize the column efficiency by maintaining the integrity of the peak shape. Copyright © 2016 Elsevier B.V. All rights reserved.

Molecular column densities in selected model atmospheres. [chemical analysis of carbon stars

NASA Technical Reports Server (NTRS)

Johnson, H. R.; Beebe, R. F.; Sneden, C.

1974-01-01

From an examination of predicted column densities, the following conclusions were drawn: (1) The SiO ought to be visible in carbon stars which were generated from triple alpha burning, but absent from carbon stars generated from the CNO bi-cycle. (2) Variation in the observed relative strengths of TiO and ZrO is indicative of real differences in the ratio Ti/Zr. (3) The TiO/ZrO ratio shows a small variation as C/O and effective temperature is changed. (4) Column density of silicon dicarbide (SiC2) is sensitive to abundance, temperature, and gravity; hence all relationships between the strength of SiC2 and other stellar parameters will show appreciable scatter. There is however, a substantial luminosity effect present in the SiC2 column densities. (5) Unexpectedly, SiC2 is anti-correlated with C2. (6) The presence of SiC2 in a carbon star eliminates the possibility of these stars having temperatures greater than or equal to 3000 K, or being produced through the CNO bi-cycle.

Multi-wavelength campaign on NGC 7469. II. Column densities and variability in the X-ray spectrum

NASA Astrophysics Data System (ADS)

Peretz, U.; Behar, E.; Kriss, G. A.; Kaastra, J.; Arav, N.; Bianchi, S.; Branduardi-Raymont, G.; Cappi, M.; Costantini, E.; De Marco, B.; Di Gesu, L.; Ebrero, J.; Kaspi, S.; Mehdipour, M.; Middei, R.; Paltani, S.; Petrucci, P. O.; Ponti, G.; Ursini, F.

2018-01-01

We have investigated the ionic column density variability of the ionized outflows associated with NGC 7469, to estimate their location and power. This could allow a better understanding of galactic feedback of AGNs to their host galaxies. Analysis of seven XMM-Newton grating observations from 2015 is reported. We used an individual-ion spectral fitting approach, and compared different epochs to accurately determine variability on timescales of years, months, and days. We find no significant column density variability in a ten-year period implying that the outflow is far from the ionizing source. The implied lower bound on the ionization equilibrium time, ten years, constrains the lower limit on the distance to be at least 12 pc, and up to 31 pc, much less but consistent with the 1 kpc wide starburst ring. The ionization distribution of column density is reconstructed from measured column densities, nicely matching results of two 2004 observations, with one large high ionization parameter (ξ) component at 2 < log ξ< 3.5, and one at 0.5 < log ξ< 1 in cgs units. The strong dependence of the expression for kinetic power, ∝ 1 /ξ, hampers tight constraints on the feedback mechanism of outflows with a large range in ionization parameter, which is often observed and indicates a non-conical outflow. The kinetic power of the outflow is estimated here to be within 0.4 and 60% of the Eddington luminosity, depending on the ion used to estimate ξ.

[The wearable cardioverter/defibrillator : Temporary protection from sudden cardiac death].

PubMed

Duncker, D; Bauersachs, J; Veltmann, C

2016-09-01

In the majority of cases sudden cardiac death (SCD) is caused by ventricular tachyarrhythmia. Implantable cardioverter-defibrillators (ICD) represent an evidence-based and established method for prevention of SCD. For patients who do not fulfill the criteria for guideline-conform implantation of an ICD but still have an increased, e.g. transient risk for SCD, a wearable cardioverter-defibrillator (WCD) vest was developed to temporarily prevent SCD. Numerous studies have shown the safety and efficacy of the WCD, although there is still a gap in evidence concerning a reduction in overall mortality and improvement in prognosis. This article gives an overview on the currently available literature on WCD, the indications, potential risks and complications.

Soluble CD163 is increased in patients with acute pancreatitis independent of disease severity.

PubMed

Karrasch, Thomas; Brünnler, Tanja; Hamer, Okka W; Schmid, Karin; Voelk, Markus; Herfarth, Hans; Buechler, Christa

2015-10-01

Macrophages are crucially involved in the pathophysiology of acute pancreatitis. Soluble CD163 (sCD163) is specifically released from macrophages and systemic levels are increased in inflammatory diseases. Here, sCD163 was measured in serum of 50 patients with acute pancreatitis to find out possible associations with disease activity. Admission levels of systemic sCD163 were nearly three-fold higher in patients with acute pancreatitis compared to controls. In patients sCD163 did not correlate with C-reactive protein and leukocyte count as established markers of inflammation. Levels were not associated with disease severity assessed by the Schroeder score, Balthazar score, Acute Physiology, Age, and Chronic Health Evaluation (Apache) II score and peripancreatic necrosis score. Soluble CD163 was not related to complications of acute pancreatitis. These data show that serum sCD163 is increased in acute pancreatitis indicating activation of macrophages but is not associated with disease severity and outcome. Copyright © 2015 Elsevier Inc. All rights reserved.

Elevated stearoyl-CoA desaturase-1 expression in skeletal muscle contributes to abnormal fatty acid partitioning in obese humans

PubMed Central

Hulver, Matthew W.; Berggren, Jason R.; Carper, Michael J.; Miyazaki, Makoto; Ntambi, James M.; Hoffman, Eric P.; Thyfault, John P.; Stevens, Robert; Dohm, G. Lynis; Houmard, Joseph A.; Muoio, Deborah M.

2014-01-01

Summary Obesity and type 2 diabetes are strongly associated with abnormal lipid metabolism and accumulation of intramyocellular triacylglycerol, but the underlying cause of these perturbations are yet unknown. Herein, we show that the lipogenic gene, stearoyl-CoA desaturase 1 (SCD1), is robustly up-regulated in skeletal muscle from extremely obese humans. High expression and activity of SCD1, an enzyme that catalyzes the synthesis of monounsaturated fatty acids, corresponded with low rates of fatty acid oxidation, increased triacylglycerol synthesis and increased monounsaturation of muscle lipids. Elevated SCD1 expression and abnormal lipid partitioning were retained in primary skeletal myocytes derived from obese compared to lean donors, implying that these traits might be driven by epigenetic and/or heritable mechanisms. Overexpression of human SCD1 in myotubes from lean subjects was sufficient to mimic the obese phenotype. These results suggest that elevated expression of SCD1 in skeletal muscle contributes to abnormal lipid metabolism and progression of obesity. PMID:16213227

Elevated stearoyl-CoA desaturase-1 expression in skeletal muscle contributes to abnormal fatty acid partitioning in obese humans.

PubMed

Hulver, Matthew W; Berggren, Jason R; Carper, Michael J; Miyazaki, Makoto; Ntambi, James M; Hoffman, Eric P; Thyfault, John P; Stevens, Robert; Dohm, G Lynis; Houmard, Joseph A; Muoio, Deborah M

2005-10-01

Obesity and type 2 diabetes are strongly associated with abnormal lipid metabolism and accumulation of intramyocellular triacylglycerol, but the underlying cause of these perturbations are yet unknown. Herein, we show that the lipogenic gene, stearoyl-CoA desaturase 1 (SCD1), is robustly up-regulated in skeletal muscle from extremely obese humans. High expression and activity of SCD1, an enzyme that catalyzes the synthesis of monounsaturated fatty acids, corresponded with low rates of fatty acid oxidation, increased triacylglycerol synthesis and increased monounsaturation of muscle lipids. Elevated SCD1 expression and abnormal lipid partitioning were retained in primary skeletal myocytes derived from obese compared to lean donors, implying that these traits might be driven by epigenetic and/or heritable mechanisms. Overexpression of human SCD1 in myotubes from lean subjects was sufficient to mimic the obese phenotype. These results suggest that elevated expression of SCD1 in skeletal muscle contributes to abnormal lipid metabolism and progression of obesity.

Health policy for sickle cell disease in Africa: experience from Tanzania on interventions to reduce under-five mortality.

PubMed

Makani, Julie; Soka, Deogratias; Rwezaula, Stella; Krag, Marlene; Mghamba, Janneth; Ramaiya, Kaushik; Cox, Sharon E; Grosse, Scott D

2015-02-01

Tanzania has made considerable progress towards reducing childhood mortality, achieving a 57% decrease between 1980 and 2011. This epidemiological transition will cause a reduction in the contribution of infectious diseases to childhood mortality and increase in contribution from non-communicable diseases (NCDs). Haemoglobinopathies are amongst the most common childhood NCDs, with sickle cell disease (SCD) being the commonest haemoglobinopathy in Africa. In Tanzania, 10,313 children with SCD under 5 years of age (U5) are estimated to die every year, contributing an estimated 7% of overall deaths in U5 children. Key policies that governments in Africa are able to implement would reduce mortality in SCD, focusing on newborn screening and comprehensive SCD care programmes. Such programmes would ensure that interventions such as prevention of infections using penicillin plus prompt diagnosis and treatment of complications are provided to all individuals with SCD. © 2014 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.

State of the Art Management of Acute Vaso-occlusive Pain in Sickle Cell Disease.

PubMed

Puri, Latika; Nottage, Kerri A; Hankins, Jane S; Anghelescu, Doralina L

2018-02-01

Acute vaso-occlusive crisis (VOC) is a hallmark of sickle cell disease (SCD). Multiple complex pathophysiological processes can result in pain during a VOC. Despite significant improvements in the understanding and management of SCD, little progress has been made in the management of pain in SCD, although new treatments are being explored. Opioids and non-steroidal anti-inflammatory drugs (NSAIDs) remain the mainstay of treatment of VOC pain, but new classes of drugs are being tested to prevent and treat acute pain. Advancements in the understanding of the pathophysiology of SCD and pain and the pharmacogenomics of opioids have yet to be effectively utilized in the management of VOC. Opioid tolerance and opioid-induced hyperalgesia are significant problems associated with the long-term use of opioids, and better strategies for chronic pain therapy are needed. This report reviews the mechanisms of pain associated with acute VOC, describes the current management of VOC, and describes some of the new therapies under evaluation for the management of acute VOC in SCD.

Quantification of cardiovascular disease biomarkers via functionalized magnetic beads and on-demand detachable quantum dots

NASA Astrophysics Data System (ADS)

Park, Hoyoung; Lee, Jong-Wook; Hwang, Mintai P.; Lee, Kwan Hyi

2013-08-01

Cardiovascular disease (CVD) is a potent cause of mortality in both advanced and developing countries. While soluble CD40L (sCD40L) has been implicated as a correlative factor among CVD patients, methods to quantify sCD40L are not yet well-established. In this paper, we present an ability to separate and quantify sCD40L via a simple immunomagnetic assay. Composed of functionalized magnetic beads conferred with directionality and on-demand detachable quantum dots for subsequent optical analysis, our system utilizes the competitive nature of imidazole and nickel ions for histidine. In essence, we demonstrate the capacity to effectively separate and detect sCD40L within a clinically relevant range that contains the cut-off value for acute coronary disease. While sCD40L was used to conduct this study, we envision the use of our system for the separation and quantification of other biomarkers.

mTOR Inhibition Improves Anaemia and Reduces Organ Damage in a Murine Model of Sickle Cell Disease

PubMed Central

Wang, Jintao; Tran, Jennifer; Wang, Hui; Guo, Chiao; Harro, David; Campbell, Andrew D.; Eitzman, Daniel T.

2016-01-01

Summary Mechanistic target of rapamycin (mTOR) has been shown to play an important role in red blood cell physiology, with inhibition of mTOR signalling leading to alterations in erythropoiesis. To determine if mTOR inhibition would improve anaemia in sickle cell disease (SCD), mice with SCD were treated with the dual mTORC1/2 inhibitor, INK128. 1 week after daily oral drug treatment, erythrocyte count, haemoglobin, and haematocrit were all significantly increased while reticulocyte counts were reduced. These parameters remained stable during 3 weeks of treatment. Similar effects were observed following oral treatment with the mTORC1 inhibitor, sirolimus. Sirolimus treatment prolonged the lifespan of sickle cell erythrocytes in circulation, reduced spleen size, and reduced renal and hepatic iron accumulation in SCD mice. Following middle cerebral artery occlusion, stroke size was reduced in SCD mice treated with sirolimus. In conclusion, mTOR inhibition is protective against anaemia and organ damage in a murine model of SCD. PMID:27030515

Randomized Trial of Hypnosis as a Pain and Symptom Management Strategy in Adults with Sickle Cell Disease

PubMed Central

Wallen, Gwenyth R; Middleton, Kimberly R; Ames, Nancy; Brooks, Alyssa T; Handel, Daniel

2014-01-01

Sickle cell disease (SCD) is the most common genetic disease in African-Americans, characterized by recurrent painful vaso-occlusive crises. Medical therapies for controlling or preventing crises are limited because of efficacy and/or toxicity. This is a randomized, controlled, single-crossover protocol of hypnosis for managing pain in SCD patients. Participants receive hypnosis from a trained hypnosis therapist followed by six weeks of self-hypnosis using digital media. Those in the control arm receive SCD education followed by a six-week waiting period before crossing over to the hypnosis arm of the study. Outcome measures include assessments of pain (frequency, intensity and quality), anxiety, coping strategies, sleep, depression, and health care utilization. To date, there are no published randomized, controlled trials evaluating the efficacy of hypnosis on SCD pain modulation in adults. Self-hypnosis for pain management may be helpful in modulating chronic pain, improving sleep quality, and decreasing use of narcotics in patients with SCD. TRIAL REGISTRATION ClinicalTrials.gov: NCT00393250 PMID:25520557

Physical properties of Southern infrared dark clouds

NASA Astrophysics Data System (ADS)

Vasyunina, T.; Linz, H.; Henning, Th.; Stecklum, B.; Klose, S.; Nyman, L.-Å.

2009-05-01

Context: What are the mechanisms by which massive stars form? What are the initial conditions for these processes? It is commonly assumed that cold and dense Infrared Dark Clouds (IRDCs) represent the birth-sites of massive stars. Therefore, these clouds have been receiving an increasing amount of attention, and their analysis offers the opportunity to tackle the afore mentioned questions. Aims: To enlarge the sample of well-characterised IRDCs in the southern hemisphere, where ALMA will play a major role in the near future, we have developed a program to study the gas and dust of southern infrared dark clouds. The present paper attempts to characterize the continuum properties of this sample of IRDCs. Methods: We cross-correlated 1.2 mm continuum data from SIMBA bolometer array mounted on SEST telescope with Spitzer/GLIMPSE images to establish the connection between emission sources at millimeter wavelengths and the IRDCs that we observe at 8 μm in absorption against the bright PAH background. Analysing the dust emission and extinction enables us to determine the masses and column densities, which are important quantities in characterizing the initial conditions of massive star formation. We also evaluated the limitations of the emission and extinction methods. Results: The morphology of the 1.2 mm continuum emission is in all cases in close agreement with the mid-infrared extinction. The total masses of the IRDCs were found to range from 150 to 1150 M_⊙ (emission data) and from 300 to 1750 M_⊙ (extinction data). We derived peak column densities of between 0.9 and 4.6 × 1022 cm-2 (emission data) and 2.1 and 5.4 × 1022 cm-2 (extinction data). We demonstrate that the extinction method is unreliable at very high extinction values (and column densities) beyond AV values of roughly 75 mag according to the Weingartner & Draine (2001) extinction relation RV = 5.5 model B (around 200 mag when following the common Mathis (1990, ApJ, 548, 296) extinction calibration). By taking the spatial resolution effects into account and restoring the column densities derived from the dust emission to a linear resolution of 0.01 pc, peak column densities of 3-19 × 1023 cm-2 are obtained, which are much higher than typical values for low-mass cores. Conclusions: Taking into account the spatial resolution effects, the derived column densities are beyond the column density threshold of 3.0 × 1023 cm-2 required by theoretical considerations for massive star formation. We conclude that the values of column densities derived for the selected IRDC sample imply that these objects are excellent candidates for objects in the earliest stages of massive star formation.

Intestine-specific Disruption of Hypoxia-inducible Factor (HIF)-2α Improves Anemia in Sickle Cell Disease.

PubMed

Das, Nupur; Xie, Liwei; Ramakrishnan, Sadeesh K; Campbell, Andrew; Rivella, Stefano; Shah, Yatrik M

2015-09-25

Sickle cell disease (SCD) is caused by genetic defects in the β-globin chain. SCD is a frequently inherited blood disorder, and sickle cell anemia is a common type of hemoglobinopathy. During anemia, the hypoxic response via the transcription factor hypoxia-inducible factor (HIF)-2α is highly activated in the intestine and is essential in iron absorption. Intestinal disruption of HIF-2α protects against tissue iron accumulation in iron overload anemias. However, the role of intestinal HIF-2α in regulating anemia in SCD is currently not known. Here we show that in mouse models of SCD, disruption of intestinal HIF-2α significantly decreased tissue iron accumulation. This was attributed to a decrease in intestinal iron absorptive genes, which were highly induced in a mouse model of SCD. Interestingly, disruption of intestinal HIF-2α led to a robust improvement in anemia with an increase in RBC, hemoglobin, and hematocrit. This was attributed to improvement in RBC survival, hemolysis, and insufficient erythropoiesis, which is evident from a significant decrease in serum bilirubin, reticulocyte counts, and serum erythropoietin following intestinal HIF-2α disruption. These data suggest that targeting intestinal HIF-2α has a significant therapeutic potential in SCD pathophysiology. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

SCD1 inhibition causes cancer cell death by depleting mono-unsaturated fatty acids.

PubMed

Mason, Paul; Liang, Beirong; Li, Lingyun; Fremgen, Trisha; Murphy, Erin; Quinn, Angela; Madden, Stephen L; Biemann, Hans-Peter; Wang, Bing; Cohen, Aharon; Komarnitsky, Svetlana; Jancsics, Kate; Hirth, Brad; Cooper, Christopher G F; Lee, Edward; Wilson, Sean; Krumbholz, Roy; Schmid, Steven; Xiang, Yibin; Booker, Michael; Lillie, James; Carter, Kara

2012-01-01

Increased metabolism is a requirement for tumor cell proliferation. To understand the dependence of tumor cells on fatty acid metabolism, we evaluated various nodes of the fatty acid synthesis pathway. Using RNAi we have demonstrated that depletion of fatty-acid synthesis pathway enzymes SCD1, FASN, or ACC1 in HCT116 colon cancer cells results in cytotoxicity that is reversible by addition of exogenous fatty acids. This conditional phenotype is most pronounced when SCD1 is depleted. We used this fatty-acid rescue strategy to characterize several small-molecule inhibitors of fatty acid synthesis, including identification of TOFA as a potent SCD1 inhibitor, representing a previously undescribed activity for this compound. Reference FASN and ACC inhibitors show cytotoxicity that is less pronounced than that of TOFA, and fatty-acid rescue profiles consistent with their proposed enzyme targets. Two reference SCD1 inhibitors show low-nanomolar cytotoxicity that is offset by at least two orders of magnitude by exogenous oleate. One of these inhibitors slows growth of HCT116 xenograft tumors. Our data outline an effective strategy for interrogation of on-mechanism potency and pathway-node-specificity of fatty acid synthesis inhibitors, establish an unambiguous link between fatty acid synthesis and cancer cell survival, and point toward SCD1 as a key target in this pathway.

The severity of anaemia depletes cerebrovascular dilatory reserve in children with sickle cell disease: a quantitative magnetic resonance imaging study.

PubMed

Kosinski, Przemyslaw D; Croal, Paula L; Leung, Jackie; Williams, Suzan; Odame, Isaac; Hare, Gregory M T; Shroff, Manohar; Kassner, Andrea

2017-01-01

Overt ischaemic stroke is one of the most devastating complications in children with sickle cell disease (SCD). The compensatory response to anaemia in SCD includes an increase in cerebral blood flow (CBF) by accessing cerebrovascular dilatory reserve. Exhaustion of dilatory reserve secondary to anaemic stress may lead to cerebral ischaemia. The purpose of this study was to investigate CBF and cerebrovascular reactivity (CVR) using magnetic resonance imaging (MRI) in children with SCD and to correlate these with haematological markers of anaemia. Baseline CBF was measured using arterial spin labelling. Blood-oxygen level-dependent MRI in response to a CO 2 stimulus was used to acquire CVR. In total, 28 children with SCD (23 not on any disease-modifying treatment, 5 on chronic transfusion) and 22 healthy controls were imaged using MRI. Transfusion patients were imaged at two time points to assess the effect of changes in haematocrit after a transfusion cycle. In children with SCD, CBF was significantly elevated compared to healthy controls, while CVR was significantly reduced. Both measures were significantly correlated with haematocrit. For transfusion patients, CBF decreased and CVR increased following a transfusion cycle. Lastly, a significant correlation was observed between CBF and CVR in both children with SCD and healthy controls. © 2016 John Wiley & Sons Ltd.

Free tissue transfer in patients with sickle cell disease: Considerations for multi-disciplinary peri-operative management.

PubMed

Cooper, Lilli; Seth, Rohit; Rhodes, Elizabeth; Alousi, Mohammed; Sivakumar, Bran

2017-01-01

Sickle cell disease (SCD) is an increasingly common condition in the UK. The safety of free tissue transfer in these patients is controversial, and no specific guidelines exist. The aim of this paper is to create recommendations for the plastic surgical multidisciplinary team for use in the assessment and management of SCD patients undergoing free tissue transfer and reconstruction. A literature review was performed in PubMed of 'sickle [TiAb] AND plast* adj3 surg*. Sickle cell disease is explained, as is the relative peri-operative risk in different genotypes of SCD. Acute and chronic manifestations of SCD are described by system, for consideration at pre-operative assessment and post-operative review. The evidence surrounding free tissue transfer and SCD is discussed and the outcomes in published cases summarised. An algorithm for peri-operative multi-disciplinary management is outlined and justified. Free tissue transfer theoretically carries a high risk of a crisis, due not only to long anaesthetic times, but the potential requirement for tourniquet use, and the relatively hypoxic state of the transferred tissue. This paper outlines a useful, practical algorithm to optimise the safety of free tissue transfer in patients with SCD. Copyright © 2016 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Targeting novel mechanisms of pain in sickle cell disease.

PubMed

Tran, Huy; Gupta, Mihir; Gupta, Kalpna

2017-11-30

Patients with sickle cell disease (SCD) suffer from intense pain that can start during infancy and increase in severity throughout life, leading to hospitalization and poor quality of life. A unique feature of SCD is vaso-occlusive crises (VOCs) characterized by episodic, recurrent, and unpredictable episodes of acute pain. Microvascular obstruction during a VOC leads to impaired oxygen supply to the periphery and ischemia reperfusion injury, inflammation, oxidative stress, and endothelial dysfunction, all of which may perpetuate a noxious microenvironment leading to pain. In addition to episodic acute pain, patients with SCD also report chronic pain. Current treatment of moderate to severe pain in SCD is mostly reliant upon opioids; however, long-term use of opioids is associated with multiple side effects. This review presents up-to-date developments in our understanding of the pathobiology of pain in SCD. To help focus future research efforts, major gaps in knowledge are identified regarding how sickle pathobiology evokes pain, pathways specific to chronic and acute sickle pain, perception-based targets of "top-down" mechanisms originating from the brain and neuromodulation, and how pain affects the sickle microenvironment and pathophysiology. This review also describes mechanism-based targets that may help develop novel therapeutic and/or preventive strategies to ameliorate pain in SCD. © 2017 by The American Society of Hematology.

Sickle cell disease biochip: a functional red blood cell adhesion assay for monitoring sickle cell disease

PubMed Central

ALAPAN, YUNUS; KIM, CEONNE; ADHIKARI, ANIMA; GRAY, KAYLA E.; GURKAN-CAVUSOGLU, EVREN; LITTLE, JANE A.; GURKAN, UMUT A.

2016-01-01

Sickle cell disease (SCD) afflicts millions of people worldwide and is associated with considerable morbidity and mortality. Chronic and acute vaso-occlusion are the clinical hallmarks of SCD and can result in pain crisis, widespread organ damage, and early movtality. Even though the molecular underpinnings of SCD were identified more than 60 years ago, there are no molecular or biophysical markers of disease severity that are feasibly measured in the clinic. Abnormal cellular adhesion to vascular endothelium is at the root of vaso-occlusion. However, cellular adhesion is not currently evaluated clinically. Here, we present a clinically applicable microfluidic device (SCD biochip) that allows serial quantitative evaluation of red blood cell (RBC) adhesion to endothelium-associated protein-immobilized microchannels, in a closed and preprocessing-free system. With the SCD biochip, we have analyzed blood samples from more than 100 subjects and have shown associations between the measured RBC adhesion to endothelium-associated proteins (fibronectin and laminin) and individual RBC characteristics, including hemoglobin content, fetal hemoglobin concentration, plasma lactate dehydrogenase level, and reticulocyte count. The SCD biochip is a functional adhesion assay, reflecting quantitative evaluation of RBC adhesion, which could be used at baseline, during crises, relative to various long-term complications, and before and after therapeutic interventions. PMID:27063958

Exploring APOE genotype effects on Alzheimer's disease risk and amyloid β burden in individuals with subjective cognitive decline: The FundacioACE Healthy Brain Initiative (FACEHBI) study baseline results.

PubMed

Moreno-Grau, Sonia; Rodríguez-Gómez, Octavio; Sanabria, Ángela; Pérez-Cordón, Alba; Sánchez-Ruiz, Domingo; Abdelnour, Carla; Valero, Sergi; Hernández, Isabel; Rosende-Roca, Maitée; Mauleón, Ana; Vargas, Liliana; Lafuente, Asunción; Gil, Silvia; Santos-Santos, Miguel Ángel; Alegret, Montserrat; Espinosa, Ana; Ortega, Gemma; Guitart, Marina; Gailhajanet, Anna; de Rojas, Itziar; Sotolongo-Grau, Óscar; Ruiz, Susana; Aguilera, Nuria; Papasey, Judith; Martín, Elvira; Peleja, Esther; Lomeña, Francisco; Campos, Francisco; Vivas, Assumpta; Gómez-Chiari, Marta; Tejero, Miguel Ángel; Giménez, Joan; Serrano-Ríos, Manuel; Orellana, Adelina; Tárraga, Lluís; Ruiz, Agustín; Boada, Mercè

2018-05-01

Subjective cognitive decline (SCD) has been proposed as a potential preclinical stage of Alzheimer's disease (AD). Nevertheless, the genetic and biomarker profiles of SCD individuals remain mostly unexplored. We evaluated apolipoprotein E (APOE) ε4's effect in the risk of presenting SCD, using the Fundacio ACE Healthy Brain Initiative (FACEHBI) SCD cohort and Spanish controls, and performed a meta-analysis addressing the same question. We assessed the relationship between APOE dosage and brain amyloid burden in the FACEHBI SCD and Alzheimer's Disease Neuroimaging Initiative cohorts. Analysis of the FACEHBI cohort and the meta-analysis demonstrated SCD individuals presented higher allelic frequencies of APOE ε4 with respect to controls. APOE dosage explained 9% (FACEHBI cohort) and 11% (FACEHBI and Alzheimer's Disease Neuroimaging Initiative cohorts) of the variance of cerebral amyloid levels. The FACEHBI sample presents APOE ε4 enrichment, suggesting that a pool of AD patients is nested in our sample. Cerebral amyloid levels are partially explained by the APOE allele dosage, suggesting that other genetic or epigenetic factors are involved in this AD endophenotype. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Symptoms of depression and anxiety in adolescents with sickle cell disease: the role of intrapersonal characteristics and stress processing variables.

PubMed

Simon, Katherine; Barakat, Lamia P; Patterson, Chavis A; Dampier, Carlton

2009-06-01

Sickle cell disease (SCD) complications place patients at risk for poor psychosocial adaptation, including depression and anxiety symptoms. This study aimed to test a mediator model based on the Risk and Resistance model to explore the role of intrapersonal characteristics and stress processing variables in psychosocial functioning. Participants were 44 adolescents with SCD, 15 healthy siblings, and 43 primary caregivers, recruited from an East Coast comprehensive sickle cell center. The participants completed paper and pencil measures of resilience factors (attributional style, hope, coping) and internalizing symptoms (depression, anxiety). Internalizing symptoms among adolescents with SCD and healthy siblings did not differ and were within non-clinical ranges. Self-esteem of adolescents with SCD was correlated with less depression and anxiety and sense of inadequacy was associated with poorer functioning. There were no findings to support the role of coping in psychosocial adjustment. Although the mediation hypothesis was not supported, findings highlighted the resilience of this sample of adolescents with SCD. Determining how these resilience factors protect adolescents with SCD may aid in the development of psychosocial interventions. In particular, interventions should focus on improving intrapersonal skills and coping with stress and investigate ways to tailor these interventions to African-American populations.

Learning from a Special Care Dentistry Needs Assessment.

PubMed

Johnson, Ilona

2015-05-01

The General Dental Council recognised special care dentistry (SCD) as a speciality in 2008 and local service reviews have been carried out in order to develop SCD services. A needs assessment was completed to inform the implementation of recommendations from a 2010 review of SCD in Wales. The aim of this paper is to outline the process, findings and learning from the needs assessment and the implications for SCD. A focused needs assessment approach was used. Stakeholder consultations were used to develop a working definition for the needs assessment. Data were collected from existing health and social care sources and analysed using descriptives and geographic information system (GIS) mapping. Data sources for needs assessment were limited. Analysis showed that health conditions were common in the population and increased with age. The majority of people who reported seeing a dentist were seen in general dental practice. Older people with health conditions were less likely to report seeing a dentist. Patients often needed to travel for specialist care services. General dental practice teams have a significant role in caring for SCD patients. Careful planning of specialist care, joint working and enhancing skills across the general practice team will reduce the burden of care and enhance patient safety. Improvements in data for assessment of SCD needs are required to help this process.

Soluble CD30 concentrations in ESRD patients with and without panel reactive HLA antibodies.

PubMed

Vaidya, Smita; Partlow, David; Barnes, Titus; Thomas, Phillip; Gugliuzza, Kristin

2006-01-01

In this retrospective study we compared accuracy of panel reactive antibodies (PRA) with serum soluble CD30 (sCD30) contents in predicting acute rejection crisis post-renal transplant. Pre-transplant sera from 115 patients were evaluated for their PRA and sCD30 concentrations. All patients received calcineurin inhibitor-based immunosuppressive therapy. Objective measurements for rejection were biopsy-proven acute rejection (AR) episodes within first six months of the transplant. Post-transplant sera of patients with AR were tested for the presence of donor-specific HLA antibodies (DSA). Overall AR rate was 16% (18/115). Patients positive for PRA and sCD30 tests were at significantly higher risk for AVR compared with those patients negative for both the tests (36% vs. 5%, p=0.01). Among negative PRA patients risk for AR was significantly elevated if they were also tested positive for sCD30 concentrations (21% vs. 5%, p=0.04). Of the 18 patients with AR, 14 were positive for sCD30, and 13 of them (93%) developed DSA post-transplant (p=0.001). These data showed that patients positive for sCD30 contents are at high risk for the development of DSA and AR post-transplant regardless of their pre-transplant PRA.

cDNA nucleotide sequence coding for stearoyl-CoA desaturase and its expression in the zebrafish (Danio rerio) embryo.

PubMed

Hsieh, S L; Liu, R W; Wu, C H; Cheng, W T; Kuo, Ching-Ming

2003-12-01

A cDNA sequence of stearoyl-CoA desaturase (SCD) was determined from zebrafish (Danio rerio) and compared to the corresponding genes in several teleosts. Zebrafish SCD cDNA has a size of 1,061 bp, encodes a polypeptide of 325 amino acids, and shares 88, 85, 84, and 83% similarities with tilapia (Oreochromis mossambicus), grass carp (Ctenopharyngodon idella), common carp (Cyprinus carpio), and milkfish (Chanos chanos), respectively. This 1,061 bp sequence specifies a protein that, in common with other fatty acid desaturases, contains three histidine boxes, believed to be involved in catalysis. These observations suggested that SCD genes are highly conserved. In addition, an oligonucleotide probe complementary to zebrafish SCD mRNA was hybridized to mRNA of approximately 396 bases with Northern blot analysis. The Northern blot and RT-PCR analyses showed that the SCD mRNA was expressed predominantly in the liver, intestine, gill, and muscle, while a lower level was found in the brain. Furthermore, we utilized whole-mount in situ hybridization and real-time quantitative RT-PCR to identify expression of the zebrafish SCD gene at five different stages of development. This revealed that very high levels of transcripts were found in zebrafish at all stages during embryogenesis and early development. Copyright 2003 Wiley-Liss, Inc.

STELLARATOR INJECTOR

DOEpatents

Post, R.F.

1962-09-01

A method and means are described for injecting energetic neutral atoms or molecular ions into dense magnetically collimated plasma columns of stellarators and the like in such a manner that the atoms or ions are able to significantly penetrate the column before being ionized by collision with the plasma constituent particles. Penetration of the plasma column by the neutral atoms or molecular ions is facilitated by superposition of two closely spaced magnetic mirrors on the plasma confinement field. The mirrors are moved apart to magnetically sweep plasma from a region between the mirrors and establish a relatively low plasma density therein. By virture of the low density, neutral atoms or molecular ions injected into the region significantly penetrate the plasma column before being ionized. Thereafter, the mirrors are diminished to permit the injected material to admix with the plasma in the remainder of the column. (AEC)

Definitions of the Phenotypic Manifestations of Sickle Cell Disease

PubMed Central

Ballas, Samir K.; Lieff, Susan; Benjamin, Lennette J.; Dampier, Carlton D.; Heeney, Matthew M.; Hoppe, Carolyn; Johnson, Cage S.; Rogers, Zora R.; Smith-Whitley, Kim; Wang, Winfred C.; Telen, Marilyn J.

2016-01-01

Sickle cell disease (SCD) is a pleiotropic genetic disorder of hemoglobin that has profound multi-organ effects. The low prevalence of SCD (~100,000/US) has limited progress in clinical, basic, and translational research. Lack of a large, readily accessible population for clinical studies has contributed to the absence of standard definitions and diagnostic criteria for the numerous complications of SCD and inadequate understanding of SCD pathophysiology. In 2005, the Comprehensive Sickle Cell Centers initiated a project to establish consensus definitions of the most frequently occurring complications. A group of clinicians and scientists with extensive expertise in research and treatment of SCD gathered to identify and categorize the most common complications. From this group, a formal writing team was formed that further reviewed the literature, sought specialist input, and produced definitions in a standard format. This manuscript provides an overview of the process and describes twelve body system categories and the most prevalent or severe complications within these categories. A detailed Appendix provides standardized definitions for all complications identified within each system. This report proposes use of these definitions for studies of SCD complications, so future studies can be comparably robust and treatment efficacy measured. Use of these definitions will support greater accuracy in genotype-phenotype studies, thereby achieving a better understanding of SCD pathophysiology. This should nevertheless be viewed as a dynamic rather than final document; phenotype descriptions should be reevaluated and revised periodically to provide the most current standard definitions as etiologic factors are better understood and new diagnostic options are developed. PMID:19902523

Acute appendicitis in patients with sickle cell disease.

PubMed

Al-Nazer, Mona A; Al-Saeed, Hussain H; Al-Salem, Ahmed H

2003-09-01

Patients with sickle cell disease (SCD) often present with abdominal pain, usually attributed to vaso-occlusive crisis, but not rarely, it may be caused by other surgical conditions. Acute appendicitis although common in patients with SCD, it is rare and has a rapid course with a high incidence of perforation. Over a period of 7 years from 1995 to 2001, only 8 patients with SCD out of 1563 (0.5%) patients with acute appendicitis underwent operation at Qatif Central Hospital, Qatif, Kingdom of Saudi Arabia. Their histological slides were reviewed and the findings were compared to those with sickle cell trait (9 patients) and control group (28 patients). All patients with SCD and in spite of a short duration of symptoms had a moderate to severe inflammation and the vessels were packed with sickle red blood cells (RBCs) except one who had an intact mucosa, extensive transmural hemorrhage and congested blood vessels with sickled RBCs without inflammatory cell infiltrate. The mucosa was intact in only one patient with SCD when compared to 5 (55.6%) in those with sickle cell trait and 6 (21.4%) in the control group and in the majority (87.5%) of those with SCD there were moderate to severe mucosal ulcerations when compared to those with sickle cell trait (44.4%) or controls (64.3%). In patients with SCD, acute appendicitis is rare, and these appendicular changes were a sequelae of blockage of appendiceal vessels by sickled RBCs leading to congestion, edema, and ischemia with subsequent mucosal ulceration and marked inflammatory cell infiltrate.

Comparison of immunodulatory properties of dental pulp stem cells derived from healthy and inflamed teeth.

PubMed

Yazid, Farinawati Binti; Gnanasegaran, Nareshwaran; Kunasekaran, Wijenthiran; Govindasamy, Vijayendran; Musa, Sabri

2014-12-01

The aim of this study was to investigate the immunodulatory properties of dental pulp stem cells derived from healthy (SCD) and inflamed pulp deciduous (SCDIP) tissues. The overall hypothesis is that SCDIP possess equal immune properties with SCD and could be used as an alternative tissue source in regenerative medicine. An intra-oral examination was carried out to assess the status of the pulp tissues and group them according to healthy or inflamed. Primary cells were established from these groups, and basic mesenchymal stem cells (MSC) characterizations were conducted. The expression of human leukocyte antigen (HLA), namely HLA-G, HLA-DR, and HLA-ABC were examined in both cell lines using flow cytometry. We further compared the immunosuppressive effects of SCD and SCDIP on phytohemagglutinin-induced T cell proliferation. Supernatants were tested for cytokine profiling using multiplex array. While SCD exhibited typical MSC characteristics, SCDIP on the other hand, did not. Compared with SCDIP, SCD effectively suppresses mitogen-induced T cells proliferation in a dose-dependent manner, as well as express a higher percentage of HLA-ABC and HLA-G. In addition, levels of several cytokines, such as TNF-α, TNF-β, and IL-2, were drastically suppressed in SCD than SCDIP. Furthermore, a high level of IL-10, an important anti-inflammatory cytokine, was present in SCD compared with SCDIP. These findings suggest that SCDIP is highly dysfunctional in terms of their stemness and immunomodulatory properties. SCDIP is not a viable therapeutic cell source especially when used in graft versus host disease (GvHD) and organ rejection.

Safety and Efficacy of High-dose Daily Vitamin D3 Supplementation in Children and Young Adults With Sickle Cell Disease.

PubMed

Dougherty, Kelly A; Bertolaso, Chiara; Schall, Joan I; Smith-Whitley, Kim; Stallings, Virginia A

2015-07-01

Suboptimal vitamin D (vit D) status (<32 ng/mL) is ubiquitous among African American children with type SS sickle cell disease (SCD-SS). The vit D supplemental dose to normalize vit D status is unknown. Five to 20-year-old African American children with (n=21) and without (n=23) SCD-SS were randomized to vit D3 supplementation (4000 or 7000 IU/d) and evaluated at 6 and 12 weeks for changes in vit D and SCD status. A dose was considered unsafe if serum calcium was elevated associated with elevated serum 25 hydroxyvitamin D (25(OH)D). At baseline 95% of subjects with SCD-SS and 87% of healthy controls had suboptimal vit D status (mean±SD, 19.2±7.2 and 22.3±9.3 ng/mL, respectively). After 12 weeks supplementation, both D3 doses were safe and well tolerated. Neither group achieved the a priori efficacy criterion of 25(OH)D≥32 ng/mL in >80% of subjects (45% in SCD-SS and 63% in controls). However, for both subjects with SCD-SS and healthy subjects by 12 weeks, deficient (<20 ng/mL) vit D status was eliminated only in those receiving 7000 IU/d. For subjects with SCD-SS, by 12 weeks there was a significant (all P<0.05) increase in fetal hemoglobin, decrease in high-sensitivity C-reactive protein, and reduction in the percentage of subjects with a high platelet count.

Prediction of acute renal allograft rejection in early post-transplantation period by soluble CD30.

PubMed

Dong, Wang; Shunliang, Yang; Weizhen, Wu; Qinghua, Wang; Zhangxin, Zeng; Jianming, Tan; He, Wang

2006-06-01

To evaluate the feasibility of serum sCD30 for prediction of acute graft rejection, we analyzed clinical data of 231 patients, whose serum levels of sCD30 were detected by ELISA before and after transplantation. They were divided into three groups: acute rejection group (AR, n = 49), uncomplicated course group (UC, n = 171) and delayed graft function group (DGF, n = 11). Preoperative sCD30 levels of three groups were 183 +/- 74, 177 +/- 82 and 168 +/- 53 U/ml, respectively (P = 0.82). Significant decrease of sCD30 was detected in three groups on day 5 and 10 post-transplantation respectively (52 +/- 30 and 9 +/- 5 U/ml respectively, P < 0.001). Compared with Group UC and DGF, patients of Group AR had higher sCD30 values on day 5 post-transplantation (92 +/- 27 U/ml vs. 41 +/- 20 U/ml and 48 +/- 18 U/ml, P < 0.001). However, sCD30 levels on day 10 post-transplantation were virtually similar in patients of three groups (P = 0.43). Receiver operating characteristic (ROC) curve demonstrated that sCD30 level on day 5 post-transplantation could differentiate patients who subsequently suffered acute allograft rejection from others (area under ROC curve 0.95). According to ROC curve, 65 U/ml may be the optimal operational cut-off level to predict impending graft rejection (specificity 91.8%, sensitivity 87.1%). Measurement of soluble CD30 on day 5 post-transplantation might offer a noninvasive means to recognize patients at risk of impending acute graft rejection during early post-transplantation period.

Development, Content Validity, and User Review of a Web-based Multidimensional Pain Diary for Adolescent and Young Adults With Sickle Cell Disease.

PubMed

Bakshi, Nitya; Stinson, Jennifer N; Ross, Diana; Lukombo, Ines; Mittal, Nonita; Joshi, Saumya V; Belfer, Inna; Krishnamurti, Lakshmanan

2015-06-01

Vaso-occlusive pain, the hallmark of sickle cell disease (SCD), is a major contributor to morbidity, poor health-related quality of life, and health care utilization associated with this disease. There is wide variation in the burden, frequency, and severity of pain experienced by patients with SCD. As compared with health care utilization for pain, a daily pain diary captures the breadth of the pain experience and is a superior measure of pain burden and its impact on patients. Electronic pain diaries based on real-time data capture methods overcome methodological barriers and limitations of paper pain diaries, but their psychometric properties have not been formally established in patients with SCD. To develop and establish the content validity of a web-based multidimensional pain diary for adolescents and young adults with SCD and conduct an end-user review to refine the prototype. Following identification of items, a conceptual model was developed. Interviews with adolescents and young adults with SCD were conducted. Subsequently, end-user review with use of the electronic pain diary prototype was conducted. Two iterative cycles of in-depth cognitive interviews in adolescents and young adults with SCD informed the design and guided the addition, removal, and modification of items in the multidimensional pain diary. Potential end-users provided positive feedback on the design and prototype of the electronic diary. A multidimensional web-based electronic pain diary for adolescents and young adults with SCD has been developed and content validity and initial end-user reviews have been completed.

CaMKIIα underlies spontaneous and evoked pain behaviors in Berkeley sickle cell transgenic mice.

PubMed

He, Ying; Chen, Yan; Tian, Xuebi; Yang, Cheng; Lu, Jian; Xiao, Chun; DeSimone, Joseph; Wilkie, Diana J; Molokie, Robert E; Wang, Zaijie Jim

2016-12-01

Pain is one of the most challenging and stressful conditions to patients with sickle cell disease (SCD) and their clinicians. Patients with SCD start experiencing pain as early as 3 months old and continue having it throughout their lives. Although many aspects of the disease are well understood, little progress has been made in understanding and treating pain in SCD. This study aimed to investigate the functional involvement of Ca/calmodulin-dependent protein kinase II (CaMKIIα) in the persistent and refractory pain associated with SCD. We found that nonevoked ongoing pain as well as evoked hypersensitivity to mechanical and thermal stimuli were present in Berkeley sickle cell transgenic mice (BERK mice), but not nonsickle control littermates. Prominent activation of CaMKIIα was observed in the dorsal root ganglia and spinal cord dorsal horn region of BERK mice. Intrathecal administration of KN93, a selective inhibitor of CaMKII, significantly attenuated mechanical allodynia and heat hyperalgesia in BERK mice. Meanwhile, spinal inhibition of CaMKII elicited conditioned place preference in the BERK mice, indicating the contribution of CaMKII in the ongoing spontaneous pain of SCD. We further targeted CaMKIIα by siRNA knockdown. Both evoked pain and ongoing spontaneous pain were effectively attenuated in BERK mice. These findings elucidated, for the first time, an essential role of CaMKIIα as a cellular mechanism in the development and maintenance of spontaneous and evoked pain in SCD, which can potentially offer new targets for pharmacological intervention of pain in SCD.

Study of scattering cross section of a plasma column using Green's function volume integral equation method

NASA Astrophysics Data System (ADS)

Soltanmoradi, Elmira; Shokri, Babak

2017-05-01

In this article, the electromagnetic wave scattering from plasma columns with inhomogeneous electron density distribution is studied by the Green's function volume integral equation method. Due to the ready production of such plasmas in the laboratories and their practical application in various technological fields, this study tries to find the effects of plasma parameters such as the electron density, radius, and pressure on the scattering cross-section of a plasma column. Moreover, the incident wave frequency influence of the scattering pattern is demonstrated. Furthermore, the scattering cross-section of a plasma column with an inhomogeneous collision frequency profile is calculated and the effect of this inhomogeneity is discussed first in this article. These results are especially used to determine the appropriate conditions for radar cross-section reduction purposes. It is shown that the radar cross-section of a plasma column reduces more for a larger collision frequency, for a relatively lower plasma frequency, and also for a smaller radius. Furthermore, it is found that the effect of the electron density on the scattering cross-section is more obvious in comparison with the effect of other plasma parameters. Also, the plasma column with homogenous collision frequency can be used as a better shielding in contrast to its inhomogeneous counterpart.

Plasma soluble CD163 is associated with postmortem brain pathology in human immunodeficiency virus infection.

PubMed

Bryant, Alex K; Moore, David J; Burdo, Tricia H; Lakritz, Jessica R; Gouaux, Ben; Soontornniyomkij, Virawudh; Achim, Cristian L; Masliah, Eliezer; Grant, Igor; Levine, Andrew J; Ellis, Ronald J

2017-04-24

Higher plasma soluble cluster of differentiation (CD)163 (sCD163), shed by monocytes and macrophages, correlates with neurocognitive impairment in HIV infection. We hypothesized that higher antemortem plasma or cerebrospinal fluid (CSF) sCD163 would be associated with greater postmortem neurodegeneration and/or microgliosis. Retrospective, postmortem observational study. We measured sCD163 levels in antemortem plasma (n = 54) and CSF (n = 32) samples from 74 HIV-seropositive participants (median 5 months before death) who donated their brains to research at autopsy. Postmortem, we quantified markers of synaptodendritic damage (microtubule-associated protein 2, synaptophysin), microgliosis [human leukocyte antigen DR (HLA-DR), ionized calcium-binding adaptor molecule 1], astrocytosis (glial fibrillary acidic protein), and impaired protein clearance (β-amyloid) in frontal cortex, hippocampus, putamen, and internal capsule. Multivariable least-squares regression was used to evaluate the association between plasma or CSF sCD163 and histological measures, correcting for multiple comparisons. Higher plasma sCD163 was associated with lower microtubule-associated protein 2 in frontal cortex [B = -0.23, 95% confidence interval (CI) -0.41 to -0.06, P = 0.04], putamen (B = 0.32, 95% CI -0.52 to -0.12, P = 0.02), and hippocampus (B = -0.23, 95% CI -0.35 to -0.10, P = 0.01), and with lower synaptophysin in hippocampus (B = -0.25, 95% CI -0.42 to -0.03, P = 0.02) but not putamen or frontal cortex (P > 0.05). Higher plasma sCD163 was associated with higher HLA-DR in putamen (B = 0.17, 95% CI 0.08 to 0.26, P = 0.008). CSF sCD163 was not associated with any histological measure (P > 0.05). Higher plasma sCD163 in life is associated with greater synaptodendritic damage and microglial activation in cortical and subcortical brain regions.

Sequential CD4-Coreceptor Interactions in Human Immunodeficiency Virus Type 1 Env Function: Soluble CD4 Activates Env for Coreceptor-Dependent Fusion and Reveals Blocking Activities of Antibodies against Cryptic Conserved Epitopes on gp120

PubMed Central

Salzwedel, Karl; Smith, Erica D.; Dey, Barna; Berger, Edward A.

2000-01-01

We devised an experimental system to examine sequential events by which the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) interacts with CD4 and coreceptor to induce membrane fusion. Recombinant soluble CD4 (sCD4) activated fusion between effector cells expressing Env and target cells expressing coreceptor (CCR5 or CXCR4) but lacking CD4. sCD4-activated fusion was dose dependent, occurred comparably with two- and four-domain proteins, and demonstrated Env-coreceptor specificities parallel to those reported in conventional fusion and infectivity systems. Fusion activation occurred upon sCD4 preincubation and washing of the Env-expressing effector cells but not the coreceptor-bearing target cells, thereby demonstrating that sCD4 exerts its effects by acting on Env. These findings provide direct functional evidence for a sequential two-step model of Env-receptor interactions, whereby gp120 binds first to CD4 and becomes activated for subsequent functional interaction with coreceptor, leading to membrane fusion. We used the sCD4-activated system to explore neutralization by the anti-gp120 human monoclonal antibodies 17b and 48d. These antibodies reportedly bind conserved CD4-induced epitopes involved in coreceptor interactions but neutralize HIV-1 infection only weakly. We found that 17b and 48d had minimal effects in the standard cell fusion system using target cells expressing both CD4 and coreceptor but potently blocked sCD4-activated fusion with target cells expressing coreceptor alone. Both antibodies strongly inhibited sCD4-activated fusion by Envs from genetically diverse HIV-1 isolates. Thus, the sCD4-activated system reveals conserved Env-blocking epitopes that are masked in native Env and hence not readily detected by conventional systems. PMID:10590121

Conformational Rearrangement Within the Soluble Domains of the CD4 Receptor is Ligand-Specific

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

Ashish,F.; Juncadella, I.; Garg, R.

2008-01-01

Ligand binding induces shape changes within the four modular ectodomains (D1-D4) of the CD4 receptor, an important receptor in immune signaling. Small angle x-ray scattering (SAXS) on both a two-domain and a four-domain construct of the soluble CD4 (sCD4) is consistent with known crystal structures demonstrating a bilobal and a semi-extended tetralobal Z conformation in solution, respectively. Detection of conformational changes within sCD4 as a result of ligand binding was followed by SAXS on sCD4 bound to two different glycoprotein ligands: the tick saliva immunosuppressor Salp15 and the HIV-1 envelope protein gp120. Ab initio modeling of these data showed thatmore » both Salp15 and gp120 bind to the D1 domain of sCD4 and yet induce drastically different structural rearrangements. Upon binding, Salp15 primarily distorts the characteristic lobal architecture of the sCD4 without significantly altering the semi-extended shape of the sCD4 receptor. In sharp contrast, the interaction of gp120 with sCD4 induces a shape change within sCD4 that can be described as a Z-to-U bi-fold closure of the four domains across its flexible D2-D3 linker. Placement of known crystal structures within the boundaries of the SAXS-derived models suggests that the ligand-induced shape changes could be a result of conformational changes within this D2-D3 linker. Functionally, the observed shape changes in CD4 receptor causes dissociation of lymphocyte kinase from the cytoplasmic domain of Salp15-bound CD4 and facilitates an interaction between the exposed V3 loops of CD4-bound gp120 molecule to the extracellular loops of its co-receptor, a step essential for HIV-1 viral entry.« less

Mitochondrial ROS Drive Sudden Cardiac Death and Chronic Proteome Remodeling in Heart Failure.

PubMed

Dey, Swati; DeMazumder, Deeptankar; Sidor, Agnieszka; Foster, D B; O'Rourke, Brian

2018-06-13

Rationale: Despite increasing prevalence and incidence of heart failure (HF), therapeutic options remain limited. In early stages of HF, sudden cardiac death (SCD) from ventricular arrhythmias claims many lives. Reactive oxygen species (ROS) have been implicated in both arrhythmias and contractile dysfunction. However, little is known about how ROS in specific subcellular compartments contribute to HF or SCD pathophysiology. The role of ROS in chronic proteome remodeling has not been explored. Objective: We will test the hypothesis that elevated mitochondrial ROS (mROS) is a principal source of oxidative stress in HF and in vivo reduction of mROS mitigates SCD. Methods and Results: Using a unique guinea pig model of non-ischemic HF that recapitulates important features of human HF, including prolonged QT interval and high incidence of spontaneous arrhythmic SCD. Compartment-specific ROS sensors revealed increased mROS in resting and contracting left ventricular (LV) myocytes in failing hearts. Importantly, mitochondrially-targeted antioxidant (MitoTEMPO) normalized global cellular ROS. Further, in vivo MitoTEMPO treatment of HF animals prevented and reversed HF; eliminated SCD by decreasing dispersion of repolarization and ventricular arrhythmias; suppressed chronic HF-induced remodeling of the expression proteome; and prevented specific phosphoproteome alterations. Pathway analysis of mROS-sensitive networks indicated that increased mROS in HF disrupts the normal coupling between cytosolic signals and nuclear gene programs driving mitochondrial function, antioxidant enzymes, Ca2+ handling and action potential repolarization, suggesting new targets for therapeutic intervention. Conclusions: mROS drive both acute emergent events, such as electrical instability responsibly for SCD, and those that mediate chronic HF remodeling, characterized by suppression or altered phosphorylation of metabolic, antioxidant and ion transport protein networks. In vivo reduction of mROS prevents and reverses electrical instability, SCD and HF. Our findings support the feasibility of targeting the mitochondria as a potential new therapy for HF and SCD while identifying new mROS-sensitive protein modifications.

Systematic review of the incidence of sudden cardiac death in the United States.

PubMed

Kong, Melissa H; Fonarow, Gregg C; Peterson, Eric D; Curtis, Anne B; Hernandez, Adrian F; Sanders, Gillian D; Thomas, Kevin L; Hayes, David L; Al-Khatib, Sana M

2011-02-15

The need for consistent and current data describing the true incidence of sudden cardiac arrest (SCA) and/or sudden cardiac death (SCD) was highlighted during the most recent Sudden Cardiac Arrest Thought Leadership Alliance's (SCATLA) Think Tank meeting of national experts with broad representation of key stakeholders, including thought leaders and representatives from the American College of Cardiology, American Heart Association, and the Heart Rhythm Society. As such, to evaluate the true magnitude of this public health problem, we performed a systematic literature search in MEDLINE using the MeSH headings, "death, sudden" OR the terms "sudden cardiac death" OR "sudden cardiac arrest" OR "cardiac arrest" OR "cardiac death" OR "sudden death" OR "arrhythmic death." Study selection criteria included peer-reviewed publications of primary data used to estimate SCD incidence in the U.S. We used Web of Science's Cited Reference Search to evaluate the impact of each primary estimate on the medical literature by determining the number of times each "primary source" has been cited. The estimated U.S. annual incidence of SCD varied widely from 180,000 to >450,000 among 6 included studies. These different estimates were in part due to different data sources (with data age ranging from 1980 to 2007), definitions of SCD, case ascertainment criteria, methods of estimation/extrapolation, and sources of case ascertainment. The true incidence of SCA and/or SCD in the U.S. remains unclear, with a wide range in the available estimates that are badly dated. As reliable estimates of SCD incidence are important for improving risk stratification and prevention, future efforts are clearly needed to establish uniform definitions of SCA and SCD and then to prospectively and precisely capture cases of SCA and SCD in the overall U.S. population. Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Functional Mimetics of the HIV-1 CCR5 Co-Receptor Displayed on the Surface of Magnetic Liposomes.

PubMed

Kuzmina, Alona; Vaknin, Karin; Gdalevsky, Garik; Vyazmensky, Maria; Marks, Robert S; Taube, Ran; Engel, Stanislav

2015-01-01

Chemokine G protein coupled receptors, principally CCR5 or CXCR4, function as co-receptors for HIV-1 entry into CD4+ T cells. Initial binding of the viral envelope glycoprotein (Env) gp120 subunit to the host CD4 receptor induces a cascade of structural conformational changes that lead to the formation of a high-affinity co-receptor-binding site on gp120. Interaction between gp120 and the co-receptor leads to the exposure of epitopes on the viral gp41 that mediates fusion between viral and cell membranes. Soluble CD4 (sCD4) mimetics can act as an activation-based inhibitor of HIV-1 entry in vitro, as it induces similar structural changes in gp120, leading to increased virus infectivity in the short term but to virus Env inactivation in the long term. Despite promising clinical implications, sCD4 displays low efficiency in vivo, and in multiple HIV strains, it does not inhibit viral infection. This has been attributed to the slow kinetics of the sCD4-induced HIV Env inactivation and to the failure to obtain sufficient sCD4 mimetic levels in the serum. Here we present uniquely structured CCR5 co-receptor mimetics. We hypothesized that such mimetics will enhance sCD4-induced HIV Env inactivation and inhibition of HIV entry. Co-receptor mimetics were derived from CCR5 gp120-binding epitopes and functionalized with a palmitoyl group, which mediated their display on the surface of lipid-coated magnetic beads. CCR5-peptidoliposome mimetics bound to soluble gp120 and inhibited HIV-1 infectivity in a sCD4-dependent manner. We concluded that CCR5-peptidoliposomes increase the efficiency of sCD4 to inhibit HIV infection by acting as bait for sCD4-primed virus, catalyzing the premature discharge of its fusion potential.

Functional Mimetics of the HIV-1 CCR5 Co-Receptor Displayed on the Surface of Magnetic Liposomes

PubMed Central

Kuzmina, Alona; Vaknin, Karin; Gdalevsky, Garik; Vyazmensky, Maria; Marks, Robert S.; Taube, Ran

2015-01-01

Chemokine G protein coupled receptors, principally CCR5 or CXCR4, function as co-receptors for HIV-1 entry into CD4+ T cells. Initial binding of the viral envelope glycoprotein (Env) gp120 subunit to the host CD4 receptor induces a cascade of structural conformational changes that lead to the formation of a high-affinity co-receptor-binding site on gp120. Interaction between gp120 and the co-receptor leads to the exposure of epitopes on the viral gp41 that mediates fusion between viral and cell membranes. Soluble CD4 (sCD4) mimetics can act as an activation-based inhibitor of HIV-1 entry in vitro, as it induces similar structural changes in gp120, leading to increased virus infectivity in the short term but to virus Env inactivation in the long term. Despite promising clinical implications, sCD4 displays low efficiency in vivo, and in multiple HIV strains, it does not inhibit viral infection. This has been attributed to the slow kinetics of the sCD4-induced HIV Env inactivation and to the failure to obtain sufficient sCD4 mimetic levels in the serum. Here we present uniquely structured CCR5 co-receptor mimetics. We hypothesized that such mimetics will enhance sCD4-induced HIV Env inactivation and inhibition of HIV entry. Co-receptor mimetics were derived from CCR5 gp120-binding epitopes and functionalized with a palmitoyl group, which mediated their display on the surface of lipid-coated magnetic beads. CCR5-peptidoliposome mimetics bound to soluble gp120 and inhibited HIV-1 infectivity in a sCD4-dependent manner. We concluded that CCR5-peptidoliposomes increase the efficiency of sCD4 to inhibit HIV infection by acting as bait for sCD4-primed virus, catalyzing the premature discharge of its fusion potential. PMID:26629902

Kidney function and sudden cardiac death in the community: The Atherosclerosis Risk in Communities (ARIC) Study.

PubMed

Suzuki, Takeki; Agarwal, Sunil K; Deo, Rajat; Sotoodehnia, Nona; Grams, Morgan E; Selvin, Elizabeth; Calkins, Hugh; Rosamond, Wayne; Tomaselli, Gordon; Coresh, Josef; Matsushita, Kunihiro

2016-10-01

Individuals with chronic kidney disease, particularly those requiring dialysis, are at high risk of sudden cardiac death (SCD). However, comprehensive data for the full spectrum of kidney function and SCD risk in the community are sparse. Furthermore, newly developed equations for estimated glomerular filtration rate (eGFR) and novel filtration markers might add further insight to the role of kidney function in SCD. We investigated the associations of baseline eGFRs using serum creatinine, cystatin C, or both (eGFRcr, eGFRcys, and eGFRcr-cys); cystatin C itself; and β2-microglobulin (B2M) with SCD (205 cases through 2001) among 13,070 black and white ARIC participants at baseline during 1990-1992 using Cox regression models accounting for potential confounders. Low eGFR was independently associated with SCD risk: for example, hazard ratio for eGFR <45 versus ≥90mL/(min 1.73m(2)) was 3.71 (95% CI 1.74-7.90) with eGFRcr, 5.40 (2.97-9.83) with eGFRcr-cys, and 5.24 (3.01-9.11) with eGFRcys. When eGFRcr and eGFRcys were included together in a single model, the association was only significant for eGFRcys. When three eGFRs, cystatin C, and B2M were divided into quartiles, B2M demonstrated the strongest association with SCD (hazard ratio for fourth quartile vs first quartile 3.48 (2.03-5.96) vs ≤2.7 for the other kidney markers). Kidney function was independently and robustly associated with SCD in the community, particularly when cystatin C or B2M was used. These results suggest the potential value of kidney function as a risk factor for SCD and the advantage of novel filtration markers over eGFRcr in this context. Copyright © 2016 Elsevier Inc. All rights reserved.

Cocaine- and amphetamine-regulated transcript peptide and calcium binding proteins immunoreactivity in the deep layers of the superior colliculus of the guinea pig: Implications for multisensory and visuomotor processing.

PubMed

Najdzion, Janusz

2018-03-01

The superior colliculus (SC) of mammals is a midbrain center, that can be subdivided into the superficial (SCs) and deep layers (SCd). In contrast to the visual SCs, the SCd are involved in multisensory and motor processing. This study investigated the pattern of distribution and colocalization of cocaine- and amphetamine-regulated transcript peptide (CART) and three calcium-binding proteins (CaBPs) i.e. calbindin (CB), calretinin (CR) and parvalbumin (PV) in the SCd of the guinea pig. CART labeling was seen almost exclusively in the neuropil and fibers, which differed in regard to morphology and location. CART-positive neurons were very rare and restricted to a narrow area of the SCd. The most intense CART immunoreactivity was observed in the most dorsally located sublayer of the SCd, which is anatomically and functionally connected with the SCs. CART immunoreactivity in the remaining SCd was less intensive, but still relatively high. This characteristic pattern of immunoreactivity indicates that CART as a putative neurotransmitter or neuromodulator may play an important role in processing of visual information, while its involvement in the auditory and visuomotor processing is less significant, but still possible. CaBPs-positive neurons were morphologically diverse and widely distributed throughout all SCd. From studied CaBPs, CR showed a markedly different distribution compared to CB and PV. Overall, the patterns of distribution of CB and PV were similar in the entire SCd. Consequently, the complementarity of these patterns in the guinea pig was very weak. Double immunostaining revealed that CART did not colocalize with either CaBPs, which suggested that these neurochemical substances might not coexist in the multisensory and visuomotor parts of the SC. Copyright © 2017 Elsevier B.V. All rights reserved.

Incidence and Etiology of Sudden Cardiac Death: New Updates for Athletic Departments.

PubMed

Asif, Irfan M; Harmon, Kimberly G

Sudden cardiac death (SCD) in a young athlete is a tragic event and is the leading medical cause of death in this population. The precise incidence of SCD in young athletes has been subject of debate, with studies reporting drastically different rates (1:917,000 athlete-years (AYs) to 1:3000 AYs) depending on the methodological design of the investigation or the targeted population. A literature search was performed in PubMed using the terms: incidence, sudden cardiac death, sudden death, sudden cardiac arrest, etiology, pathology, registry, athlete, young, children, and adolescents. Articles were reviewed for relevance and included if they contained information on the incidence of SCD in athletes or young persons up to the age of 35 years. Clinical review. Level 5. Studies of high quality and rigor consistently yield an incidence of 1:50,000 AYs in college athletes and between 1:50,000 and 1:80,000 AYs for high school athletes, with certain subgroups that appear to be at particularly high risk, including the following: men, basketball players, and African Americans. Initial reports suggest that the most common cause of SCD is hypertrophic cardiomyopathy (HCM). However, more comprehensive investigations in the United States and international populations-athletes, nonathletes, and military-support that the most common finding on autopsy in young individuals with SCD is actually a structurally normal heart (autopsy-negative sudden unexplained death). SCD is the leading cause of death in athletes during exercise and usually results from intrinsic cardiac conditions that are triggered by the physiologic demands of vigorous exercise. Current rates of SCD appear to be at least 4 to 5 times higher than previously estimated, with men, African Americans, and male basketball players being at greatest risk. Emerging data suggest that the leading finding associated with SCD in athletes is actually a structurally normal heart (autopsy-negative sudden unexplained death).

Pre-transplant soluble CD30 level as a predictor of not only acute rejection and graft loss but pneumonia in renal transplant recipients.

PubMed

Wang, Dong; Wu, Wei-Zhen; Chen, Jin-Hua; Yang, Shun-Liang; Wang, Qing-Hua; Zeng, Zhang-Xin; Tan, Jian-Ming

2010-02-01

Pre-transplant sera of 586 renal graft recipients were tested to investigate whether soluble CD30 (sCD30) is a useful predictor of some severe clinical episodes post-transplant. Correlation analysis showed sCD30 level was significantly correlated with acute rejection (AR) (r=0.242, P<0.001), graft loss (r=0.162, P<0.001), and pneumonia (r=-0.147, P<0.001). Higher sCD30 levels were observed in patients with AR than the others (180.0+/-89.1 vs. 135.3+/-72.7U/ml, P<0.001). And patients with pneumonia had significantly lower pre-transplant sCD30 level than the others (123.2+/-75.5 vs. 150.7+/-79.6U/ml, P=0.003). Based on statistical results, 120 and 240U/ml were selected as the optimal couple of cut-off value to divide patients into three groups: Group High (H), Group Intermedial (I) and Group Low (L). The lowest AR rate of 17.4% was observed in Group L (P<0.001). Significant difference of AR rate was also observed between Group I (29.2%) and H (42.9%) (P<0.001). There were much more patients suffering pneumonia in Group L (P=0.001). Significantly lower 5-year patient survival rate (79.4%) was observed in Group H (P=0.016). These data showed that elevated pre-transplant sCD30 level of renal allograft recipients may reflect an immune state detrimental for renal allograft survival. But sCD30 level lower than <120U/ml may be associated with a high risk of pneumonia. Pre-transplant sCD30 level is an independent predictor of acute rejection, lung infection, even graft survival. Suitable immunosuppression protocol should be selected according to pre-transplant sCD30 level in an attempt to promote patient and graft survival. Copyright 2010 Elsevier B.V. All rights reserved.

Release of soluble CD30 after allogeneic stimulation is mediated by memory T cells and regulated by IFN-γ and IL-2.

PubMed

Velásquez, Sonia Y; García, Luis F; Opelz, Gerhard; Alvarez, Cristiam M; Süsal, Caner

2013-07-27

Membrane CD30 is an important costimulatory molecule for activated T lymphocytes, and serum level of soluble CD30 (sCD30) is considered a marker for predicting outcome in kidney transplantation. We investigated the kinetics of CD30 expression on CD4 and CD8 T-cell populations and the source of sCD30 during alloimmune responses in vitro. The effect of neutralizing antibodies against interferon (IFN)-γ and other cytokines on sCD30 release and the involvement of metalloproteinases ADAM10 and ADAM17/TACE that are responsible for sCD30 shedding were also assessed. Memory phenotypes and CD30 expression on allostimulated CD3 lymphocytes were evaluated in dialysis patients and matched controls. Allogeneic stimulation resulted in conversion of naive responder cells to central memory CD4 cells (P<0.001 at 96 hr) and effector CD8 cells (P<0.01 at 120 hr), which was accompanied by increased CD30 expression. Release of sCD30 was attributed mainly to central memory cells, and neutralization of IFN-γ (P<0.001) and interleukin (IL)-2 (P<0.001) impaired the release of sCD30 during allostimulation but did not alter the levels of ADAM10 and ADAM17/TACE. CD30 expression was modulated in dialysis patients in a similar way as in healthy controls. Allostimulation results in the up-regulation of the T-cell activation marker CD30 on CD4 as well as CD8 memory T cells and increased release of sCD30 from these cells in an IFN-γ- and IL-2-dependent manner. These results may explain clinical findings on the suitability of sCD30 and IFN-γ- and IL-2-producing T cells for immune monitoring of kidney transplant recipients before and after transplantation.

High soluble CD30 levels and associated anti-HLA antibodies in patients with failed renal allografts.

PubMed

Karahan, Gonca E; Caliskan, Yasar; Ozdilli, Kursat; Kekik, Cigdem; Bakkaloglu, Huseyin; Caliskan, Bahar; Turkmen, Aydin; Sever, Mehmet S; Oguz, Fatma S

2017-01-13

Serum soluble CD30 (sCD30), a 120-kD glycoprotein that belongs to the tumor necrosis factor receptor family, has been suggested as a marker of rejection in kidney transplant patients. The aim of this study was to evaluate the relationship between sCD30 levels and anti-HLA antibodies, and to compare sCD30 levels in patients undergoing hemodialysis (HD) with and without failed renal allografts and transplant recipients with functioning grafts. 100 patients undergoing HD with failed grafts (group 1), 100 patients undergoing HD who had never undergone transplantation (group 2), and 100 kidney transplant recipients (group 3) were included in this study. Associations of serum sCD30 levels and anti-HLA antibody status were analyzed in these groups. The sCD30 levels of group 1 and group 2 (154 ± 71 U/mL and 103 ± 55 U/mL, respectively) were significantly higher than those of the transplant recipients (group 3) (39 ± 21 U/mL) (p<0.001 and p<0.001). The serum sCD30 levels in group 1 (154 ± 71 U/mL) were also significantly higher than group 2 (103 ± 55 U/mL) (p<0.001). Anti-HLA antibodies were detected in 81 (81%) and 5 (5%) of patients in groups 1 and 2, respectively (p<0.001). When multiple regression analysis was performed to predict sCD30 levels, the independent variables in group 1 were the presence of class I anti-HLA antibodies (β = 0.295; p = 0.003) and age (β = -0.272; p = 0.005), and serum creatinine (β = 0.218; p = 0.027) and presence of class II anti-HLA antibodies (standardized β = 0.194; p = 0.046) in group 3. Higher sCD30 levels and anti-HLA antibodies in patients undergoing HD with failed renal allografts may be related to higher inflammatory status in these patients.

Soluble CD163, a marker of Kupffer cell activation, is related to portal hypertension in patients with liver cirrhosis.

PubMed

Grønbaek, H; Sandahl, T D; Mortensen, C; Vilstrup, H; Møller, H J; Møller, S

2012-07-01

Activation of Kupffer cells may be involved in the pathogenesis of portal hypertension by release of vasoconstrictive substances and fibrosis due to co-activation of hepatic stellate cells. To study soluble plasma (s) CD163, a specific marker of activated macrophages, as a biomarker for portal hypertension in patients with liver cirrhosis. We measured sCD163 concentration and the hepatic venous pressure gradient (HVPG) by liver vein catheterisation in 81 cirrhosis patients (Child-Pugh CP-A: n = 26, CP-B: n = 29, CP-C: n = 26) and 22 healthy subjects. We also measured their cardiac output (CO), cardiac index and systemic vascular resistance (SVR). Liver status was examined by Child-Pugh and MELD-score. In cirrhosis, sCD163 concentration was nearly three times higher than in controls (4.7 ± 2.5 vs. 1.6 ± 0.5 mg/L, P < 0.001). sCD163 was also higher, as measured in steps by CP-score (P < 0.001). The HVPG rose steeply to an asymptote of 22 mmHg with sCD163 up to about 5 mg/L and not to higher values with higher sCD163. In a multivariate analysis, sCD163 was the only independent predictor of the HVPG but did not predict any of the systemic circulatory findings. sCD163 > 3.95 mg/L (upper normal limit) predicted HVPG ≥ 10 mmHg with a positive predictive value of 0.99. Circulating sCD163 originating from activated Kupffer cells is increased in cirrhosis with increasing Child-Pugh score and with increasing HVPG, and it is an independent predictor for HVPG. These findings support a primary role of macrophage activation in portal hypertension, and may indicate a target for biological intervention. © 2012 Blackwell Publishing Ltd.

Temporal and spatial distribution of metallic species in the upper atmosphere

NASA Astrophysics Data System (ADS)

Correira, John Thomas

2009-06-01

Every day the Earth is bombarded by approximately 100 tons of meteoric material. Much of this material is completely ablated on atmospheric entry, resulting in a layer of atomic metals in the upper atmosphere between 70 km - 150 km. These neutral atoms are ionized by solar radiation and charge exchange. Metal ions have a long lifetime against recombination loss, allowing them to be redistributed globally by electromagnetic forces, especially when lifted to altitudes >150 km. UV radiances from the Global Ozone Monitoring Experiment (GOME) spectrometer are used to determine long-term dayside variations of the total vertical column density below 795 km of the meteoric metal species Mg and Mg + in the upper atmosphere. A retrieval algorithm developed to determine magnesium column densities was applied to all available data from the years 1996-2001. Long term results show middle latitude dayside Mg + peaks in vertical content during the summer, while neutral Mg demonstrates a much more subtle maximum in summer. Atmospheric metal concentrations do not correlate strongly solar activity. An analysis of spatial variations shows geospatial distributions are patchy, with local regions of increased column density. To study short term variations and the role of meteor showers a time dependent mass flux rate is calculated using published estimates of meteor stream mass densities and activity profiles. An average daily mass flux rate is also calculated and used as a baseline against which shower mass flux rates are compared. These theoretical mass flux rates are then compared with GOME derived metal column densities. There appears to be little correlation between modeled meteor shower mass flux rates and changes in the observed neutral magnesium and Mg + metal column densities.

Temperature as a third dimension in column-density mapping of dusty astrophysical structures associated with star formation

NASA Astrophysics Data System (ADS)

Marsh, K. A.; Whitworth, A. P.; Lomax, O.

2015-12-01

We present point process mapping (PPMAP), a Bayesian procedure that uses images of dust continuum emission at multiple wavelengths to produce resolution-enhanced image cubes of differential column density as a function of dust temperature and position. PPMAP is based on the generic `point process formalism, whereby the system of interest (in this case, a dusty astrophysical structure such as a filament or pre-stellar core) is represented by a collection of points in a suitably defined state space. It can be applied to a variety of observational data, such as Herschel images, provided only that the image intensity is delivered by optically thin dust in thermal equilibrium. PPMAP takes full account of the instrumental point-spread functions and does not require all images to be degraded to the same resolution. We present the results of testing using simulated data for a pre-stellar core and a fractal turbulent cloud, and demonstrate its performance with real data from the Herschel infrared Galactic Plane Survey (Hi-GAL). Specifically, we analyse observations of a large filamentary structure in the CMa OB1 giant molecular cloud. Histograms of differential column density indicate that the warm material (T ≳ 13 K) is distributed lognormally, consistent with turbulence, but the column densities of the cooler material are distributed as a high-density tail, consistent with the effects of self-gravity. The results illustrate the potential of PPMAP to aid in distinguishing between different physical components along the line of sight in star-forming clouds, and aid the interpretation of the associated Probability distribution functions (PDFs) of column density.

Coupled Leidenfrost states as a monodisperse granular clock

NASA Astrophysics Data System (ADS)

Liu, Rui; Yang, Mingcheng; Chen, Ke; Hou, Meiying; To, Kiwing

2016-08-01

Using an event-driven molecular dynamics simulation, we show that simple monodisperse granular beads confined in coupled columns may oscillate as a different type of granular clock. To trigger this oscillation, the system needs to be driven against gravity into a density-inverted state, with a high-density clustering phase supported from below by a gaslike low-density phase (Leidenfrost effect) in each column. Our analysis reveals that the density-inverted structure and the relaxation dynamics between the phases can amplify any small asymmetry between the columns, and lead to a giant oscillation. The oscillation occurs only for an intermediate range of the coupling strength, and the corresponding phase diagram can be universally described with a characteristic height of the density-inverted structure. A minimal two-phase model is proposed and a linear stability analysis shows that the triggering mechanism of the oscillation can be explained as a switchable two-parameter Andronov-Hopf bifurcation. Numerical solutions of the model also reproduce similar oscillatory dynamics to the simulation results.

Satellite Investigation of Atmospheric Metal Deposition During Meteor Showers

NASA Astrophysics Data System (ADS)

Correira, J.; Aikin, A. C.; Grebowsky, J. M.

2008-12-01

Using the nadir-viewing Global Ozone Measuring Experiment (GOME) UV/VIS spectrometer on the ERS-2 satellite, we investigate short term variations in the magnesium column densities and any connection to possible enhanced mass deposition during a meteor shower. We derive a time dependent mass flux rate due to meteor showers using published estimates of mass density and activity profiles of meteor showers. An average daily mass flux rate is also calculated and used as a baseline against which calculated shower mass flux rates are compared. These theoretical mass flux rates are then compared with GOME derived metal column densities from the years 1996 - 2001.There appears to be little correlation between theoretical mass flux rates and changes in the Mg and Mg+ metal column densities. A possible explanation for the lack of a shower related increase in metal concentrations may be differences in the mass regimes dominating the average background mass flux and shower mass flux.

Effects of Coulomb collisions on cyclotron maser and plasma wave growth in magnetic loops

NASA Technical Reports Server (NTRS)

Hamilton, Russell J.; Petrosian, Vahe

1990-01-01

The evolution of nonthermal electrons accelerated in magnetic loops is determined by solving the kinetic equation, including magnetic field convergence and Coulomb collisions in order to determine the effects of these interactions on the induced cyclotron maser and plasma wave growth. It is found that the growth rates are larger and the possibility of cyclotron maser action is stronger for smaller loop column density, for larger magnetic field convergence, for a more isotropic injected electron pitch angle distribution, and for more impulsive acceleration. For modest values of the column density in the coronal portion of a flaring loop, the growth rates of instabilities are significantly reduced, and the reduction is much larger for the cyclotron modes than for the plasma wave modes. The rapid decrease in the growth rates with increasing loop column density suggests that, in flare loops when such phenomena occur, the densities are lower than commonly accepted.

Long-term study of longitudinal dependence in primary particle precipitation in the north Jovian aurora

NASA Technical Reports Server (NTRS)

Livengood, T. A.; Strobel, D. F.; Moos, H. W.

1990-01-01

The wavelength-dependent absorption apparent in IUE spectra of the north Jovian aurora is analyzed to determine the column density of hydrocarbons above the altitude of the FUV auroral emission. Both the magnetotail and torus auroral zone models are considered in estimating zenith angles, with very similar results obtained for both models. It is found that the hydrocarbon column density above the FUV emission displays a consistent dependence on magnetic longitude, with the peak density occurring approximately coincident with the peak in the observed auroral intensity. Two distinct scenarios for the longitude dependence of the column density are discussed. In one, the Jovian upper atmosphere is longitudinally homogeneous, and the variation in optical depth is due to a variation in penetration, and thus energy, of the primary particles. In the other, the energy of the primaries is longitudinally homogeneous, and it is aeronomic properties which change, probably due to auroral heating.

Sickle Cell Disease: New Opportunities and Challenges in Africa

PubMed Central

Makani, J.; Ofori-Acquah, S. F.; Nnodu, O.; Wonkam, A.; Ohene-Frempong, K.

2013-01-01

Sickle cell disease (SCD) is one of the most common genetic causes of illness and death in the world. This is a review of SCD in Africa, which bears the highest burden of disease. The first section provides an introduction to the molecular basis of SCD and the pathophysiological mechanism of selected clinical events. The second section discusses the epidemiology of the disease (prevalence, morbidity, and mortality), at global level and within Africa. The third section discusses the laboratory diagnosis and management of SCD, emphasizing strategies that been have proven to be effective in areas with limited resources. Throughout the review, specific activities that require evidence to guide healthcare in Africa, as well as strategic areas for further research, will be highlighted. PMID:25143960

The Zone of Avoidance as an X-ray absorber - the role of the galactic foreground modelling Swift XRT spectra

NASA Astrophysics Data System (ADS)

Racz, I. I.; Bagoly, Z.; Tóth, L. V.; Balázs, L. G.; Horvath, I.; Zahorecz, S.

2018-05-01

Gamma-ray bursts (GRBs) are the most powerful explosive events in the Universe. The prompt gamma emission is followed by an X-ray afterglow that is also detected for over nine hundred GRBs by the Swift BAT and XRT detectors. The X-ray afterglow spectrum bears essential information about the burst, and the surrounding interstellar medium (ISM). Since the radiation travels through the line of sight intergalactic medium and the ISM in the Milky Way, the observed emission is influenced by extragalactic and galactic components. The column density of the Galactic foreground ranges several orders of magnitudes, due to both the large scale distribution of ISM and its small scale structures. We examined the effect of local HI column density on the penetrating X-ray emission, as the first step towards a precise modeling of the measured X-ray spectra. We fitted the X-ray spectra using the Xspec software, and checked how the shape of the initially power low spectrum changes with varying input Galactic HI column density. The total absorbing HI column is a sum of the intrinsic and Galactic component. We also investigated the model results for the intrinsic component varying the Galactic foreground. We found that such variations may alter the intrinsic hydrogen column density up to twenty-five percent. We will briefly discuss its consequences.

Physical conditions in CaFe interstellar clouds

NASA Astrophysics Data System (ADS)

Gnaciński, P.; Krogulec, M.

2008-01-01

Interstellar clouds that exhibit strong Ca I and Fe I lines are called CaFe clouds. Ionisation equilibrium equations were used to model the column densities of Ca II, Ca I, K I, Na I, Fe I and Ti II in CaFe clouds. We find that the chemical composition of CaFe clouds is solar and that there is no depletion into dust grains. CaFe clouds have high electron densities, n_e≈1 cm-3, that lead to high column densities of neutral Ca and Fe.

Surface Current Density Mapping for Identification of Gastric Slow Wave Propagation

PubMed Central

Bradshaw, L. A.; Cheng, L. K.; Richards, W. O.; Pullan, A. J.

2009-01-01

The magnetogastrogram records clinically relevant parameters of the electrical slow wave of the stomach noninvasively. Besides slow wave frequency, gastric slow wave propagation velocity is a potentially useful clinical indicator of the state of health of gastric tissue, but it is a difficult parameter to determine from noninvasive bioelectric or biomagnetic measurements. We present a method for computing the surface current density (SCD) from multichannel magnetogastrogram recordings that allows computation of the propagation velocity of the gastric slow wave. A moving dipole source model with hypothetical as well as realistic biomagnetometer parameters demonstrates that while a relatively sparse array of magnetometer sensors is sufficient to compute a single average propagation velocity, more detailed information about spatial variations in propagation velocity requires higher density magnetometer arrays. Finally, the method is validated with simultaneous MGG and serosal EMG measurements in a porcine subject. PMID:19403355

The efficacy of the new SCD response compression system in the prevention of venous stasis.

PubMed

Kakkos, S K; Szendro, G; Griffin, M; Daskalopoulou, S S; Nicolaides, A N

2000-11-01

The current commercially available sequential intermittent pneumatic compression device used for the prevention of deep venous thrombosis has a constant cycle of 11 seconds' compression and 60 seconds' deflation. This deflation period ensures that the veins are filled before the subsequent cycle begins. It has been suggested that in some positions (eg, semirecumbent or sitting) and with different patients (eg, those with venous reflux), refilling of the veins may occur much earlier than 60 seconds, and thus a more frequent cycle may be more effective in expelling blood proximally. The aim of the study was to test the effectiveness of a new sequential compression system (the SCD Response Compression System), which has the ability to detect the change in the venous volume and to respond by initiating the subsequent cycle when the veins are substantially full. In an open controlled trial at an academic vascular laboratory, the SCD Response Compression System was tested against the existing SCD Sequel Compression System in 12 healthy volunteers who were in supine, semirecumbent, and sitting positions. The refilling time sensed by the device was compared with that determined from recordings of femoral vein flow velocity by the use of duplex ultrasound scan. The total volume of blood expelled per hour during compression was compared with that produced by the existing SCD system in the same volunteers and positions. The refilling time determined automatically by the SCD Response Compression System varied from 24 to 60 seconds in the subjects tested, demonstrating individual patient variation. The refilling time (mean +/- SD) in the sitting position was 40.6 +/- 10. 0 seconds, which was significantly longer (P <.001) than that measured in the supine and semirecumbent positions, 33.8 +/- 4.1 and 35.6 +/- 4.9 seconds, respectively. There was a linear relationship between the duplex scan-derived refill time (mean of 6 readings per leg) and the SCD Response device-derived refill time (r = 0.85, P <. 001). The total volume of blood (mean +/- SD) expelled per hour by the existing SCD Sequel device in the supine, semirecumbent, and sitting positions was 2.23 +/- 0.90 L/h, 2.47 +/- 0.86 L/h, and 3.28 +/- 1.24 L/h, respectively. The SCD Response device increased the volume expelled to 3.92 +/- 1.60 L/h or a 76% increase (P =.001) in the supine position, to 3.93 +/- 1.55 L/h or a 59% increase (P =. 001) in the semirecumbent position, and to 3.97 +/- 1.42 L/h or a 21% increase (P =.026) in the sitting position. By achieving more appropriately timed compression cycles over time, the new SCD Response System is effective in preventing venous stasis by means of a new method that improves on the clinically documented effectiveness of the existing SCD system. Further studies testing its potential for improved efficacy in preventing deep venous thrombosis are justified.

Levels of soluble CD30 in cord blood and peripheral blood during childhood are not correlated with the development of atopic disease or a family history of atopy.

PubMed

Holmlund, U; Bengtsson, A; Nilsson, C; Kusoffsky, E; Lilja, G; Scheynius, A; Sverremark-Ekström, E

2003-11-01

The CD30 molecule has been linked to Th2 responses. Furthermore, elevated levels of the soluble form of CD30 (sCD30) in blood as well as of the expression of CD30 on the plasma membrane of T cells are associated with atopic disease. To assess the potential usefulness of sCD30 levels as a prognostic indicator of and/or diagnostic marker for the development of atopic disease in children. sCD30 levels in cord blood and peripheral blood from 36 2-year-old (10 atopic and 26 non-atopic) and 74 7-year-old (35 atopic and 39 non-atopic) children were determined employing an ELISA procedure. Atopy was diagnosed on the basis of clinical evaluation in combination with a positive skin prick test. No significant correlation between sCD30 levels in cord blood and the development of atopic disease at 2 or 7 years of age was observed. At 7 years of age, the circulating sCD30 levels in children with atopic disease (median 41 U/mL, range 6-503 U/mL) did not differ from the corresponding values for non-atopic subjects (median 41 U/mL, range 8-402 U/mL). The same was true for children at 2 years of age. Furthermore, the sCD30 levels of children who had developed atopic eczema/dermatitis syndrome by the age of 7 years (median 49 U/mL, range 14-503 U/mL) were not significantly elevated in comparison with those of the non-atopic children. Finally, neither sCD30 levels in cord blood nor peripheral blood at 2 or 7 years of age could be linked to a family history of atopy. These findings indicate that the sCD30 concentration in cord blood is not a reliable prognostic indicator of, nor a useful diagnostic marker for, atopic disease in children up to 7 years of age. If such correlations do exist, they might be masked by age-dependent variations in the circulating levels of sCD30, which may reflect individual differences in the maturation of children's immunological responses.

A validation study of the 2003 American College of Cardiology/European Society of Cardiology and 2011 American College of Cardiology Foundation/American Heart Association risk stratification and treatment algorithms for sudden cardiac death in patients with hypertrophic cardiomyopathy.

PubMed

O'Mahony, Constantinos; Tome-Esteban, Maite; Lambiase, Pier D; Pantazis, Antonios; Dickie, Shaughan; McKenna, William J; Elliott, Perry M

2013-04-01

Sudden cardiac death (SCD) is a common mode of death in hypertrophic cardiomyopathy (HCM), but identification of patients who are at a high risk of SCD is challenging as current risk stratification guidelines have never been formally validated. The objective of this study was to assess the power of the 2003 American College of Cardiology (ACC)/European Society of Cardiology (ESC) and 2011 ACC Foundation (ACCF)/American Heart Association (AHA) SCD risk stratification algorithms to distinguish high risk patients who might be eligible for an implantable cardioverter defibrillator (ICD) from low risk individuals. We studied 1606 consecutively evaluated HCM patients in an observational, retrospective cohort study. Five risk factors (RF) for SCD were assessed: non-sustained ventricular tachycardia, severe left ventricular hypertrophy, family history of SCD, unexplained syncope and abnormal blood pressure response to exercise. During a follow-up period of 11 712 patient years (median 6.6 years), SCD/appropriate ICD shock occurred in 20 (3%) of 660 patients without RF (annual rate 0.45%), 31 (4.8%) of 636 patients with 1 RF (annual rate 0.65%), 27 (10.8%) of 249 patients with 2 RF (annual rate 1.3%), 7 (13.7%) of 51 patients with 3 RF (annual rate 1.9%) and 4 (40%) of 10 patients with ≥4 RF (annual rate 5.0%). The risk of SCD increased with multiple RF (2 RF: HR 2.87, p≤0.001; 3 RF: HR 4.32, p=0.001; ≥4 RF: HR 11.37, p<0.0001), but not with a single RF (HR 1.43 p=0.21). The area under time-dependent receiver operating characteristic curves (representing the probability of correctly identifying a patient at risk of SCD on the basis of RF profile) was 0.63 at 1 year and 0.64 at 5 years for the 2003 ACC/ESC algorithm and 0.61 at 1 year and 0.63 at 5 years for the 2011 ACCF/AHA algorithm. The risk of SCD increases with the aggregation of RF. The 2003 ACC/ESC and 2011 ACCF/AHA guidelines distinguish high from low risk individuals with limited power.

The dependence of gamma-ray burst X-ray column densities on the model for Galactic hydrogen

NASA Astrophysics Data System (ADS)

Arcodia, R.; Campana, S.; Salvaterra, R.

2016-05-01

We study the X-ray absorption of a complete sample of 99 bright Swift gamma-ray bursts (GRBs). In recent years, a strong correlation has been found between the intrinsic X-ray absorbing column density (NH(z)) and the redshift. This absorption excess in high-z GRBs is now thought to be due to the overlooked contribution of the absorption along the intergalactic medium (IGM), by means of both intervening objects and the diffuse warm-hot intergalactic medium along the line of sight. In this work we neglect the absorption along the IGM, because our purpose is to study the eventual effect of a radical change in the Galactic absorption model on the NH(z) distribution. Therefore, we derive the intrinsic absorbing column densities using two different Galactic absorption models: the Leiden Argentine Bonn HI survey and the more recent model that includes molecular hydrogen. We find that if, on the one hand, the new Galactic model considerably affects the single column density values, on the other hand, there is no drastic change in the distribution as a whole. It becomes clear that the contribution of Galactic column densities alone, no matter how improved, is not sufficient to change the observed general trend and it has to be considered as a second order correction. The cosmological increase of NH(z) as a function of redshift persists and, to explain the observed distribution, it is necessary to include the contribution of both the diffuse intergalactic medium and the intervening systems along the line of sight of the GRBs.

Global distribution of the He+ column density observed by Extreme Ultra Violet Imager on the International Space Station

NASA Astrophysics Data System (ADS)

Hozumi, Yuta; Saito, Akinori; Yoshikawa, Ichiro; Yamazaki, Atsushi; Murakami, Go; Yoshioka, Kazuo; Chen, Chia-Hung

2017-07-01

The global distribution of He+ in the topside ionosphere was investigated using data of the He+ resonant scattering emission at 30.4 nm obtained by the Extreme Ultra Violet Imager (EUVI) onboard the International Space Station. The optical observation by EUVI from the low-Earth orbit provides He+ column density data above the altitude of 400 km, presenting a unique opportunity to study the He+ distribution with a different perspective from that of past studies using data from in situ measurements. We analyzed data taken in 2013 and elucidated, for the first time, the seasonal, longitudinal, and latitudinal variations of the He+ column density in the dusk sector. It was found that the He+ column density in the winter hemisphere was about twice that in the summer hemisphere. In the December solstice season, the magnitude of this hemispheric asymmetry was large (small) in the longitudinal sector where the geomagnetic declination is eastward (westward). In the June solstice season, this relationship between the He+ distribution and the geomagnetic declination is reversed. In the equinox seasons, the He+ column densities in the two hemispheres are comparable at most longitudes. The seasonal and longitudinal dependence of the hemispheric asymmetry of the He+ distribution was attributed to the geomagnetic meridional neutral wind in the F region ionosphere. The neutral wind effect on the He+ distribution was examined with an empirical neutral wind model, and it was confirmed that the transport of ions in the topside ionosphere is predominantly affected by the F region neutral wind and the geomagnetic configuration.

Stochastic Accumulation by Cortical Columns May Explain the Scalar Property of Multistable Perception

NASA Astrophysics Data System (ADS)

Cao, Robin; Braun, Jochen; Mattia, Maurizio

2014-08-01

The timing of certain mental events is thought to reflect random walks performed by underlying neural dynamics. One class of such events—stochastic reversals of multistable perceptions—exhibits a unique scalar property: even though timing densities vary widely, higher moments stay in particular proportions to the mean. We show that stochastic accumulation of activity in a finite number of idealized cortical columns—realizing a generalized Ehrenfest urn model—may explain these observations. Modeling stochastic reversals as the first-passage time of a threshold number of active columns, we obtain higher moments of the first-passage time density. We derive analytical expressions for noninteracting columns and generalize the results to interacting columns in simulations. The scalar property of multistable perception is reproduced by a dynamic regime with a fixed, low threshold, in which the activation of a few additional columns suffices for a reversal.

Envelope conformational changes induced by human immunodeficiency virus type 1 attachment inhibitors prevent CD4 binding and downstream entry events.

PubMed

Ho, Hsu-Tso; Fan, Li; Nowicka-Sans, Beata; McAuliffe, Brian; Li, Chang-Ben; Yamanaka, Gregory; Zhou, Nannan; Fang, Hua; Dicker, Ira; Dalterio, Richard; Gong, Yi-Fei; Wang, Tao; Yin, Zhiwei; Ueda, Yasutsugu; Matiskella, John; Kadow, John; Clapham, Paul; Robinson, James; Colonno, Richard; Lin, Pin-Fang

2006-04-01

BMS-488043 is a small-molecule human immunodeficiency virus type 1 (HIV-1) CD4 attachment inhibitor with demonstrated clinical efficacy. The compound inhibits soluble CD4 (sCD4) binding to the 11 distinct HIV envelope gp120 proteins surveyed. Binding of BMS-488043 and that of sCD4 to gp120 are mutually exclusive, since increased concentrations of one can completely block the binding of the other without affecting the maximal gp120 binding capacity. Similarly, BMS-488043 inhibited virion envelope trimers from binding to sCD4-immunoglobulin G (IgG), with decreasing inhibition as the sCD4-IgG concentration increased, and BMS-488043 blocked the sCD4-induced exposure of the gp41 groove in virions. In both virion binding assays, BMS-488043 was active only when added prior to sCD4. Collectively, these results indicate that obstruction of gp120-sCD4 interactions is the primary inhibition mechanism of this compound and that compound interaction with envelope must precede CD4 binding. By three independent approaches, BMS-488043 was further shown to induce conformational changes within gp120 in both the CD4 and CCR5 binding regions. These changes likely prevent gp120-CD4 interactions and downstream entry events. However, BMS-488043 could only partially inhibit CD4 binding to an HIV variant containing a specific envelope truncation and altered gp120 conformation, despite effectively inhibiting the pseudotyped virus infection. Taken together, BMS-488043 inhibits viral entry primarily through altering the envelope conformation and preventing CD4 binding, and other downstream entry events could also be inhibited as a result of these induced conformational changes.

Newborn Screening for Sickle Cell Disease in Liberia: A Pilot Study.

PubMed

Tubman, Venée N; Marshall, Roseda; Jallah, Wilhemina; Guo, Dongjing; Ma, Clement; Ohene-Frempong, Kwaku; London, Wendy B; Heeney, Matthew M

2016-04-01

In malaria-endemic countries in West Africa, sickle cell disease (SCD) contributes to childhood mortality. Historically, Liberia had regions wherein hemoglobin S and beta-thalassemia trait were mutually exclusive. Data on hemoglobinopathies in the Monrovia, the capital, are outdated and do not reflect urban migration. Updating the epidemiology of SCD is necessary to plan a public health and clinical agenda. Neither newborn screening (NBS) nor screening tools were available in country. This pilot study aimed to determine the feasibility of NBS using a South-South partnership and define the incidence of sickle cell trait (SCT) and SCD in Monrovia. This descriptive epidemiologic feasibility study collected dried blood spots from 2,785 consecutive newborns delivered at a hospital in Monrovia. Samples were analyzed by isoelectric focusing at a regional reference laboratory. Infants with SCD were referred for preventive care. SCT occurred in 10.31% of infants screened. SCD occurred in 33 infants screened [1.19% (95% confidence interval [CI]: 0.79-1.59%)] (FS: 28/33, FSB: 2/33, FSA: 2/33, FSX: 1/33). There were no infants with FSC phenotype observed. Nonsickling hemoglobin phenotypes "FC" and "F" were each present in three infants screened. Seventy-six percent of infants with SCD were brought to care, demonstrating the feasibility of our approach. The incidence of SCD and other hemoglobinopathies remains high in Liberia. Additional studies are needed to clarify sickle genotypes and identify the contribution of silent beta-thalassemia alleles. By developing regional partnerships, countries similar to Liberia can acquire current data to inform NBS as an important public health initiative toward improving child health. © 2016 Wiley Periodicals, Inc.

Newborn Screening for Sickle Cell Disease in Liberia: A Pilot Study

PubMed Central

Tubman, Venée N; Marshall, Roseda; Jallah, Wilhemina; Guo, Dongjing; Ma, Clement; Ohene-Frempong, Kwaku; London, Wendy B; Heeney, Matthew M

2015-01-01

Background In malaria-endemic countries in West Africa, sickle cell disease (SCD) contributes to childhood mortality. Historically, Liberia had regions wherein hemoglobin S and beta-thalassemia trait were mutually exclusive. Data on hemoglobinopathies in the Monrovia, the capital, are outdated and do not reflect urban migration. Updating the epidemiology of SCD is necessary to plan a public health and clinical agenda. Neither newborn screening (NBS) nor screening tools were available in-country. This pilot study aimed to determine the feasibility of NBS using a South-South partnership and define the incidence of sickle cell trait (SCT) and SCD in Monrovia. Procedure This descriptive epidemiologic feasibility study collected dried blood spots from 2785 consecutive newborns delivered at a hospital in Monrovia. Samples were analyzed by isoelectric focusing at a regional reference laboratory. Infants with SCD were referred for preventive care. Results SCT occurred in 10.31% of infants screened. SCD occurred in 33 infants screened [1.19% (95% CI: 0.79%–1.59%)](FS: 28/33, FSB: 2/33, FSA: 2/33, FSX 1/33). There were no infants with FSC phenotype observed. Non-sickling hemoglobin phenotypes ‘FC’ and ‘F’ were each present in 3 infants screened. Seventy-six percent of infants with SCD were brought to care, demonstrating the feasibility of our approach. Conclusions The incidence of SCD and other hemoglobinopathies remain high in Liberia. Additional studies are needed to clarify sickle genotypes and identify the contribution of silent beta-thalassemia alleles. By developing regional partnerships, countries similar to Liberia can acquire current data to inform NBS as an important public health initiative toward improving child health. PMID:26739520

Intellectual function evaluation of first generation immigrant children with sickle cell disease: the role of language and sociodemographic factors.

PubMed

Montanaro, Maria; Colombatti, Raffaella; Pugliese, Marisa; Migliozzi, Camilla; Zani, Fabiana; Guerzoni, Maria Elena; Manoli, Sheila; Manara, Renzo; Meneghetti, Giorgio; Rampazzo, Patrizia; Cavalleri, Francesca; Giordan, Marco; Paolucci, Paolo; Basso, Giuseppe; Palazzi, Giovanni; Sainati, Laura

2013-06-04

Sickle Cell Disease (SCD) is the most common genetic disease worldwide. Neurological events are among the most worrisome clinical complications of SCD and are frequently accompanied by cognitive impairment. Intellectual function in SCD may vary according to genetic and environmental factors. Immigrant children with SCD are increasing at a global level and display specific health care needs. The aim of our multicenter study was to describe the intellectual function of first generation African immigrants with SCD and the influence of sociodemographic factors on its characteristics. The Wechsler Intelligence Scales were administered to evaluate broad intellectual functions in children with SCD and in age-matched healthy siblings. Patients' clinical, socio-demographic, Magnetic Resonance Imaging (MRI) and Angiography (MRA) data were correlated to intellectual function scores. 68 children, mean age 8.95 years were evaluated. 72% spoke three languages, 21% two. FSIQ was <75 in 25% of the children. Mean VIQ was lower than PIQ in 75%. Mean verbal subtest scores were lower than performance scores. Female gender, number of languages spoken at home and mother's employment were associated with single subtest performances (p < 0.05). MRA was abnormal in 73.4% and MRI in 35.9%. No significant correlation was established between silent lesions and intellectual function, even if patients with lesions performed worse. Fifteen siblings performed better than patients on cognitive domains, including language (p < 0.05). Immigrant bilingual children with SCD seem to display a rate of cognitive impairment similar to their monolingual counterparts but a more pronounced and precocious onset of language difficulties. Adjunctive tests need to be considered in this group of patients to better define their specific deficits.

Relation between glutathione S-transferase genes (GSTM1, GSTT1, and GSTP1) polymorphisms and clinical manifestations of sickle cell disease in Egyptian patients.

PubMed

Ellithy, Hend N; Yousri, Sherif; Shahin, Gehan H

2015-12-01

Clinical manifestations of sickle cell disease (SCD) result from sickling of Hb S due to oxidation, which is augmented by accumulation of oxygen-free radicals. Deficiencies in normal antioxidant protective mechanism might lead to clinical manifestations of SCD like vaso-occlusive crisis (VOC) and acute chest syndrome (ACS). The glutathione system plays an important role in the removal of endogenous products of peroxidation of lipids, thus protecting cells and tissue against damage from oxidative stress. Impairment of the glutathione system due to genetic polymorphisms of glutathione S-transferase (GST) genes is expected to increase the severity of SCD manifestations. This report describes a case control study aimed at studying the ethnic-dependent variation in the frequency of GST gene polymorphisms among participants selected from the Egyptian population and to find out the association between GST gene polymorphisms and the severity of SCD manifestations. We measured the frequency distribution of the three GSTs gene polymorphisms in 100 Egyptian adult SCD patients and 80 corresponding controls. GSTM1 and GSTT1 genotypes were determined by multiplex polymerase chain reaction (PCR). GSTP1 genotyping was conducted with a PCR-restriction fragment length polymorphism assay. The GSTM1 null genotype was significantly associated with ACS and VOC (P = 0.03 and 0.01, respectively). The GSTT1 null genotype was associated with significantly increased requirement of blood transfusion (P = 0.01). Absence of both GSTM1 and GSTT1 genes was significantly associated with pulmonary hypertension (P = 0.04). The non-wild-type GSTP1 polymorphism was not associated with clinical manifestations of SCD. Some GST gene polymorphisms were significantly associated with the worsening of the clinical manifestations of SCD.

‘All her children are born that way’: gendered experiences of stigma in families affected by sickle cell disorder in rural Kenya

PubMed Central

Marsh, Vicki M.; Kamuya, Dorcas M.; Molyneux, Sassy S.

2011-01-01

Objectives. To explore early experiences of sickle cell disorder (SCD) in families with a young affected child, and the way these experiences influence relations within families. To consider ways in which stigma could be counteracted in health and research programmes in sub Saharan Africa. Design. A qualitative study was conducted in a rural area of coastal Kenya including in-depth interviews with 13 families affected by SCD and 12 staff of a local biomedical research progamme. Purposive selection aimed to maximize diversity in socioeconomic and educational status, religion, severity of illness burden and religion amongst families and draw on relevant experience for staffs. Interviews were recorded, transcribed and analysed using the constant comparative method for family interviews and a thematic framework approach for staff data. Results. Low initial recognition of SCD and its cause were associated with lay practices of surveillance within affected families, contributing to stigmatisation that occurred independently of genetic knowledge. Blame was often placed on mothers, including a risk of blame for misaligned paternity. Mothers are often particularly affected by SCD through the loss of independent livelihoods and their limited options in coping with this chronic condition. Conclusions. Mothers of children with SCD were particularly vulnerable to stigmatisation within families, with underlying structural influences that suggest these findings may apply to other similar settings in Africa, and have relevance for other genetic conditions. The potential, nature and form of stigmatisation point to the role of effective communication and SCD management in addressing for blame and discriminative effects of having a child with SCD. The findings highlight the importance of broader social programmes targeting underlying gender and economic inequalities. PMID:21797722

Trends in sudden cardiac death and its risk factors in Japan from 1981 to 2005: the Circulatory Risk in Communities Study (CIRCS)

PubMed Central

Maruyama, Minako; Ohira, Tetsuya; Imano, Hironori; Kitamura, Akihiko; Kiyama, Masahiko; Okada, Takeo; Maeda, Kenji; Yamagishi, Kazumasa; Noda, Hiroyuki; Ishikawa, Yoshinori; Shimamoto, Takashi

2012-01-01

Objective There is little evidence whether sudden cardiac death (SCD) is increasing in Asia, although the incidence of coronary heart disease among urban middle-aged Japanese men has increased recently. We examined trends in the incidence of SCD and its risk factors in the Circulatory Risk in Communities Study. Design and setting This was a population-based longitudinal study. Surveillance of men and women for SCD incidence and risk factors was conducted from 1981 to 2005. Subjects The surveyed population was all men and women aged 30–84 years who lived in three rural communities and one urban community in Japan. Main outcome measures Trends in SCD incidence and its risk factors. Results Age-adjusted and sex-adjusted incidence of SCD decreased from 1981–1985 to 1991–1995, and plateaued thereafter. The annual incidence per 100 000 person-years was 76.0 in 1981–1985, 57.9 in 1986–1990, 39.3 in 1991–1995, 31.6 in 1996–2000 and 36.8 in 2001–2005. The prevalence of hypertension decreased from 1981–1985 to 1991–1995, and plateaued thereafter for men and women. The age-adjusted prevalence of current smoking for men decreased while that of diabetes mellitus increased for both sexes from 1981–1985 to 2001–2005. Conclusions The incidence of SCD decreased from 1981 to 1995 but was unchanged from 1996 to 2005. Continuous surveillance is necessary to clarify future trends in SCD in Japan because of an increasing incidence of diabetes mellitus. PMID:22446988

Subjective Cognitive Decline in Older Adults: An Overview of Self-Report Measures Used Across 19 International Research Studies

PubMed Central

Rabin, Laura A.; Smart, Colette M.; Crane, Paul K.; Amariglio, Rebecca E.; Berman, Lorin M.; Boada, Mercè; Buckley, Rachel F.; Chételat, Gaël; Dubois, Bruno; Ellis, Kathryn A.; Gifford, Katherine A.; Jefferson, Angela L.; Jessen, Frank; Katz, Mindy J.; Lipton, Richard B.; Luck, Tobias; Maruff, Paul; Mielke, Michelle M.; Molinuevo, José Luis; Naeem, Farnia; Perrotin, Audrey; Petersen, Ronald C.; Rami, Lorena; Reisberg, Barry; Rentz, Dorene M.; Riedel-Heller, Steffi G.; Risacher, Shannon L.; Rodriguez, Octavio; Sachdev, Perminder S.; Saykin, Andrew J.; Slavin, Melissa J.; Snitz, Beth E.; Sperling, Reisa A.; Tandetnik, Caroline; van der Flier, Wiesje M.; Wagner, Michael; Wolfsgruber, Steffen; Sikkes, Sietske A.M.

2015-01-01

Research increasingly suggests that subjective cognitive decline (SCD) in older adults, in the absence of objective cognitive dysfunction or depression, may be a harbinger of non-normative cognitive decline and eventual progression to dementia. Little is known, however, about the key features of self-report measures currently used to assess SCD. The Subjective Cognitive Decline Initiative (SCD-I) Working Group is an international consortium established to develop a conceptual framework and research criteria for SCD (Jessen et al., 2014, Alzheimers Dement 10, 844–852). In the current study we systematically compared cognitive self-report items used by 19 SCD-I Working Group studies, representing 8 countries and 5 languages. We identified 34 self-report measures comprising 640 cognitive self-report items. There was little overlap among measures—approximately 75% of measures were used by only one study. Wide variation existed in response options and item content. Items pertaining to the memory domain predominated, accounting for about 60% of items surveyed, followed by executive function and attention, with 16% and 11% of the items, respectively. Items relating to memory for the names of people and the placement of common objects were represented on the greatest percentage of measures (56% each). Working group members reported that instrument selection decisions were often based on practical considerations beyond the study of SCD specifically, such as availability and brevity of measures. Results document the heterogeneity of approaches across studies to the emerging construct of SCD. We offer preliminary recommendations for instrument selection and future research directions including identifying items and measure formats associated with important clinical outcomes. PMID:26402085

Thirty-year experience in preventing haemoglobinopathies in Greece: achievements and potentials for optimisation.

PubMed

Ladis, Vassilis; Karagiorga-Lagana, Markissia; Tsatra, Ioanna; Chouliaras, Giorgos

2013-04-01

Beta thalassaemia major (β-TM) and sickle-cell disease (SCD) are severe haemogobinopathies requiring life-lasting, advanced medical management. In the Mediterranean region, both conditions occur with high frequency. We assessed the efficacy of the National Program for the Prevention of Haemoglobinopathies in Greece during the last 30 yrs. Data of affected births between 01/01/1980 and 31/12/2009 were collected in a nationwide scale, and expected vs. observed rates of new births were calculated and compared. In a subpopulation of affected births of Greek origin, the causes for occurrence of the new affected birth were also collected and analysed. Overall, the reduction in new cases was 81.1% and 84.6% for β-TM and SCD, respectively. For β-TM, a constant declining trend was recorded over the 30-yr period, whereas for SCD, a transient reversal was observed in the mid-1990s probably due to the significant influx of immigrants of African origin. Programme failure was 2.2 times more common among new β-TM births of Greek origin compared to new SCD cases (P < 0.001). Unawareness and parental choice were more frequent in SCD compared to β-TM (unawareness: OR = 1.4, P = 0.05, parental choice: OR = 1.9, P = 0.01). The main cause for programme failure was carrier misidentification and incorrect genetic advice for β-TM and SCD, respectively. The β-TM and SCD prevention programme in Greece has significantly reduced the numbers of new affected births. The outcomes could be optimised in groups of non-Greek origin, in carrier identification and by offering specialised genetic counselling. © 2013 John Wiley & Sons A/S.

Sudden cardiac death and pump failure death prediction in chronic heart failure by combining ECG and clinical markers in an integrated risk model

PubMed Central

Orini, Michele; Mincholé, Ana; Monasterio, Violeta; Cygankiewicz, Iwona; Bayés de Luna, Antonio; Martínez, Juan Pablo

2017-01-01

Background Sudden cardiac death (SCD) and pump failure death (PFD) are common endpoints in chronic heart failure (CHF) patients, but prevention strategies are different. Currently used tools to specifically predict these endpoints are limited. We developed risk models to specifically assess SCD and PFD risk in CHF by combining ECG markers and clinical variables. Methods The relation of clinical and ECG markers with SCD and PFD risk was assessed in 597 patients enrolled in the MUSIC (MUerte Súbita en Insuficiencia Cardiaca) study. ECG indices included: turbulence slope (TS), reflecting autonomic dysfunction; T-wave alternans (TWA), reflecting ventricular repolarization instability; and T-peak-to-end restitution (ΔαTpe) and T-wave morphology restitution (TMR), both reflecting changes in dispersion of repolarization due to heart rate changes. Standard clinical indices were also included. Results The indices with the greatest SCD prognostic impact were gender, New York Heart Association (NYHA) class, left ventricular ejection fraction, TWA, ΔαTpe and TMR. For PFD, the indices were diabetes, NYHA class, ΔαTpe and TS. Using a model with only clinical variables, the hazard ratios (HRs) for SCD and PFD for patients in the high-risk group (fifth quintile of risk score) with respect to patients in the low-risk group (first and second quintiles of risk score) were both greater than 4. HRs for SCD and PFD increased to 9 and 11 when using a model including only ECG markers, and to 14 and 13, when combining clinical and ECG markers. Conclusion The inclusion of ECG markers capturing complementary pro-arrhythmic and pump failure mechanisms into risk models based only on standard clinical variables substantially improves prediction of SCD and PFD in CHF patients. PMID:29020031

Clinical impact of factor V Leiden, prothrombin G20210A, and MTHFR C677T mutations among sickle cell disease patients of Central India.

PubMed

Nishank, Sudhansu Sekhar; Singh, Mendi Prema Shyam Sunder; Yadav, Rajiv

2013-11-01

It is known that patients with sickle cell disease (SCD) present activation of the blood coagulation and fibrinolytic systems, especially during vaso-occlusive crises and also during the steady state of the disease. We determined whether the presence of the factor prothrombin gene G20210A variant, factor V gene G1691A mutation (factor V Leiden), and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphisms may be risk factors for vascular complications in individuals with SCD. The study involved 150 patients with sickle cell anemia and 150 healthy controls of Central India. Genotyping of three thrombophilic mutations was carried out by PCR-RFLP methods using MnlI, Hind III, and Hinf I, respectively, for factor V Leiden, prothrombin, and MTHFR mutations. Patients with SCD had significantly higher prevalence of mutant variants of MTHFR gene (28.0% heterozygotes and 14.6% homozygotes) and FVL gene (14.6% heterozygotes) as compared to normal/control individuals, but complete absence of mutant variants of prothrombin gene. The patients with SCD having mutant variants of MTHFR and FVL genes showed higher incidence of pain in chest, abdomen, and bone joints along with early age of onset of clinical manifestations as well as frequent dependence on blood transfusion than those patients with SCD having wild variants of these thrombotic genes. As compared to control subjects, SCD individuals having mutant variants of FVL and MTHFR genes had significant association with higher levels of prothrombin fragment (F1+2), D-dimer, thrombin-antithrombin (TAT), and lower level of protein C. MTHFR C677T and FVL G1691A polymorphisms may be risk factors for increased vascular complications in patient with SCD. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Are Patients with Spontaneous CSF Otorrhea and Superior Canal Dehiscence Congenitally Predisposed to Their Disorders?

PubMed

Stevens, Shawn M; Hock, Kiefer; Samy, Ravi N; Pensak, Myles L

2018-04-01

Objectives (1) Compare lateral skull base (LSB) height/thickness in patients with spontaneous cerebrospinal fluid otorrhea (CSF), superior canal dehiscence (SCD), acoustic neuromas (AN), and otosclerosis (OTO). (2) Perform correlations between age, body mass index (BMI), sex, and LSB height/thickness. Study Design Case series with chart review. Setting Tertiary referral center. Subjects and Methods Patients with CSF, SCD, AN, and OTO diagnosed from 2006 to 2016 were included if they had high-definition temporal bone computed tomography (CT) and absence of trauma, radiation, chronic ear disease, and/or congenital anomaly. CT-based measurements included LSB height/thickness and pneumatization rates overlaying the external auditory canal (EAC), tegmen tympani (TgT), perigeniculate region (PG), and internal auditory canal (IAC). LSB height/thickness, age, sex, and BMI were statistically correlated. In total, 256 patients and 493 ears (109 CSF, 115 SCD, 269 AN/OTO) were measured. Results Patients with CSF had significantly higher BMIs than the other groups ( P < .001). Patients with CSF and SCD had similar radiographic LSB phenotypes at most measured locations. Both groups exhibited a significantly lower LSB height compared to the AN and OTO groups (mean, 3.9-4.2 mm vs 4.9-5.6 mm; P < .001). Patients with CSF and SCD also demonstrated significantly lower pneumatization rates, as low as 17% to 23% overlaying the PG and IAC ( P < .001). There were no statistically significant correlations found between age, sex, BMI, and LSB height/thickness at any measurement location in any group. Conclusions Patients with CSF and SCD exhibit similar radiographic LSB phenotypes. Age, sex, and BMI do not significantly correlate with LSB height/thickness. These data support the theory that CSF and SCD arise via similar congenital pathoetiologic mechanisms.

Sudden cardiac death and pump failure death prediction in chronic heart failure by combining ECG and clinical markers in an integrated risk model.

PubMed

Ramírez, Julia; Orini, Michele; Mincholé, Ana; Monasterio, Violeta; Cygankiewicz, Iwona; Bayés de Luna, Antonio; Martínez, Juan Pablo; Laguna, Pablo; Pueyo, Esther

2017-01-01

Sudden cardiac death (SCD) and pump failure death (PFD) are common endpoints in chronic heart failure (CHF) patients, but prevention strategies are different. Currently used tools to specifically predict these endpoints are limited. We developed risk models to specifically assess SCD and PFD risk in CHF by combining ECG markers and clinical variables. The relation of clinical and ECG markers with SCD and PFD risk was assessed in 597 patients enrolled in the MUSIC (MUerte Súbita en Insuficiencia Cardiaca) study. ECG indices included: turbulence slope (TS), reflecting autonomic dysfunction; T-wave alternans (TWA), reflecting ventricular repolarization instability; and T-peak-to-end restitution (ΔαTpe) and T-wave morphology restitution (TMR), both reflecting changes in dispersion of repolarization due to heart rate changes. Standard clinical indices were also included. The indices with the greatest SCD prognostic impact were gender, New York Heart Association (NYHA) class, left ventricular ejection fraction, TWA, ΔαTpe and TMR. For PFD, the indices were diabetes, NYHA class, ΔαTpe and TS. Using a model with only clinical variables, the hazard ratios (HRs) for SCD and PFD for patients in the high-risk group (fifth quintile of risk score) with respect to patients in the low-risk group (first and second quintiles of risk score) were both greater than 4. HRs for SCD and PFD increased to 9 and 11 when using a model including only ECG markers, and to 14 and 13, when combining clinical and ECG markers. The inclusion of ECG markers capturing complementary pro-arrhythmic and pump failure mechanisms into risk models based only on standard clinical variables substantially improves prediction of SCD and PFD in CHF patients.

T-Wave Morphology Restitution Predicts Sudden Cardiac Death in Patients With Chronic Heart Failure.

PubMed

Ramírez, Julia; Orini, Michele; Mincholé, Ana; Monasterio, Violeta; Cygankiewicz, Iwona; Bayés de Luna, Antonio; Martínez, Juan Pablo; Pueyo, Esther; Laguna, Pablo

2017-05-19

Patients with chronic heart failure are at high risk of sudden cardiac death (SCD). Increased dispersion of repolarization restitution has been associated with SCD, and we hypothesize that this should be reflected in the morphology of the T-wave and its variations with heart rate. The aim of this study is to propose an electrocardiogram (ECG)-based index characterizing T-wave morphology restitution (TMR), and to assess its association with SCD risk in a population of chronic heart failure patients. Holter ECGs from 651 ambulatory patients with chronic heart failure from the MUSIC (MUerte Súbita en Insuficiencia Cardiaca) study were available for the analysis. TMR was quantified by measuring the morphological variation of the T-wave per RR increment using time-warping metrics, and its predictive power was compared to that of clinical variables such as the left ventricular ejection fraction and other ECG-derived indices, such as T-wave alternans and heart rate variability. TMR was significantly higher in SCD victims than in the rest of patients (median 0.046 versus 0.039, P <0.001). When TMR was dichotomized at TMR=0.040, the SCD rate was significantly higher in the TMR≥0.040 group ( P <0.001). Cox analysis revealed that TMR≥0.040 was strongly associated with SCD, with a hazard ratio of 3.27 ( P <0.001), independently of clinical and ECG-derived variables. No association was found between TMR and pump failure death. This study shows that TMR is specifically associated with SCD in a population of chronic heart failure patients, and it is a better predictor than clinical and ECG-derived variables. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Inflammatory Markers Related to Microbial Translocation Among HIV-Infected Pregnant Women: A Risk Factor of Preterm Delivery.

PubMed

López, Marta; Figueras, Francesc; Coll, Oriol; Goncé, Anna; Hernández, Sandra; Loncá, Montse; Vila, Jordi; Gratacós, Eduard; Palacio, Montse

2016-02-01

This study was performed to assess the role of lipopolysaccharide modulators as a marker of microbial translocation among human immunodeficiency virus (HIV)-infected women during pregnancy and to evaluate their association with preterm delivery. The study had a prospective cohort design and was performed at the Hospital Clínic in Barcelona, Spain. Thirty-six pregnant women with and 36 without HIV infection, matched on the basis of age and parity, were included. Maternal blood samples were obtained during the first trimester, during the third trimester, and at delivery. Levels of soluble CD14 (sCD14), human lipopolysaccharide-binding protein (LBP), immunoglobulin M endotoxin core antibodies to lipopolysaccharide (EndoCAb), and interleukin 6 (IL-6) were determined. Fetal cord blood levels of sCD14, LBP, and IL-6 were determined. Results were compared between groups. First trimester sCD14 and LBP levels and third trimester sCD14 levels were significantly higher in the HIV-infected group. HIV-infected women with preterm births and spontaneous preterm births had significantly increased levels of sCD14 throughout pregnancy and significantly increased levels of LBP during the first trimester, compared with HIV-infected women with delivery at term or with HIV-negative women. On multivariate analysis, an independent association was observed between first trimester sCD14 levels and preterm delivery among HIV-infected women. This is the first study to assess inflammatory markers related to microbial translocation during pregnancy among HIV-infected women. Higher levels of sCD14 and LBP were observed in HIV-infected pregnant women and were associated with preterm delivery. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Pharmacokinetics and Analgesic Effects of Methadone in Children and Adults with Sickle Cell Disease

PubMed Central

Horst, Jennifer; Frei-Jones, Melissa; Deych, Elena; Shannon, William; Kharasch, Evan D.

2017-01-01

Background Vaso-occlusive episodes (VOE) are a significant source of morbidity among children and adults with sickle cell disease (SCD). There is little information on methadone use for SCD pain. This investigation evaluated methadone pharmacokinetics in children and adults with SCD, with a secondary aim to assess pain relief and opioid consumption. Procedure Participants included children (<18 yr) and adults with a VOE requiring hospitalization. Patients were randomly assigned to receive standard care (opioid patient controlled analgesia; control group) or one dose of intravenous methadone (0.1–0.125 mg/kg) in addition to standard care (methadone group). Venous methadone and metabolite concentrations were measured. Pain scores, pain relief scores, and opioid consumption were recorded. Results Twenty-four children (12 methadone, 12 controls) and twenty-three adults (11 methadone, 12 controls) were studied. In children, the half-life of R-and S-methadone enantiomers was 34±16 and 24±9 hr, respectively. In adults, R- and S-methadone half-lives were 52±17 and 38±12 hr. Pain scores were lower (p=0.002) and pain relief scores were higher (p=0.0396) in children receiving methadone vs controls. There was no difference in pain scores and pain relief in adults receiving methadone vs controls. There was no difference in opioid consumption between methadone and control groups, in both adults and children. Conclusions Intravenous methadone disposition in children and adults with SCD was comparable to subjects without SCD from prior studies. Methadone produced more pain relief than standard care in children with SCD. Higher methadone doses may be more effective and should be evaluated in both children and adults with SCD. PMID:27572136

Evaluation of pretransplant immunologic status in kidney-transplant recipients by panel reactive antibody and soluble CD30 determinations.

PubMed

Cinti, Paola; Pretagostini, Renzo; Arpino, Alessia; Tamburro, Maria Luisa; Mengasini, Sonia; Lattanzi, Roberto; De Simone, Paolo; Berloco, Pasquale; Molajoni, Elvira Renna

2005-05-15

To retrospectively compare the accuracy of pretransplant panel of reactivity antibodies (PRA) and serum level of soluble CD30 (sCD30) in predicting early (<6 months) acute rejection (AR) in living-donor and deceased-donor kidney-transplant (KT) patients. Pretransplant sera of 24 KT recipients were retrospectively tested for sCD30 and compared with PRA. Inclusion criteria were de novo graft patients on calcineurin-inhibitor-based immunosuppression, minimum follow-up of 1 year, alive with a functioning graft, and stable renal function over the last 12 months. Objective measures were incidence of biopsy-proven AR (BPAR) within 6 months of KT and sCD30 and PRA diagnostic indexes. The relative risk (RR) of BPAR for each test was also obtained. Fourteen (58.3%) patients presented at least one episode of BPAR within 6 months of KT. All rejection episodes were responsive to steroid treatment. PRA was positive in six (25%) patients, and four (66.7%) of them presented at least one episode of BPAR. sCD30 tested positive in nine (37.5%) patients, and all these later presented at least one episode of BPAR. sCD30 and PRA diagnostic indexes in predicting early (< 6months) BPAR were sensitivity 64.2% versus 28.5%; specificity 100% versus 80%; accuracy 79.1% versus 50%; positive predictive value 100% versus 66.6%; and negative predictive value 66.6% versus 44.4%. The RR of early AR was 1.4 in PRA-positive patients and extremely higher in the sCD30-positive group. Pretransplant sCD30 is a more accurate predictor of AR when compared with PRA. These results support its use in the pretransplant work-up of kidney-graft recipients.

Pretransplantation soluble CD30 level as a predictor of acute rejection in kidney transplantation: a meta-analysis.

PubMed

Chen, Yile; Tai, Qiang; Hong, Shaodong; Kong, Yuan; Shang, Yushu; Liang, Wenhua; Guo, Zhiyong; He, Xiaoshun

2012-11-15

The question of whether high pretransplantation soluble CD30 (sCD30) level can be a predictor of kidney transplant acute rejection (AR) is under debate. Herein, we performed a meta-analysis on the predictive efficacy of sCD30 for AR in renal transplantation. PubMed (1966-2012), EMBASE (1988-2012), and Web of Science (1986-2012) databases were searched for studies concerning the predictive efficacy of sCD30 for AR after kidney transplantation. After a careful review of eligible studies, sensitivity, specificity, and other measures of the accuracy of sCD30 were pooled. A summary receiver operating characteristic curve was used to represent the overall test performance. Twelve studies enrolling 2507 patients met the inclusion criteria. The pooled estimates for pretransplantation sCD30 in prediction of allograft rejection risk were poor, with a sensitivity of 0.70 (95% confidence interval (CI), 0.66-0.74), a specificity of 0.48 (95% CI, 0.46-0.50), a positive likelihood ratio of 1.35 (95% CI, 1.20-1.53), a negative likelihood ratio of 0.68 (95% CI, 0.55-0.84), and a diagnostic odds ratio of 2.07 (95% CI, 1.54-2.80). The area under curve of the summary receiver operating characteristic curve was 0.60, indicating poor overall accuracy of the serum sCD30 level in the prediction of patients at risk for AR. The results of the meta-analysis show that the accuracy of pretransplantation sCD30 for predicting posttransplantation AR was poor. Prospective studies are needed to clarify the usefulness of this test for identifying risks of AR in transplant recipients.

Soluble CD30 levels in recipients undergoing heart transplantation do not predict post-transplant outcome.

PubMed

Ypsilantis, Efthymios; Key, Timothy; Bradley, J Andrew; Morgan, C Helen; Tsui, Stephen; Parameshwar, Jayan; Taylor, Craig J

2009-11-01

The pre-transplant serum level of soluble CD30 (sCD30), a proteolytic derivative of the lymphocyte surface receptor CD30, has been suggested as a biomarker for immunologic risk after organ transplantation. Pre-transplant serum sCD30 levels were determined in 200 consecutive adult heart transplant recipients undertaken at a single center. Transplant outcome (acute rejection in the first 12 months and patient survival up to 5 years post-transplant) was determined. Patients treated with a left ventricular assist device (LVAD) prior to transplantation (n = 28) had higher levels of sCD30 (median 64 U/ml, range 12 to 112 U/ml) than those (n = 172) with no LVAD (median 36 U/ml, range 1 to 158 U/ml, p < 0.0001). Recipients were categorized according to whether sCD30 levels were "low" (lower quartile, <24 U/ml, n = 50), "intermediate" (24 to 58 U/ml, n = 100) or "high" (upper quartile, >58 U/ml, n = 50). Neither acute rejection nor recipient survival differed according to sCD30 level, with values (mean +/- SEM) of 0.30 +/- 0.04, 0.23 +/- 0.03 and 0.30 +/- 0.05 acute rejection episodes per 100 days in the low, intermediate and high groups, respectively, with recipient survival rates at 1 year of 77.7%, 84.9% and 86% and at 5 years of 73.6%, 67.9% and 75.8%, respectively. Pre-transplant serum sCD30 level does not predict acute allograft rejection or recipient survival after heart transplantation, although sCD30 levels are increased by LVAD, possibly as a result of biomaterial-host immune interaction.

Value of soluble CD30 in liver transplantation.

PubMed

Fábrega, E; Unzueta, M G; Cobo, M; Casafont, F; Amado, J A; Romero, F P

2007-09-01

CD30 is a membrane glycoprotein that belongs to the tumor necrosis factor superfamily. It is expressed on activated T cells. After activation of CD30(+) T cells, a soluble form of CD30 (sCD30) released into the bloodstream, can be measured in the serum. The aim of our study was to investigate the time course of serum levels of sCD30 during hepatic allograft rejection. Serum levels of sCD30 were determined in 30 healthy subjects and 50 hepatic transplant recipients. These patients were divided into two groups: group I, 35 patients without rejection; and group II, 15 patients with acute rejection. Samples were collected on day 1 and 7 after transplantation and on the day of liver biopsy. The concentrations of sCD30 were similar in the rejection (40.4 +/- 16.5 U/mL) and nonrejection groups (43.0 +/- 18.2 U/mL) on postoperative day 1. We observed a significant increase in sCD30 levels in the rejection group on postoperative day 7 (76.3 +/- 61.8 U/mL vs 46.8 +/- 20.5 U/mL; P = .01). The difference increased when a diagnosis of acute rejection had been established: namely 133.0 +/- 113.5 U/mL versus 40.1 +/- 22.0 U/mL; (P = .001). These levels were also significantly higher during the entire postoperative period in all the patients, with or without rejection, than those observed in healthy controls (26.6 +/- 5.3 U/mL; P = .005). The release of circulating sCD30 is a prominent feature coinciding with the first episode of hepatic allograft rejection. So, monitoring of sCD30 levels may be useful for the early diagnosis of an acute rejection episode.

TH1/TH2 cytokines and soluble CD30 levels in kidney allograft patients with donor bone marrow cell infusion.

PubMed

Solgi, G; Amirzagar, A A; Pourmand, G; Mehrsai, A R; Taherimahmoudi, M; Baradaran, N; Nicknam, M H; Ebrahimi Rad, M R; Saraji, A; Asadpoor, A A; Moheiydin, M; Nikbin, B

2009-09-01

We investigated the relevance of donor bone marrow cell infusion (DBMI) and serum levels of interferon-gamma (IFN-gamma), interleukin-10 (IL-10), and soluble CD30 (sCD30) in kidney recipients. We analyzed the allograft outcomes correlated with sCD30, IFN-gamma, and IL-10 levels using pre- and posttransplantation sera from 40 live donor renal transplants (20 patients with DBMI [2.1 x 10(9) +/- 1.3 x 10(9) mononuclear cells/body] and 20 controls). Patients with acute rejection episodes (ARE)-3/20 DBMI and 6/20 controls-showed increased sCD30 and IFN-gamma as well as decreased IL-10 posttransplantation compared with nonrejectors. Significant differences were observed for sCD30 and IFN-gamma levels: 59.54 vs 30.92 ng/mL (P = .02) and 11.91 vs 3.01 pg/mL (P = .01), respectively. Comparison of pre- and posttransplant levels of IFN-gamma, IL-10, and sCD30 in ARE patients showed higher levels in posttransplant sera except for IFN-gamma in controls (6.37 vs 11.93; P = .01). Increased IFN-gamma and IL-10 were correlated with rejection (r = .93; P = .008). sCD30 correlated with serum creatinine among ARE patients in control and DBMI groups (r = .89; P = .019; and r = 1.00; P < .0001, respectively). Higher levels of sCD30, IFN-gamma, and IL-10 posttransplantation in rejecting patients provided evidence for coexistence of cellular and humoral responses in ARE. There appeared to be a down-regulatory effect of infusion on alloresponses.

Evaluation of pretransplant immunologic status in kidney-transplant recipients by panel reactive antibody and soluble CD30 determinations.

PubMed

Cinti, Paola; Pretagostini, Renzo; Arpino, Alessia; Tamburro, Maria Luisa; Mengasini, Sonia; Lattanzi, Roberto; De Simone, Paolo; Berloco, Pasquale; Molajoni, Elvira Renna

2005-03-15

To retrospectively compare the accuracy of pretransplant panel of reactivity antibodies (PRA) and serum level of soluble CD30 (sCD30) in predicting early (< 6 months) acute rejection (AR) in living-donor and deceased-donor kidney-transplant (KT) patients. Pretransplant sera of 24 KT recipients were retrospectively tested for sCD30 and compared with PRA. Inclusion criteria were de novo graft patients on calcineurin-inhibitor-based immunosuppression, minimum follow-up of 1 year, alive with a functioning graft, and stable renal function over the last 12 months. Objective measures were incidence of biopsy-proven AR (BPAR) within 6 months of KT and sCD30 and PRA diagnostic indexes. The relative risk (RR) of BPAR for each test was also obtained. Fourteen (58.3%) patients presented at least one episode of BPAR within 6 months of KT. All rejection episodes were responsive to steroid treatment. PRA was positive in six (25%) patients, and four (66.7%) of them presented at least one episode of BPAR. sCD30 tested positive in nine (37.5%) patients, and all these later presented at least one episode of BPAR. sCD30 and PRA diagnostic indexes in predicting early (< 6 months) BPAR were sensitivity 64.2% versus 28.5%; specificity 100% versus 80%; accuracy 79.1% versus 50%; positive predictive value 100% versus 66.6%; and negative predictive value 66.6% versus 44.4%. The RR of early AR was 1.4 in PRA-positive patients and extremely higher in the sCD30-positive group. Pretransplant sCD30 is a more accurate predictor of AR when compared with PRA. These results support its use in the pretransplant work-up of kidney-graft recipients.