Publications by authors named "Lia D"

5 Publications

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DCD Renal Transplantation From Donors With Acute Kidney Injury.

Transplantation 2021 04;105(4):886-890

Division of Transplant Surgery, Department of Surgery, Northwell Health, Manhasset, NY.

Background: Deceased donor kidneys with acute kidney injury (AKI) and donation after circulatory death (DCD) kidneys are viable sources of organs. The outcomes of renal transplantation from DCD donors with AKI are not known.

Methods: A retrospective review of deceased donor renal transplants performed from 2006 to 2016 was conducted using the United Network for Organ Sharing dataset. Donors were stratified by DCD or brain dead status and by AKI stage. Recipients were followed until graft failure or the end of study. Cox regression was used to adjust for donor, recipient, and transplant covariates known to affect the incidence of delayed graft function and graft survival.

Results: A total of 135 644 patients were included in the study. The odds of delayed graft function among DCD recipients were significantly higher across all donor AKI stages. The unadjusted risk of overall and death-censored graft failure were similar between the 2 groups. After adjusting for covariates, there was a significant increase in the risk of overall graft failure in recipients of DCD allografts from donors with stage 2 AKI. There was also a higher risk of death-censored graft failure among stage 1 and 2 AKI DCD recipients.

Conclusions: DCD renal allografts from donors experiencing stage 1 and 2 AKI have a higher adjusted risk of death-censored graft failure than AKI stage-matched donation after brain death renal allografts. Their use, however, is still associated with improved outcomes compared with waitlist mortality.
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http://dx.doi.org/10.1097/TP.0000000000003317DOI Listing
April 2021

Age at onset of genetic (E200K) and sporadic Creutzfeldt-Jakob diseases is modulated by the gene.

J Neurol Neurosurg Psychiatry 2018 12 21;89(12):1243-1249. Epub 2018 Jul 21.

Department of Neuroscience, Istituto Superiore di Sanità, Roma, Italy

Objectives: The Glu to Lys change at codon 200 (E200K) of the gene is the most frequent mutation associated to genetic Creutzfeldt-Jakob disease (CJD) and the only one responsible for geographical clusters. Patients carrying this mutation develop disease at different ages and show variable clinical phenotypes that are not affected by the methione/valine polymorphism at codon 129 of the gene suggesting the influence of other factors. The objective of this study is to look for genes other than that might be responsible of this variability.

Methods: We searched for other genes by performing genome-wide analyses (GWA) on 19 patients with genetic CJD and 18 healthy subjects carrying the E200K mutation of and belonging to the Calabrian cluster in Italy. We then validate this result in 32 patients with E200K CJD from non-cluster areas and 259 patients with sporadic CJD referred to the Italian CJD national registry.

Results And Conclusions: We identified two single nucleotide polymorphisms on the  gene locus as candidate disease modifiers in patients with E200K CJD of the cluster area and confirmed this finding in 32 patients with E200K CJD from non-cluster areas and 259 patients with sporadic CJD. Our results indicate that the  gene modulates the onset of disease in patients with E200K genetic and sporadic CJD. This finding improves our understanding on the pathogenesis of CJD, suggests new targets for developing novel therapeutic strategies and might be useful for the stratification of patients in future preventive treatment trials.
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http://dx.doi.org/10.1136/jnnp-2018-318756DOI Listing
December 2018

Mitochondrial maintenance under oxidative stress depends on mitochondrially localised α-OGG1.

J Cell Sci 2018 06 25;131(12). Epub 2018 Jun 25.

Institut de Biologie François Jacob (IBFJ), Institute of Cellular and Molecular Radiobiology, CEA, UMR967 INSERM, 96265 Fontenay aux Roses, France

Accumulation of 8-oxoguanine (8-oxoG) in mitochondrial DNA and mitochondrial dysfunction have been observed in cells deficient for the DNA glycosylase OGG1 when exposed to oxidative stress. In human cells, up to eight mRNAs for OGG1 can be generated by alternative splicing and it is still unclear which of them codes for the protein that ensures the repair of 8-oxoG in mitochondria. Here, we show that the α-OGG1 isoform, considered up to now to be exclusively nuclear, has a functional mitochondrial-targeting sequence and is imported into mitochondria. We analyse the sub-mitochondrial localisation of α-OGG1 with unprecedented resolution and show that this DNA glycosylase is associated with DNA in mitochondrial nucleoids. We show that the presence of α-OGG1 inside mitochondria and its enzymatic activity are required to preserve the mitochondrial network in cells exposed to oxidative stress. Altogether, these results unveil a new role of α-OGG1 in the mitochondria and indicate that the same isoform ensures the repair of 8-oxoG in both nuclear and mitochondrial genomes. The activity of α-OGG1 in mitochondria is sufficient for the recovery of organelle function after oxidative stress.
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http://dx.doi.org/10.1242/jcs.213538DOI Listing
June 2018

Optimized design and data analysis of tag-based cytosine methylation assays.

Genome Biol 2010 1;11(4):R36. Epub 2010 Apr 1.

Department of Genetics (Computational Genetics), Center for Epigenomics, Albert Einstein College of Medicine, 1301 Morris Park Avenue, Bronx, NY 10461, USA.

Using the type III restriction-modification enzyme EcoP15I, we isolated sequences flanking sites digested by the methylation-sensitive HpaII enzyme or its methylation-insensitive MspI isoschizomer for massively parallel sequencing. A novel data transformation allows us to normalise HpaII by MspI counts, resulting in more accurate quantification of methylation at >1.8 million loci in the human genome. This HELP-tagging assay is not sensitive to sequence polymorphism or base composition and allows exploration of both CG-rich and depleted genomic contexts.
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http://dx.doi.org/10.1186/gb-2010-11-4-r36DOI Listing
October 2010

Scintillator avalanche photoconductor with high resolution emitter readout for low dose x-ray imaging: lag.

Med Phys 2009 Sep;36(9):4047-58

Department of Radiology, State University of New York at Stony Brook, L-4 120 Health Science Center, Stony Brook, New York 11794-8460, USA.

Purpose: A new concept of indirect conversion flat-panel imager with avalanche gain and field emitter array (FEA) readout is being investigated. It is referred to as scintillator avalanche photoconductor with high resolution emitter readout (SAPHIRE). The present work investigates the temporal performance, i.e., lag, of SAPHIRE.

Methods: Since the temporal performance of the x-ray detection materials, i.e., the structured scintillator and avalanche amorphous selenium (a-Se) photoconductor, has been studied previously, the investigation is focused on lag due to the FEA readout method. The principle of FEA readout is similar to that of scanning electron beam readout used in camera tubes, where the dominant source of lag is the energy spread of electrons. Since the principles of emission and beam focusing methods for FEA are different from thermionic emission used in camera tubes, its electron beam energy spread and hence lag is expected to be different. In the present work, the energy spread of the electrons emitted from a FEA was investigated theoretically by analyzing different contributing factors due to the FEA design and operations: The inherent energy spread of field emission, the FEA driving pulse delay, and the angular distribution of emitted electrons. The electron energy spread determined the beam acceptance characteristic curve of the photoconductive target, i.e., the accepted beam current (I(a)) as a function of target potential (V(t)), from which lag could be calculated numerically. Lag calculation was performed using FEA parameters of two prototype HARP-FEA image sensors, and the results were compared with experimental measurements. Strategies for reducing lag in SAPHIRE were proposed and analyzed.

Results: The theoretical analysis shows that the dominant factor for lag is the angular distribution of electrons emitted from the FEA. The first frame lags for two prototype sensors with 4 and 25 microm HARP layer thicknesses were 62.1% and 9.1%, respectively. A lag clearance procedure can be implemented by turning on all the FEA pixels simultaneously between subsequent frames without negative impact of readout speed. For large-area SAPHIRE, the bias electrode for the HARP needs to be divided into strips to allow parallel readout. With typical cardiac detector parameters, SAPHIRE with 128 parallel strips can provide real-time readout (30 frames/s) with first frame lag of -4%.

Conclusions: The investigation of lag in SAPHIRE shows that the angular distribution of emitted electrons from FEA can result in substantial lag if the readout was performed pixel by pixel. Effective strategies for reducing lag include dividing the bias electrode into multiple strips to allow parallel readout and the incorporation of rapid charge clearance procedure between subsequent frames or rows.
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http://dx.doi.org/10.1118/1.3187227DOI Listing
September 2009
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