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3. NAIF: A novel artificial intelligence-based tool for accurate diagnosis of stage F3/F4 liver fibrosis in the general adult population, validated with three external datasets

Author

Hassoun, S, Bruckmann, C, Ciardullo, S, Perseghin, G, Marra, F, Curto, A, Arena, U, Broccolo, F, Di Gaudio, F, Hassoun, Samir, Bruckmann, Chiara, Ciardullo, Stefano, Perseghin, Gianluca, Marra, Fabio, Curto, Armando, Arena, Umberto, Broccolo, Francesco, Di Gaudio, Francesca, Hassoun, S, Bruckmann, C, Ciardullo, S, Perseghin, G, Marra, F, Curto, A, Arena, U, Broccolo, F, Di Gaudio, F, Hassoun, Samir, Bruckmann, Chiara, Ciardullo, Stefano, Perseghin, Gianluca, Marra, Fabio, Curto, Armando, Arena, Umberto, Broccolo, Francesco, and Di Gaudio, Francesca

Abstract

Objective: The purpose of this study was to determine the effectiveness of a new AI-based tool called NAIF (NAFLD-AI-Fibrosis) in identifying individuals from the general population with advanced liver fibrosis (stage F3/F4). We compared NAIF's performance to two existing risk score calculators, aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis-4 (Fib4). Methods: To set up the algorithm for diagnosing severe liver fibrosis (defined as Fibroscan® values E ≥ 9.7 KPa), we used 19 blood biochemistry parameters and two demographic parameters in a group of 5,962 individuals from the NHANES population (2017–2020 pre-pandemic, public database). We then assessed the algorithm's performance by comparing its accuracy, precision, sensitivity, specificity, and F1 score values to those of APRI and Fib4 scoring systems. Results: In a kept-out sub dataset of the NHANES population, NAIF achieved a predictive precision of 72 %, a sensitivity of 61 %, and a specificity of 77 % in correctly identifying adults (aged 18–79 years) with severe liver fibrosis. Additionally, NAIF performed well when tested with two external datasets of Italian patients with a Fibroscan® score E ≥ 9.7 kPa, and with an external dataset of patients with diagnosis of severe liver fibrosis through biopsy. Conclusions: The results of our study suggest that NAIF, using routinely available parameters, outperforms in sensitivity existing scoring methods (Fib4 and APRI) in diagnosing severe liver fibrosis, even when tested with external validation datasets. NAIF uses routinely available parameters, making it a promising tool for identifying individuals with advanced liver fibrosis from the general population. Word count abstract: 236.

Published
2024

5. Setting up of a machine learning algorithm for the identification of severe liver fibrosis profile in the general US population cohort

Author

Hassoun, S, Bruckmann, C, Ciardullo, S, Perseghin, G, Di Gaudio, F, Broccolo, F, Hassoun, Samir, Bruckmann, Chiara, Ciardullo, Stefano, Perseghin, Gianluca, Di Gaudio, Francesca, Broccolo, Francesco, Hassoun, S, Bruckmann, C, Ciardullo, S, Perseghin, G, Di Gaudio, F, Broccolo, F, Hassoun, Samir, Bruckmann, Chiara, Ciardullo, Stefano, Perseghin, Gianluca, Di Gaudio, Francesca, and Broccolo, Francesco

Abstract

Background The progress of digital transformation in clinical practice opens the door to transforming the current clinical line for liver disease diagnosis from a late-stage diagnosis approach to an early-stage based one. Early diagnosis of liver fibrosis can prevent the progression of the disease and decrease liver-related morbidity and mortality. We developed here a machine learning (ML) algorithm containing standard parameters that can identify liver fibrosis in the general US population. Materials and methods Starting from a public database (National Health and Nutrition Examination Survey, NHANES), representative of the American population with 7265 eligible subjects (control population n = 6828, with Fibroscan values E < 9.7 KPa; target population n = 437 with Fibroscan values E ≥ 9.7 KPa), we set up an SVM algorithm able to discriminate for individuals with liver fibrosis among the general US population. The algorithm set up involved the removal of missing data and a sampling optimization step to managing the data imbalance (only ∼ 5 % of the dataset is the target population). Results For the feature selection, we performed an unbiased analysis, starting from 33 clinical, anthropometric, and biochemical parameters regardless of their previous application as biomarkers of liver diseases. Through PCA analysis, we identified the 26 more significant features and then used them to set up a sampling method on an SVM algorithm. The best sampling technique to manage the data imbalance was found to be oversampling through the SMOTE-NC. For final model validation, we utilized a subset of 300 individuals (150 with liver fibrosis and 150 controls), subtracted from the main dataset prior to sampling. Performances were evaluated on multiple independent runs. Conclusions We provide proof of concept of an ML clinical decision support tool for liver fibrosis diagnosis in the general US population. Though the presented ML model represents at this stage only a prototype, in

Published
2023

6. Opioid epidemic spread from Northern and Eastern Europe to Mediterranean Area

Author

Di Gaudio F., Mortali C., Tini A., Di Gaudio F., Mortali C., and Tini A.

Subjects
Europe, SARS-CoV-2, Synthetic opioid, COVID-19, Humans, Opioid-Related Disorder, Opioid Epidemic, Opioid-Related Disorders, Fentanyl analogs, Opioid epidemic, Pandemics, Human
Abstract

The addiction to illicit opioid and the misuse of prescription synthetic opioids pain relievers and fentanyl analogs generated an opioid epidemic in North America over the last two decades that affected public health with a constantly rising number of overdoses deaths. This health treat moved to Europe with a significant increase starting from 2015 involving mainly norther and eastern countries and finally also the Mediterranean area. The "lock down" isolation and economic recession caused by COVID-19 pandemic showed a resurgence in opioid use and harms.

Published
2021

7. Co-circulation of SARS-CoV-2 Alpha and Gamma variants in Italy, February and March 2021

Author

Stefanelli, P., Trentini, F., Guzzetta, G., Marziano, V., Mammone, A., Schepisi, M. S., Poletti, P., Grane, C. M., Manica, M., del Manso, M., Andrianou, X., Ajelli, M., Rezza, G., Brusaferro, S., Merler, S., Di Martino, A., Ambrosio, L., Lo Presti, A., Fiore, S., Fabiani, C., Benedetti, E., Di Mario, G., Facchini, M., Puzelli, S., Calzoletti, L., Fontana, S., Venturi, G., Fortuna, C., Marsili, G., Amendola, A., Stuppia, L., Savini, G., Picerno, A., Lopizzo, T., Dell'Edera, D., Minchella, P., Greco, F., Viglietto, G., Atripaldi, L., Limone, A., D'Agaro, P., Licastro, D., Pongolini, S., Sambri, V., Dirani, G., Zannoli, S., Affanni, P., Colucci, M. E., Capobianchi, M. R., Icardi, G., Bruzzone, B., Lillo, F., Orsi, A., Pariani, E., Baldanti, F., Molecolare, U. V., Gismondo, M. R., Maggi, F., Caruso, A., Ceriotti, F., Boniotti, M. B., Barbieri, I., Bagnarelli, P., Menzo, S., Garofalo, S., Scutella, M., Pagani, E., Collini, L., Ghisetti, V., Brossa, S., Ru, G., Bozzetta, E., Chironna, M., Parisi, A., Rubino, S., Serra, C., Piras, G., Coghe, F., Vitale, F., Tramuto, F., Scalia, G., Palermo, C. I., Mancuso, G., Pollicino, T., Di Gaudio, F., Vullo, S., Reale, S., Cusi, M. G., Rossolini, G. M., Pistello, M., Mencacci, A., Camilloni, B., Severini, S., Di Benedetto, M., Terregino, C., Monne, I., Biscaro, V., Stefanelli P, Trentini F, Guzzetta G, Marziano V, Mammone A, Sane Schepisi M, Poletti P, Molina Grané C, Manica M, Del Manso M, Andrianou X, Ajelli M, Rezza G, Brusaferro S, Merler S, Vitale F, Tramuto F, Stefanelli P., Trentini F., Guzzetta G., Marziano V., Mammone A., Sane Schepisi M., Poletti P., Molina Grane C., Manica M., Del Manso M., Andrianou X., Ajelli M., Rezza G., Brusaferro S., Merler S., Sambri V, and (membro del COVID-19 National Microbiology Surveillance Study Group)

Subjects
Epidemiology, SARS-CoV-2, Public Health, Environmental and Occupational Health, COVID-19, co-circulation, lineage, SARS-CoV-2 variant of concern, transmissibility, Humans, Italy, Models, Theoretical, Settore MED/42 - Igiene Generale E Applicata, SARS-COV-2 VARIANT OF CONCERN, CO-CIRCULATION, LINEAGE, TRANSMISSIBILITY, HUMANS, ITALY, MODELS, THEORETICAL, COVID-19, SARS-COV-2, Theoretical, Models, Virology, Human
Abstract

Background Several SARS-CoV-2 variants of concern (VOC) have emerged through 2020 and 2021. There is need for tools to estimate the relative transmissibility of emerging variants of SARS-CoV-2 with respect to circulating strains. Aim We aimed to assess the prevalence of co-circulating VOC in Italy and estimate their relative transmissibility. Methods We conducted two genomic surveillance surveys on 18 February and 18 March 2021 across the whole Italian territory covering 3,243 clinical samples and developed a mathematical model that describes the dynamics of co-circulating strains. Results The Alpha variant was already dominant on 18 February in a majority of regions/autonomous provinces (national prevalence: 54%) and almost completely replaced historical lineages by 18 March (dominant across Italy, national prevalence: 86%). We found a substantial proportion of the Gamma variant on 18 February, almost exclusively in central Italy (prevalence: 19%), which remained similar on 18 March. Nationally, the mean relative transmissibility of Alpha ranged at 1.55–1.57 times the level of historical lineages (95% CrI: 1.45–1.66). The relative transmissibility of Gamma varied according to the assumed degree of cross-protection from infection with other lineages and ranged from 1.12 (95% CrI: 1.03–1.23) with complete immune evasion to 1.39 (95% CrI: 1.26–1.56) for complete cross-protection. Conclusion We assessed the relative advantage of competing viral strains, using a mathematical model assuming different degrees of cross-protection. We found substantial co-circulation of Alpha and Gamma in Italy. Gamma was not able to outcompete Alpha, probably because of its lower transmissibility.

Published
2022

8. Characteristics of SARS-CoV-2 variants of concern B.1.1.7, B.1.351 or P.1: data from seven EU/EEA countries, weeks 38/2020 to 10/2021

Author

Funk T., Pharris A., Spiteri G., Bundle N., Melidou A., Carr M., Gonzalez G., Garcia-Leon A., Crispie F., O'Connor L., Murphy N., Mossong J., Vergison A., Wienecke-Baldacchino A. K., Abdelrahman T., Riccardo F., Stefanelli P., Di Martino A., Bella A., Lo Presti A., Casaca P., Moreno J., Borges V., Isidro J., Ferreira R., Gomes J. P., Dotsenko L., Suija H., Epstein J., Sadikova O., Sepp H., Ikonen N., Savolainen-Kopra C., Blomqvist S., Mottonen T., Helve O., Gomes-Dias J., Adlhoch C., Macori G., Russell L., Yandle Z., Bennett C., O'Byrne E., Murphy A., Tuite G., Conroy A., Duffy M., Morley U., Keoghan B., Ford I., Kennedy M., McDonnell S., Flynn A., Clarke A., Crowley A., Martin C., Kelly E., Foxton J., Hare D., Dunford L., Connell J., Moran J., Dean J., Fanning S., Rajan L., De Gascun C., Kenny J., Cotter P., Walsh C., Lawton E., Fitzpatrick A., Mullins E., Della Bartola M., McCabe M., Stapleton P., Meaney C., Fanning L., Prentice M., MacSharry J., Dempsey C., Mallon P., Leon A., Chaturvedi A., Coughlan S., McAndrew G., Reddington K., Walsh F., Fitzpatrick D., Smyth C., O'Dwyer T., Chambers T., Clarke L., Jebb D., Klopp J., Kavanagh D., Haslam K., Buckley P., Lemass K., Fitzpatrick F., Burns K., Cafferkey J., Richmond A., Foley M., Sanchez-Morgado J., Chalapati S., Pinnamaneni N., Crosbie C., Limbachiya D., Tinago W., Garcia Leon A. A., Miles S., Alalwan D., Negi R., Macken A., Feeney E., Kenny G., McCann K., Kelly N., Blair M., McCann R., Kenny C., O'Brion C., Waqas S., Savinelli S., Doran P., Bracken T., Varghese P., Lambert J. S., Cotter A., Muldoon E., Sheehan G., McGinty T., Lambert J., Green S., Leamy K., de Barra E., McConkey S., Kelly C., Horgan M., Sadlier C., Yousif O., O'Donnell J., Fitzgerald M., Petty-Saphon N., Cuddihy J., Fiore S., Fabiani C., Benedetti E., Di Mario G., Facchini M., Puzelli S., Calzoletti L., Fontana S., Venturi G., Fortuna C., Marsili G., Amendola A., Stuppia L., Savini G., Picerno A., Lopizzo T., Dell'Edera D., Minchella P., Greco F., Mauro M. V., Viglietto G., Atripaldi L., Limone A., D'Agaro P., Licastro D., Marcello A., Capobianchi M. R., Icardi G., Bruzzone B., Lillo F., Orsi A., Pariani E., Baldanti F., Gismondo M. R., Maggi F., Caruso A., Ceriotti F., Boniotti B., Bagnarelli P., Garofalo S., Scutella M., Pagani E., Collini L., Ghisetti V., Ru G., Chironna M., Parisi A., Rubino S., Serra C., Piras G., Coghe F., Vitale F., Tramuto F., Scalia G., Palermo C. I., Mancuso G., Di Gaudio F., Vullo S., Reale S., Cusi M. G., Rossolini G. M., Pistello M., Mencacci A., Camilloni B., Severini S., Di Benedetto M., Calogero T., Monne I., Biscaro V., COVID Study Groups, Funk T., Pharris A., Spiteri G., Bundle N., Melidou A., Carr M., Gonzalez G., Garcia-Leon A., Crispie F., O'Connor L., Murphy N., Mossong J., Vergison A., Wienecke-Baldacchino A.K., Abdelrahman T., Riccardo F., Stefanelli P., Di Martino A., Bella A., Lo Presti A., Casaca P., Moreno J., Borges V., Isidro J., Ferreira R., Gomes J.P., Dotsenko L., Suija H., Epstein J., Sadikova O., Sepp H., Ikonen N., Savolainen-Kopra C., Blomqvist S., Mottonen T., Helve O., Gomes-Dias J., Adlhoch C., Macori G., Russell L., Yandle Z., Bennett C., O'Byrne E., Murphy A., Tuite G., Conroy A., Duffy M., Morley U., Keoghan B., Ford I., Kennedy M., McDonnell S., Flynn A., Clarke A., Crowley A., Martin C., Kelly E., Foxton J., Hare D., Dunford L., Connell J., Moran J., Dean J., Fanning S., Rajan L., De Gascun C., Kenny J., Cotter P., Walsh C., Lawton E., Fitzpatrick A., Mullins E., Della Bartola M., McCabe M., Stapleton P., Meaney C., Fanning L., Prentice M., MacSharry J., Dempsey C., Mallon P., Leon A., Chaturvedi A., Coughlan S., McAndrew G., Reddington K., Walsh F., Fitzpatrick D., Smyth C., O'Dwyer T., Chambers T., Clarke L., Jebb D., Klopp J., Kavanagh D., Haslam K., Buckley P., Lemass K., Fitzpatrick F., Burns K., Cafferkey J., Richmond A., Foley M., Sanchez-Morgado J., Chalapati S., Pinnamaneni N., Crosbie C., Limbachiya D., Tinago W., Garcia Leon A.A., Miles S., Alalwan D., Negi R., Macken A., Feeney E., Kenny G., McCann K., Kelly N., Blair M., McCann R., Kenny C., O'Brion C., Waqas S., Savinelli S., Doran P., Bracken T., Varghese P., Lambert J.S., Cotter A., Muldoon E., Sheehan G., McGinty T., Lambert J., Green S., Leamy K., de Barra E., McConkey S., Kelly C., Horgan M., Sadlier C., Yousif O., O'Donnell J., Fitzgerald M., Petty-Saphon N., Cuddihy J., Fiore S., Fabiani C., Benedetti E., Di Mario G., Facchini M., Puzelli S., Calzoletti L., Fontana S., Venturi G., Fortuna C., Marsili G., Amendola A., Stuppia L., Savini G., Picerno A., Lopizzo T., Dell'Edera D., Minchella P., Greco F., Mauro M.V., Viglietto G., Atripaldi L., Limone A., D'Agaro P., Licastro D., Marcello A., Capobianchi M.R., Icardi G., Bruzzone B., Lillo F., Orsi A., Pariani E., Baldanti F., Gismondo M.R., Maggi F., Caruso A., Ceriotti F., Boniotti B., Bagnarelli P., Garofalo S., Scutella M., Pagani E., Collini L., Ghisetti V., Ru G., Chironna M., Parisi A., Rubino S., Serra C., Piras G., Coghe F., Vitale F., Tramuto F., Scalia G., Palermo C.I., Mancuso G., Di Gaudio F., Vullo S., Reale S., Cusi M.G., Rossolini G.M., Pistello M., Mencacci A., Camilloni B., Severini S., Di Benedetto M., Calogero T., Monne I., Biscaro V., and COVID Study Groups

Subjects
Infecções Respiratórias, 2019-20 coronavirus outbreak, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Critical Care, Epidemiology, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), variants of concern, Settore MED/42 - Igiene Generale E Applicata, 03 medical and health sciences, 0302 clinical medicine, Virology, Internal medicine, Medicine, Humans, Intensive care admission, 030212 general & internal medicine, COVID-19, Europe, SARS-CoV-2, surveillance, Surveillance, business.industry, 030503 health policy & services, Public Health, Environmental and Occupational Health, Odds ratio, Confidence interval, Variants of Concern, COVID-19, Europe, SARS-CoV-2, surveillance, variants of concern, 0305 other medical science, business, Rapid Communication, Human
Abstract

COVID study groups - PORTUGAL: Portuguese Laboratory Network for the Diagnosis of COVID-19 and Public Health Department of the Health Administrative Regions, Physicians that provided data and samples from suspected cases and SARS-CoV-2 genetic characterization. INSA laboratory team for the diagnosis of SARS-CoV-2. Algarve Biomedical Center and Unilabs. We compared 19,207 cases of SARS-CoV-2 variant B.1.1.7/S gene target failure (SGTF), 436 B.1.351 and 352 P.1 to non-variant cases reported by seven European countries. COVID-19 cases with these variants had significantly higher adjusted odds ratios for hospitalisation (B.1.1.7/SGTF: 1.7, 95% confidence interval (CI): 1.0-2.9; B.1.351: 3.6, 95% CI: 2.1-6.2; P.1: 2.6, 95% CI: 1.4-4.8) and B.1.1.7/SGTF and P.1 cases also for intensive care admission (B.1.1.7/SGTF: 2.3, 95% CI: 1.4-3.5; P.1: 2.2, 95% CI: 1.7-2.8). ECDC internal funds. The ICSC and the AIID Cohort are supported by Science Foundation Ireland under the Science Foundation Ireland, Enterprise Ireland, IDA Ireland COVID-19 Rapid Response Funding Call (Grant number: COVID-RRC 20/COV/0103 and COVID-RRC 20/COV/0305). info:eu-repo/semantics/publishedVersion

Published
2021

9. Poster presentation

Author

Duparc, F., Noyon, M., Ozeel, J., Gerometta, A., Michot, C., Tadjalli, M., Moslemy, H., Safaei, S., Heiman, A., Wish-Baratz, S., Melnikov, T., Smoliar, E., Hakan, A. Y., Yucel, F., Kachlík, D. K., Pešl, M. P., Báča, V. B., Stingl, J. S., Kachlík, K. D., Čech, Č. P., Báča, B. V., Mompeó, B., Marrero-Rodriguez, A., Zeybek, A., Sağlam, B., Çikler, E., Çetinel, Ş., Ercan, F., Şener, G., Kawawa, Y., Kohda, E., Tatsuya, T., Moroi, M., Kunimasa, T., Nagamoto, M., Terada, H., Labuschagne, B. C. J., van der Krieke, T. J., Hoogland, P. V., Muller, C. J. F., Lyners, R., Vorster, W., Matusz, P., Zaboi, D. E., Xu, S. C., Tu, L. L., Wang, Q., Zhang, M., Han, H., Tao, W., Jiao, Y., Pang, G., Aydin, M. E., Kopuz, C., Demir, M. T., Yildirim, M., Kale, A., Ince, Y., Khamanarong, K., Jeeravipoolvarn, P., Chaijaroonkhanarak, W., Gawgleun, W., Fujino, T., Uz, A., Apaydin, N., Bozkurt, M., Elhan, A., Sheibani, M. T., Adibmoradi, M., Jahovic, N., Alican, I., Erkanli, G., Arbak, S., Karakaş, S., Taşer, F., Güneş, H., Yildiz, Y., Yazici, Y., Aland, R. C., Kippers, V., Song, W. C., Park, S. H., Shin, C., Koh, K. S., Russo, G., Pomara, F., Veca, M., Cacciola, F., Martorana, U., Gravante, G., Tobenas-Dujardin, A. C., Laquerrière, A., Muller, J. M., Fréger, P., López-Serna, N., Álvarez-González, E., Torres-Gonzàlez, V., Laredo-López, G., Esparza-González, G. V., Álvarez-Cantú, R., Garza-González, C. E., Guzmán-López, S., Aldur, M. M., Çelik, H. H., Sürücü, S., Denk, C., Yang, H. J., Gil, Y. C., Kim, T. J., Lee, H. Y., Lee, W. J., Lee, H., Hu, K. S., Akita, K., Kim, H. J., Jung, H. S., Gurbuz, H., Balik, S., Wavreille, G., Chantelot, C., Demondion, X., Fontaine, C., Çavdar, S., Yalin, A., Saka, E., Özdoǧmuş, Ö., Çakmak, Ö., Elevli, L., Saǧlam, B., Coquerel-Beghin, D., Milliez, P. Y., Lemierre, G., Oktem, G., Vatansever, S., Ayla, S., Uysal, A., Aktas, S., Karabulut, B., Bilir, A., Uslu, S., Aktug, H., Yurtseven, M. E., Celik, H. H., Tatar, I., Surucu, S., Karaduman, A., Tunali, S., Neuhüttler, S., Kröll, A., Moriggl, B., Brenner, E., Loukas, M., Arora, S., Louis, Jr, R. G., Fogg, Q. A., Wagner, T., Tedman, R. A., Ching, H. Y., Eze, N., Bottrill, I. D., Blyth, P., Faull, R. L. M., Vuletic, J., Elizondo-Omaña, R. E., Rodríguez, M. A. García, López, S. Guzmán, de la Garza, O. Tijerina, Liu, Y. H., Zhang, K. L., Lu, D. H., Kwak, H. H., Park, H. D., Youn, K. H., Kang, H. J., Kang, H. C., Han, S. H., Ikiz, Z. A. Aktan, Ucerler, H., Uygur, M., Kutoglu, T., Dina, C., Iliescu, D., Şapte, E., Bordei, P., Lekšan, I., Marcikić, M., Radić, R., Nikolić, V., Kurbel, S., Selthofer, R., Báča, V., Doubková, A., Kachlík, D., Stingl, J., Džupa, V., Grill, R., Nam, Y. S., Paik, D. J., Shin, C. S., Kim, S. J., Kim, D. G., Jin, C. S., Kim, D. I., Lee, U. Y., Kwak, D. S., Lee, J. H., Han, C. H., Carpino, A., Rago, V., Romeo, F., Carani, C., Andò, S., Arican, R. Y., Coskun, N., Sarikcioglu, L., Sindel, M., Arican, Y. R., Altun, U., Ozsoy, U., Oguz, N., Yildirim, F. B., Nakajima, K., Duygulu, E., Aydin, H., Gurer, E. Inanc, Ozkan, O., Tuzuner, S., Özsoy, U., Çubukçu, S., Demirel, B. M., Akkin, S. M., Marur, T., Weiglein, A. H., Maghiar, T. T., Borza, C., Bumbu, A., Bumbu, G., Polle, G., Auquit-Auckbur, I., Dujardin, F., Biga, N., Olivier, E., Defives, T., Ghazali, S., Anastasi, G., Rizzo, G., Favaloro, A., Miliardi, D., Giacobbe, O., Santoro, G., Trimarchi, F., Cutroneo, G., Govsa, F., Bilge, O., Ozer, M. A., Erdogmus, S., Grizzi, F., Pelillo, F., Mori, M., Franceschini, B., Portinaro, N., Godlewski, G., Viala, M., Rouanet, J. P., Prat, D., Rahmé, Z. S., Prudhomme, M., Eken, E., Kwiatkowska, M., Liegmann, J., Chmielewski, R., Grimmond, J., Kwiatkowski, M., Schintler, M. V., Windisch, G., Wittgruber, G., Prandl, E. C., Prodinger, P., Anderhuber, F., Scharnagl, E., Gerbino, A., Buscemi, M., Leone, A., Mandracchia, R., Peri, G., Lipari, D., Farina-Lipari, E., Valentino, B., D’Arpa, S., Cordova, A., Bucchieri, F., Ribbene, A., David, S., Palma, A., Davies, D. E., Haitchi, H. M., Holgate, S. T., La Rocca, G., Anzalone, R., Campanella, C., Rappa, F., Bartolotta, T., Cappello, F., Bellafiore, M., Sivverini, G., Palumbo, D., Macaluso, F., Farina, F., Di Felice, V., Montalbano, A., Ardizzone, N., Marcianò, V., Zummo, G., Tanyeli, E., Üzel, M., Carini, F., Scardina, G. A., Varia, P., Valenza, V., Messina, P., Meiring, J. H., Schumann, C., Whitmore, I., Greyling, L. M., Hamel, O., Hamel, A., Robert, R., Garçon, M., Lagier, S., Blin, Y., Armstrong, O., Rogez, J. M., Le Borgne, J., Ifrim, C. Feng, Maghiar, A., Botea, M., Ifrim, M., Pop, O., Sandor, M., Behdadipour, Z., Saberi, M., Esfandiary, E., Gentile, C., Marconi, A., Livrea, M. A., Uzan, G., D’Alessio, P., Ridola, C. G., Grassi, N., Pantuso, G., Bottino, A., Cacace, E., Li Petri, S., Di Gaudio, F., Guercio, G., Latteri, M. A., Nobile, D., Cipolla, C., Caruso, G., Salvaggio, G., Lo Cascio, A., Fatta, G., Lagalla, R., Campisi, A., Verderame, F., Martegani, A., Cardinale, A. E., and Luedinghausen, M. V.

Published
2005
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12. Epstein-Barr virus infection as a trigger of autoimmune hepatitis: case report

Author

Cabibi, D., Scaduti, S., Cacciatore, M., and Di Gaudio, F.

Subjects
Chronic active hepatitis -- Risk factors, Chronic active hepatitis -- Diagnosis, Chronic active hepatitis -- Drug therapy, Chronic active hepatitis -- Patient outcomes, Chronic active hepatitis -- Case studies, Epstein-Barr virus diseases -- Complications and side effects, Immunosuppressive agents -- Dosage and administration, Biological sciences
Abstract

Abstract: The study underlines the importance of the differential diagnosis between primary EpsteinBarr virus EBV associated hepatitis with features of autoimmunity, in which there is a direct pathogenetic role of [...]

Published
2008

13. Occurrence and transformation of illicit drugs in wastewater treatment plants

Author

Cosenza, A., Viviani, G., Fanara, S., Indelicato, S., Piscionieri, D., Di Gaudio, F., Maida, C., Cosenza A, Viviani G, Fanara S, Indelicato S, Piscionieri D, Di Gaudio F, and Maida CM

Subjects
Micropollutants, WWTP, drugs, wastewater, Settore ICAR/03 - Ingegneria Sanitaria-Ambientale
Abstract

Illicit drugs (IDs) and their metabolites have been recently recognized as a new group of water emerging contaminants (ECs) with potent psychoactive properties and unknown effects to the aquatic environment (Pal et al., 2013). IDs are excreted via urine and feces and arrive at wastewater treatment plants (WWTPs) where can reach ppb levels (Castiglioni et al., 2006). Over the past few years, it has been demonstrated that conventional biological processes in WWTPs are not or scarcely able to remove IDs. Thus, they are discharged into water bodies through the treated effluent (Postigo et al., 2011). Therefore, monitoring the IDs concentration in WWTPs can have a twofold advantage: i. increase knowledge on the amount of IDs discharged in the environment and estimate their effect; ii. estimating indirectly the community level consumption (Senta et al., 2014). The objective of this paper is to provide a comprehensive analysis of the occurrence and behaviour of illicit drugs and their metabolites in two Sicilian WWTPs. Specifically, two WWTPs (namely, WWTP-1 and WWTP-2) located at the north-western Sicilian coast have been monitored for 5 months (one sampling per week). The two WWTPs have a conventional scheme and mainly differ for their potentiality. Indeed, the average daily flow expressed as m3d-1 for WWTP-1 and WWTP-2 was equal to 153,600 and 19,704, respectively. Samples were analyzed for total suspended solids (TSS), illicit drugs and their metabolites (metham-phetamine; COC = cocaine; MDMA = 3,4-methylenedioxymethamphetamine; METH = methadone; EDDP = 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine; MDA = 3,4-methylenedioxy amphetamine; MDEA = 3,4-methylenedioxy ethylamphetamine; THC-COOH = 11-nor-9-carboxy-Δ9-tetrahydrocannabinol; BEG= Benzoylecgonine). In order to provide a fast and sensitive approach to quantify IDs, an automated online sample preparation method has been developed. The method uses a Thermo Scientific Transcend TLX-1 system powered by TurboFlowTM technology coupled with a TSQ Quantiva Triple Quadrupole Mass Spectrometer. Specifically, THC-COOH has been extracted from 75 µL of pre-filtered water (using 7 and 0.4 µm paper filters) by an online sample extraction method and quantified using an isotopic dilution approach between 30 and 2000 ng L-1.

Published
2016

14. Endothelial function and serum concentration of toxic metals in frequent consumers of fish

Author

Buscemi, S, Vasto, S, Di Gaudio, F, Grosso, G, Bergante, S, Galvano, Fabio, Massenti, Fm, Amodio, E, Rosafio, G, Verga, S., Grosso, Giuseppe, Buscemi, S, Vasto, S, Di Gaudio, F, Grosso, G, Bergante, S, Galvano, F, Massenti, MF, Amodio, E, Rosafio, G, and Verga, S

Subjects
Male, Settore MED/09 - Medicina Interna, lcsh:Medicine, Toxicology, Heavy Metals, Carotid Intima-Media Thickness, Vascular Medicine, Risk Factors, Medicine and Health Sciences, Ingestion, Toxins, Settore MED/49 - Scienze Tecniche Dietetiche Applicate, Endothelial dysfunction, lcsh:Science, Multidisciplinary, Poisoning, Fishes, Middle Aged, medicine.anatomical_structure, Female, Research Article, Adult, medicine.medical_specialty, Endothelium, Toxic Agents, chemistry.chemical_element, Food Contamination, Biology, Peripheral Arterial Disease, Insulin resistance, Diabetes mellitus, Internal medicine, Metals, Heavy, medicine, Animals, Humans, Arsenic, Nutrition, lcsh:R, Biology and Life Sciences, Feeding Behavior, medicine.disease, Atherosclerosis, Mercury (element), Diet, Heavy Metal Poisoning, Endocrinology, chemistry, lcsh:Q, endothelial function, fish, toxic metals, cardiovascular risk, Endothelium, Vascular, Insulin Resistance, Selenium
Abstract

BACKGROUND:Endothelial dysfunction is involved in the pathogenesis of atherosclerosis. Consumption of fish is associated with reduced cardiovascular risk, but there is paucity of data concerning its effect on endothelial function. Furthermore, investigation of the effects of fish consumption on health must take into account the ingestion of contaminants, including transition metals and some metalloids, which may have unfavorable effects on health, including those on the cardiovascular system. We investigated the association between fish consumption, endothelial function (flow mediated dilation of the brachial artery), and serum concentration of some toxic metals in apparently healthy people. METHODS:Twenty-nine high fish consumers (at least 3 portions a week) were compared with 25 low fish consumers (less than 1 portion a week). All participants were free of diabetes, cardiovascular or other systemic diseases. Serum metal (antimonium, arsenic, mercury, lead, cobalt, copper, zinc, selenium, strontium) concentrations were measured in subgroups of 24 high fish consumers and 19 low fish consumers. RESULTS:Both groups exhibited similar habitual dietary patterns, age and anthropometric characteristics. The high fish consumers had higher flow mediated dilation (9.7 ± 1.8 vs. 7.3 ± 1.9%; P

Published
2014

15. Rapid Identification by MALDITOF of Neisseria elongata Subspecies nitroreducens in an Endocarditis Case

Author

C. Bonura, A. Giammanco, Indelicato S, G Giordano, Novo S, Aquilina G, Cinzia Calà, Di Gaudio F, T. Fasciana, Parrinello R, Fasciana, T, Di Gaudio, F2, Novo, S, Aquilina, G, Indelicato, S, Giordano, G, Parrinello, R, Bonura, C, Calà, C, and Giammanco, A

Subjects
biology, business.industry, Subspecies, Neisseria elongata, biology.organism_classification, medicine.disease, Microbiology, Rapid identification, Infective endocarditis, medicine, Endocarditis, infective endocarditis, business, Pathogen
Abstract

Background: Neisseria elongata subspecies nitroreducens is considered to be an important pathogen responsible for infective endocarditis, even if it is infrequently reported. We report the first case of endocarditis in Italy due to N. elongata subsp. nitroreducens. Case presentation: The infection occurs in a 40-year-old male affected by Marfan syndrome with a prosthetic aortic valve. The patient had had a fever for a week which had been resistant to antibiotic therapy. Conclusion: we propose a correct and rapid identification of Neisseria elongata subspecies nitroreducens by mass spectrometry directly from the positive blood culture. The rapidly identification obtained by MALDI-TOF it has enabled us to administer a correct empirical therapy.

Published
2016

17. A non common BRAF mutation c1799-1801 delTGA identified in sporadic colon rectal cancer of sicilian patients

Author

Bruno, L., Calò, V., Rizzo, S., Bronte, G., Marganese, N., Cimino, S., Napoli, L., Damiani, G., Di Gaudio, F., La Paglia, L., Di Piazza, F., Miraglia, M., Bazan, V., Russo, A., Bruno, L, Calò, V, Rizzo, S, Bronte, G, Marganese, N, Cimino, S, Napoli, L, Damiani, GB, Di Gaudio, F, La Paglia, L, Di Piazza, F, Miraglia, MC, Bazan, V, and Russo, A.

Subjects
BRAF mutation sicilian patients
Abstract

Anthracycline has been shown to induce heart failure. To monitor this toxic damage, echocardiographic parameters of left ventricular (LV) systolic function are usually used. Aim of this study was to evaluate in lymphoma’s patients the reliability of echocardiographic data in comparison with a LV systo-diastolic parameter function: the Tei index.

Published
2010

19. Chimica e propedeutica biochimica

Author

Bono, A, Cammarota, M, Cimini, D, Coletta, M, D'Agostino, A, Damonte, G, De Rosa, M, Di Gaudio, F, Galliano, M, Giuliano, M, La Gatta, A, Marini, S, Meggio, F, Minchiotti, L, Restaino, O, Santucci, R, Schiraldi, C, and Spisni, A

Subjects
Settore BIO/10
Published
2012

22. Islet beta-cell apoptosis triggered in vivo by interleukin-1 beta is not related to the inducible nitric oxide synthase pathway: Evidence for mitochondrial function impairment and lipoperoxidation

Author

Todaro, M, Di Gaudio, F, Lavitrano, M, Stassi, G, Papaccio, G, Papaccio, G., LAVITRANO, MARIALUISA, Todaro, M, Di Gaudio, F, Lavitrano, M, Stassi, G, Papaccio, G, Papaccio, G., and LAVITRANO, MARIALUISA

Abstract

IL-1beta is recognized as an effector cytokine contributing to islet beta-cell destruction during diabetes. We have previously shown in vitro that IL-1beta induces nitric oxide (NO) and beta-cell damage. Here, we show that IL-1beta administration in vivo to Wistar rats transiently increases manganese superoxide dismutase activity, whereas inducible NO synthase is not detected, and the levels of nitrate?? do not change. Moreover, a significant decrease of mitochondrial aconitase, leading to a rise of hydroperoxides, and islet beta-cell apoptosis, involving caspase-3 and -8, is observed. Analysis of adhesion molecules in beta-cells showed that intercellular adhesion molecule-1 is highly expressed 48 h after IL-1beta administration and that this is concomitant to the fall of manganese superoxide dismutase activity. Thus, IL-1beta exerts a proapoptotic effect in vivo through mitochondrial enzyme alteration, which is not related to the inducible NO synthase pathway, and dysregulates the immune system through the up-regulation of adhesion molecules.

Published
2003

23. 2 A NON COMMON BRAF MUTATION, c.1799-1801delTGA, IDENTIFIED IN SPORADIC COLORECTAL CANCER OF SICILIAN PATIENT

Author

Bruno, L., primary, Calò, V., additional, Rizzo, S., additional, Bronte, G., additional, Marganese, N., additional, Cimino, S., additional, Napoli, L., additional, Damiani, G.B., additional, Di Gaudio, F., additional, La Paglia, L., additional, Di Piazza, F., additional, Miraglia, M.C., additional, Bazan, V., additional, and Russo, A., additional

Published
2010
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24. 79 VUS VARIANTS IN BRCA GENES OF HEREDITARY BREAST/OVARIAN CANCER

Author

Perez, M., primary, Margarese, N., additional, Calò, V., additional, Bruno, L., additional, La Paglia, L., additional, Cimino, S., additional, Corsini, L.R., additional, Terrasi, M., additional, Fanale, D., additional, Amodeo, V., additional, Insalaco, L., additional, Napoli, L., additional, Di Gaudio, F., additional, Di Piazza, F., additional, Miraglia, M.C., additional, Bazan, V., additional, and Russo, A., additional

Published
2010
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25. Opioid epidemic spread from Northern and Eastern Europe to Mediterranean Area.

Author

di Gaudio, F., Mortali, C., and Tini, A.

Subjects
OPIOIDS, DRUGS of abuse, PUBLIC health, COVID-19 pandemic, RECESSIONS
Abstract

The addiction to illicit opioid and the misuse of prescription synthetic opioids pain relievers and fentanyl analogs generated an opioid epidemic in North America over the last two decades that affected public health with a constantly rising number of overdoses deaths. This health treat moved to Europe with a significant increase starting from 2015 involving mainly norther and eastern countries and finally also the Mediterranean area. The “lock down” isolation and economic recession caused by COVID-19 pandemic showed a resurgence in opioid use and harms. [ABSTRACT FROM AUTHOR]

Published
2021
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28. NF-kappaB protects Behçet's disease T cells against CD95-induced apoptosis up-regulating antiapoptotic proteins.

Author

Todaro M, Zerilli M, Triolo G, Iovino F, Patti M, Accardo-Palumbo A, di Gaudio F, Turco MC, Petrella A, de Maria R, and Stassi G

Abstract

OBJECTIVE: To determine whether prolongation of the inflammatory reaction in patients with Behçet's disease (BD) is related to apoptosis resistance and is associated with the up-regulation of antiapoptotic factors. METHODS: The percentage of cell death was evaluated by flow cytometry in peripheral blood mononuclear cells from 35 patients with BD and 30 healthy volunteers. The expression levels of antiapoptotic factors and NF-kappaB regulatory proteins were measured using Western blotting and immunohistochemical analyses. To down-regulate NF-kappaB nuclear translocation, BD T lymphocytes were exposed in vitro to thalidomide and subjected to transfection with NF-kappaB small interfering RNA. RESULTS: Although CD95 is highly expressed in BD T cells, the absence of sensitivity to CD95-induced apoptosis observed may be attributable to the inhibitory action of antiapoptotic genes. Immunoblot analysis for major antiapoptotic proteins showed considerable up-regulation of the short form of cellular FLIP (cFLIP) and Bcl-x(L) in BD activated T cells, while levels of Bcl-2, caspase 3, and caspase 8 in activated T cells from patients with BD were comparable with those in activated T cells from normal donors. Moreover, expression of IKK and IkappaB was up-regulated, whereas NF-kappaB translocated to the nucleus in BD T cells, suggesting that NF-kappaB activation may modulate the expression of antiapoptotic genes. Interestingly, thalidomide and NF-kappaB small interfering RNA down-regulated cFLIP and Bcl-x(L) expression levels and sensitized BD activated T cells to CD95-induced apoptosis. CONCLUSION: Taken together, these results indicate that NF-kappaB contributes to the regulation of the apoptosis-related factors and death receptors leading to apoptosis resistance in BD T cell subsets. Our results suggest that NF-kappaB plays a crucial role in the pathogenesis of BD, and that its pharmacologic control could represent a key strategy in modulating specific immune-mediated disease. [ABSTRACT FROM AUTHOR]

Published
2005
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29. Setting up of a machine learning algorithm for the identification of severe liver fibrosis profile in the general US population cohort

Author

Samir Hassoun, Chiara Bruckmann, Stefano Ciardullo, Gianluca Perseghin, Francesca Di Gaudio, Francesco Broccolo, Hassoun S., Bruckmann C., Ciardullo S., Perseghin G., Di Gaudio F., Broccolo F., Hassoun, S, Bruckmann, C, Ciardullo, S, Perseghin, G, Di Gaudio, F, and Broccolo, F

Subjects
Imbalanced dataset, Machine learning, Oversampling technique, Liver fibrosi, NHANES, Health Informatics, test performance evaluation
Abstract

Background: The progress of digital transformation in clinical practice opens the door to transforming the current clinical line for liver disease diagnosis from a late-stage diagnosis approach to an early-stage based one. Early diagnosis of liver fibrosis can prevent the progression of the disease and decrease liver-related morbidity and mortality. We developed here a machine learning (ML) algorithm containing standard parameters that can identify liver fibrosis in the general US population.Materials and methods: Starting from a public database (National Health and Nutrition Examination Survey, NHANES), representative of the American population with 7265 eligible subjects (control population n = 6828, with Fibroscan values E < 9.7 KPa; target population n = 437 with Fibroscan values E >= 9.7 KPa), we set up an SVM algorithm able to discriminate for individuals with liver fibrosis among the general US population. The algorithm set up involved the removal of missing data and a sampling optimization step to managing the data imbalance (only similar to 5 % of the dataset is the target population).Results: For the feature selection, we performed an unbiased analysis, starting from 33 clinical, anthropometric, and biochemical parameters regardless of their previous application as biomarkers of liver diseases. Through PCA analysis, we identified the 26 more significant features and then used them to set up a sampling method on an SVM algorithm. The best sampling technique to manage the data imbalance was found to be oversampling through the SMOTE-NC. For final model validation, we utilized a subset of 300 individuals (150 with liver fibrosis and 150 controls), subtracted from the main dataset prior to sampling. Performances were evaluated on multiple independent runs.Conclusions: We provide proof of concept of an ML clinical decision support tool for liver fibrosis diagnosis in the general US population. Though the presented ML model represents at this stage only a prototype, in the future, it might be implemented and potentially applied to program broad screenings for liver fibrosis.

Published
2022

30. Technical and health governance aspects of the External Quality Assessment Scheme for the SARS-CoV-2 molecular tests: institutional experience performed in all clinical laboratories of a Regional Health Service

Author

Francesca Di Gaudio, Giuseppina Brunacci, Flavia Contino, Alessia Gallo, Fabio Centineo, Di Gaudio F., Brunacci G., Contino F., Gallo A., and Centineo F.

Subjects
ISO 15189, ISO/IEC 17025, test performance evaluation, SARS-CoV-2, Biochemistry (medical), Clinical Biochemistry, COVID-19, General Medicine, Clinical Laboratory Services, regional laboratories quality control, United States, COVID-19 Testing, Humans, External Quality Assessment, Covid437, Laboratories, ISO/IEC 17043, Laboratories, Clinical
Abstract

Objectives Since December 2019, the worldwide public health has been threatened by a severe acute respiratory syndrome caused by Coronavirus-2. From the beginning, a turning point has been the identification of new cases of infection, in order to minimize the virus spreading among the population. For this reason, it was necessary introducing a panel of tests able to identify positive cases, which became crucial for all countries. Methods As a Regional Reference Centre, the CRQ Laboratory (Regional Laboratory for the Quality Control) developed and conducted an External Quality Assessment (EQA) panel of assay, so as to evaluate the quality of real-time reverse transcription polymerase chain reaction (PCR), which were used by 62 Sicilian laboratories, previously authorized to issue certificates for the COVID-19 diagnosis, on behalf of the Public Health Service. Results The qualitative performance test was based on pooled samples with different viral loads of SARS-CoV-2 or human Coronavirus OC43. 75% of the participating laboratories tested all core samples correctly, while the remaining 25% interpreted incorrectly the EQA exercise samples matching negatively the standards required. Conclusions Subsequent inspection visits confirmed the issue of incorrect positive and negative certifications for COVID-19 by private and public laboratories, despite the possession of the authorization requirements currently provided for by current regulations, with a significant impact on the SSR.

Published
2022

31. Diallyldimethylammonium Chloride (DADMAC) in Water Treated with Poly-Diallyldimethylammonium Chloride (PDADMAC) by Reversed-Phase Ion-Pair Chromatography—Electrospray Ionization Mass Spectrometry

Author

Francesca Di Gaudio, Salvatore Barreca, Santino Orecchio, Di Gaudio F., Barreca S., and Orecchio S.

Subjects
water treatment, drinking waters, diallyldimethylammonium chloride, poly-diallyldimethylammonium chloride, mass spectrometry, drinking water, Filtration and Separation, Poly-diallyldimethylammonium chloride, Analytical Chemistry
Abstract

Poly-diallyldimethylammonium (PDADMAC) chloride is a flocculant agent extensively used in water clarification treatments. Commercial polyelectrolyte formulations often contain residual monomer (DADMAC), reaction by-products and other reactants as contaminants that could potentially affect human health. In the present study, we optimized an analytical method based on reversed-phase ion-pair chromatography coupled with mass spectrometry for quantifying ultra-trace levels of DADMAC, without preliminary treatments, in drinking water distributed by the Palermo aqueduct. The method was validated in terms of accuracy (recovery between 80 to 120%), precision (RSD < 10%), linearity range (from 0.5 to 15 µg/L), limit of quantification and limit of detection (LOQ 0.42 µg/L and LOD 0.12 µg/L). DADMAC was detected in all analysed water samples and the concentration ranged from 1.2 to 3.8 µg/L whit a mean value of 1.7 µg/L. To the best of our knowledge, this paper represents the first study concerning DADMAC concentration in water samples collected in Italy and, in this context, this paper can be considered very interesting when comparing future data on DADMAC monitoring in water. Moreover, this is one of a few cases where DADMAC was found in drinking water.

Published
2023

32. Current Perspectives on Adult Mesenchymal Stromal Cell-Derived Extracellular Vesicles: Biological Features and Clinical Indications

Author

Giusi Alberti, Eleonora Russo, Simona Corrao, Rita Anzalone, Peter Kruzliak, Vitale Miceli, Pier Giulio Conaldi, Francesca Di Gaudio, Giampiero La Rocca, Alberti G., Russo E., Corrao S., Anzalone R., Kruzliak P., Miceli V., Conaldi P.G., Di Gaudio F., and La Rocca G.

Subjects
Settore BIO/17 - Istologia, adult mesenchymal stromal cells, bone marrow, inflammation, regeneration, cell-free therapies, cancer, Medicine (miscellaneous), tissue repair, extracellular vesicles, General Biochemistry, Genetics and Molecular Biology, adipose tissue
Abstract

Extracellular vesicles (EVs) constitute one of the main mechanisms by which cells communicate with the surrounding tissue or at distance. Vesicle secretion is featured by most cell types, and adult mesenchymal stromal cells (MSCs) of different tissue origins have shown the ability to produce them. In recent years, several reports disclosed the molecular composition and suggested clinical indications for EVs derived from adult MSCs. The parental cells were already known for their roles in different disease settings in regulating inflammation, immune modulation, or transdifferentiation to promote cell repopulation. Interestingly, most reports also suggested that part of the properties of parental cells were maintained by isolated EV populations. This review analyzes the recent development in the field of cell-free therapies, focusing on several adult tissues as a source of MSC-derived EVs and the available clinical data from in vivo models.

Published
2022

33. Impact on Glucose Homeostasis: Is Food Biofortified with Molybdenum a Workable Solution? A Two-Arm Study

Author

Sonya Vasto, Francesca Di Gaudio, Maria Raso, Leo Sabatino, Rosalia Caldarella, Claudio De Pasquale, Luigi Di Rosa, Sara Baldassano, Vasto S., Di Gaudio F., Raso M., Sabatino L., Caldarella R., De Pasquale C., Di Rosa L., and Baldassano S.

Subjects
Blood Glucose, Molybdenum, GIP, Minerals, Nutrition and Dietetics, PYY, digestive, oral, and skin physiology, Human health, Gastric Inhibitory Polypeptide, Lettuce, biofortification, lettuce, human heath, minerals, gut peptides, Glucose, Diabetes Mellitus, Type 2, Glucagon-Like Peptide 1, Food, Fortified, Glucagon-Like Peptide 2, Gut peptides, Homeostasis, Humans, Insulin, Peptide YY, Insulin Resistance, Biofortification, hormones, hormone substitutes, and hormone antagonists, Food Science
Abstract

Diabetes is expected to increase up to 700 million people worldwide with type 2 diabetes being the most frequent. The use of nutritional interventions is one of the most natural approaches for managing the disease. Minerals are of paramount importance in order to preserve and obtain good health and among them molybdenum is an essential component. There are no studies about the consumption of biofortified food with molybdenum on glucose homeostasis but recent studies in humans suggest that molybdenum could exert hypoglycemic effects. The present study aims to assess if consumption of lettuce biofortified with molybdenum influences glucose homeostasis and whether the effects would be due to changes in gastrointestinal hormone levels and specifically Peptide YY (PYY), Glucagon-Like Peptide 1 (GLP-1), Glucagon-Like Peptide 2 (GLP-2), and Gastric Inhibitory Polypeptide (GIP). A cohort of 24 people was supplemented with biofortified lettuce for 12 days. Blood and urine samples were obtained at baseline (T0) and after 12 days (T2) of supplementation. Blood was analyzed for glucose, insulin, insulin resistance, β-cell function, and insulin sensitivity, PYY, GLP-1, GLP-2 and GIP. Urine samples were tested for molybdenum concentration. The results showed that consumption of lettuce biofortified with molybdenum for 12 days did not affect beta cell function but significantly reduced fasting glucose, insulin, insulin resistance and increased insulin sensitivity in healthy people. Consumption of biofortified lettuce did not show any modification in urine concentration of molybdenum among the groups. These data suggest that consumption of lettuce biofortified with molybdenum improves glucose homeostasis and PYY and GIP are involved in the action mechanism.

Published
2022
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34. Biofortification: Effect of Iodine Fortified Food in the Healthy Population, Double-Arm Nutritional Study

Author

Sara Baldassano, Francesca Di Gaudio, Leo Sabatino, Rosalia Caldarella, Claudio De Pasquale, Luigi Di Rosa, Domenico Nuzzo, Pasquale Picone, Sonya Vasto, Baldassano S., Di Gaudio F., Sabatino L., Caldarella R., De Pasquale C., Di Rosa L., Nuzzo D., Picone P., and Vasto S.

Subjects
biofortification, functional food, calcium, Nutrition and Dietetics, iodine, Endocrinology, Diabetes and Metabolism, vitamin D, Food Science
Abstract

It is estimated that one-third of the world’s population lives in areas where iodine (I) is scarce and its deficiency is responsible for many related disorders, such as goiter, reproductive failure, hearing loss, growth impairment, congenital I deficiency syndrome, and numerous kinds of brain injury. Mineral deficiencies can be overcomeviadietary diversification and mineral supplementation. An alternative or even complementary way is represented by the intake of biofortified foods, which can tackle this lack of micronutrients. In this short-term double-arm nutritional intervention study, a cohort of ten people was supplemented with curly endive leaf biofortified with I and ten people with curly endive without biofortification (Intervention Study on Iodine Biofortification Vegetables (Nutri-I-Food – Full-Text View -ClinicalTrials.gov). The effects on whole-body homeostasis and specifically on I, glucose, lipid, and hepatic, iron metabolism was investigated. Blood samples were obtained at baseline and after 12 days of supplementation with curly endive and compared with controls. Hematochemical and urinary parameters were analyzed at baseline and after 12 days. The results showed that short-term I curly endive intervention did not affect the whole body homeostasis in healthy people and revealed an increase in I concentration in urine samples and an increase in vitamin D, calcium, and potassium concentration in blood samples only in the biofortified cohort respect to controls. This study suggests that short-term consumption of I curly endive crops is safe and could positively impact body health.

Published
2022

35. Islet beta-cell apoptosis triggered in vivo by interleukin-1beta is not related to the inducible nitric oxide synthase pathway: evidence for mitochondrial function impairment and lipoperoxidation

Author

Matilde Todaro, Francesca Di Gaudio, Gianpaolo Papaccio, Giorgio Stassi, Marialuisa Lavitrano, Todaro, M, Di Gaudio, F, Lavitrano, M, Stassi, G, Papaccio, G, DI GAUDIO, F, and Papaccio, Gianpaolo

Subjects
medicine.medical_specialty, Lipid Peroxides, Nitric Oxide Synthase Type II, Apoptosis, Biology, Mitochondrion, In Vitro Techniques, Aconitase, Nitric oxide, chemistry.chemical_compound, Islets of Langerhans, Endocrinology, In vivo, Internal medicine, medicine, Animals, Rats, Wistar, Nitrites, Aconitate Hydratase, geography, Caspase 8, geography.geographical_feature_category, Nitrates, Cell adhesion molecule, Caspase 3, Superoxide Dismutase, Islet, Intercellular Adhesion Molecule-1, Caspase 9, Cell biology, Mitochondria, Rats, Nitric oxide synthase, Biochemistry, chemistry, Caspases, biology.protein, Nitric Oxide Synthase, Interleukin-1
Abstract

IL-1beta is recognized as an effector cytokine contributing to islet beta-cell destruction during diabetes. We have previously shown in vitro that IL-1beta induces nitric oxide (NO) and beta-cell damage. Here, we show that IL-1beta administration in vivo to Wistar rats transiently increases manganese superoxide dismutase activity, whereas inducible NO synthase is not detected, and the levels of nitrate+nitrate do not change. Moreover, a significant decrease of mitochondrial aconitase, leading to a rise of hydroperoxides, and islet beta-cell apoptosis, involving caspase-3 and -8, is observed. Analysis of adhesion molecules in beta-cells showed that intercellular adhesion molecule-1 is highly expressed 48 h after IL-1beta administration and that this is concomitant to the fall of manganese superoxide dismutase activity. Thus, IL-1beta exerts a proapoptotic effect in vivo through mitochondrial enzyme alteration, which is not related to the inducible NO synthase pathway, and dysregulates the immune system through the up-regulation of adhesion molecules.

Published
2003

36. Diagnostic Accuracy of a New Antigen Test for SARS-CoV-2 Detection

Author

Marina Di Domenico, Andrea Marotta, Davide Castrianni, Pietro Internicola, Nicola Salzano, Francesca Di Gaudio, Mariarosaria Boccellino, Alfredo De Rosa, Cinzia Bettini, Di Domenico M., De Rosa A., Di Gaudio F., Internicola P., Bettini C., Salzano N., Castrianni D., Marotta A., Boccellino M., Di Domenico, Marina, De Rosa, Alfredo, Di Gaudio, Francesca, Internicola, Pietro, Bettini, Cinzia, Salzano, Nicola, Castrianni, Davide, Marotta, Andrea, and Boccellino, Mariarosaria

Subjects
medicine.medical_specialty, respiratory disease COVID-19, Coronavirus disease 2019 (COVID-19), Health, Toxicology and Mutagenesis, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), cyto-salivary test, RT-PCR, Diagnostic accuracy, Immunologic Tests, Gastroenterology, Asymptomatic, Sensitivity and Specificity, Article, lateral flow test, Lateral flow test, 03 medical and health sciences, 0302 clinical medicine, Antigen, Internal medicine, medicine, Humans, Immunologic Test, 030212 general & internal medicine, Pandemics, 030304 developmental biology, 0303 health sciences, business.industry, SARS-CoV-2, Public Health, Environmental and Occupational Health, COVID-19, Gold standard (test), Antigen test, Medicine, ELISA, medicine.symptom, business, Human
Abstract

Background and aims: Quick and reliable diagnostic tools play an important role in controlling the spread of the SARS-Cov-2 pandemic. The aim of this study was to evaluate the diagnostic accuracy of a new cyto-salivary antigen test aimed at detecting the presence of antigens for SARS-CoV-2, as compared by the gold standard RT-PCR and a lateral flow test. Methods: A total of 433 healthy volunteers were enrolled in the study and the sensitivity and specificity of the new cyto-salivary antigen test were calculated, as compared to the RT-PCR nasopharyngeal swab and to the lateral flow test. Results: A total of 433 samples were collected and tested at the Mediterranean Fair in Palermo from February 2021 until April 2021. The new cyto-salivary antigen had a sensitivity of 100% and a specificity of 94.2%. The sensitivity and the specificity of the lateral flow test were 55% and 100%, respectively. Conclusions: The new cyto-salivary antigen test detected more positive cases than the RT-PCR in a sample of asymptomatic subjects, demonstrating to be a promising tool for a more sensitive diagnosis of COVID-19. Further studies are warranted to better characterize its diagnostic accuracy.

Published
2021
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37. Iodine Biofortification Counters Micronutrient Deficiency and Improve Functional Quality of Open Field Grown Curly Endive

Author

Rosario Paolo Mauro, Beppe Benedetto Consentino, Giovanni Iapichino, Sonya Vasto, Fabio D'Anna, Youssef Rouphael, Leo Sabatino, F. Di Gaudio, S. La Bella, Rosalia Caldarella, C. De Pasquale, Christophe El-Nakhel, Sabatino, L., Di Gaudio, F., Consentino, B. B., Rouphael, Y., El-Nakhel, C., La Bella, S., Vasto, S., Mauro, R. P., D'Anna, F., Iapichino, G., Caldarella, R., De Pasquale, C., Sabatino, Leo, Di Gaudio, Francesca, Consentino, Beppe, Rouphael, Youssef, El-Nakhel, Christophe, La Bella, Salvatore, Vasto, Sonya, Mauro, Rosario, D’Anna, Fabio, Iapichino, Giovanni, Caldarella, Rosalia, and De Pasquale, Claudio

Subjects
0106 biological sciences, Micronutrient deficiency, Biofortification, Growing season, chemistry.chemical_element, Plant Science, Horticulture, Biology, lcsh:Plant culture, Iodine, 01 natural sciences, World health, Functional compound, Ingestion, Dry matter, Cichorium endivia L. var. crispum Hegi, lcsh:SB1-1110, Sugar, growing season, functional compounds, food and beverages, 04 agricultural and veterinary sciences, Ascorbic acid, yield, chemistry, sugars, 040103 agronomy & agriculture, 0401 agriculture, forestry, and fisheries, iodine concentration, 010606 plant biology & botany, mineral profile
Abstract

Human iodine (I) shortage disorders are documented as an imperative world-wide health issue for a great number of people. The World Health Organization (WHO) recommends I consumption through ingestion of seafood and biofortified food such as vegetables. The current work was carried out to appraise the effects of different I concentrations (0, 50, 250, and 500 mg L−1), supplied via foliar spray on curly endive grown in the fall or spring–summer season. Head fresh weight, stem diameter, head height, and soluble solid content (SSC) were negatively correlated to I dosage. The highest head dry matter content was recorded in plants supplied with 250 mg I L−1, both in the fall and spring–summer season, and in those cultivated in the fall season and supplied with 50 mg I L−1. The highest ascorbic acid concentration was recorded in plants cultivated in the spring–summer season and biofortified with the highest I dosage. The highest fructose and glucose concentrations in leaf tissues were obtained in plants cultivated in the spring–summer season and treated with 250 mg I L−1. Plants sprayed with 250 mg I L−1 and cultivated in the fall season had the highest I leaf concentration. Overall, our results evidently suggested that an I application of 250 mg L−1 in both growing seasons effectively enhanced plant quality and functional parameters in curly endive plants.

Published
2021

38. Blood metal levels after minimally invasive repair of pectus excavatum

Author

Maria Raso, Maria Grazia Calevo, Sebastiano Barco, Francesca Di Gaudio, Michela Wong, Luca Genova Gaia, Michele Torre, Giuliana Cangemi, Torre M., Genova Gaia L., Calevo M.G., Wong M., Raso M., Barco S., Di Gaudio F., and Cangemi G.

Subjects
Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Adolescent, Thoracic, Metallosi, MIRPE, 03 medical and health sciences, 0302 clinical medicine, Stabilizer - ingredient, Pectus excavatum, medicine, Humans, Minimally Invasive Surgical Procedures, Metallosis, In patient, Thoracoplasty, 030212 general & internal medicine, Child, Metal release, Retrospective Studies, Paediatric patients, 030222 orthopedics, Surgical approach, business.industry, Prostheses and Implants, Plastic Surgery Procedures, medicine.disease, Surgery, Funnel Chest, Metal toxicity, Female, Implant, Metallic bar, Cardiology and Cardiovascular Medicine, business
Abstract

OBJECTIVES Minimally invasive repair of pectus excavatum (MIRPE) is the most popular surgical approach for paediatric patients with pectus excavatum. A substernal stainless still bar is inserted and left in place for 3 years and then removed. Our goal was to investigate blood metal levels after MIRPE and to correlate them with surgical details, such as the numbers of bars and stabilizers and the length of time the bar was in place. METHODS Blood levels of iron, chromium, manganese, molybdenum and nickel were analysed in 130 teenagers (108 boys and 22 girls) who had MIRPE using inductively coupled plasma mass spectrometry. A total of 62 patients were operated on using MIRPE (study group) and 68 patients were evaluated at implant time (control group). Differences between the numbers of bars implanted and the presence or absence of stabilizers were also considered. RESULTS Significant increases in the levels of abnormal chromium were found in patients in the study group compared with the controls (P = 0.02). When we compared the group of patients with 2 or more bars with the group with 1 bar, the percentage of patients with a value above the threshold increased by 29 (P = 0.05). A significant increase in chromium levels was observed in patients with stabilizers (P = 0.03). Above-threshold levels of molybdenum were found in 5.1% of patients in the control group, but the number was not statistically significant (P = 0.09). CONCLUSIONS We demonstrated that stainless steel devices used in MIRPE can elevate blood metal levels in paediatric patients. Moreover, we demonstrated that the use of metal stabilizers is associated with higher metal levels, probably due to increased dispersion.

Published
2021

39. Reverse transcriptase loop-mediated isothermal amplification (RT-LAMP) as a user-friendly system to detect SARS-CoV-2 infection: a multicentric study

Author

Stefano, Stracquadanio, Francesca, Di Gaudio, Elena, Giunta, Giuseppe, Falliti, Daniele, Caruso, Carmelo, Pinzone, Patrizia, Noto, Concettina, Di Naso, Sebastiano Fabio, Garozzo, Andrea, Amodeo, Diana, Cinà, Maria Concetta, Cardillo, Simona, Zappalà, Alessandro, Consoli, Stefania, Stefani, Stracquadanio S., Di Gaudio F., Giunta E., Falliti G., Caruso D., Pinzone C., Noto P., Di Naso C., Garozzo S.F., Amodeo A., Cina D., Cardillo M.C., Zappala S., Consoli A., and Stefani S.

Subjects
Multicentric study, RT-LAMP, Diagnostic power, Reverse Transcriptase Polymerase Chain Reaction, SARS-CoV-2, COVID-19, RNA-Directed DNA Polymerase, Sensitivity and Specificity, Molecular Diagnostic Techniques, Humans, RNA, Viral, RNA, Viral, Nucleic Acid Amplification Techniques
Abstract

Although reverse transcriptase quantitative PCR remains the gold standard to perform viral detection, reverse transcriptase loop-mediated isothermal amplification (RT-LAMP) is already used to perform diagnosis of various infections. This work reports the results of a multicentric study performed in Sicily to evaluate the diagnostic power of an RT-LAMP kit for the diagnosis of SARS-CoV-2 infection on a total of 551 samples collected in January and February 2021, revealing sensitivity, specificity, accuracy, positive and negative predictive values ≥95%. Our results suggest the potential employment of this kit as a screening test to be used where fast and reliable results are demanded without the need for expensive instruments and highly-skilled personnel.

Published
2021

40. Automated untargeted stable isotope assisted lipidomics of liver cells on high glucose shows alteration of sphingolipid kinetics

Author

C. Scrimali, Serena Indelicato, Massimiliano Greco, Rossella Spina, Maurizio Averna, Ida Altieri, Antonina Giammanco, Francesca Di Gaudio, Davide Noto, Angelo B. Cefalù, David Bongiorno, Francesca Fayer, Sergio Indelicato, Alessandro Mattina, Noto D., Di Gaudio F., Altieri I.G., Cefalu A.B., Indelicato S., Fayer F., Spina R., Scrimali C., Giammanco A., Mattina A., Greco M., Bongiorno D., and Averna M.

Subjects
Kinetics, Palmitic Acid, Hep G2 Cell, Fatty Acids, Nonesterified, Orbitrap, High resolution mass spectrometry, 01 natural sciences, Gas Chromatography-Mass Spectrometry, Workflow, law.invention, Palmitic acid, Automation, 03 medical and health sciences, chemistry.chemical_compound, Insulin resistance, law, Lipidomics, medicine, Humans, Molecular Biology, 030304 developmental biology, Kinetic, Sphingolipids, 0303 health sciences, Chromatography, Chemistry, Lipidomic, 010401 analytical chemistry, Lipid metabolism, Hep G2 Cells, Cell Biology, Deuterium, Lipid Metabolism, medicine.disease, Culture Media, 0104 chemical sciences, Glucose, Isotope Labeling, Cell model, Hepatocytes, Monoisotopic mass, Sphingomyelin, Algorithms, Software
Abstract

Untargeted lipidomics is a powerful tool to discover new biomarkers and to understand the physiology and pathology of lipids. The use of stable isotopes as tracers to investigate the kinetics of lipids is another tool able to supply dynamic information on lipid synthesis and catabolism. Coupling the two methodology is then very appealing in the study of lipid metabolism. The main issue to face is to perform thousands of calculations in order to obtain kinetic parameters starting from the MS raw data. An automated computerized routine able to do accomplish such task is presented in this paper. We analyzed the lipid kinetics of palmitic acid (PA) in hepatoma liver cells cultured in vitro in which insulin resistance has been induced by high glucose supplementation. The deuterated palmitate tracer (d5PA) was administered as a bolus and the cells were harvested daily for 48 h. 5dPA was incorporated into 326 monoisotopic compounds and in 84 of their [M + 1] isotopologues detected by high resolution orbitrap MS. The differences between the kinetics curves showed that at least four long chain triglycerides (TG) species incorporated more PA in glucose treated cells, while phosphocholines, sphingomyelins, mono- and di-glycerides and ceramides (Cer) incorporated less tracer under glucose treatment. Nevertheless, Cer amount was increased by glucose treatment. In conclusion we developed an automated powerful algorithm able to model simultaneously hundreds of kinetic curves obtained in a cell culture spiked with a stable isotope tracer, and to analyze the difference between the two different cell models.

Published
2020

41. Clinical and hormonal characteristics in heterozygote carriers of congenital adrenal hyperplasia

Author

Carmelo Fabiano, Carla Giordano, Marianna Bono, Serena Marchese, Marcello Niceta, Piernicola Garofalo, Serena Indelicato, Francesca Di Gaudio, Valentina Guarnotta, Guarnotta V., Niceta M., Bono M., Marchese S., Fabiano C., Indelicato S., Di Gaudio F., Garofalo P., and Giordano C.

Subjects
0301 basic medicine, Hirsutism, Hydrocortisone, endocrine system diseases, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Physiology, Overweight, urologic and male genital diseases, Biochemistry, Settore MED/13 - Endocrinologia, 0302 clinical medicine, Endocrinology, Settore BIO/10 - Biochimica, Genotype, Medicine, Child, hirsutism, Polycystic ovary, female genital diseases and pregnancy complications, 030220 oncology & carcinogenesis, Cohort, Molecular Medicine, Female, medicine.symptom, Adult, Heterozygote, congenital, hereditary, and neonatal diseases and abnormalities, Adolescent, Young Adult, 03 medical and health sciences, Humans, Congenital adrenal hyperplasia, Molecular Biology, Heterozygous carrier, Adrenal Hyperplasia, Congenital, business.industry, Hyperandrogenism, nutritional and metabolic diseases, Heterozygote advantage, Cell Biology, medicine.disease, Oligomenorrhea, 17OHProgesterone deficiency, 030104 developmental biology, Mutation, Steroid 21-Hydroxylase, business
Abstract

Non-classical congenital adrenal hyperplasia (NC-CAH) includes a group of genetic disorders due to a broad class of CYP21A2 variants identifying a disease-causing ‘C’ genotype. The heterozygous carriers of CYP21 mutations are at increased risk of developing clinically evident hyperandrogenism, even though clinical and laboratory characteristics are still underestimated. With the aim of obtaining a more accurate delineation of the phenotype of heterozygous carrier of CAH, we analyzed clinical, biochemical and molecular characteristics in a cohort of Sicilian subjects. Fifty-seven females with biallelic and monoallelic CYP21A2 variants classifying NC-CAH (24) and heterozygous carriers of CAH (33), respectively were selected. Forty-four females age-matched healthy controls were also enrolled and genotyped for CYP21A2. Clinical, hormonal and genetic data were collected. CYP21A2 monoallelic mutations, defining the heterozygous carriers state, were identified in subjects with clinical features including hirsutism, oligomenorrhoea, overweight and a PCO-like phenotype, particularly occurring in the age of adolescence. Consistently, levels of 17OHP and cortisol were found to be significantly different from NC-CAH. Overall, some clinical and laboratory findings including oligomenorrhea and 17OHP/cortisol ratio were observed as independent markers associated with carriers of CAH. Here we report a high prevalence of late-onset signs of polycystic ovary syndrome (PCOS) and hyperandrogenism in heterozygous carriers. The 17OHP/cortisol ratio may be a predictive tool to identify the carriers of CAH, even though specific cut-off values have not yet been identified.

Published
2020

42. Illicit drugs consumption evaluation by wastewater-based epidemiology in the urban area of Palermo city (Italy)

Author

MAIDA, Carmelo Massimo, DI GAUDIO, Francesca, TRAMUTO, Fabio, MAZZUCCO, Walter, PISCIONIERI, DONATELLA, COSENZA, Alida, VIVIANI, Gaspare, Maida CM, Di Gaudio F, Tramuto F, Mazzucco W, Piscionieri D, Cosenza A, and Viviani G

Subjects
drugs consumption, Settore ICAR/03 - Ingegneria Sanitaria-Ambientale, Illicit Drugs, Substance-Related Disorders, cocaine, amphetamines, cannabinoid, Wastewater, Settore MED/42 - Igiene Generale E Applicata, wastewater-based epidemiology, Italy, Tandem Mass Spectrometry, wastewater analysi, Prevalence, Humans, wastewater analysis, cannabinoids, Chromatography, High Pressure Liquid
Abstract

Introduction. A wastewater-based epidemiology approach was performed to estimate the drug consumption in Palermo city, the fifth largest city of Italy with a population of 671 696 inhabitants, and to investigate the monthly variability of drug loads in wastewater from different areas of the city. A seven-months detection campaign was conducted at the two wastewater treatment plants of the city. Methods. Following a pre-treatment, 32 samples of wastewater were analyzed by liquid chromatography-tandem mass spectrometry. Results. We estimated a mean cocaine use in Palermo of 0.19 g/day/1000 people, corresponding to 1.90 doses/1000 people and cannabinoids use of 2.85 g/day/1000 people, corresponding to 35.62 doses/1000 people. Amphetamines residues in wastewater were always recovered in concentrations lower than the limit of quantification. Conclusion. Our findings showed that drugs consumption in Palermo is in line with those of other Italian cities and that no significant differences on prevalence on cocaine and cannabinoids consumption were recorded in the different months of the survey, except for the summer period in a wastewater treatment plant of the city.

Published
2017

43. Ceftaroline modulates the innate immune and host defense responses of immunocompetent cells exposed to cigarette smoke

Author

Elisabetta Pace, Mark Gjomarkaj, S. Di Vincenzo, Andreina Bruno, Liboria Siena, Paola Dino, Chiara Cipollina, F. Di Gaudio, Bruno A., Cipollina C., Di Vincenzo S., Siena L., Dino P., Di Gaudio F., Gjomarkaj M., and Pace E.

Subjects
0301 basic medicine, Lipopolysaccharides, beta-Defensins, Cell Survival, Cephalosporin, Lipopolysaccharide, Toxicology, Monocytes, 03 medical and health sciences, Immunologic Factor, 0302 clinical medicine, Immune system, Cell Line, Tumor, Smoke, Anti-Bacterial Agent, medicine, Humans, Immunologic Factors, Innate immune system, Immunocompetent cell, Dose-Response Relationship, Drug, business.industry, Tumor Necrosis Factor-alpha, Monocyte, Macrophages, Smoking, Antibiotic, Cigarette smoke, General Medicine, Immunity, Innate, Toll-Like Receptor 2, Anti-Bacterial Agents, Cephalosporins, Host-Pathogen Interaction, Toll-Like Receptor 4, TLR2, 030104 developmental biology, medicine.anatomical_structure, Beta defensin, Cell culture, Immunology, Host-Pathogen Interactions, TLR4, lipids (amino acids, peptides, and proteins), Tumor necrosis factor alpha, business, Immunocompetence, 030215 immunology
Abstract

Background Cigarette smoke, the principal risk factor for chronic obstructive pulmonary disease (COPD), negatively influences the effectiveness of the immune system’s response to a pathogen. The antibiotic ceftaroline exerts immune-modulatory effects in bronchial epithelial cells exposed to cigarette smoke. Aims and methods The present study aims to assess the effects of ceftaroline on TLR2 and TLR4 expression, LPS binding and TNF-α and human beta defensin (HBD2) release in an undifferentiated and PMA-differentiated human monocyte cell line (THP-1) exposed or not to cigarette smoke extracts (CSE). TLR2, TLR4, and LPS binding were assessed by flow cytometry, TNF-α and HBD2 release were evaluated by ELISA. Results The constitutive expression of TLR2 and TLR4 and LPS binding were higher in differentiated compared to undifferentiated THP-1 cells. In undifferentiated THP-1 cells, CSE increased TLR2 and TLR4 protein levels, LPS binding and TNF-α release and reduced HBD2 release and ceftaroline counteracted all these effects. In differentiated THP-1, CSE did not significantly affect TLR2 and TLR4 expression and LPS binding but reduced HBD2 release and increased TNF-α release. Ceftaroline counteracted the effects of CSE on HBD2 release in differentiated THP-1. Conclusion Ceftaroline counteracts the effect of CSE in immune cells by increasing the effectiveness of the innate immune system. This effect may also assist in reducing pathogen activity and recurrent exacerbations in COPD patients.

Published
2017

44. Nandrolone decanoate interferes with testosterone biosynthesis altering blood-testis barrier components

Author

Valentina Di Felice, Alessandro Pitruzzella, Francesca Di Gaudio, Gabriele Sani, Emanuela Turillazzi, Nicola Locorotondo, Cristoforo Pomara, Venerando Rapisarda, Luigi Cipolloni, Amos Tambo, Antonella Marino Gammazza, Rosario Barone, Monica Salerno, Daniela D’Amico, Francesco Cappello, Claudia Sangiorgi, Fulvio Barone, Francesca Rappa, Stefania Schiavone, Barone, R., Pitruzzella, A., Marino Gammazza, A., Rappa, F., Salerno, M., Barone, F., Sangiorgi, C., D'Amico, D., Locorotondo, N., Di Gaudio, F., Cipolloni, L., Di Felice, V., Schiavone, S., Rapisarda, V., Sani, G., Tambo, A., Cappello, F., Turillazzi, E., and Pomara, C.

Subjects
Male, 0301 basic medicine, medicine.medical_specialty, Nandrolone decanoate, Stimulation, Endogeny, MUC1, Biology, Male infertility, Mice, 03 medical and health sciences, Anabolic Agents, Western blot, Physical Conditioning, Animal, Internal medicine, Testis, Gene expression, medicine, Animals, Nandrolone, Blood-testis barrier, MMP-2, MMP-9, Testosterone, TJP1, Molecular Medicine, Cell Biology, blood–testis barrier, Inducer, Blood–testis barrier, MMP‐9, medicine.diagnostic_test, Mucin-1, Tissue Inhibitor of Metalloproteinases, Original Articles, medicine.disease, Protein Transport, 030104 developmental biology, Endocrinology, Gene Expression Regulation, Matrix Metalloproteinase 9, Zonula Occludens-1 Protein, Matrix Metalloproteinase 2, Original Article, MMP‐2, Sedentary Behavior, Signal Transduction
Abstract

The aim of this study was to investigate whether nandrolone decanoate (ND) use affects testosterone production and testicular morphology in a model of trained and sedentary mice. A group of mice underwent endurance training while another set led a sedentary lifestyle and were freely mobile within cages. All experimental groups were treated with either ND or peanut oil at different doses for 6 weeks. Testosterone serum levels were measured via liquid chromatography–mass spectrometry. Western blot analysis and quantitative real‐time PCR were utilized to determine gene and protein expression levels of the primary enzymes implicated in testosterone biosynthesis and gene expression levels of the blood–testis barrier (BTB) components. Immunohistochemistry and immunofluorescence were conducted for testicular morphological evaluation. The study demonstrated that moderate to high doses of ND induced a diminished serum testosterone level and altered the expression level of the key steroidogenic enzymes involved in testosterone biosynthesis. At the morphological level, ND induced degradation of the BTB by targeting the tight junction protein‐1 (TJP1). ND stimulation deregulated metalloproteinase‐9, metalloproteinase‐2 (MMP‐2) and the tissue inhibitor of MMP‐2. Moreover, ND administration resulted in a mislocalization of mucin‐1. In conclusion, ND abuse induces a decline in testosterone production that is unable to regulate the internalization and redistribution of TJP1 and may induce the deregulation of other BTB constituents via the inhibition of MMP‐2. ND may well be considered as both a potential inducer of male infertility and a potential risk factor to a low endogenous bioavailable testosterone.

Published
2017

45. Biocompatible Lipid Nanoparticles as Carriers to Improve Curcumin Efficacy in Ovarian Cancer Treatment

Author

Melchiorre Cervello, Maria Rita Emma, Maria Luisa Bondì, Chiara Botto, Antonina Azzolina, Emanuela Fabiola Craparo, Gennara Cavallaro, Giuseppa Augello, Dimcho Bachvarov, Francesca Di Gaudio, Bondì, M., Emma, M., Botto, C., Augello, G., Azzolina, A., Di Gaudio, F., Craparo, E., Cavallaro, G., Bachvarov, D., and Cervello, M.

Subjects
nanostructured lipid carriers, curcumin, drug release, cancer, epithelial ovarian cells, Curcumin, Nanoparticle, Administration, Oral, 02 engineering and technology, Pharmacology, nanostructured lipid carrier, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Drug Delivery Systems, Settore BIO/10 - Biochimica, medicine, Humans, cancer, Particle Size, Drug Carrier, drug release, Cell Proliferation, Ovarian Neoplasms, Drug Carriers, Ovarian Neoplasm, Chemistry (all), General Chemistry, Lipid, 021001 nanoscience & nanotechnology, Biocompatible material, medicine.disease, Controlled release, Lipids, Bioavailability, chemistry, Agricultural and Biological Sciences (all), Settore CHIM/09 - Farmaceutico Tecnologico Applicativo, 030220 oncology & carcinogenesis, Drug delivery, Nanoparticles, Female, Nanocarriers, 0210 nano-technology, General Agricultural and Biological Sciences, Ovarian cancer, Drug Delivery System, epithelial ovarian cell, Human
Abstract

Curcumin is a natural molecule with proved anticancer efficacy on several human cancer cell lines. However, its clinical application has been limited due to its poor bioavailability. Nanocarrier-based drug delivery approaches could make curcumin dispersible in aqueous media, thus overtaking the limits of its low solubility. The aim of this study was to increase the bioavailability and the antitumoral activity of curcumin, by entrapping it into nanostructured lipid carriers (NLCs). For this purpose here we describe the preparation and characterization of three kinds of curcumin-loaded NLCs. The nanosystems allowed the achievement of a controlled release of curcumin, the amounts of curcumin released after 24 h from Compritol-Captex, Compritol-Miglyol, and Compritol NLCs being, respectively, equal to 33, 28, and 18% w/w on the total entrapped curcumin. Considering the slower curcumin release profile, Compritol NLCs were chosen to perform successive in vitro studies on ovarian cancer cell lines. The results show that curcumin-loaded NLCs maintain anticancer activity, and reduce cell colony survival more effectively than free curcumin. As an example, the ability of A2780S cells to form colonies was decreased after treatment with 5 μM free curcumin by 50% ± 6, whereas, at the same concentration, the delivery of curcumin with NLC significantly (p < 0.05) inhibited colony formation to approximately 88% ± 1, therefore potentiating the activity of curcumin to inhibit A2780S cell growth. The obtained results clearly suggest that the entrapment of curcumin into NLCs increases curcumin efficacy in vitro, indicating the potential use of NLCs as curcumin delivery systems.

Published
2017

46. SANIST: optimization of a technology for compound identification based on the European Union directive with applications in forensic, pharmaceutical and food analyses

Author

Cristoni, Simone, Dusi, Guglielmo, Brambilla, Paolo, Albini, Adriana, Conti, Matteo, Brambilla, Maura, Bruno, Antonino, Di Gaudio, Francesca, Ferlin, Luca, Tazzari, Valeria, Mengozzi, Silvia, Barera, Simone, Sialer, Carlos, Trenti, Tommaso, Cantu, Marco, Rossi Bernardi, Luigi, Noonan, Douglas, Cristoni S., Dusi G., Brambilla P., Albini A., Conti M., Brambilla M., Bruno A., Di Gaudio F., Ferlin L., Tazzari V., Mengozzi S., Barera S., Sialer C., Trenti T., Cantu M., Rossi Bernardi L., Noonan D.M., Cristoni, S, Dusi, G, Brambilla, P, Albini, A, Conti, M, Brambilla, M, Bruno, A, Digaudio, F, Ferlin, L, Tazzari, V, Mengozzi, S, Barera, S, Salier, C, Trenti, T, Cantu, M, Rossi Bernardi, L, and Noonan, D

Subjects
BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA, Forensic Science, bioinformatic, Databases, Factual, algorithm, compounds identification, database search, EU law, Spectroscopy, Chemistry, Pharmaceutical, Forensic Sciences, Bayes Theorem, Biomarker, Algorithm, Tandem Mass Spectrometry, Humans, European Union, Algorithms, Biomarkers, Food Analysis, Chromatography, High Pressure Liquid
Abstract

Electrospray Ionization and collision induced dissociation tandem mass spectrometry are usually employed to obtain compound identification through a mass spectra match. Different algorithms have been developed for this purpose (for example the nist match algorithm). These approaches compare the tandem mass spectra of the unknown analyte with the tandem mass spectra spectra of known compounds inserted in a database. The compounds are usually identified on the basis of spectral match value associated with a probability of recognition. However, this approach is not usually applied to multiple reaction monitoring transition spectra achieved by means of triple quadrupole apparatus, mainly due to the lack of a transition spectra database. The Surface Activated Chemical Ionization-Electrospray-NIST Bayesian model database search (SANIST) platform has been recently developed for new potential metabolite biomarker discovery, to confirm their identity and to use them for clinical and diagnostic applications. Here, we present an improved version of the SANIST platform that extends its application to forensic, pharmaceutical, and food analysis studies, where the compound identification rules are strict. The European Union (EU) has set directives for compound identification (EU directive 2002/657/EC). We have applied the SANIST method to identification of 11-nor-9-carboxytetrahydro-cannabinol in urine samples (an example of a forensic application), circulating levels of the immunosuppressive drug tacrolimus in blood (an example of a pharmaceutical application) and glyphosate in fruit juice (an example of a food analysis application) that meet the EU directive requirements. Copyright © 2016 John Wiley & Sons, Ltd.

Published
2017

47. Determination of trace elements in gluten-free food for celiac people by ICP-MS

Author

Maria Raso, Francesca Di Gaudio, Salvatore Barreca, Diana Amorello, Santino Orecchio, Claudia Lino, Orecchio, S, Amorello, D, Raso, M, Barreca, S, Lino, C, and Di Gaudio, F

Subjects
Chemistry, chemistry.chemical_element, Heavy metals, Contamination, Reference Daily Intake, Analytical Chemistry, Metal, Nickel, Gluten-free foods Metals ICP-MS Celiac, Environmental chemistry, visual_art, visual_art.visual_art_medium, Gluten-free foodsMetalsICP-MSCeliac, Gluten free, Inductively coupled plasma mass spectrometry, Spectroscopy, Arsenic
Abstract

This paper is the first analytical approach to the study of twenty heavy metals in the gluten-free foods for celiac people. Only the ICP-MS technique was used. One of the advantages about the use of ICP-MS for this characterization is the high sensitivity that improved the limits of quantification levels for some elements that are present at low quantities in some samples. The concentration values of As, Ba, Cd, Co, Cr, Cu, Fe, Hg, Mn, Mo, Ni, Pb, Sb, Se, Sn, V and Zn in seventeen gluten-free food samples are reported. The highest arsenic and molybdenum levels were measured in Rice noodle from China (0.088 and 0.47 mg kg − 1 , respectively). The highest concentrations of some metals (Cu, Ba, Cd, Pb, Hg, Sr and V) were found in bread and breadstick samples produced in different bakeries located at Palermo. To examine the overall heavy metal concentrations in all gluten-free samples analyzed, metal pollution index (MPI) was calculated. Gluten-free foods analyzed contain levels of trace elements under the limits tolerated by the law. Considering the average concentrations of some trace elements found in the present study, it can be concluded that they are inadequate if compared with the recommended daily intake by international organisms, providing from 1.1 to 53% of the RDI for the essential metals. These conclusions are in good agreement to some authors affirming that commercial gluten-free cereal foods, made of refined flours or starches, are of lower nutritional value compared to their wheat counterparts. The metal pollution index and health risk index of heavy metals also suggest that Cd, Pb and Ni contamination in most of the test gluten-free food had potential for human health risk due to consumption of food at contaminated not industrial laboratory. Considering our data, health risk index was lower than 1 for all the samples except nickel in a sample of pasta.

Published
2014

48. FORENSIC INVESTIGATION OF KERATIN MATRIX: DEVELOPMENT OF A METHOD BY TURBOFLOW™ HPLC-MS/MS FOR CANNABINOIDS QUANTITATIVE ANALYSIS

Author

Castelli, V., INDELICATO, Sergio, Fanara, S., FONTANA, Manuela, Pisciotta, R., VENTURELLA, Fabio, DI GAUDIO, Francesca, Castelli, V., Indelicato, S., Fanara, S., Fontana, M., Pisciotta, R., Venturella, F., and Di Gaudio, F.

Subjects
Settore BIO/10 - Biochimica, Cannabis, Turboflow, Cannabi
Abstract

The products of cannabis are the most frequently used illicit drugs of abuse detected in workplace drug-testing programs or in cases of driving under the influence of drugs. For this reason, there is a great need for sensitive and specific methods which can confirm the chronic exposure and which take account of the cut-off values that have been proposed in Italy by the GTFI Guidelines (Group of Italian Forensic Toxicologists). The method currently more appropriate for quantification of Δ9-Tetrahydrocannabinol (THC) and its major metabolite 11-nor-9-Carboxy-Δ9-THC (THCA) appears to be one that involves HPLC-MS/MS and keratin matrix. The purpose of this work, performed at the Mass Spectrometry Laboratory for Clinical Risk and Quality Control (CQRC) in A.O.U.P. “Paolo Giaccone” of Palermo, is the developing of an accurate method equally or more sensitive than those used routinely in forensic toxicology laboratories. A pre-analytical phase has seen the preparation of hair samples, comprising basic hydrolysis, and a subsequent Liquid-Liquid Extraction (LLE). In the analytical phase, the step of detection was performed using the Thermo Scientific™ Transcend™ II system which combines the online sample preparation technology TurboFlow™ with the chromatographic separation technique of High Performance Liquid Chromatography (HPLC) and the detection technique of tandem Mass Spectrometry (MS/MS) using a high sensitive Thermo Scientific™ TSQ Quantiva™ Triple Quadrupole Mass Spectrometer. During the phase of the developing method a series of experimental tests regarding the analytical conditions have been performed, on six different chromatographic columns. This has highlighted the main advantages of TurboFlow™, the adequate selectivity in the sample cleaning and the possibility of injecting more volumes of sample than the normal LC-MS techniques, leading to an appreciable increase in the sensitivity. According to the aim of the work, the latter steps of sample preparation, including LLE, were replaced with a simple hydrolyzate filtration and direct injection into TurboFlow™ system. In the light of the results we obtained it can be said that the method developed by TurboFlow™ -HPLC-MS/MS that involves the short phase of sample preparation procedure allows accurate quantification of cannabinoids in the keratin matrix. This technique, showing an adequate sensitivity, can be compared and preferred to used routine techniques. The short phase of preparation of the sample, also, results in a considerable saving of time and materials and in the reduction of possible errors caused by the operator.

Published
2016

49. La metodica wastewater based epidemiology come proxy di quantificazione del consumo di sostanze stupefacenti nella popolazione: l’esperienza della città di Palermo

Author

MAIDA, Carmelo Massimo, DI GAUDIO, Francesca, MAZZUCCO, Walter, TRAMUTO, Fabio, Piscionieri, D., COSENZA, Alida, VIVIANI, Gaspare, Maida, C.M., Di Gaudio, F., Mazzucco, W., Tramuto, F., Piscionieri, D., Cosenza, A., and Viviani, G.

Subjects
wastewater based epidemiology, acque reflue, sostanze stupefacenti, Settore MED/42 - Igiene Generale E Applicata
Abstract

INTRODUZIONE Le istituzioni europee e la comunità scientifica hanno, recentemente, definito un nuovo modello di sorveglianza attiva della potenziale diffusione delle droghe nella collettività, la Wastewater Based Epidemiology (WBE), attraverso la ricerca analitica delle molecole e dei loro metaboliti nelle acque reflue cittadine. Lo scopo di questo lavoro è stato la valutazione di una preliminare applicazione di METODIca WBE nella città di Palermo, poco studiata in precedenti analisi a livello nazionale e internazionale. METODI Sono stati prelevati 28 campioni (2 litri cad) di refluo medio delle 24 ore in ingresso ai due depuratori di Palermo (WP1=45.000 ab. eq.; WP2=330.000 ab. eq.) in un periodo compreso tra giugno e novembre 2015. I campioni sono stati prefiltrati, concentrati ed infine analizzati (200 mml) mediante tecnica di spettrometria di massa LC-MS/MS. Gli analiti ricercati sono stati Cocaina, Benzoilecgonina (BEG), THC-COOH e Amfetamine (MDA, MDE, MDMA, Metamfetamine). È stato effettuato, inoltre, il calcolo della quantità di sostanza stupefacente consumata nella popolazione (gr/die/1.000 abitanti e dosi/die/1.000 abitanti). RISULTATI I RISULTATI ottenuti sono illustrati nella tabella 1. I consumi di sostanze stupefacenti registrati nella città di Palermo (gr/die/1000 ab) sono RISULTATI i seguenti = Cocaina=0,145 (1,45 dosi/1000 ab); THC=4,37 (35,00 dosi/1000 ab), Amfetamine=Non quantificabili. CONCLUSIONI L’applicazione della metodologia WBE può essere considerata uno strumento aggiuntivo ai classici indicatori indiretti del consumo di droghe nella collettività a disposizione delle istituzioni per comprendere meglio il fenomeno delle tossicodipendenze e per attuare azioni di contrasto e politiche di educazione sanitaria più efficaci finalizzate alla prevenzione.

Published
2016

50. Effects of Nandrolone Stimulation on Testosterone Biosynthesis in Leydig Cells

Author

Nicola Locorotondo, Antonella Marino Gammazza, Fulvio Barone, Monica Salerno, Claudia Sangiorgi, Francesca Di Gaudio, Francesco Cappello, Francesca Maglietta, Cristoforo Pomara, Antonio Luciano Sarni, Emanuela Turillazzi, Valentina Di Felice, Rosario Barone, Alessandro Pitruzzella, Pomara, C., Barone, R., Marino Gammazza, A., Sangiorgi, C., Barone, F., Pitruzzella, A., Locorotondo, N., Di Gaudio, F., Salerno, M., Maglietta, F., Sarni, A., Di Felice, V., Cappello, F., and Turillazzi, E.

Subjects
0301 basic medicine, Enzymologic, Male, Physiology, Clinical Biochemistry, Androgen, Anabolic Agents, Androgens, Animals, Cell Line, Cell Survival, Dose-Response Relationship, Drug, Gene Expression Regulation, Enzymologic, Leydig Cells, Nandrolone, Phosphoproteins, Rats, Steroid 17-alpha-Hydroxylase, Testosterone, Cell Biology, Original Research Articles, Original Research Article, Medicine (all), Steroidogenic acute regulatory protein, CYP17A1, Phosphoprotein, Drug, Luteinizing hormone, medicine.drug, Leydig Cell, endocrine system, medicine.medical_specialty, Biology, Dose-Response Relationship, 03 medical and health sciences, Downregulation and upregulation, In vivo, Internal medicine, medicine, Animal, 030104 developmental biology, Endocrinology, Gene Expression Regulation, Anabolic Agent, Rat, Hormone
Abstract

Anabolic androgenic steroids (AAS) are among the drugs most used by athletes for improving physical performance, as well as for aesthetic purposes. A number of papers have showed the side effects of AAS in different organs and tissues. For example, AAS are known to suppress gonadotropin‐releasing hormone, luteinizing hormone, and follicle‐stimulating hormone. This study investigates the effects of nandrolone on testosterone biosynthesis in Leydig cells using various methods, including mass spectrometry, western blotting, confocal microscopy and quantitative real‐time PCR. The results obtained show that testosterone levels increase at a 3.9 μM concentration of nandrolone and return to the basal level a 15.6 μM dose of nandrolone. Nandrolone‐induced testosterone increment was associated with upregulation of the steroidogenic acute regulatory protein (StAR) and downregulation of 17a‐hydroxylase/17, 20 lyase (CYP17A1). Instead, a 15.6 µM dose of nandrolone induced a down‐regulation of CYP17A1. Further in vivo studies based on these data are needed to better understand the relationship between disturbed testosterone homeostasis and reproductive system impairment in male subjects. J. Cell. Physiol. 231: 1385–1391, 2016. © 2015 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.

Published
2016

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