Anderson-Fabry disease: Ten-year outcome of enzyme replacement therapy in a renal transplant patient

Anderson‑Fabry disease (AFd) is a rare disorder characterised by the deficiency or absence of lysosomal enzymatic alpha‑galactosidase A activity (α‑Gal A) that leads to progressive and systemic accumulation of glycosphingolipids. The clinical manifestations are variable but kidney disease usually manifests before the fourth decade of life and chronic renal failure rapidly progresses to end‑stage renal disease (ESRD), requiring dialysis and kidney transplantation (KT). In patients with a definite diagnosis, enzyme replacement therapy (ERT) is recommended as soon as there are early clinical signs of kidney, heart or brain involvement. We present a case of a kidney transplant patient who was diagnosed with AFd nine years after KT, confirming the difficulty that may exist in na early diagnosis of this disease even among high‑risk groups. At this stage, in addition to renal damage, the patient already had advanced disease and established organ injury, including ocular, pulmonary, cerebrovascular and cardiac. He started agalsidase beta (Fabrazyme®) intravenously every two weeks at a dose of 1 mg/kg body weight. During ten years of treatment no major adverse events were reported and our experience indicates that ERT is a safe and effective treatment for extra‑renal Fabry manifestations in KT patientsinfo:eu-repo/semantics/publishedVersio

Fertilization capacity with rainbow trout DNA-damaged sperm and embryo developmental success

Mammalian spermatozoa undergo a strong selection process along the female tract to guarantee fertilization by good quality cells, but risks of fertilization with DNA-damaged spermatozoa have been reported. In contrast, most external fertilizers such as fish seem to have weaker selection procedures. This fact, together with their high prolificacy and external embryo development, indicates that fish could be useful for the study of the effects of sperm DNA damage on embryo development. We cryopreserved sperm from rainbow trout using egg yolk and low-density lipoprotein as additives to promote different rates of DNA damage. DNA fragmentation and oxidization were analyzed using comet assay with and without digestion with restriction enzymes, and fertilization trials were performed. Some embryo batches were treated with 3-aminobenzamide (3AB) to inhibit DNA repair by the poly (ADP-ribose) polymerase, which is an enzyme of the base excision repair pathway. Results showed that all the spermatozoa cryopreserved with egg yolk carried more than 10% fragmented DNA, maintaining fertilization rates of 61.1+/-2.3 but a high rate of abortions, especially during gastrulation, and only 14.5+/-4.4 hatching success. Furthermore, after 3AB treatment, hatching dropped to 3.2+/-2.2, showing that at least 10% DNA fragmentation was repaired. We conclude that trout sperm maintains its ability to fertilize in spite of having DNA damage, but that embryo survival is affected. Damage is partially repaired by the oocyte during the first cleavage. Important advantages of using rainbow trout for the study of processes related to DNA damage and repair during development have been reported. Reproduction (2010) 139 989-997Junta de Castilla y Leon (Spain) [LE007A06]; University of Leoninfo:eu-repo/semantics/publishedVersio

Familial ATTR amyloidosis: microalbuminuria as a predictor of symptomatic disease and clinical nephropathy

Familial ATTR amyloidosis: microalbuminuria as a predictor of symptomatic disease and clinical nephropathy. Lobato L, Beirão I, Silva M, Bravo F, Silvestre F, Guimarães S, Sousa A, Noël LH, Sequeiros J. SourceDepartment of Nephrology and Centro de Estudos de Paramiloidose, Hospital Geral de Santo António and Institute for Molecular and Cell Biology, Porto, Portugal. [email protected] Abstract BACKGROUND: Portuguese type familial amyloid polyneuropathy (FAP) is a neuropathic amyloidosis caused by a mutant transthyretin (TTR). Varying degrees of renal involvement have been reported. Our aim was to assess the value of microalbuminuria (MA) for predicting clinical neurological disease and overt nephropathy in TTR-related amyloidosis. METHODS: All subjects had the TTR Val30Met mutation, and were recruited between 1993 and 1999. We have prospectively evaluated 22 asymptomatic gene carriers (7 male, 15 female; mean age 41.6+/-9.6 years) and 32 patients with neuropathy (14 male, 18 female; 36.8+/-8.8 years, on average, 33.0+/-9.3 years at the onset of neuropathy). We measured urinary albumin excretion every year, if asymptomatic, or every 6 months if already affected. Kidney biopsies were performed in patients with normal urinary albumin excretion, MA, and overt nephropathy, respectively. RESULTS: In asymptomatic carriers, persistent MA was detected in eight (36%) subjects. The presence of MA in asymptomatic gene carriers, compared with those having normal urinary albumin excretion, conferred a 4.8-fold risk of developing neuropathy, usually within the subsequent 3 years. Once neurological signs appeared, nephropathy, manifested as MA, progressed to overt nephropathy in one-half of subjects. In patients with neuropathy, 24 (75%) had MA during follow-up: evolution towards clinical renal disease occurred in 14 (58%) and renal failure occurred in five (21%), always after a course of MA. Proteinuria or renal failure without prior persistent MA were never observed in the present patient cohort. Histopathological evaluation did not reveal glomerular lesions other than amyloid deposits to explain abnormal urinary albumin excretion. The amount of mesangial and vascular-pole amyloid deposits was correlated with the degree of albuminuria. CONCLUSIONS: Microalbuminuria represents the first stage of clinical TTR amyloid nephropathy and is premonitory of neuropathy. Its presence identifies a subgroup of patients who are more prone to develop overt nephropathy. Screening of MA may be important to assess disease onset and to recommend liver transplantation in individuals at risk

A far-IR view of the starburst driven superwind in NGC 2146

NGC 2146, a nearby luminous infrared galaxy (LIRG), presents evidence for outflows along the disk minor axis in all gas phases (ionized, neutral atomic and molecular). We present an analysis of the multi-phase starburst driven superwind in the central 5 kpc as traced in spatially resolved spectral line observations, using far-IR Herschel PACS spectroscopy, to probe the effects on the atomic and ionized gas, and optical integral field spectroscopy to examine the ionized gas through diagnostic line ratios. We observe an increased ~250 km/s velocity dispersion in the [OI] 63 micron, [OIII] 88 micron, [NII] 122 micron and [CII] 158 micron fine-structure lines that is spatially coincident with high excitation gas above and below the disk. We model this with a slow ~200 km/s shock and trace the superwind to the edge of our field of view 2.5 kpc above the disk. We present new SOFIA 37 micron observations to explore the warm dust distribution, and detect no clear dust entrainment in the outflow. The stellar kinematics appear decoupled from the regular disk rotation seen in all gas phases, consistent with a recent merger event disrupting the system. We consider the role of the superwind in the evolution of NGC 2146 and speculate on the evolutionary future of the system. Our observations of NGC 2146 in the far-IR allow an unobscured view of the wind, crucial for tracing the superwind to the launching region at the disk center, and provide a local analog for future ALMA observations of outflows in high redshift systems.Comment: 16 pages, 13 figures, accepted for publication in Ap

Overlapping schwarz methods for isogeometric analysis

We construct and analyze an overlapping Schwarz preconditioner for elliptic problems discretized with isogeometric analysis. The preconditioner is based on partitioning the domain of the problem into overlapping subdomains, solving local isogeometric problems on these subdomains, and solving an additional coarse isogeometric problem associated with the subdomain mesh. We develop an $h$-analysis of the preconditioner, showing in particular that the resulting algorithm is scalable and its convergence rate depends linearly on the ratio between subdomain and \u201eoverlap sizes\u201d for fixed polynomial degree $p$ and regularity $k$ of the basis functions. Numerical results in two- and three-dimensional tests show the good convergence properties of the preconditioner with respect to the isogeometric discretization parameters $h, p, k$, number of subdomains $N$, overlap size, and also jumps in the coefficients of the elliptic operator

Isogeometric BDDC Preconditioning with Deluxe Scaling

A balancing domain decomposition by constraints (BDDC) preconditioner with a novel scaling, introduced by Dohrmann for problems with more than one variable coefficient and here denoted as deluxe scaling, is extended to isogeometric analysis of scalar elliptic problems. This new scaling turns out to be more powerful than the standard ?- and stiffness scalings considered in a previous isogeometric BDDC study. Our h-analysis shows that the condition number of the resulting deluxe BDDC preconditioner is scalable with a quasi-optimal polylogarithmic bound which is also independent of coefficient discontinuities across subdomain interfaces. Extensive numerical experiments support the theory and show that the deluxe scaling yields a remarkable improvement over the older scalings, in particular for large isogeometric polynomial degree and high regularity

The Ionized Gas in Nearby Galaxies as Traced by the [NII] 122 and 205 \mu m Transitions

The [NII] 122 and 205 \mu m transitions are powerful tracers of the ionized gas in the interstellar medium. By combining data from 21 galaxies selected from the Herschel KINGFISH and Beyond the Peak surveys, we have compiled 141 spatially resolved regions with a typical size of ~1 kiloparsec, with observations of both [NII] far-infrared lines. We measure [NII] 122/205 line ratios in the ~0.6-6 range, which corresponds to electron gas densities $n_e$~1-300 cm$^{-3}$, with a median value of $n_e$=30 cm$^{-3}$. Variations in the electron density within individual galaxies can be as a high as a factor of ~50, frequently with strong radial gradients. We find that $n_e$ increases as a function of infrared color, dust-weighted mean starlight intensity, and star formation rate surface density ($\Sigma_{SFR}$). As the intensity of the [NII] transitions is related to the ionizing photon flux, we investigate their reliability as tracers of the star formation rate (SFR). We derive relations between the [NII] emission and SFR in the low-density limit and in the case of a log-normal distribution of densities. The scatter in the correlation between [NII] surface brightness and $\Sigma_{SFR}$ can be understood as a property of the $n_e$ distribution. For regions with $n_e$ close to or higher than the [NII] line critical densities, the low-density limit [NII]-based SFR calibration systematically underestimates the SFR since [NII] emission is collisionally quenched. Finally, we investigate the relation between [NII] emission, SFR, and $n_e$ by comparing our observations to predictions from the MAPPINGS-III code.Comment: 18 pages, 9 figures, accepted for publication in The Astrophysical Journa

Coherent vortex structures and 3D enstrophy cascade

Existence of 2D enstrophy cascade in a suitable mathematical setting, and under suitable conditions compatible with 2D turbulence phenomenology, is known both in the Fourier and in the physical scales. The goal of this paper is to show that the same geometric condition preventing the formation of singularities - 1/2-H\"older coherence of the vorticity direction - coupled with a suitable condition on a modified Kraichnan scale, and under a certain modulation assumption on evolution of the vorticity, leads to existence of 3D enstrophy cascade in physical scales of the flow.Comment: 15 pp; final version -- to appear in CM

Far-Infrared Line Imaging of the Starburst Ring in NGC 1097 with the Herschel/PACS Spectrometer

NGC 1097 is a nearby SBb galaxy with a Seyfert nucleus and a bright starburst ring. We study the physical properties of the interstellar medium (ISM) in the ring using spatially resolved far-infrared spectral maps of the circumnuclear starburst ring of NGC 1097, obtained with the PACS spectrometer on board the Herschel Space Telescope. In particular, we map the important ISM cooling and diagnostic emission lines of [OI] 63 $\mu$m, [OIII] 88 $\mu$m, [NII] 122 $\mu$m, [CII] 158 $\mu$m and [NII] 205 $\mu$m. We observe that in the [OI] 63 $\mu$m, [OIII] 88 $\mu$m, and [NII] 122 $\mu$m line maps, the emission is enhanced in clumps along the NE part of the ring. We observe evidence of rapid rotation in the circumnuclear ring, with a rotation velocity of ~220$km s$^{-1}$(inclination uncorrected) measured in all lines. The [OI] 63$\mu$m/[CII] 158$\mu$m ratio varies smoothly throughout the central region, and is enhanced on the northeastern part of the ring, which may indicate a stronger radiation field. This enhancement coincides with peaks in the [OI] 63$\mu$m and [OIII] 88$\mu$m maps. Variations of the [NII] 122$\mu$m/[NII] 205$\mu$m ratio correspond to a range in the ionized gas density between 150 and 400 cm$^{-3}$.Comment: Accepted for publication on the A&A Herschel Special Issu