155 results on '"Guarnieri V"'
Search Results
2. Correction to: The diagnosis of hypophosphatasia in children as a multidisciplinary effort: an expert opinion
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Baroncelli, G. I., Carlucci, G., Freri, E., Giuca, M. R., Guarnieri, V., Navarra, G., Toschi, B., and Mora, S.
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- 2024
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3. Clinical, biochemical and genetic findings in adult patients with chronic hypophosphatasemia
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Guarnieri, V., Sileri, F., Indirli, R., Guabello, G., Longhi, M., Dito, G., Verdelli, C., and Corbetta, S.
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- 2022
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4. Denosumab for the treatment of primary pediatric osteoporosis
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Anastasilakis, A.D., Makras, P., Doulgeraki, A., Polyzos, S.A., Guarnieri, V., and Papapoulos, S.E.
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- 2021
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5. Gas Sensor System for the Determination of Methane in Water
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Vasiliev, A.A., Pisliakov, A.V., Sokolov, A.V., Polovko, O.V., Samotaev, N.N., Kujawski, W., Rozicka, A., Guarnieri, V., and Lorencelli, L.
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- 2014
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6. RF sputtering of ZnO films in Ar and Ar–H2 gas mixtures: Role of H incorporation in developing transparent conductive coatings
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Gottardi, G., Bartali, R., Micheli, V., Guarnieri, V., Luciu, I., Pu, P., Pandiyan, R., and Laidani, N.
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- 2011
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7. A novel CDC73 gene mutation in an Italian family with hyperparathyroidism-jaw tumour (HPT-JT) syndrome
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Chiofalo, M. G., Sparaneo, A., Chetta, M., Franco, R., Baorda, F., Cinque, L., Granatiero, M., D’Agruma, L., Pezzullo, L., Scillitani, A., and Guarnieri, V.
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- 2014
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8. Integration of a technique for the deposition of nanostructured films with MEMS-based microfabrication technologies: Application to micro gas sensors
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Decarli, Massimiliano, Lorenzelli, L., Guarnieri, V., Barborini, E., Vinati, S., Ducati, C., and Milani, P.
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- 2009
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9. Fabrication of a MEMS-based separation module for liquid chromatography
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Benvenuto, A., Guarnieri, V., Lorenzelli, L., Collini, C., Decarli, M., Adami, A., Potrich, C., Lunelli, L., Canteri, R., and Pederzolli, C.
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- 2008
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10. Linear temperature microhotplate gas sensor array for automotive cabin air quality monitoring
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Francioso, L., Forleo, A., Taurino, A.M., Siciliano, P., Lorenzelli, L., Guarnieri, V., Adami, A., and Agnusdei, G.
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- 2008
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11. Paraoxonase gene variants are associated with autism in North America, but not in Italy: possible regional specificity in gene–environment interactions
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D'Amelio, M, Ricci, I, Sacco, R, Liu, X, D'Agruma, L, Muscarella, L A, Guarnieri, V, Militerni, R, Bravaccio, C, Elia, M, Schneider, C, Melmed, R, Trillo, S, Pascucci, T, Puglisi-Allegra, S, Reichelt, K-L, Macciardi, F, Holden, J J A, and Persico, A M
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- 2005
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12. Radiation exposure and Mission Strategies for Interplanetary Manned Missions (REMSIM)
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Cougnet, C., Crosby, N. B., Eckersley, S., Foullon, C., Guarnieri, V., Guatelli, S., Heynderickx, D., Holmes-Siedle, A., Lobascio, C., Masiello, S., Nieminen, P., Parisi, G., Parodi, P., Perino, M. A., Pia, M. G., Rampini, R., Spillantini, P., Tamburini, V., and Tracino, E.
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- 2004
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13. RADIATION EXPOSURE AND MISSION STRATEGIES FOR INTERPLANETARY MANNED MISSIONS (REMSIM)
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Cougnet, C., Crosby, N. B., Foullon, C., Heynderickx, D., Eckersley, S., Guarnieri, V., Lobascio, C., Masiello, S., Parodi, P., Perino, M. A., Rampini, R., Guatelli, S., Pia, M. G., Holmes-Siedle, A., Nieminen, P., Parisi, G., Tamburini, V., Spillantini, P., and Tracino, E.
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- 2005
14. Low-power thick-film gas sensor obtained by a combination of screen printing and micromachining techniques
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Vincenzi, D, Butturi, M.A, Stefancich, M, Malagù, C, Guidi, V, Carotta, M.C, Martinelli, G, Guarnieri, V, Brida, S, Margesin, B, Giacomozzi, F, Zen, M, Vasiliev, A.A, and Pisliakov, A.V
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- 2001
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15. The Sileye–Altcriss experiment on board the International Space Station
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Casolino, M., Altamura, F., Minella, A., Minori, M., Picozza, P., Reali, E., Esposito, A., Bedogni, R., Mazzenga, G., Ricci, M., Durante, M., Pugliese, M., Roca, V., Galper, A., Korotkov, M., Popov, A., Bengin, V., Lobascio, C., Guarnieri, V., Fortezza, R., and Castagnolo, D.
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- 2007
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16. PO-450 Interplay between coding and non-coding genome in human parathyroid tumours
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Morotti, A., Forno, I., Verdelli, C., Guarnieri, V., Terrasi, A., Silipigni, R., Guerneri, S., Cetani, F., Corbetta, S., and Vaira, V.
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- 2018
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17. THU-397 - Multifactor risk evaluation in patients who have eradicated HCV infection: an interim analysis in the PITER cohort
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Kondili, L., Quaranta, M.G., Rosato, S., Monti, M., Coco, B., Filomia, R., Biliotti, E., Iannone, A., Zanetto, A., Bruno, S., Giorgini, A., Loi, M., Baragli, F., Baiguera, C., Vinci, M., Eleonora, C., Ciaccio, A., Corsini, R., D’ambrosio, R., Labanca, S., Dallio, M., Orlandini, A., Ciancio, A., Buonomo, A.R., Guarnieri, V., Cossiga, V., Masarone, M., Ieluzzi, D., Cannizzaro, M., Soria, A., Siciliano, M., Amoruso, D.C., Brancaccio, G., Weimer, L.E., Ferrigno, L., Tosti, M.E., Estes, C., Razavi, H., and Calvaruso, V.
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- 2018
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18. Tumour-associated fibroblasts contribute to neoangiogenesis in human parathyroid neoplasia.
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Verdelli, C., Avagliano, L., Creo, P., Guarnieri, V., Scillitani, A., Vicentini, L., Steffano, G. B., Beretta, E., Soldati, L., Costa, E., Spada, A., Bulfamante, G. P., and Corbetta, S.
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CANCER ,FIBROBLASTS ,TUMORS ,IMMUNOHISTOCHEMISTRY ,ACTIN ,SMOOTH muscle ,MESENCHYMAL stem cells ,GENE expression - Abstract
Components of the tumour microenvironment initiate and promote cancer development. In this study, we investigated the stromal component of parathyroid neoplasia. Immunohistochemistry for alpha-smooth muscle actin (a-SMA) showed an abundant periacinar distribution of α-SMAC cells in normal parathyroid glands (n = 3). This pattern was progressively lost in parathyroid adenomas (PAds; n = 6) where α-SMA
+ cells were found to surround new microvessels, as observed in foetal parathyroid glands (n= 2). Moreover, in atypical adenomas (n = 5) and carcinomas (n = 4), α-SMA+ cells disappeared from the parenchyma and accumulated in the capsula and fibrous bands. At variance with normal glands, parathyroid tumours (n = 37) expressed high levels of fibroblast-activation protein (FAP) transcripts, a marker of tumour-associated fibroblasts. We analysed the ability of PAd-derived cells to activate fibroblasts using human bone-marrow mesenchymal stem cells (hBM-MSCs). PAd-derived cells induced a significant increase in FAP and vascular endothelial growth factor A (VEGFA) mRNA levels in co-cultured hBM-MSCs. Furthermore, the role of the calcium-sensing receptor (CASR) and of the CXCL12/CXCR4 pathway in the PAd-induced activation of hBM-MSCs was investigated. Treatment of co-cultures of hBM-MSCs and PAd-derived cells with the CXCR4 inhibitor AMD3100 reduced the stimulated VEGFA levels, while CASR activation by the R568 agonist was ineffective. PAd-derived cells co-expressing parathyroid hormone (PTH)/CXCR4 and PTH/CXCL12 were identified by FACS, suggesting a paracrine/autocrine signalling. Finally, CXCR4 blockade by AMD3100 reduced PTH gene expression levels in PAd-derived cells. In conclusion, i) PAd-derived cells activated cells of mesenchymal origin; ii) PAd-associated fibroblasts were involved in tumuor neoangiogenesis and iii) CXCL12/CXCR4 pathway was expressed and active in PAd cells, likely contributing to parathyroid tumour neoangiogenesis and PTH synthesis modulation. [ABSTRACT FROM AUTHOR]- Published
- 2015
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19. ACCELERATOR-BASED TESTS OF RADIATION SHIELDING PROPERTIES OF MATERIALS USED IN HUMAN SPACE INFRASTRUCTURES.
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Lobascio, C., Briccarello, M., Destefanis, R., Faraud, M., Gialanella, G., Grossi, G., Guarnieri, V., Manti, L., Pugliese, M., Rusek, A., Scampoli, P., and Durante, M.
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ASTROPHYSICAL radiation ,RADIATION shielding ,POLYPHENYLENETEREPHTHALAMIDE ,COSMIC rays ,HEAVY ion accelerators ,POLYMETHYLMETHACRYLATE ,LUCITE ,POLYETHYLENE ,ASTRONAUTS ,METEOROIDS - Abstract
The article discusses astronaut protection from space radiation provided by Kevlar and Nextel shielding materials. The authors compared the response to simulated heavy-ion cosmic radiation of these micrometeoroid shielding materials with Lucite (PMMA), polyethelene and aluminum. They utilized an accelerator to generate high-energy iron and titanium ions. They concluded that Kevlar is nearly as effective as polyethylene and can be more efficient in reducing chromosomal damage than Lucite (PMMA). Nextel was only about half as efficient as polyethylene as a radiation shield.
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- 2008
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20. Gas-sensing device implemented on a micromachined membrane: A combination of thick-film and very large scale integrated technologies.
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Vincenzi, D., Butturi, M. A., Guidi, V., Carotta, M. C., Martinelli, G., Guarnieri, V., Brida, S., Margesin, B., Giacomozzi, F., Zen, M., Giusti, D., Soncini, G., Vasiliev, A. A., and Pisliakov, A. V.
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- 2000
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21. INDOCYANINE GREEN VIDEOANGIOGRAPHY USING COOLED CHARGE-COUPLED DEVICES IN CENTRAL SEROUS CHOROIDOPATHY.
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Ciamberlini, C., Guarnieri, V., Longobardi, Giuseppe, Poggi, Pasquale, Donati, M. C., and Panzardi, G.
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- 1997
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22. Candidate gene study of HOXB1 in autism spectrum disorder
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Muscarella Lucia A, Guarnieri Vito, Sacco Roberto, Curatolo Paolo, Manzi Barbara, Alessandrelli Riccardo, Giana Grazia, Militerni Roberto, Bravaccio Carmela, Lenti Carlo, Saccani Monica, Schneider Cindy, Melmed Raun, D'Agruma Leonardo, and Persico Antonio M
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Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Background HOXB1 plays a major role in brainstem morphogenesis and could partly determine the cranial circumference in conjunction with HOXA1. In our sample, HOXA1 alleles significantly influence head growth rates both in autistic patients and in population controls. An initial report, suggesting that HOXB1 could confer autism vulnerability in interaction with HOXA1, was not confirmed by five small association studies. Methods Our sample includes 269 autistic individuals, belonging to 219 simplex and 28 multiplex families. A mutational analysis of the two exons and flanking intronic sequences of the HOXB1 gene was carried out in 84 autistic patients by denaturing high performance liquid chromatography, followed by DNA sequencing. Identified rare variants were then searched by a restriction analysis in 236 autistic patients and 325-345 controls. Case-control and family-based association studies were performed on two common variants in 169 Italian patients versus 184 Italian controls and in 247 trios. Results We identified three common polymorphisms, rs72338773 [c.82insACAGCGCCC (INS/nINS)], rs12939811 [c.309A>T (Q103H)], and rs7207109 [c.450G>A (A150A)] and three rare variants, namely IVS1+63G>A, rs35115415 [c.702G>A (V234V)] and c.872_873delinsAA (S291N). SNPs rs72338773 and rs12939811 were not associated with autism, using either a case-control (alleles, exact P = 0.13) or a family-based design [transmission/disequilibrium test (TDT)χ2 = 1.774, P = 0.183]. The rare variants, all inherited from one of the parents, were present in two Italian and in two Caucasian-American families. Autistic probands in two families surprisingly inherited a distinct rare variant from each parent. The IVS1+63A allele was present in 3/690 control chromosomes, whereas rare alleles at rs35115415 and c.872_873delinsAA (S291N) were not found in 662 and 650 control chromosomes, respectively. The INS-T309 allele influenced head size, but its effect appears more modest and shows no interaction with HOXA1 alleles. The INS-T309 allele is also associated with more severe stereotypic behaviours, according to ADI-R scores (N = 60 patients, P < 0.01). Conclusions HOXB1 mutations do not represent a common cause of autism, nor do HOXB1 common variants play important roles in autism vulnerability. HOXB1 provides minor, albeit detectable contributions to head circumference in autistic patients, with HOXA1 displaying more prominent effects. HOXB1 variants may modulate the clinical phenotype, especially in the area of stereotypic behaviours.
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- 2010
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23. New methods for microbial contamination monitoring: An experiment on board the mir orbital station
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Guarnieri, V., Gaia, E., Battocchio, L., Pitzurra, M., Savino, A., Pasquarella, C., Vago, T., and Cotronei, V.
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- 1997
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24. The microgravity data bank for scientific and industrial communities
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Monti, R., Guarnieri, V., and Lavitola, M. S.
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- 1989
25. A WO3-based gas sensor array with linear temperature gradient for wine quality monitoring
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Adami, A., Lorenzelli, L., Guarnieri, V., Francioso, L., Forleo, A., Agnusdei, G., Taurino, A.M., Zen, M., and Siciliano, P.
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SOLID state electronics , *THIN films , *SURFACE coatings , *DIELECTRIC films - Abstract
Abstract: In this work we describe the design implementation, validated by experimental results, of an innovative gas sensor array for wine quality monitoring. The main innovation of this integrated array deals with the simultaneous outputs, from a single chip on custom SMD socket, of eight different signals coming from a WO3 thin film structure heated in a linear temperature gradient mode, allowing an overall evaluation of gas sensing properties of the material in a 100°C-wide window, typically from 300 to 400°C. The implemented sensitive layer is a WO3 film deposed by RF-sputtering. Preliminary tests of gas sensing showed good responses to the target analytes for the specific application (1-heptanol, 3-methylbutanol, benzaldehyde and ethyl-hexanoate). [Copyright &y& Elsevier]
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- 2006
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26. Non-silicon MEMS platforms for gas sensors.
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Vasiliev, A.A., Pisliakov, A.V., Sokolov, A.V., Samotaev, N.N., Soloviev, S.A., Oblov, K., Guarnieri, V., Lorenzelli, L., Brunelli, J., Maglione, A., Lipilin, A.S., Mozalev, A., and Legin, A.V.
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SILICON , *DETECTORS , *ELECTRIC power consumption , *ALUMINUM oxide , *ZIRCONIUM - Abstract
The target of this work is the demonstration of advanced approaches able to provide non-silicon MEMS platforms for chemical sensor operating under harsh environmental conditions and, on the other hand, to assure microhotplate stable at high temperature, which can be used for the deposition of refractory gas-sensing materials, for example, oxides of gallium, zirconium, or hafnium. Non-silicon materials that can be used for these MEMS platforms include aluminum oxide, yttria-stabilized zirconia and thin borosilicate glass. It was shown that thin ceramic films made of oxide materials can withstand annealing temperature up to 1000 °C, MEMS sensor based on these films consumes <70 mW at continuous heating at 450 °C and ∼1 mW in pulsed heating operation mode. Ceramic MEMS show higher stability at high temperature compared to silicon technology based MEMS, whereas power consumption of both types of devices is comparable. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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27. 125 HEPATITIS DELTA VIRUS (HDV) INDUCES SPECIFIC DNA METHYLATION EVENTS TOWARDS MALIGNANCY IN HEPATOMA CELLS.
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Benegiamo, G., Vinciguerra, M., Guarnieri, V., Niro, G.A., Andriulli, A., and Pazienza, V.
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- 2013
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28. The Altcriss project on board the International Space Station
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Casolino, M., Altamura, F., Minori, M., Picozza, P., Fuglesang, C., Galper, A., Popov, A., Benghin, V., Petrov, V.M., Nagamatsu, A., Berger, T., Reitz, G., Durante, M., Pugliese, M., Roca, V., Sihver, L., Cucinotta, F., Semones, E., Shavers, M., and Guarnieri, V.
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SPACE exploration , *ASTRONAUTICS , *METAPHYSICAL cosmology , *SPACE sciences - Abstract
Abstract: The Altcriss project aims to perform a long term survey of the radiation environment on board the International Space Station. Measurements are being performed with active and passive devices in different locations and orientations of the Russian segment of the station. The goal is to perform a detailed evaluation of the differences in particle fluence and nuclear composition due to different shielding material and attitude of the station. The Sileye-3/Alteino detector is used to identify nuclei up to Iron in the energy range above ≃60MeV/n. Several passive dosimeters (TLDs, CR39) are also placed in the same location of Sileye-3 detector. Polyethylene shielding is periodically interposed in front of the detectors to evaluate the effectiveness of shielding on the nuclear component of the cosmic radiation. The project was submitted to ESA in reply to the AO in the Life and Physical Science of 2004 and data taking began in December 2005. Dosimeters and data cards are rotated every 6 months: up to now three launches of dosimeters and data cards have been performed and have been returned with the end of expedition 12 and 13. [Copyright &y& Elsevier]
- Published
- 2007
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29. 438 HEPATITIS DELTA VIRUS UPREGULATES DNMT3B THROUGH STAT3 ACTIVATION IN HUH-7 CELLS
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Benegiamo, G., Vinciguerra, M., Mazzoccoli, G., Guarnieri, V., Niro, G., Andriulli, A., and Pazienza, V.
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- 2012
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30. RF sputtering of ZnO films in Ar and Ar–H2 gas mixtures: Role of H incorporation in developing transparent conductive coatings
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Gottardi, G., Bartali, R., Micheli, V., Guarnieri, V., Luciu, I., Pu, P., Pandiyan, R., and Laidani, N.
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ZINC oxide thin films , *RADIO frequency , *SPUTTERING (Physics) , *MIXTURES , *SURFACE coatings , *X-ray photoelectron spectroscopy , *X-ray diffraction , *HYDROGEN - Abstract
Abstract: Fundamental and applied investigation of ZnO has been recently experiencing a renaissance due to its prospective use in various technological domains and, in particular, as transparent conductive oxide (TCO). In this respect, the present work aims to study the structural and physical properties of ZnO thin films deposited by RF sputtering in pure Ar and Ar–H2 plasmas, at various concentrations (0–50%). The plasma chemical species were followed in function of the different gas mixture settings by optical emission spectroscopy (OES). X-ray photoelectron spectroscopy (XPS) and ATR-FTIR (Attenuated Total Reflection Fourier-Transformed Infrared) spectroscopy were used to study the bulk and surface chemical composition of the films, X-ray Diffraction (XRD) analysis allowed lattice structure and grain size determination while samples morphology was checked with a scanning electron microscope (SEM). The films were also characterized for their electrical and optical properties. The introduction of hydrogen in the plasma phase strongly affected the structural, chemical and physical properties of the films. In particular a pronounced change in the film electrical behavior was observed which become conductive when H is added in the gas mixture ([H2]>6%). The film transparency was on the other hand maintained. By combining XPS, ATR-FTIR and OES data we could correlate the established conductivity and its variations with intentional hydrogen incorporation in the crystal structure in the form of hydroxide species. [Copyright &y& Elsevier]
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- 2011
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31. Impact of respiratory syncytial virus on older children: Exploring the potential for preventive strategies beyond the age of 2 years.
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Guarnieri V, Macucci C, Mollo A, Trapani S, Moriondo M, Vignoli M, Ricci S, and Indolfi G
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- Humans, Infant, Child, Preschool, Retrospective Studies, Male, Female, Child, Adolescent, Infant, Newborn, Respiratory Tract Infections prevention & control, Respiratory Tract Infections epidemiology, Respiratory Tract Infections virology, Risk Factors, Comorbidity, Seasons, Respiratory Syncytial Virus Infections prevention & control, Respiratory Syncytial Virus Infections epidemiology, Hospitalization statistics & numerical data, Respiratory Syncytial Virus, Human immunology
- Abstract
Objective: Respiratory syncytial virus (RSV) causes significant lower respiratory tract infections (LRTIs) in infants and young children. Current prevention targets those under 2 years. This study aims to evaluate RSV patterns and severity in children older than 2 years and to explore the potential extension of preventive strategies to this demographic group., Methods: An observational retrospective study at Meyer Children's Hospital (from October 2019 to March 2023) analyzed data from patients between 28 days and 18 years of age with RSV infection. Severity indicators and patient characteristics were compared between two age groups: under 2 years and 2 years and above., Results: 584 infants and young children were hospitalized due to RSV infection. Epidemic seasons saw a rise in hospitalizations among children older than 2 years. Older children had higher comorbidity (41% versus 9% p=0.000) and prematurity (26% versus 14% p = 0.001) rates than those under 2 years., Conclusion: The study highlights the increased risk of severe RSV LRTIs in children older than 2 years and with prematurity or comorbidities, overlooked by current preventive measures. Prospective studies and cost-effectiveness analyses are needed to determine the necessity of targeted immunization for older children with specific risk factors, aiming to reduce RSV-related morbidity and mortality., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2024
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32. Multiple Endocrine Neoplasia Type 1 Regulates TGFβ-Mediated Suppression of Tumor Formation and Metastasis in Melanoma.
- Author
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Boudreault J, Canaff L, Ghozlan M, Wang N, Guarnieri V, Salcuni AS, Scillitani A, Goltzman D, Ali S, and Lebrun JJ
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- Humans, Animals, Cell Line, Tumor, Mice, Neoplasm Metastasis, Proto-Oncogene Proteins metabolism, Proto-Oncogene Proteins genetics, Apoptosis genetics, Carcinogenesis genetics, Carcinogenesis pathology, Skin Neoplasms genetics, Skin Neoplasms pathology, Skin Neoplasms metabolism, Proteasome Endopeptidase Complex metabolism, Cell Proliferation genetics, Gene Expression Regulation, Neoplastic, Melanoma genetics, Melanoma pathology, Melanoma metabolism, Transforming Growth Factor beta metabolism, Signal Transduction
- Abstract
Over the past few decades, the worldwide incidence of cutaneous melanoma, a malignant neoplasm arising from melanocytes, has been increasing markedly, leading to the highest rate of skin cancer-related deaths. While localized tumors are easily removed by excision surgery, late-stage metastatic melanomas are refractory to treatment and exhibit a poor prognosis. Consequently, unraveling the molecular mechanisms underlying melanoma tumorigenesis and metastasis is crucial for developing novel targeted therapies. We found that the multiple endocrine neoplasia type 1 (MEN1) gene product Menin is required for the transforming growth factor beta (TGFβ) signaling pathway to induce cell growth arrest and apoptosis in vitro and prevent tumorigenesis in vivo in preclinical xenograft models of melanoma. We further identified point mutations in two MEN1 family members affected by melanoma that led to proteasomal degradation of the MEN1 gene product and to a loss of TGFβ signaling. Interestingly, blocking the proteasome degradation pathway using an FDA-approved drug and RNAi targeting could efficiently restore MEN1 expression and TGFβ transcriptional responses. Together, these results provide new potential therapeutic strategies and patient stratification for the treatment of cutaneous melanoma.
- Published
- 2024
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33. Expanded Newborn Screening for Inborn Errors of Immunity: The Experience of Tuscany.
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Ricci S, Guarnieri V, Capitanini F, Pelosi C, Astorino V, Boscia S, Calistri E, Canessa C, Cortimiglia M, Lippi F, Lodi L, Malvagia S, Moriondo M, La Marca G, and Azzari C
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- Humans, Infant, Newborn, Italy epidemiology, Retrospective Studies, Male, Female, Severe Combined Immunodeficiency diagnosis, Severe Combined Immunodeficiency epidemiology, Severe Combined Immunodeficiency immunology, Severe Combined Immunodeficiency genetics, Receptors, Antigen, T-Cell genetics, Receptors, Antigen, T-Cell immunology, Neonatal Screening
- Abstract
Background: Inborn errors of immunity (IEIs) include 485 inherited disorders characterized by an increased susceptibility to life-threatening infectious diseases, autoimmunity, and malignant diseases with a high mortality rate in the first years of life. Severe combined immunodeficiency is the most severe of the IEIs, and its detection should be a primary goal in a newborn screening (NBS) program. The term "actionable" has recently been used for all IEIs with outcomes that can be demonstrably improved through early specialized intervention., Objective: To evaluate the results of the expanded NBS strategy for IEIs in Tuscany Region (Italy), based on T-cell receptor excision circle, kappa recombining excision circle, and tandem mass-based assays., Methods: This is a retrospective study collecting data from all infants born in Tuscany from October 10, 2018, to October 10, 2022. Tandem mass assay to identify adenosine deaminase and purine nucleoside phosphorylase deficiency, together with T-cell receptor excision circle and kappa recombining excision circle molecular analysis, was conducted on dried blood spot from the newborns' Guthrie Cards. A new dried blood spot and evaluation by an immunologist were carried out when the results of the first test were outside the diagnostic cutoffs., Results: A total of 94,319 newborns were evaluated. Referral rates for T-cell recombining excision circles (0.031%) and kappa recombining excision circles (0.074%) in this study are in line with the data available in literature. The results from the expanded NBS strategy revealed an incidence rate of 1 per 9431 affected newborns., Conclusions: This work represents the first description of a sustainable and real-life-based expanded NBS program for IEIs with a high diagnostic incidence facilitating prompt management of identified patients., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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34. Cross-sectional survey evaluating the psychological impact of the COVID-19 vaccination campaign in patients with cancer: The VACCINATE study.
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Tregnago D, Avancini A, Belluomini L, Trestini I, Sposito M, Insolda J, Bianchi F, Sava T, Gaiani C, Del Piccolo L, Guarnieri V, Verlato G, Tfaily A, Vesentini R, Zuliani S, Pilotto S, and Milella M
- Subjects
- Adult, Female, Humans, Middle Aged, Anxiety epidemiology, Cross-Sectional Studies, Depression epidemiology, Pandemics, Stress, Psychological epidemiology, Male, Young Adult, Aged, Aged, 80 and over, COVID-19 epidemiology, COVID-19 prevention & control, COVID-19 Vaccines administration & dosage, Neoplasms complications, Vaccination psychology
- Abstract
The COVID-19 pandemic has profoundly impacted on cancer patients' psychological well-being and clinical status. We assessed the levels of anxiety, depression, and distress and the attitude towards COVID-19 vaccination in cancer patients, accepting vaccination at the Verona University Hospital and Camposampiero Hospital in the Veneto region. Self-reported questionnaires were administered to patients undergoing COVID-19 vaccination between March and May 2021 (first and second dose). Twenty-seven items were investigated: i) demographics/clinical characteristics; ii) anxiety, depression, and distress (Hospital Anxiety and Depression Scale-HADS-and Distress Thermometer-DT); iii) four specific items regarding awareness about infection risks, interference with anticancer treatments, and vaccine side effects. Sixty-two and 57% of the patients who accepted to be vaccinated responded to the survey in the two participating Hospitals, respectively. Mean age was 63 years (SD: 12 years; range 19-94 years), women were slightly more prevalent (57.6%), most participants were married (70%), and either worker or retired (60%). Borderline and clinical levels of anxiety were recorded in 14% and 10% of respondents; borderline and clinical levels of depression in 14% and 8%; and moderate and severe distress levels in 33% and 9%. Overall, there was high confidence that vaccination would reduce the risk of contracting COVID-19 (70%), which would make patients feel less worried about contracting the infection (60%). Fear that vaccine-related side effects would interfere with anticancer treatment and/or global health status was low (10% and 9% for items 3 and 4, respectively) and significantly associated with baseline levels of anxiety, depression, and distress at multivariate analysis. Results did not differ between the Verona and Camposampiero cohorts. During the COVID-19 vaccination campaign, adult cancer patients demonstrated high levels of confidence towards vaccination; baseline levels of anxiety, depression, and distress were the only significant predictors of reduced confidence., Competing Interests: The authors declare that they have no conflict of interest., (Copyright: © 2024 Tregnago et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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- 2024
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35. Clinical Factors Predicting Multiple Endocrine Neoplasia Type 1 and Type 4 in Patients with Neuroendocrine Tumors.
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Faggiano A, Fazzalari B, Mikovic N, Russo F, Zamponi V, Mazzilli R, Guarnieri V, Piane M, Visco V, and Petrucci S
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- Humans, Adult, Genetic Testing, Gastrointestinal Tract pathology, Multiple Endocrine Neoplasia Type 1 diagnosis, Multiple Endocrine Neoplasia Type 1 genetics, Neuroendocrine Tumors diagnosis, Neuroendocrine Tumors genetics, Neuroendocrine Tumors pathology, Pituitary Neoplasms genetics
- Abstract
The aim of this study is to evaluate the predictive role of specific clinical factors for the diagnosis of Multiple Endocrine Neoplasia type-1 (MEN1) and type-4 (MEN4) in patients with an initial diagnosis of gastrointestinal, bronchial, or thymic neuroendocrine tumor (NET)., Methods: Patients referred to the NET Unit between June 2021 and December 2022 with a diagnosis of NET and at least one clinical criterion of suspicion for MEN1 and MEN4 underwent molecular analysis of the MEN1 and CDKN1B genes. Phenotypic criteria were: (1) age ≤ 40 years; (2) NET multifocality; (3) MEN1/4-associated manifestations other than NETs; and (4) endocrine syndrome related to NETs or pituitary/adrenal tumors., Results: A total of 22 patients were studied. In 18 patients (81.8%), the first-level genetic test was negative (Group A), while four patients (25%) were positive for MEN1 (Group B). No patient was positive for MEN4 . In Group A, 10 cases had only one clinical criterion, and three patients met three criteria. In Group B, three patients had three criteria, and one met all criteria., Conclusion: These preliminary data show that a diagnosis of NET in patients with a negative family history is suggestive of MEN1 in the presence of ≥three positive phenotypic criteria, including early age, multifocality, multiple MEN-associated manifestations, and endocrine syndromes. This indication may allow optimization of the diagnosis of MEN in patients with NET.
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- 2023
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36. Clinical and molecular description of the first Italian cohort of 33 subjects with hypophosphatasia.
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Cinque L, Pugliese F, Salcuni AS, Trombetta D, Battista C, Biagini T, Augello B, Nardella G, Conti F, Corbetta S, Fischetto R, Foiadelli T, Gaudio A, Giannini C, Grosso E, Guabello G, Massuras S, Palermo A, Politano L, Pigliaru F, Ruggeri RM, Scarano E, Vicchio P, Cannavò S, Celli M, Petrizzelli F, Mastroianno M, Castori M, Scillitani A, and Guarnieri V
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- Adult, Humans, Phylogeny, Computational Biology, Diagnosis, Differential, Italy epidemiology, Rare Diseases, Hypophosphatasia diagnosis, Hypophosphatasia epidemiology, Hypophosphatasia genetics
- Abstract
Introduction: Hypophosphatasia (HPP) is a rare genetic disease caused by inactivating variants of the ALPL gene. Few data are available on the clinical presentation in Italy and/or on Italian HPP surveys., Methods: There were 30 suspected HPP patients recruited from different Italian tertiary cares. Biological samples and related clinical, biochemical, and anamnestic data were collected and the ALPL gene sequenced. Search for large genomic deletions at the ALPL locus (1p36) was done. Phylogenetic conservation and modeling were applied to infer the effect of the variants on the protein structure., Results: There were 21 ALPL variants and one large genomic deletion found in 20 out of 30 patients. Unexpectedly, NGS-driven differential diagnosis allowed uncovering three hidden additional HPP cases, for a total of 33 HPP subjects. Eight out of 24 coding variants were novel and classified as "pathogenic", "likely pathogenic", and "variants of uncertain significance". Bioinformatic analysis confirmed that all the variants strongly destabilize the homodimer structure. There were 10 cases with low ALP and high VitB6 that resulted negative to genetic testing, whereas two positive cases have an unexpected normal ALP value. No association was evident with other biochemical/clinical parameters., Discussion: We present the survey of HPP Italian patients with the highest ALPL mutation rate so far reported and confirm the complexity of a prompt recognition of the syndrome, mostly for HPP in adults. Low ALP and high VitB6 values are mandatory for the genetic screening, this latter remaining the gold standard not only to confirm the clinical diagnosis but also to make differential diagnosis, to identify carriers, to avoid likely dangerous therapy in unrecognized cases., Competing Interests: LC was the recipient of a fellowship by Alexion, AstraZeneca Rare Disease. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Cinque, Pugliese, Salcuni, Trombetta, Battista, Biagini, Augello, Nardella, Conti, Corbetta, Fischetto, Foiadelli, Gaudio, Giannini, Grosso, Guabello, Massuras, Palermo, Politano, Pigliaru, Ruggeri, Scarano, Vicchio, Cannavò, Celli, Petrizzelli, Mastroianno, Castori, Scillitani and Guarnieri.)
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- 2023
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37. Four-Component Recombinant Protein-Based Vaccine Effectiveness Against Serogroup B Meningococcal Disease in Italy.
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Lodi L, Barbati F, Amicizia D, Baldo V, Barbui AM, Bondi A, Costantino C, Da Dalt L, Ferrara L, Fortunato F, Guarnieri V, Icardi G, Indolfi G, Martinelli D, Martini M, Moriondo M, Nieddu F, Peroni DG, Prato R, Ricci S, Russo F, Tirelli F, Vitale F, Ladhani SN, and Azzari C
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- Child, Infant, Humans, Case-Control Studies, Cohort Studies, Retrospective Studies, Serogroup, Vaccine Efficacy, Italy epidemiology, Meningococcal Infections epidemiology, Meningococcal Infections prevention & control, Meningococcal Vaccines
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Importance: Population-based data on the 4-component recombinant protein-based (4CMenB) vaccine effectiveness and reduction in incidence rate ratios (IRRs) are continuously needed to assess vaccine performance in the prevention of serogroup B invasive meningococcal disease (IMD)., Objective: To assess the effectiveness and reduction in IRRs associated with the 4CMenB vaccine in the pediatric population in 6 regions in Italy., Design, Setting, and Participants: This retrospective cohort screening study and case-control study included data from children aged younger than 6 years in 6 highly populated Italian regions from January 1, 2006, to January 1, 2020. Participants included children younger than 6 years diagnosed with serogroup B IMD without predisposing factors. Data were collected from regional surveillance and vaccination registries and were analyzed from September 2021 to January 2022., Exposures: Routine 4CMenB vaccination, per regional vaccination programs., Main Outcomes and Measures: The main outcome was the effectiveness of the 4CMenB vaccine in the prevention of serogroup B IMD in the population of children aged younger than 6 years in 6 Italian regions. The percentages of vaccine effectiveness (VE) were obtained through the concomitant use of a screening method and a case-control study. Secondary outcomes were the comparison of effectiveness results obtained using the 2 different computational methods, the description of serogroup B IMD incidence rates, and reduction in IRRs before and after 4CMenB introduction, as a proxy for vaccine impact., Results: The cohort screening study included a resident population of 587 561 children younger than 6 years in 3 regions with similar surveillance protocols, and the matched-case controls study assessed a resident population of 1 080 620 children younger than 6 years in 6 regions. Analyses found that 4CMenB VE in fully immunized children was 94.9% (95% CI, 83.1%-98.4%) using the screening method and 91.7% (95% CI, 24.4%-98.6%) using the case-control method. Overall reduction in IRR was 50%, reaching 70% in regions with early-start vaccination schedules. The case-control method involving 6 highly-populated Italian regions included 26 cases and 52 controls and found an estimated VE of 92.4% (95% CI, 67.6%-97.9%) in children old enough for the first vaccine dose and 95.6% (95% CI, 71.7%-99.1%) in fully immunized children. VE was more than 90% for partially immunized children. Even in regions where the first dose was administered at age 2 months, almost 20% of unvaccinated cases were among infants too young to receive the first 4CMenB dose., Conclusions and Relevance: This screening cohort study and matched case-controls study found high effectiveness of 4CMenB vaccination and greater reduction in IRR for early-start vaccination schedules in preventing invasive serogroup B meningococcal disease. The high proportion of children too young to be vaccinated among unvaccinated cases suggests that starting the vaccination even earlier may prevent more cases. Screening and case-control methods provided similar estimates of VE: either method may be used in different study settings, but concomitant use can provide more robust estimates.
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- 2023
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38. Specifications and validation of the ACMG/AMP criteria for clinical interpretation of sequence variants in collagen genes associated with joint hypermobility.
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Leone MP, Morlino S, Nardella G, Pracella R, Giachino D, Celli L, Baldo D, Turolla L, Piccione M, Salzano E, Busè M, Lastella P, Zollino M, Cantone R, Grosso E, Zonta A, Pasini B, Piscopo C, De Maggio I, Priolo M, Mammi C, Foiadelli T, Trabatti C, Savasta S, Iolascon A, Ferraris A, Lodato V, Di Giosaffatte N, Majore S, Selicorni A, Petracca A, Fusco C, Celli M, Guarnieri V, Micale L, and Castori M
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- Humans, United States, Genetic Testing methods, Sequence Analysis, DNA methods, Genetic Variation, Joint Instability diagnosis, Joint Instability genetics
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Deleterious variants in collagen genes are the most common cause of hereditary connective tissue disorders (HCTD). Adaptations of the American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) criteria are still lacking. A multidisciplinary team was set up for developing specifications of the ACMG/AMP criteria for COL1A1, COL1A2, COL2A1, COL3A1, COL5A1, COL5A2, COL11A1, COL11A2 and COL12A1, associated with various forms of HCTD featuring joint hypermobility, which is becoming one of the most common reasons of referral for molecular testing in this field. Such specifications were validated against 209 variants, and resulted effective for classifying as pathogenic and likely pathogenic null alleles without downgrading of the PVS1 level of strength and recurrent Glycine substitutions. Adaptations of selected criteria reduced uncertainties on private Glycine substitutions, intronic variants predicted to affect the splicing, and null alleles with a downgraded PVS1 level of strength. Segregation and multigene panel sequencing data mitigated uncertainties on non-Glycine substitutions by the attribution of one or more benignity criteria. These specifications may improve the clinical utility of molecular testing in HCTD by reducing the number of variants with neutral/conflicting interpretations. Close interactions between laboratory and clinicians are crucial to estimate the a priori utility of molecular test and to improve medical reports., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2023
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39. Generation of an induced pluripotent stem cell line CSSi015-A (9553), carrying a point mutation c.2915C > T in the human calcium sensing receptor (CasR) gene.
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Rotundo G, Turco EM, Ruotolo G, Torrente I, Candido O, Lopez G, Ferrari D, Caputi C, Mastrangelo M, Pisani F, Gelati M, Guarnieri V, Vescovi AL, and Rosati J
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- Humans, Point Mutation, Receptors, Calcium-Sensing genetics, Receptors, Calcium-Sensing metabolism, Mutation, Calcium, Induced Pluripotent Stem Cells metabolism, Hypercalcemia genetics
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Familial Hypocalciuric Hypercalcemia (FHH1) is a rare autosomal dominant disease with low penetrance, caused by inactivating mutations of the calcium-sensing receptor (CaSR) gene, characterized by significant hypercalcemia, inappropriately normal serum PTH levels and a low urinary calcium level. Human induced pluripotent stem cells (hiPSCs) from a patient carrying a previously identified heterozygous mutation, a p.T972M amino acid substitution in cytoplasmic tail of CasR, were produced using a virus, xeno-free and non-integrative protocol., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jessica Rosati reports financial support was provided by Ministry of Health., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)
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- 2023
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40. Relapse or worsening of chronic spontaneous urticaria during SARS-CoV-2 infection and vaccination in children: A telemedicine follow-up.
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Lascialfari G, Sarti L, Barni S, Liccioli G, Paladini E, Guarnieri V, Ricci S, Giovannini M, and Mori F
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- Child, Chronic Disease, Follow-Up Studies, Humans, Pandemics, Recurrence, SARS-CoV-2, COVID-19 complications, COVID-19 epidemiology, COVID-19 prevention & control, COVID-19 Vaccines adverse effects, Chronic Urticaria, Telemedicine, Urticaria
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Background: Chronic urticaria (CU), characterized by daily wheals and/or angioedema lasting more than 6 weeks, is a common skin disease. CU is classified as spontaneous or inducible. Because of Coronavirus Disease-19 (COVID-19) pandemic, face-to-face visits were reduced, and many centers started remote consultations to minimize hospital admissions and risk for viral diffusion. Telemedicine became a valuable tool for evaluating and monitoring patients with chronic diseases, such as CU. This study aims to evaluate the effectiveness of telemedicine as a means for the follow-up of patients with chronic spontaneous urticaria (CSU) during the COVID-19 pandemic. In particular, we collected data related to CSU evolution and treatment by remote consultation. Moreover, we specifically investigated the impact of SARS-CoV-2 infection or vaccination on CSU in relapsing or worsening of such a disease., Methods: The electronic charts were reviewed for patients diagnosed with CSU, who were referred to the allergy unit of Meyer Children's Hospital, Florence. For each patient, a review of demographic characteristics, diagnostic workup, efficacy, and tolerability of the treatment was performed. Patients with a physical agent triggering CU were excluded from the study. Disease activity was monitored using the Urticaria Activity Score (UAS7). In addition, when the COVID-19 pandemic started, follow-up continued through telemedicine after an initial face-to-face visit when possible. Approximately 1 year after the diagnosis of CSU, patients were recontacted to investigate whether they had experienced a relapse or worsening of urticaria during a possible COVID-19 or immediately after receiving a COVID-19 vaccine., Results: From January 2020 to March 2021, 84 cases of CSU were identified, with 71 (84.5%) of these being evaluated via televisit (remote consultation). During the remote follow-up period, 38/71 (53.5%) patients who were evaluated via televisit recovered completely from CSU, while 24 (33.8%) made therapy adjustments, and 9 (12.7%) had to discontinue follow-up through remote visits and return to face-to-face visits. In February 2022, we recontacted the 71 patients with CSU, and 50 (70.4%) of them answered by phone call interview. Four (19.2%) of the 26 patients who had COVID-19 showed CSU relapse, while 1 (3.8%) had a CSU worsening. Instead, 1 (3.8%) patient of the 26 who were vaccinated had a relapse of CSU, and 1 (3.8%) had a worsening of CSU, both after the first dose., Conclusion: Our data showed that telemedicine can be an effective tool for the follow-up of patients with CSU. Moreover, COVID-19, as well as COVID-19 vaccination, may trigger CSU relapse or worsening, but both are unspecific triggers, and urticaria shows a very short duration in most cases., Competing Interests: The authors have no conflict of interest relevant to this article to disclose.
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- 2022
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41. Severe pertussis disease in a paediatric population: The role of age, vaccination status and prematurity.
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Guarnieri V, Giovannini M, Lodi L, Astorino V, Pisano L, Di Cicco E, Canessa C, Citera F, Peroni D, Azzari C, and Ricci S
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- Child, Humans, Infant, Infant, Low Birth Weight, Infant, Newborn, Infant, Premature, Pertussis Vaccine, Retrospective Studies, Vaccination, Whooping Cough epidemiology, Whooping Cough prevention & control
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Aim: To estimate hospitalisation rate and investigate the role of age, prematurity and vaccination status in severe pertussis cases., Methods: We retrospectively evaluated 200 children aged 0-14 years, admitted to the emergency rooms of Meyer Hospital of Florence and Pisa Hospital with a diagnosis of pertussis from 1 October 2010 to 31 January 2020., Results: Children younger than 12 months were 63.0%. Preterm infants were 6.5%. The rate of hospitalisation was 49.0%. Among hospitalised cases, 80.6% were younger than 5 months. Overall, 62.0% were unvaccinated; this percentage increased among hospitalised (73.5%) and preterm subsamples (76.9%). Delays in pertussis vaccination were found in 57.7% of term infants and in 80.0% of preterms. Multivariable analysis confirmed the age under 2 months as the variable at higher risk for hospitalisation (OR 4.49, 95% CI 1.85-10.96, p < 0.001). Being fully vaccinated represented a significant protective factor (OR 0.12, 95% CI 0.04-0.35, p < 0.001)., Conclusion: Older classes of age and a complete vaccination, in time with the recommended schedule, are both protective factors for hospitalisation in severe pertussis disease. The widespread vaccination delay frequently observed in preterm children may be the cause for their higher rate of hospitalisation., (© 2022 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)
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- 2022
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42. Adverse reactions to BNT162B2 vaccine in health care workers from an Italian Tertiary Care Hospital.
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Guarnieri V, Barni S, Giovannini M, Liccioli G, Sarti L, Ricci S, Lodi L, Canessa C, Lippi F, Moriondo M, Pisano L, Citera F, Azzari C, and Mori F
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- Health Personnel, Humans, Tertiary Care Centers, BNT162 Vaccine, Vaccines
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- 2022
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43. The Long Non-Coding BC200 Is a Novel Circulating Biomarker of Parathyroid Carcinoma.
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Morotti A, Cetani F, Passoni G, Borsari S, Pardi E, Guarnieri V, Verdelli C, Tavanti GS, Valenti L, Bianco C, Ferrero S, Corbetta S, and Vaira V
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- Biomarkers, Cell Proliferation genetics, Humans, Parathyroid Neoplasms blood, Parathyroid Neoplasms diagnosis, Parathyroid Neoplasms genetics, RNA, Long Noncoding blood, RNA, Long Noncoding genetics
- Abstract
Long non-coding RNAs (lncRNAs) are an important class of epigenetic regulators involved in both physiological processes and cancer development. Preliminary evidence suggested that lncRNAs could act as accurate prognostic and diagnostic biomarkers. Parathyroid cancer is a rare endocrine neoplasia, whose management represents a clinical challenge due to the lack of accurate molecular biomarkers. Our previous findings showed that human parathyroid tumors are characterized by a different lncRNAs signature, suggesting heterogeneity through the different histotypes. Particularly, we found that the lncRNA BC200/BCYRN1 could represent a candidate biomarker for parathyroid carcinomas (PCas). Here we aimed to extend our preliminary data evaluating whether BC200 could be an accurate non-invasive biomarker of PCas to support the clinical management of patients affected by parathyroid tumors at diagnosis, prognosis and follow-up. To provide a non-invasive point-of-care for parathyroid carcinoma diagnosis and follow-up, we analyzed BC200 expression in patients' serum through digital PCR. Our results show that BC200 counts are higher in serum from patients harboring PCa (n=4) compared to patients with parathyroid adenoma (PAd; n=27). Further, in PAd patients circulating BC200 levels are positively correlated with serum total calcium. Then, we found that BC200 is overexpressed in metastatic PCas (n=4) compared to non-metastatic ones (n=9). Finally, the lncRNA expression in PCa patients' serum drops are reduced after parathyroidectomy, suggesting its possible use in the post-operative setting for patients follow-up. Overall, these findings extend the knowledge on BC200 in parathyroid tumors, supporting its role as a useful biomarker for management of PCa., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Morotti, Cetani, Passoni, Borsari, Pardi, Guarnieri, Verdelli, Tavanti, Valenti, Bianco, Ferrero, Corbetta and Vaira.)
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- 2022
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44. Novel Glial Cells Missing-2 (GCM2) variants in parathyroid disorders.
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Canaff L, Guarnieri V, Kim Y, Wong BYL, Nolin-Lapalme A, Cole DEC, Minisola S, Eller-Vainicher C, Cetani F, Repaci A, Turchetti D, Corbetta S, Scillitani A, and Goltzman D
- Subjects
- Adult, Aged, Aged, 80 and over, Animals, Binding Sites, Calcium blood, Calcium urine, DNA blood, DNA metabolism, Female, Humans, Hyperparathyroidism metabolism, Hyperparathyroidism pathology, Hypoparathyroidism blood, Infant, Male, Mice, Middle Aged, Nuclear Proteins chemistry, Nuclear Proteins metabolism, Parathyroid Glands pathology, Parathyroid Glands surgery, Parathyroid Hormone blood, Parathyroid Hormone genetics, Parathyroid Neoplasms metabolism, Parathyroid Neoplasms pathology, Pedigree, Promoter Regions, Genetic, Sequence Analysis, DNA, Transcription Factors chemistry, Transcription Factors metabolism, Hyperparathyroidism genetics, Hypoparathyroidism genetics, Mutation, Nuclear Proteins genetics, Parathyroid Neoplasms genetics, Transcription Factors genetics
- Abstract
Objective: The aim of this study was to analyze variants of the gene glial cells missing-2 (GCM2), encoding a parathyroid cell-specific transcription factor, in familial hypoparathyroidism and in familial isolated hyperparathyroidism (FIHP) without and with parathyroid carcinoma., Design: We characterized 2 families with hypoparathyroidism and 19 with FIHP in which we examined the mechanism of action of GCM2 variants., Methods: Leukocyte DNA of hypoparathyroid individuals was Sanger sequenced for CASR, PTH, GNA11 and GCM2 mutations. DNA of hyperparathyroid individuals underwent MEN1, CDKN1B, CDC73, CASR, RET and GCM2 sequencing. The actions of identified GCM2 variants were evaluated by in vitro functional analyses., Results: A novel homozygous p.R67C GCM2 mutation which failed to stimulate transcriptional activity in a luciferase assay was identified in affected members of two hypoparathyroid families. Oligonucleotide pull-down assay and in silico structural modeling indicated that this mutant had lost the ability to bind the consensus GCM recognition sequence of DNA. Two novel (p.I383M and p.T386S) and one previously reported (p.Y394S) heterozygous GCM2 variants that lie within a C-terminal conserved inhibitory domain were identified in three affected individuals of the hyperparathyroid families. One family member, heterozygous for p.I138M, had parathyroid carcinoma (PC), and a heterozygous p.V382M variant was found in another patient affected by sporadic PC. These variants exerted significantly enhanced in vitrotranscriptional activity, including increased stimulation of the PTH promoter., Conclusions: We provide evidence that two novel GCM2 R67C inactivating mutations with an inability to bind DNA are causative of hypoparathyroidism. Additionally, we provide evidence that two novel GCM2 variants increased transactivation of the PTH promoter in vitro and are associated with FIHP. Furthermore, our studies suggest that activating GCM2 variants may contribute to facilitating more aggressive parathyroid disease.
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- 2022
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45. Case Report: Unusual Presentations of Loss-of-Function Mutations of the Calcium-Sensing Receptor.
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Palmieri S, Grassi G, Guarnieri V, Chiodini I, Arosio M, and Eller-Vainicher C
- Abstract
Background: In recent years, heterozygous loss-of-function mutations of the Calcium Sensing Receptor gene (CaSR) were implicated in different hypercalcemic syndromes besides familial hypocalciuric hypercalcemia (FHH), including neonatal severe primary hyperparathyroidism (NSHPT) and primary hyperparathyroidism (PHPT)., Cases Presentation: Here we describe two unusual presentations of heterozygous inactivating CaSR mutations. Case 1: a case of NSHPT due to a de novo , p.(ArgR185Gln) CaSR mutation and successfully treated with cinacalcet monotherapy for 8 years until definitive surgical resolution. Case 2: a 37 years-old woman with PHPT complicated with hypercalcemia and nephrocalcinosis with a novel heterozygous p.(Pro393Arg) CaSR mutation and cured with parathyroidectomy., Conclusions: These cases reinforce the fact that the clinical spectrum of inactivating mutations of the CaSR has widened and, although carrying a mutation suggestive of FHH, some patients may have different clinical phenotypes and complications requiring individualized therapies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Palmieri, Grassi, Guarnieri, Chiodini, Arosio and Eller-Vainicher.)
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- 2022
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46. Occurrence of chronic myeloid leukemia in a patient with CDC73 gene deletion: "Chance or Causality?"
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De Candia MS, Sgherza N, Bernardini L, Giuffrida MG, Bardi MA, Coppi MR, Guarnieri V, Gagliardi VP, Russo Rossi AV, Musto P, and Pastore D
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- Adult, Gene Expression Regulation, Neoplastic, Humans, Male, Gene Deletion, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics, Tumor Suppressor Proteins genetics
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- 2021
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47. Normocalcemic primary hyperparathyroidism: an update.
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Salcuni AS, Battista C, Pugliese F, Columbu C, Guarnieri V, Carnevale V, and Scillitani A
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- Calcium, Humans, Parathyroid Hormone, Prevalence, Hyperparathyroidism, Primary diagnosis, Hyperparathyroidism, Secondary
- Abstract
Normocalcemic primary hyperparathyroidism (NPHPT) is diagnosed in the setting of elevated PTH concentrations with consistently normal albumin-adjusted and ionized serum calcium levels, in absence of secondary causes for elevated PTH concentrations. In order to confirm persistence of the hyperparathyroid state, PTH levels should be elevated on at least two occasions over a 3 to 6 months period. The prevalence of NPHPT depends on the population studied. Data from different studies are often not comparable; indeed, different criteria have been used to exclude secondary hyperparathyroidism. Notwithstanding such limits, the prevalence of NPHPT in studies including ionized calcium dosage was between 0.5% and 0.7%. Available data suggest that patients with NPHPT are likely to have more skeletal, kidney and metabolic complications compared to healthy subjects, but almost all studies suffer from possible misclassification of patients due to lack of ionized calcium dosage. The management of NPHPT is controversial in part due to lack of solid data about the natural history. However, surgical treatment is currently performed more frequently than in the past, although studies do not show, so far, a clear benefit from intervention.
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- 2021
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48. Surveillance on Healthcare Workers During the First Wave of SARS-CoV-2 Pandemic in Italy: The Experience of a Tertiary Care Pediatric Hospital.
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Guarnieri V, Moriondo M, Giovannini M, Lodi L, Ricci S, Pisano L, Barbacci P, Bini C, Indolfi G, Zanobini A, and Azzari C
- Subjects
- Child, Health Personnel, Hospitals, Pediatric, Humans, Italy epidemiology, Pandemics, Tertiary Healthcare, COVID-19, SARS-CoV-2
- Abstract
Healthcare workers (HCWs) play a central role in handling the ongoing coronavirus disease 2019 (COVID-19) pandemic. Monitoring HCWs, both symptomatic and asymptomatic, through screening programs, are critical to avoid the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the hospital environment to rapidly identify and isolate infected individuals and to allow their prompt return to work as soon as necessary. We aim to describe our healthcare surveillance experience (April 2-May 6, 2020) based on a combined screening consisting of real-time PCR (RT-PCR) on nasopharyngeal (NP) swabs and rapid serologic tests (RST) for SARS-CoV-2 in all HCWs of Meyer Children's University Hospital in Florence. Among the analyzed workers, 13/1690 (0.8%), all of them without clinical manifestations, was found positive for SARS-CoV-2 by using RT-PCR on NP swab: 8/1472 (0.5%) were found positive during the screening, 1/188 (0.5%) during contact with a positive individual ( p > 0.05 vs. screening group), while 4/30 (13.3%) were found positive on the day of re-admission at work after an influenza-like-illness ( p < 0.05). Concerning working areas, the majority of RT-PCR positivity (12/13) and serologic positivity (34/42) was found in non-COVID-19 dedicated areas ( p > 0.05 vs. COVID-19 dedicated areas). No cases were registered among non-patients-facing workers ( p = 0.04 vs. patient-facing group). Nurses and residents represented, respectively, the working role with the highest and lowest percentage of RT-PCR positivity. In conclusion, accurate surveillance is essential to reduce virus spread among HCWs, patients, and the community and to limit the shortage of skilled professionals. The implementation of the surveillance system through an efficient screening program was offered to all professionals, regardless of the presence of clinical manifestations and the level of working exposure risk, maybe wise and relevant., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Guarnieri, Moriondo, Giovannini, Lodi, Ricci, Pisano, Barbacci, Bini, Indolfi, Zanobini and Azzari.)
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- 2021
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49. How home anterior self-collected nasal swab simplifies SARS-CoV-2 testing: new surveillance horizons in public health and beyond.
- Author
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Ricci S, Lodi L, Citera F, Nieddu F, Moriondo M, Guarnieri V, Giovannini M, Indolfi G, Resti M, Zanobini A, and Azzari C
- Subjects
- Adult, COVID-19 epidemiology, COVID-19 Nucleic Acid Testing, Cross-Sectional Studies, Epidemiological Monitoring, Female, France epidemiology, Hospitals, Humans, Male, Middle Aged, SARS-CoV-2 genetics, Surveys and Questionnaires, COVID-19 diagnosis, Nasal Cavity virology, SARS-CoV-2 isolation & purification, Specimen Handling methods
- Abstract
The sample collection procedure for SARS-CoV-2 has a strong impact on diagnostic capability, contact tracing approach, ultimately affecting the infection containment performance. This study demonstrates that self-collected nasal-swab has shown to be a valid and well tolerated procedure to SARS-CoV-2 surveillance in a healthcare system. More significantly, no performance adequacy difference was detected in self-administered swabs between healthcare worker (HCW) and non-HCW which allows to speculate that this procedure could be successfully extended to the entire population for mass screening.
- Published
- 2021
- Full Text
- View/download PDF
50. Yes-Associated Protein 1 Is a Novel Calcium Sensing Receptor Target in Human Parathyroid Tumors.
- Author
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Tavanti GS, Verdelli C, Morotti A, Maroni P, Guarnieri V, Scillitani A, Silipigni R, Guerneri S, Maggiore R, Mari G, Vicentini L, Dalino Ciaramella P, Vaira V, and Corbetta S
- Subjects
- 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine analogs & derivatives, 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine pharmacology, Adaptor Proteins, Signal Transducing metabolism, Amides pharmacology, Cell Nucleus drug effects, Cell Nucleus metabolism, Gene Expression drug effects, HEK293 Cells, Humans, Parathyroid Neoplasms metabolism, Phenethylamines pharmacology, Propylamines pharmacology, Protein Serine-Threonine Kinases genetics, Protein Serine-Threonine Kinases metabolism, Proto-Oncogene Proteins genetics, Proto-Oncogene Proteins metabolism, Pyridines pharmacology, RNA Interference, Receptors, Calcium-Sensing agonists, Receptors, Calcium-Sensing metabolism, Transcription Factors metabolism, Tumor Cells, Cultured, Tumor Suppressor Proteins genetics, Tumor Suppressor Proteins metabolism, YAP-Signaling Proteins, rho-Associated Kinases antagonists & inhibitors, rho-Associated Kinases metabolism, Adaptor Proteins, Signal Transducing genetics, Parathyroid Glands metabolism, Parathyroid Neoplasms genetics, Receptors, Calcium-Sensing genetics, Transcription Factors genetics
- Abstract
The Hippo pathway is involved in human tumorigenesis and tissue repair. Here, we investigated the Hippo coactivator Yes-associated protein 1 (YAP1) and the kinase large tumor suppressor 1/2 (LATS1/2) in tumors of the parathyroid glands, which are almost invariably associated with primary hyperparathyroidism. Compared with normal parathyroid glands, parathyroid adenomas (PAds) and carcinomas show variably but reduced nuclear YAP1 expression. The kinase LATS1/2, which phosphorylates YAP1 thus promoting its degradation, was also variably reduced in PAds. Further, YAP1 silencing reduces the expression of the key parathyroid oncosuppressor multiple endocrine neoplasia type 1 (MEN1) , while MEN1 silencing increases YAP1 expression. Treatment of patient-derived PAds-primary cell cultures and Human embryonic kidney 293A (HEK293A) cells expressing the calcium-sensing receptor (CASR) with the CASR agonist R568 induces YAP1 nuclear accumulation. This effect was prevented by the incubation of the cells with RhoA/Rho-associated coiled-coil-containing protein kinase (ROCK) inhibitors Y27632 and H1152. Lastly, CASR activation increased the expression of the YAP1 gene targets CYR61 , CTGF , and WNT5A , and this effect was blunted by YAP1 silencing. Concluding, here we provide preliminary evidence of the involvement of the Hippo pathway in human tumor parathyroid cells and of the existence of a CASR-ROCK-YAP1 axis. We propose a tumor suppressor role for YAP1 and LATS1/2 in parathyroid tumors.
- Published
- 2021
- Full Text
- View/download PDF
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