D'Angelo Dott.ssa Luciana
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Monitoring tafamidis treatment with quantitative SPECT/CT in transthyretin amyloid cardiomyopathy.
Eur Heart J Cardiovasc Imaging2023 Mar;():. doi: jead030.
Rettl René, Wollenweber Tim, Duca Franz, Binder Christina, Cherouny Bernhard, Dachs Theresa-Marie, Luciana Camuz Ligios, Schrutka Lore, Dalos Daniel, Beitzke Dietrich, Loewe Christian, Eslam Roza Badr, Kastner Johannes, Hacker Marcus, Bonderman Diana
Tafamidis treatment positively affects left ventricular (LV) structure and function and improves outcomes in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). We aimed to investigate the relationship between treatment response and cardiac amyloid burden identified by serial quantitative 99mTc-DPD SPECT/CT. We furthermore aimed to identify nuclear imaging biomarkers that could be used to quantify and monitor response to tafamidis therapy.
METHODS AND RESULTS:
Forty wild-type ATTR-CM patients who underwent 99mTc-DPD scintigraphy and SPECT/CT imaging at baseline and after treatment with tafamidis 61?mg once daily [median, 9.0 months (interquartile range 7.0-10.0)] were divided into two cohorts based on the median (-32.3%) of the longitudinal percent change in standardized uptake value (SUV) retention index. ATTR-CM patients with a reduction greater than or equal to the median (n = 20) had a significant decrease in SUV retention index (P
Treatment with tafamidis in ATTR-CM patients results in a significant reduction in SUV retention index, associated with significant benefits for LV and RV function and cardiac biomarkers. Serial quantitative 99mTc-DPD SPECT/CT imaging with SUV may be a valid tool to quantify and monitor response to tafamidis treatment in affected patients.
99mTc-DPD SPECT/CT imaging with determination of SUV retention index as part of a routine annual examination can provide evidence of treatment response in ATTR-CM patients receiving disease-modifying therapy. Further long-term studies with 99mTc-DPD SPECT/CT imaging may help to evaluate the relationship between tafamidis-induced reduction in SUV retention index and outcome in patients with ATTR-CM and will demonstrate whether highly disease-specific 99mTc-DPD SPECT/CT imaging is more sensitive than routine diagnostic monitoring.
© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: firstname.lastname@example.org.
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Engineered human hepatocyte organoids enable CRISPR-based target discovery and drug screening for steatosis.
Nat Biotechnol2023 Feb;():. doi: 10.1038/s41587-023-01680-4.
Hendriks Delilah, Brouwers Jos F, Hamer Karien, Geurts Maarten H, Luciana Léa, Massalini Simone, López-Iglesias Carmen, Peters Peter J, Rodríguez-Colman Maria J, Chuva de Sousa Lopes Susana, Artegiani Benedetta, Clevers Hans
The lack of registered drugs for nonalcoholic fatty liver disease (NAFLD) is partly due to the paucity of human-relevant models for target discovery and compound screening. Here we use human fetal hepatocyte organoids to model the first stage of NAFLD, steatosis, representing three different triggers: free fatty acid loading, interindividual genetic variability (PNPLA3 I148M) and monogenic lipid disorders (APOB and MTTP mutations). Screening of drug candidates revealed compounds effective at resolving steatosis. Mechanistic evaluation of effective drugs uncovered repression of de novo lipogenesis as the convergent molecular pathway. We present FatTracer, a CRISPR screening platform to identify steatosis modulators and putative targets using APOB and MTTP organoids. From a screen targeting 35?genes implicated in lipid metabolism and/or NAFLD risk, FADS2 (fatty acid desaturase?2) emerged as an important determinant of hepatic steatosis. Enhancement of FADS2 expression increases polyunsaturated fatty acid abundancy which, in turn, reduces de novo lipogenesis. These organoid models facilitate study of steatosis etiology and drug targets.
© 2023. The Author(s).
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Age-related changes and longitudinal stability of individual differences in ABCD Neurocognition measures.
Dev Cogn Neurosci2022 Apr;54():101078. doi: 101078.
Anokhin Andrey P, Luciana Monica, Banich Marie, Barch Deanna, Bjork James M, Gonzalez Marybel R, Gonzalez Raul, Haist Frank, Jacobus Joanna, Lisdahl Krista, McGlade Erin, McCandliss Bruce, Nagel Bonnie, Nixon Sara Jo, Tapert Susan, Kennedy James T, Thompson Wesley
Temporal stability of individual differences is an important prerequisite for accurate tracking of prospective relationships between neurocognition and real-world behavioral outcomes such as substance abuse and psychopathology. Here we report age-related changes and longitudinal test-retest stability (TRS) for the Neurocognition battery of the Adolescent Brain and Cognitive Development (ABCD) study, which included the NIH Toolbox (TB) Cognitive Domain and additional memory and visuospatial processing tests administered at baseline (ages 9-11) and two-year follow-up. As expected, performance improved significantly with age, but the effect size varied broadly, with Pattern Comparison and the Crystallized Cognition Composite showing the largest age-related gain (Cohen's d:.99 and.97, respectively). TRS ranged from fair (Flanker test: r = 0.44) to excellent (Crystallized Cognition Composite: r = 0.82). A comparison of longitudinal changes and cross-sectional age-related differences within baseline and follow-up assessments suggested that, for some measures, longitudinal changes may be confounded by practice effects and differences in task stimuli or procedure between baseline and follow-up. In conclusion, a subset of measures showed good stability of individual differences despite significant age-related changes, warranting their use as prospective predictors. However, caution is needed in the interpretation of observed longitudinal changes as indicators of neurocognitive development.
Copyright © 2022. Published by Elsevier Ltd.
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Staining and High-Resolution Imaging of Three-Dimensional Organoid and Spheroid Models.
J Vis Exp2021 Mar;(169):. doi: 10.3791/62280.
Gonzalez Alejandro Lopez, Luciana Léa, Le Nevé Clémentine, Valantin Julie, Francols Laura, Gadot Nicolas, Vanbelle Christophe, Davignon Laurianne, Broutier Laura
In vitro three-dimensional (3D) cell culture models, such as organoids and spheroids, are valuable tools for many applications including development and disease modeling, drug discovery, and regenerative medicine. To fully exploit these models, it is crucial to study them at cellular and subcellular levels. However, characterizing such in vitro 3D cell culture models can be technically challenging and requires specific expertise to perform effective analyses. Here, this paper provides detailed, robust, and complementary protocols to perform staining and subcellular resolution imaging of fixed in vitro 3D cell culture models ranging from 100 µm to several millimeters. These protocols are applicable to a wide variety of organoids and spheroids that differ in their cell-of-origin, morphology, and culture conditions. From 3D structure harvesting to image analysis, these protocols can be completed within 4-5 days. Briefly, 3D structures are collected, fixed, and can then be processed either through paraffin-embedding and histological/immunohistochemical staining, or directly immunolabeled and prepared for optical clearing and 3D reconstruction (200 µm depth) by confocal microscopy.
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Effect of metals on Daphnia magna and cladocerans representatives of the Argentinean fluvial littoral.
J Environ Biol2014 Jul;35(4):689-97.
Luciana Regaldo, Reno Ulises, Gervasio Susana, Horacio Troiani, Gagneten Ana María
Chronic toxicity tests were conducted to assess the effect of Cu, Cr and Pb on Moinodaphnia macleayi and Ceriodaphnia dubia -two cladoceran species from the Argentinian Fluvial Littoral Zone (AFLZ)- and Daphnia magna -an holarctic species-. The specimens were exposed to three concentrations of each metal. As endpoints, the number of living and dead organisms, molts, neonates released, and the age of first reproduction were recorded. Chronic assays showed that Cu significantly affected the analyzed life history traits in the three species. The lowest Pb and Cr concentrations did not affect survival, molting or fecundity in D. magna. Conversely, in M. macleayi and C. dubia, survival, molting and fecundity showed highly significant differences in all the concentrations tested compared to control assay. The present study stresses the importance of using biological parameters as bioindicators, as well as the study species from the Southern Hemisphere to assess metal pollution.
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Ameliorative effects of ethanolic leaf extract of Azadirachta indica on renal histologic alterations in streptozotocin-induced diabetic rats.
Am J Chin Med2011 ;39(5):903-16. doi: 10.1142/S0192415X11009299.
Oluwole Busayo Akinola, Laura Zatta, Olufunke Olubusola Dosumu, Oluwafunmike Sharon Akinola, Luciana Dini, Ezekiel Ademola Caxton-Martins
We studied the effect of ethanolic leaf extract of Azadirachta indica (AIE) on the microanatomy of the kidney of streptozotocin-induced diabetic rats. Thirty male Wistar rats (161-190 g) were randomly assigned to one of five treatment groups of six animals each: control, diabetic, diabetic + AIE, diabetic + metformin, AIE only. Diabetes was induced with a single intraperitoneal dose of streptozotocin (70 mg/kg body weight). AIE and metformin were administered orally for 50 days (50 d) at 500 mg/kg bw/d and 350 mg/kg bw/d, respectively. Blood glucose was estimated by glucose oxidase method; plasma urea and creatinine were assayed; and paraffin sections of the kidney were stained by periodic acid-Schiff technique. Untreated diabetic rats exhibited marked hyperglycemia. Renal histopathology of these animals showed features of diabetic nephropathy, with nodular glomerulosclerosis and vacuolation of proximal tubule cells (Armanni-Ebstein phenomenon). These feature were absent in the diabetic rats treated with AIE. Besides, plasma urea and creatinine were not significantly different from the control in this group (p > 0.05), in contrast to the untreated diabetic rats, where significant increases in these markers (p
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Perinatal iron deficiency decreases cytochrome c oxidase (CytOx) activity in selected regions of neonatal rat brain.
Pediatr Res2000 Aug;48(2):169-76.
de Deungria M, Rao R, Wobken J D, Luciana M, Nelson C A, Georgieff M K
Intrauterine growth retardation and diabetes mellitus during human gestation result in significant losses of fetal and neonatal brain iron. Brain iron deficiency is associated with impaired cognitive processes including memory and attention. The regional distribution of iron staining and cytochrome c oxidase (CytOx) activity have not been mapped in the iron-sufficient or -deficient neonatal rat. CytOx is the iron-containing terminal enzyme in oxidative phosphorylation; its activity reflects neuronal metabolism. We hypothesized that neonatal brain iron deficiency differentially decreases iron and CytOx activity in brain regions, with more pronounced losses in structures involved in recognition memory. Pregnant Sprague Dawley rats were fed either an iron-deficient or -fortified diet from gestational d 1 until postnatal d 10. Iron staining and CytOx activity of 20 brain structures were mapped histochemically in 25 rats from each group. Brain iron staining was reduced from 75% to 100% and CytOx staining was decreased from 0% to 42% in the iron deficient group (p
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