Pubblicazioni - Trivella Dott.ssa Maria Giovanna - Associato di ricerca CNR

• Correction to: Correlates of olfactory impairment in middle-aged non-diabetic Caucasian subjects with stage I-II obesity.
  Eur Arch Otorhinolaryngol

  2021 Jan;():. doi: 10.1007/s00405-021-06618-7.
  
  Campolo Jonica, Corradi Ettore, Rizzardi Alice, Parolini Marina, Dellanoce Cinzia, Di Guglielmo Maria Luisa, Tarlarini Patrizia, Cattaneo Marina, Trivella Maria Giovanna, De Maria Renata
  
  
  
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• Correlates of olfactory impairment in middle-aged non-diabetic Caucasian subjects with stage I-II obesity.
  Eur Arch Otorhinolaryngol

  2020 Oct;():. doi: 10.1007/s00405-020-06442-5.
  
  Campolo Jonica, Corradi Ettore, Rizzardi Alice, Parolini Marina, Dellanoce Cinzia, Di Guglielmo Maria Luisa, Tarlarini Patrizia, Cattaneo Marina, Trivella Maria Giovanna, De Maria Renata
  
  Abstract
  
  PURPOSE:
  This study evaluates among middle-aged subjects with obesity the prevalence of olfactory impairment (OI) with respect to normative values and its correlation with body composition, cognition, sleep quality, and inflammation.
  
  METHODS:
  In 60 (31 women, 29 men) volunteers with a body mass index???30 to ??40 kg/m, aged???50 to???70 years, we assessed olfaction by the Sniffin' Stick test. We measured anthropometrics, body composition and metabolic profiles and evaluated cognition by the MiniMental State Examination (MMSE) and sleep disturbances by the Insomnia Severity Index (ISI). Patients were classified into two groups according to a total olfactory score (odor Threshold, Discrimination, Identification, TDI) below or above the 25th percentile from age and gender-adjusted normative data.
  
  RESULTS:
  Overall, 25 subjects (42%) had OI (TDI?
  CONCLUSIONS:
  Among middle-aged subjects with stage I and II obesity, OI is highly prevalent and is independently associated with poor self-reported sleep quality, lower cognition scores and higher levels of the inflammatory marker neopterin.
  
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• Pathophysiology and molecular signalling in pediatric heart failure and VAD therapy.
  Clin Chim Acta

  2020 Nov;510():751-759. doi: S0009-8981(20)30442-3.
  
  Ragusa Rosetta, Di Molfetta Arianna, Amodeo Antonio, Trivella Maria Giovanna, Caselli Chiara
  
  Abstract
  
  Heart Failure (HF) is a progressive clinical syndrome characterized by molecular and structural abnormalities that result in impaired ventricular filling and a reduced blood ejection. In pediatric patients, HF represents an important cause of morbidity and mortality, but underlying cause, presentation and disease course remains unclear in many cases. It is evident that a child is not a "small adult" and findings are not comparable. The adoption of a standardized clinical and surgical tools as well as increased biomolecular research and therapeutic trials targeting pediatric patients with HF would greatly improve the management of this special class of patients. This review examines the most current information about the pathophysiology and molecular mechanisms related to HF in children to identify gaps in our knowledge base to further improve clinical care and outcomes.
  
  Copyright © 2020 Elsevier B.V. All rights reserved.
  
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• Potential markers of healing from near infrared spectroscopy imaging of venous leg ulcer. A randomized controlled clinical trial comparing conventional with hyperbaric oxygen treatment.
  Wound Repair Regen

  2020 Nov;28(6):856-866. doi: 10.1111/wrr.12853.
  
  Longobardi Pasquale, Hartwig Valentina, Santarella Luigi, Hoxha Klarida, Campos Jhonny, Laurino Marco, Salvo Pietro, Trivella Maria Giovanna, Coceani Flavio, Rocco Monica, L'Abbate Antonio
  
  Abstract
  
  The aim of this study is to ascertain whether the simultaneous measurement of hemoglobin O saturation (StO ) and dimension of venous leg ulcers (VLU) by near infrared spectroscopy (NIRS) imaging can predict the healing course with protocols employing a conventional treatment alone or in combination with hyperbaric oxygen therapy (HBOT). NIRS 2D images of wound region were obtained in 81 patients with hard-to-heal VLU that had been assigned, in a randomized controlled clinical trial, to the following protocols: 30 HBOT sessions, adjunctive to the conventional therapy, either twice daily over 3?weeks (group A) or once daily over 6?weeks (group B), and conventional therapy without HBOT (group C). Seventy-three patients completed the study with a total of 511 NIRS images being analyzed. At the end of treatment, wound area was significantly smaller in all three groups. However, at the 3-week mark the wound area reduction tended to be less evident in group A than in the other groups. This trend continued up to the 6-week end-point when a significantly greater area reduction was found with group B (65.5%) and group C (56.8%) compared to group A (29.7%) (P?
  © 2020 The Wound Healing Society.
  
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• Salivary lactate and 8-isoprostaglandin F as potential non-invasive biomarkers for monitoring heart failure: a pilot study.
  Sci Rep

  2020 05;10(1):7441. doi: 10.1038/s41598-020-64112-2.
  
  Ghimenti Silvia, Lomonaco Tommaso, Bellagambi Francesca G, Biagini Denise, Salvo Pietro, Trivella Maria G, Scali Maria C, Barletta Valentina, Marzilli Mario, Di Francesco Fabio, Errachid Abdelhamid, Fuoco Roger
  
  Abstract
  
  Heart failure (HF) is a cardiovascular disease affecting about 26 million people worldwide costing about $100 billons per year. HF activates several compensatory mechanisms and neurohormonal systems, so we hypothesized that the concomitant monitoring of a panel of potential biomarkers related to such conditions might help predicting HF evolution. Saliva analysis by point-of-care devices is expected to become an innovative and powerful monitoring approach since the chemical composition of saliva mirrors that of blood. The aims of this study were (i) to develop an innovative procedure combining MEPS with UHPLC-MS/MS for the simultaneous determination of 8-isoprostaglandin F and cortisol in saliva and (ii) to monitor lactate, uric acid, TNF-?, cortisol, ?-amylase and 8-isoprostaglandin F concentrations in stimulated saliva samples collected from 44 HF patients during their hospitalisation due to acute HF. Limit of detection of 10?pg/mL, satisfactory recovery (95-110%), and good intra- and inter-day precisions (RSD???10%) were obtained for 8-isoprostaglandin F and cortisol. Salivary lactate and 8-isoprostaglandin F were strongly correlated with NT-proBNP. Most patients (about 70%) showed a significant decrease (a factor of 3 at least) of both lactate and 8-isoprostaglandin F levels at discharge, suggesting a relationship between salivary levels and improved clinical conditions during hospitalization.
  
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• Variations of circulating miRNA in paediatric patients with Heart Failure supported with Ventricular Assist Device: a pilot study.
  Sci Rep

  2020 04;10(1):5905. doi: 10.1038/s41598-020-62757-7.
  
  Ragusa Rosetta, Di Molfetta Arianna, D'Aurizio Romina, Del Turco Serena, Cabiati Manuela, Del Ry Silvia, Basta Giuseppina, Pitto Letizia, Amodeo Antonio, Trivella Maria Giovanna, Rizzo Milena, Caselli Chiara
  
  Abstract
  
  Circulating miRNAs (c-miRNAs) are promising biomarkers for HF diagnosis and prognosis. There are no studies on HF pediatric patients undergoing VAD-implantation. Aims of this study were: to examine the c-miRNAs profile in HF children; to evaluate the effects of VAD on c-miRNAs levels; to in vitro validate putative c-miRNA targets. c-miRNA profile was determined in serum of HF children by NGS before and one month after VAD-implant. The c-miRNA differentially expressed were analyzed by real time-PCR, before and at 4 hrs,1,3,7,14,30 days after VAD-implant. A miRNA mimic transfection study in HepG2 cells was performed to validate putative miRNA targets selected through miRWalk database. Thirteen c-miRNAs were modified at 30 days after VAD-implant compared to pre-VAD at NSG, and, among them, six c-miRNAs were confirmed by Real-TimePCR. Putative targets of the validated c-miRNAs are involved in the hemostatic process. The in vitro study confirmed a down-regulatory effect of hsa-miR-409-3p towards coagulation factor 7 (F7) and F2. Of note, all patients had thrombotic events requiring pump change. In conclusion, in HF children, the level of six c-miRNAs involved in the regulation of hemostatic events changed after 30 days of VAD-treatment. In particular, the lowering of c-miR-409-3p regulating both F7 and F2 could reflect a pro-thrombotic state after VAD-implant.
  
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• Irisin and markers of metabolic derangement in non-diabetic Caucasian subjects with stage I-II obesity during early aging.
  PLoS One

  2020 ;15(2):e0229152. doi: 10.1371/journal.pone.0229152.
  
  Campolo Jonica, Corradi Ettore, Rizzardi Alice, Parolini Marina, Dellanoce Cinzia, Di Guglielmo Maria Luisa, Tarlarini Patrizia, Cattaneo Marina, Trivella Maria Giovanna, De Maria Renata
  
  Abstract
  
  Irisin concentrations are decreased in subjects with overt diabetes and upregulated in those with obesity or impaired fasting glucose. However, gender-balanced data in older populations, in whom risk factors commonly culminate in overt cardiovascular disease, are scarce. We assessed in non-diabetic Caucasian subjects with stage I-II obesity in the early aging range (50 to 70 years), the relationship between irisin, body composition and markers of metabolic derangement by gender. In 60 (31 women, 29 men) non-diabetics with a body mass index ?30 - ?40 kg/m2, we measured anthropometrics and body composition (Air Displacement Plethysmography). We assayed lipid and glucose profile by routine methods, plasma irisin by ELISA and measured insulin resistance by the HOMA index. Irisin levels were higher in women than in men (161 [105-198]) vs 83 [33-115] ng/ml, P<0.001), and correlated directly with HOMA index in both (rho 0.735, P<0.001 M, rho 0.452, P = 0.011 F). Sex differences were maintained across insulin resistance severity stages. In men, irisin concentrations correlated directly with body mass index (rho 0.755, P<0.001), waist circumference (rho 0.623, P<0.001), fat mass index (rho 0.762, P<0.001), glucose (rho 0.408, P = 0.028), the fatty liver index (rho 0.705, P<0.001) and FINDRISC score (rho 0.536, P = 0.003). Among non-diabetic Caucasian subjects with obesity in the early stages of aging, irisin levels reflect the amount of body fat and insulin resistance severity, independently of between-gender differences in the adipomyokine concentrations and are associated with markers of visceral adiposity in men but not in women.
  
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• Healthy aging: the INTECMAN project.
  Aging Clin Exp Res

  2020 Jan;():. doi: 10.1007/s40520-019-01444-8.
  
  Laurino Marco, Alfì Gaspare, Billeci Lucia, Bortone Ilaria, Buzzigoli Emma, Cecchi Antonella, Del Ry Silvia, Gastaldelli Amalia, Lai Elisa, Morales Maria Aurora, Pagni Cristina, Passino Claudio, Severino Silvia, Tonacci Alessandro, Gemignani Angelo, Trivella Maria Giovanna
  
  Abstract
  
  Aging is associated not only with the reduction of psychophysical and sensory capacities but also with different types of neurodegenerative disorders up to dementia manifestations. Aging in health and self-sufficiency is strictly dependent on the prevention and correction of factors that may determine reduction of psychophysical capacities (e.g., cardiovascular, locomotor and neurodegenerative ones). To reach this goal, due to the dynamics of social and family changes and to the aging of the population, health professionals can be supported by technologies which provide noninvasive monitoring of physiologic parameters and rely on telemedicine, both instruments of support and care for better aging in the home setting. The authors, starting from the initial idea of a personalized monitoring of different psychophysical variables, defined a pilot study to assess the role of a 12-month individually tailored lifestyle counseling on parameters of mild cognitive impairment in a group of elderly subjects. Data derived from the applied approach appeared promising and may open the road to the possible implementation of individual counseling, based on multiparametric non-obtrusive technologies which take into consideration both psychological and physical aspects, to be followed in the home environment.
  
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• Near-infrared spectroscopic imaging of the whole hand: A new tool to assess tissue perfusion and peripheral microcirculation in scleroderma.
  Semin Arthritis Rheum

  2019 04;48(5):867-873. doi: S0049-0172(18)30230-0.
  
  Gargani Luna, Bruni Cosimo, Barskova Tatiana, Hartwig Valentina, Marinelli Martina, Trivella Maria Giovanna, Matucci-Cerinic Marco, L'Abbate Antonio
  
  Abstract
  
  OBJECTIVES:
  Systemic sclerosis (SSc) causes functional and structural microcirculatory dysfunction, affecting also distal extremities. Optical Near-InfraRed Spectroscopy (NIRS) of blood HbO saturation (stO) is able to evaluate O delivery/consumption balance in the explored tissue. The NIRS-sensitive camera non-invasively detects stO values in superficial tissues, automatically generating 2D-imaging maps in real time. We aimed at testing whether NIRS hand imaging may evaluate peripheral microcirculatory dysfunction and its spatial heterogeneity in SSc patients compared to controls.
  
  METHODS:
  Forty SSc patients (aged 55.1?±?15.6 years) and twenty-one healthy controls (aged 54.3?±?14.5years, p?=?0.89) were studied by palmar hand NIRS-2D imaging. A blood pressure cuff was applied to the forearm and 3 min ischemia was induced. Images were acquired at basal conditions and every 10 seconds during 3 minutes of ischemia and 5 minutes of reperfusion. Five regions of interest were positioned on each fingertip, from the second to the fifth finger and one on the thenar eminence.
  
  RESULTS:
  A significant difference was found between controls and SSc patients in basal stO (84.3?±?7.5?vs. 75.4?±?10.9%, p?
  CONCLUSION:
  NIRS-2D imaging is a simple, automated tool to non-invasively detect regional microcirculatory impairment in SSc, which seems to add significant functional information to the morphological picture of nailfold-videocapillaroscopy.
  
  Copyright © 2018 Elsevier Inc. All rights reserved.
  
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• Time-course of circulating cardiac and inflammatory biomarkers after Ventricular Assist Device implantation: Comparison between paediatric and adult patients.
  Clin Chim Acta

  2018 Nov;486():88-93. doi: S0009-8981(18)30383-8.
  
  Ragusa Rosetta, Prontera Concetta, Di Molfetta Arianna, Cabiati Manuela, Masotti Silvia, Del Ry Silvia, Amodeo Antonio, Trivella Maria Giovanna, Clerico Aldo, Caselli Chiara
  
  Abstract
  
  BACKGROUND:
  Ventricular Assist Device (VAD) as bridge to transplantation is a common therapy for adult with heart failure (HF), but VAD use is increasing also in children. Cardiac and inflammatory biomarkers have an important role in the diagnosis and prognosis of HF in adults, but their role in paediatric setting is unknown. The aim of this study was to examine changes in cardiac and inflammatory biomarkers, both in HF paediatric and adult patients, before and following VAD.
  
  METHODS:
  Cardiac (NT-proBNP, cTnI, sST2,Gal-3) and inflammatory (IL-6,IL-8) biomarkers were determined in plasma collected from 12 paediatric patients and 7 adult patients with HF, before and at 4?h,1,3,7,14 and 30?days after VAD implant.
  
  RESULTS:
  All biomarkers increased up to 1?day after VAD implant and then decreased at pre-VAD levels in 1?month in both groups. Only in children, NT-proBNP decreased significantly after 30?days Post-VAD treatment compared to pre-VAD levels. During the post-operative time-course, NT-proBNP and sST2 were significantly higher in children than adults, while IL-6 was lower.
  
  CONCLUSIONS:
  Cardiac and inflammatory biomarkers were differently modified by VAD implant in children compared to adults. These preliminary data could suggest that different molecular pathways may underlie HF patho-physiology of the two groups, possibly paving the way to a specific and targeted therapeutic intervention in the near future.
  
  Copyright © 2018 Elsevier B.V. All rights reserved.
  
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• A computational approach for the estimation of heart failure patients status using saliva biomarkers.
  Annu Int Conf IEEE Eng Med Biol Soc

  2017 Jul;2017():3648-3651. doi: 10.1109/EMBC.2017.8037648.
  
  Tripoliti Evanthia E, Papadopoulos Theofilos G, Karanasiou Georgia S, Kalatzis Fanis G, Goletsis Yorgos, Bechlioulis Aris, Ghimenti Silvia, Lomonaco Tommaso, Bellagambi Francesca, Trivella Maria Giovanna, Fuoco Roger, Marzilli Mario, Scali Maria Chiara, Naka Katerina K, Errachid Abdelhamid, Fotiadis Dimitrios I
  
  Abstract
  
  The aim of this work is to present a computational approach for the estimation of the severity of heart failure (HF) in terms of New York Heart Association (NYHA) class and the characterization of the status of the HF patients, during hospitalization, as acute, progressive or stable. The proposed method employs feature selection and classification techniques. However, it is differentiated from the methods reported in the literature since it exploits information that biomarkers fetch. The method is evaluated on a dataset of 29 patients, through a 10-fold-cross-validation approach. The accuracy is 94 and 77% for the estimation of HF severity and the status of HF patients during hospitalization, respectively.
  
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• Editorial: Physiology in Extreme Conditions: Adaptations and Unexpected Reactions.
  Front Physiol

  2017 ;8():748. doi: 10.3389/fphys.2017.00748.
  
  Trivella Maria G, Capobianco Enrico, L'Abbate Antonio
  
  
  
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• Percutaneous cardiac support during myocardial infarction drastically reduces mortality: perspectives from a swine model.
  Int J Artif Organs

  2017 Jul;40(7):338-344. doi: 10.5301/ijao.5000604.
  
  Trivella Maria Giovanna, Piersigilli Alessandra, Bernini Fabio, Pelosi Gualtiero, Burchielli Silvia, Puzzuoli Stefano, Kusmic Claudia, L'Abbate Antonio
  
  Abstract
  
  BACKGROUND/AIMS:
  Acute myocardial infarction (AMI) with cardiogenic shock (CS) remains the leading cause of in-hospital death in acute coronary syndromes. In the AMI-CS pig model we tested the efficacy of temporary percutaneous cardiorespiratory assist device (PCRA) in rescuing the failing heart and reducing early mortality.
  
  METHODS:
  In open-chest pigs we induced AMI by proximal left anterior descending coronary artery (LAD) ligation. Eight animals without PCRA (C group) were compared with 12 animals otherwise treated with PCRA (T group), starting approximately at 60 minutes post-occlusion and lasting 120-180 minutes. In 3 animals of the T group, regional myocardial oxygen content was also imaged by two-dimensional near infrared spectroscopy (2D-NIRS) with and without PCRA, before and after LAD reperfusion.
  
  RESULTS:
  All animals without PCRA died despite unrelenting resuscitation maneuvers (120 minutes average survival time). Conversely, animals treated with PCRA showed a reduction in life-threatening arrhythmia and maintenance of aortic pressure, allowing interruption of PCRA in all cases early in the experiments, with sound hemodynamics at the end of the observation period. During LAD occlusion, NIRS showed severe de-oxygenation of the LAD territory that improved with PCRA. After PCRA suspension and LAD reperfusion, the residual de-oxygenated area proved to be smaller than the initial risk area.
  
  CONCLUSIONS:
  In AMI, PCRA initiated during advanced CS drastically reduced early mortality from 100% to 0% in a 4-5 hour observation period. PCRA promoted oxygenation of the ischemic area during LAD occlusion. Results support the use of PCRA as first line of treatment in AMI-CS, improving myocardial rescue and short-term survival.
  
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• Antioxidant and inflammatory biomarkers for the identification of prodromal Parkinson's disease.
  J Neurol Sci

  2016 Nov;370():167-172. doi: S0022-510X(16)30615-3.
  
  Campolo Jonica, De Maria Renata, Cozzi Lorena, Parolini Marina, Bernardi Stefano, Proserpio Paola, Nobili Lino, Gelosa Giorgio, Piccolo Immacolata, Agostoni Elio C, Trivella Maria G, Marraccini Paolo
  
  Abstract
  
  OBJECTIVES:
  We explored the role of oxidative stress and inflammatory molecules as potential Parkinson (PD) biomarkers and correlated biological with non-motor abnormalities (olfactory impairment and dysautonomia), in patients with idiopathic REM behavior disorder (iRBD) (prodromal PD) and established PD.
  
  METHODS:
  We recruited 11 iRBD and 15 patients with idiopathic PD (Hohen&Yahr 1-3, on L-DOPA and dopamine agonists combination therapy) and 12 age- and sex-matched controls (CTRL). We measured total olfactory score (TOS), autonomic function [deep breathing (DB), lying to standing (LS) and Valsalva manoeuvre (VM) ratios], blood reduced glutathione (Br-GSH), oxidative stress and inflammatory markers (neopterin).
  
  RESULTS:
  Anosmia was similarly prevalent in iRBD (36%) and PD (33%) patients, but absent in CTRL. Orthostatic hypotension was more common among iRBD (73%) and PD (60%) than in CTRL (25%). By univariable ordinal logistic regression, TOS, Br-GSH, LS and VM ratio worsened from CTRL to iRBD and PD groups. Only reduced Br-GSH levels (p=0.037, OR=0.994; 95%CI 0.988-1.000) were independently associated to PD. TOS correlated with Br-GSH (R=0.34, p=0.037), VM ratio (R=0.43, p=0.015), and neopterin (rho=0.39, p=0.016).
  
  CONCLUSIONS:
  Reduced systemic antioxidant capacity is found in prodromal and overt PD and may represent, in association with olfactory loss and cardiovascular dysautonomia, a useful biomarker for an integrative, early diagnosis of PD.
  
  Copyright © 2016 Elsevier B.V. All rights reserved.
  
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• Distribution of circulating cardiac biomarkers in healthy children: from birth through adulthood.
  Biomark Med

  2016 ;10(4):357-65. doi: 10.2217/bmm-2015-0044.
  
  Caselli Chiara, Ragusa Rosetta, Prontera Concetta, Cabiati Manuela, Cantinotti Massimiliano, Federico Giovanni, Del Ry Silvia, Trivella Maria Giovanna, Clerico Aldo
  
  Abstract
  
  AIM:
  While circulating biomarkers are critical tools for cardiovascular adult care, their relevance in childhood is unknown.
  
  METHODS:
  We evaluated the behavior of plasma concentrations of clinically relevant cardiac biomarkers (NT-proBNP, hs-cTnI, sST2, Galectin-3) in 106 healthy children.
  
  RESULTS:
  Subjects were divided into age subgroups: 24 newborns (0-30 days), 26 infants (1-12 months), 30 children (1-12 years) and 26 adolescents (13-18 years). Healthy adults were used as control. NT-proBNP (newborns: 504.3 [211.07-942.7] ng/L, median [25-75 percentiles]; infants: 200.64 [76.88-306.73]; children: 97.27 [49.24-271.80]; adolescents: 24.35 [13.14-58.83]; p < 0.001) and hs-cTnI (newborns: 9.3 [3.3-93.8] ng/L; infants: 13.8 [4.82-72.52]; children: 11.45 [4.0-48.10]; adolescents: 2.6[2.07-3.90]; p < 0.001) were highest in the first month of life, showing a decline in the next years. sST2 and Galectin-3 showed no differences.
  
  CONCLUSION:
  Changes in hs-cTnI and NT-proBNP suggest the design of age- and sex-based reference intervals that will have to be explored in a larger population.
  
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• Simulation of acute haemodynamic outcomes of the surgical strategies for the right ventricular failure treatment in pediatric LVAD.
  Int J Artif Organs

  2015 Dec;38(12):638-45. doi: 10.5301/ijao.5000462.
  
  Di Molfetta Arianna, Ferrari Gianfranco, Iacobelli Roberta, Filippelli Sergio, Fresiello Libera, Gagliardi Maria G, Toscano Alessandro, Trivella Maria G, Amodeo Antonio
  
  Abstract
  
  BACKGROUND:
  Right ventricular failure (RVF) is one of the major complications during LVAD. Apart from drug therapy, the most reliable option is the implantation of RVAD. However, BIVAD have a poor prognosis and increased complications. Experiments have been conducted on alternative approaches, such as the creation of an atrial septal defect (ASD), a cavo-aortic shunt (CAS) including the LVAD and a cavo-pulmonary connection (CPC). This work aims at realizing a lumped parameter model (LPM) to compare the acute hemodynamic effects of ASD, CPC, CAS, RVAD in LVAD pediatric patients with RVF.
  
  METHODS:
  Data of 5 pediatric patients undergoing LVAD were retrospectively collected to reproduce patients baseline hemodynamics with the LPM. The effects of continuous flow LVAD implantation complicated by RVF was simulated and then the effects of ASD, CPC, CAS and RVAD treatments were simulated for each patient.
  
  RESULTS:
  The model successfully reproduced patients' baseline and the hemodynamic effects of the surgical strategies. Simulating the different surgical strategies, an unloading of the right ventricle and an increment of left ventricular preload were observed with an improvement of the hemodynamics (total cardiac output: ASD +15%, CPC +10%, CAS +70% RVAD +20%; right ventricular external work: ASD -19%, CPC -46%, CAS -76%, RVAD -32%; left ventricular external work: ASD +12%, CPC +28%, RVAD +64%).
  
  CONCLUSIONS:
  The use of numerical model could offer an additional support for clinical decision-making, also potentially reducing animal experiments, to compare the outcome of different surgical strategies to treat RVF in LVAD.
  
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• Hemodynamic Effects of Ventricular Assist Device Implantation on Norwood, Glenn, and Fontan Circulation: A Simulation Study.
  Artif Organs

  2016 Jan;40(1):34-42. doi: 10.1111/aor.12591.
  
  Di Molfetta Arianna, Amodeo Antonio, Gagliardi Maria G, Trivella Maria G, Fresiello Libera, Filippelli Sergio, Toscano Alessandra, Ferrari Gianfranco
  
  Abstract
  
  The growing population of failing single-ventricle (SV) patients might benefit from ventricular assist device (VAD) support as a bridge to heart transplantation. However, the documented experience is limited to isolated case reports. Considering the complex and different physiopathology of Norwood, Glenn, and Fontan patients and the lack of established experience, the aim of this work is to realize and test a lumped parameter model of the cardiovascular system able to simulate SV hemodynamics and VAD implantation effects to support clinical decision. Hemodynamic and echocardiographic data of 30 SV patients (10 Norwood, 10 Glenn, and 10 Fontan) were retrospectively collected and used to simulate patients' baseline. Then, the effects of VAD implantation were simulated. Simulation results suggest that the implantation of VAD: (i) increases the cardiac output and the mean arterial systemic pressure in all the three palliation conditions (Norwood 77.2 and 19.7%, Glenn 38.6 and 32.2%, and Fontan 17.2 and 14.2%); (ii) decreases the SV external work (Norwood 55%, Glenn 35.6%, and Fontan 41%); (iii) decreases the pressure pulsatility index (Norwood 65.2%, Glenn 81.3%, and Fontan 64.8%); (iv) increases the pulmonary arterial pressure in particular in the Norwood circulation (Norwood 39.7%, Glenn 12.1% and Fontan 3%); and (v) decreases the atrial pressure (Norwood 2%, Glenn 10.6%, and Fontan 8.6%). Finally, the VAD work is lower in the Norwood circulation (30.4?mL·mm?Hg) in comparison with Fontan (40.3?mL·mm?Hg) and to Glenn (64.5?mL·mm?Hg) circulations. The use of VAD in SV physiology could be helpful to bridge patients to heart transplantations by increasing the CO and unloading the SV with a decrement of the atrial pressure and the SV external work. The regulation of the pulmonary flow is challenging because the Pap is increased by the presence of VAD. The hemodynamic changes are different in the different SV palliation step. The use of numerical models could be helpful to support patient and VAD selection to optimize the clinical outcome.
  
  Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.
  
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• Quantitative micro-CT based coronary artery profiling using interactive local thresholding and cylindrical coordinates.
  Technol Health Care

  2015 ;23(5):557-70. doi: 10.3233/THC-151010.
  
  Panetta Daniele, Pelosi Gualtiero, Viglione Federica, Kusmic Claudia, Terreni Marianna, Belcari Nicola, Guerra Alberto Del, Athanasiou Lambros, Exarchos Themistoklis, Fotiadis Dimitrios I, Filipovic Nenad, Trivella Maria Giovanna, Salvadori Piero A, Parodi Oberdan
  
  Abstract
  
  BACKGROUND:
  Micro-CT is an established imaging technique for high-resolution non-destructive assessment of vascular samples, which is gaining growing interest for investigations of atherosclerotic arteries both in humans and in animal models. However, there is still a lack in the definition of micro-CT image metrics suitable for comprehensive evaluation and quantification of features of interest in the field of experimental atherosclerosis (ATS).
  
  OBJECTIVE:
  A novel approach to micro-CT image processing for profiling of coronary ATS is described, providing comprehensive visualization and quantification of contrast agent-free 3D high-resolution reconstruction of full-length artery walls.
  
  METHODS:
  Accelerated coronary ATS has been induced by high fat cholesterol-enriched diet in swine and left coronary artery (LCA) harvested en bloc for micro-CT scanning and histologic processing. A cylindrical coordinate system has been defined on the image space after curved multiplanar reformation of the coronary vessel for the comprehensive visualization of the main vessel features such as wall thickening and calcium content. A novel semi-automatic segmentation procedure based on 2D histograms has been implemented and the quantitative results validated by histology.
  
  RESULTS:
  The potentiality of attenuation-based micro-CT at low kV to reliably separate arterial wall layers from adjacent tissue as well as identify wall and plaque contours and major tissue components has been validated by histology. Morphometric indexes from histological data corresponding to several micro-CT slices have been derived (double observer evaluation at different coronary ATS stages) and highly significant correlations (R2 > 0.90) evidenced. Semi-automatic morphometry has been validated by double observer manual morphometry of micro-CT slices and highly significant correlations were found (R2 > 0.92).
  
  CONCLUSION:
  The micro-CT methodology described represents a handy and reliable tool for quantitative high resolution and contrast agent free full length coronary wall profiling, able to assist atherosclerotic vessels morphometry in a preclinical experimental model of coronary ATS and providing a link between in vivo imaging and histology.
  
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• Site-Specific Secretome Map Evidences VSMC-Related Markers of Coronary Atherosclerosis Grade and Extent in the Hypercholesterolemic Swine.
  Dis Markers

  2015 ;2015():465242. doi: 10.1155/2015/465242.
  
  Rocchiccioli Silvia, Cecchettini Antonella, Ucciferri Nadia, Terreni Marianna, Viglione Federica, Trivella Maria Giovanna, Citti Lorenzo, Parodi Oberdan, Pelosi Gualtiero
  
  Abstract
  
  A major drawback in coronary atherosclerosis (ATS) research is the difficulty of investigating early phase of plaque growth and related features in the clinical context. In this study, secreted proteins from atherosclerotic coronary arteries in a hypercholesterolemic swine model were characterized by a proteomics approach and their expression was correlated to site-specific ATS stage and extent. A wide coronary artery map of secreted proteins has been obtained in high fat (HF) diet induced ATS swine model and a significantly different expression of many proteins related to vascular smooth muscle cell (VSMC) activation/migration has been identified. Significant associations with ATS stage of HF coronary lesions were found for several VSMC-derived proteins and validated for chitinase 3 like protein 1 (CHI3L1) by tissue immunoexpression. A direct correlation (R(2) = 0.85) was evidenced with intima to media thickness ratio values and ELISA confirmed the higher blood concentrations of CHI3L1 in HF cases. These findings confirmed the pivotal role of VSMCs in coronary plaque development and demonstrated a strong site-specific relation between VSMC-secreted CHI3L1 and lesion grade, suggesting that this protein could be proposed as a useful biomarker for diagnosing and staging of atherosclerotic lesions in coronary artery disease.
  
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• Simulation of Ventricular, Cavo-Pulmonary, and Biventricular Ventricular Assist Devices in Failing Fontan.
  Artif Organs

  2015 Jul;39(7):550-8. doi: 10.1111/aor.12434.
  
  Di Molfetta Arianna, Amodeo Antonio, Fresiello Libera, Trivella Maria Giovanna, Iacobelli Roberta, Pilati Mara, Ferrari Gianfranco
  
  Abstract
  
  Considering the lack of donors, ventricular assist devices (VADs) could be an alternative to heart transplantation for failing Fontan patients, in spite of the lack of experience and the complex anatomy and physiopathology of these patients. Considering the high number of variables that play an important role such as type of Fontan failure, type of VAD connection, and setting (right VAD [RVAD], left VAD [LVAD], or biventricular VAD [BIVAD]), a numerical model could be useful to support clinical decisions. The aim of this article is to develop and test a lumped parameter model of the cardiovascular system simulating and comparing the VAD effects on failing Fontan. Hemodynamic and echocardiographic data of 10 Fontan patients were used to simulate the baseline patients' condition using a dedicated lumped parameter model. Starting from the simulated baseline and for each patient, a systolic dysfunction, a diastolic dysfunction, and an increment of the pulmonary vascular resistance were simulated. Then, for each patient and for each pathology, the RVAD, LVAD, and BIVAD implantations were simulated. The model can reproduce patients' baseline well. In the case of systolic dysfunction, the LVAD unloads the single ventricle and increases the cardiac output (CO) (35%) and the arterial systemic pressure (Pas) (25%). With RVAD, a decrement of inferior vena cava pressure (Pvci) (39%) was observed with 34% increment of CO, but an increment of the single ventricle external work (SVEW). With the BIVAD, an increment of Pas (29%) and CO (37%) was observed. In the case of diastolic dysfunction, the LVAD increases CO (42%) and the RVAD decreases the Pvci, while both increase the SVEW. In the case of pulmonary vascular resistance increment, the highest CO (50%) and Pas (28%) increment is obtained with an RVAD with the highest decrement of Pvci (53%) and an increment of the SVEW but with the lowest VAD power consumption. The use of numerical models could be helpful in this innovative field to evaluate the effect of VAD implantation on Fontan patients to support patient and VAD type selection personalizing the assistance.
  
  Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.
  
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• Differential regulation of microRNAs in end-stage failing hearts is associated with left ventricular assist device unloading.
  Biomed Res Int

  2015 ;2015():592512. doi: 10.1155/2015/592512.
  
  Barsanti Cristina, Trivella Maria Giovanna, D'Aurizio Romina, El Baroudi Mariama, Baumgart Mario, Groth Marco, Caruso Raffaele, Verde Alessandro, Botta Luca, Cozzi Lorena, Pitto Letizia
  
  Abstract
  
  Mechanical unloading by left ventricular assist devices (LVADs) in advanced heart failure (HF), in addition to improving symptoms and end-organ perfusion, is supposed to stimulate cellular and molecular responses which can reverse maladaptive cardiac remodeling. As microRNAs (miRNAs) are key regulators in remodeling processes, a comparative miRNA profiling in transplanted hearts of HF patients with/without LVAD assistance could aid to comprehend underlying molecular mechanisms. Next generation sequencing (NGS) was used to analyze miRNA differential expression in left ventricles of HF patients who underwent heart transplantation directly (n = 9) or following a period of LVAD support (n = 8). After data validation by quantitative real-time PCR, association with functional clinical parameters was investigated. Bioinformatics' tools were then used for prediction of putative targets of modulated miRNAs and relative pathway enrichment. The analysis revealed 13 upregulated and 10 downregulated miRNAs in failing hearts subjected to LVAD assistance. In particular, the expression level of some of them (miR-338-3p, miR-142-5p and -3p, miR-216a-5p, miR-223-3p, miR-27a-5p, and miR-378g) showed correlation with off-pump cardiac index values. Predicted targets of these miRNAs were involved in focal adhesion/integrin pathway and in actin cytoskeleton regulation. The identified miRNAs might contribute to molecular regulation of reverse remodeling and heart recovery mechanisms.
  
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• Dynamic 3D analysis of myocardial sympathetic innervation: an experimental study using 123I-MIBG and a CZT camera.
  J Nucl Med

  2015 Mar;56(3):464-9. doi: 10.2967/jnumed.114.143669.
  
  Giorgetti Assuero, Burchielli Silvia, Positano Vincenzo, Kovalski Gil, Quaranta Angela, Genovesi Dario, Tredici Manuel, Duce Valerio, Landini Luigi, Trivella Maria Giovanna, Marzullo Paolo
  
  Abstract
  
  UNLABELLED:
  Data on the in vivo myocardial kinetics of (123)I-metaiodobenzylguanidine ((123)I-MIBG) are scarce and have always been obtained using planar acquisitions. To clarify the normal kinetics of (123)I-MIBG in vivo over time, we designed an experimental protocol using a 3-dimensional (3D) dynamic approach with a cadmium zinc telluride (CZT) camera.
  
  METHODS:
  We studied 6 anesthetized pigs (mean body weight, 37 ± 4 kg). Left ventricular myocardial perfusion and sympathetic innervation were assessed using (99m)Tc-tetrofosmin (26 ± 6 MBq), (123)I-MIBG (54 ± 14 MBq), and a CZT camera. A normal perfusion/function match on gated SPECT was the inclusion criterion. A dynamic acquisition in list mode started simultaneously with the bolus injection of (123)I-MIBG, and data were collected every 5 min for the first 20 min and then at acquisition steps of 30, 60, 90, and 120 min. Each step was reconstructed using dedicate software and reframed (60 s/frame). On the reconstructed transaxial slice that best showed the left ventricular cavity, regions of interest were drawn to obtain myocardial and blood pool activities. Myocardial time-activity curves were generated by interpolating data between contiguous acquisition steps, corrected for radiotracer decay and injected dose, and fitted to a bicompartmental model. Time to myocardial maximum signal intensity (MSI), MSI value, radiotracer retention index (RI, myocardial activity/blood pool integral), and washout rate were calculated. The mediastinal signal was measured and fitted to a linear model.
  
  RESULTS:
  The myocardial MSI of (123)I-MIBG was reached within 5.57 ± 4.23 min (range, 2-12 min). The mean MSI was 0.426% ± 0.092%. Myocardial RI decreased over time and reached point zero at 176 ± 31 min (range, 140-229 min). The ratio between myocardial and mediastinal signal at 15 and 125 min and extrapolated at 176 and 4 h was 5.45% ± 0.61%, 4.33% ± 1.23% (not statistically significant vs. 15 min), 3.95% ± 1.46% (P < 0.03 vs. 125 min), and 3.63% ± 1.64% (P < 0.03 vs. 176 min), respectively. Mean global washout rate at 125 min was 15% ± 14% (range, 0%-34%), and extrapolated data at 176 min and 4 h were 18% ± 18% (range, 0.49%-45%) and 25% ± 23% (range, 1.7%-56.2%; not statistically significant vs. 176 min), respectively.
  
  CONCLUSION:
  3D dynamic analysis of (123)I-MIBG suggests that myocardial peak uptake is reached more quickly than previously described. Myocardial RI decreases over time and, on average, is null about 3 h after injection. The combination of an early peak and variations in delayed myocardial uptake could result in a wide physiologic range of washout rates. Mediastinal activity appears to be constant over time and significantly lower than previously described in planar studies, resulting in a higher heart-to-mediastinum ratio.
  
  © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.
  
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• Determination of sevoflurane and isopropyl alcohol in exhaled breath by thermal desorption gas chromatography-mass spectrometry for exposure assessment of hospital staff.
  J Pharm Biomed Anal

  2015 Mar;106():218-23. doi: 10.1016/j.jpba.2014.11.052.
  
  Ghimenti Silvia, Tabucchi Sara, Bellagambi Francesca G, Lomonaco Tommaso, Onor Massimo, Trivella Maria Giovanna, Fuoco Roger, Di Francesco Fabio
  
  Abstract
  
  Volatile anaesthetics and disinfection chemicals pose ubiquitous inhalation and dermal exposure risks in hospital and clinic environments. This work demonstrates specific non-invasive breath biomonitoring methodology for assessing staff exposures to sevoflurane (SEV) anaesthetic, documenting its metabolite hexafluoroisopropanol (HFIP) and measuring exposures to isopropanol (IPA) dermal disinfection fluid. Methods are based on breath sample collection in Nalophan bags, followed by an aliquot transfer to adsorption tube, and subsequent analysis by thermal desorption gas chromatography-mass spectrometry (TD-GC-MS). Ambient levels of IPA were also monitored. These methods could be generalized to other common volatile chemicals found in medical environments. Calibration curves were linear (r(2)=0.999) in the investigated ranges: 0.01-1000 ppbv for SEV, 0.02-1700 ppbv for IPA, and 0.001-0.1 ppbv for HFIP. The instrumental detection limit was 10 pptv for IPA and 5 pptv for SEV, both estimated by extracted ion-TIC chromatograms, whereas the HFIP minimum detectable concentration was 0.5 pptv as estimated in SIM acquisition mode. The methods were applied to hospital staff working in operating rooms and clinics for blood draws. SEV and HFIP were present in all subjects at concentrations in the range of 0.7-18, and 0.002-0.024 ppbv for SEV and HFIP respectively. Correlation between IPA ambient air and breath concentration confirmed the inhalation pathway of exposure (r=0.95, p<0.001) and breath-borne IPA was measured as high as 1500 ppbv. The methodology is easy to implement and valuable for screening exposures to common hospital chemicals. Although the overall exposures documented were generally below levels of health concern in this limited study, outliers were observed that indicate potential for acute exposures.
  
  Copyright © 2015. Published by Elsevier B.V.
  
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• Uncovering the cathepsin system in heart failure patients submitted to Left Ventricular Assist Device (LVAD) implantation.
  J Transl Med

  2014 Dec;12():350. doi: 10.1186/s12967-014-0350-7.
  
  D'Amico Andrea, Ragusa Rosetta, Caruso Raffaele, Prescimone Tommaso, Nonini Sandra, Cabiati Manuela, Del Ry Silvia, Trivella Maria Giovanna, Giannessi Daniela, Caselli Chiara
  
  Abstract
  
  BACKGROUND:
  In end-stage heart failure (HF), the implantation of a left ventricular assist device (LVAD) is able to induce reverse remodeling. Cellular proteases, such as cathepsins, are involved in the progression of HF. The aim of this study was to evaluate the role of cathepsin system in HF patients supported by LVAD, in order to determine their involvement in cardiac remodeling.
  
  METHODS:
  The expression of cysteine (CatB, CatK, CatL, CatS) and serine cathepsin (CatG), and relative inhibitors (Cystatin B, C and SerpinA3, respectively) was determined in cardiac biopsies of 22 patients submitted to LVAD (pre-LVAD) and compared with: 1) control stable chronic HF patients on medical therapy at the moment of heart transplantation without prior LVAD (HT, n?=?7); 2) patients supported by LVAD at the moment of transplantation (post-LVAD, n?=?6).
  
  RESULTS:
  The expression of cathepsins and their inhibitors was significantly higher in pre-LVAD compared to the HT group and LVAD induced a further increase in the cathepsin system. Significant positive correlations were observed between cardiac expression of cathepsins and their inhibitors as well as inflammatory cytokines. In the pre-LVAD group, a relationship of cathepsins with dilatative etiology and length of hospitalization was found.
  
  CONCLUSIONS:
  A parallel activation of cathepsins and their inhibitors was observed after LVAD support. The possible clinical importance of these modifications is confirmed by their relation with patients' outcome. A better discovery of these pathways could add more insights into the cardiac remodeling during HF.
  
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• The relationship between R-wave magnitude and ventricular volume during continuous left ventricular assist device assistance: experimental study.
  Artif Organs

  2015 May;39(5):446-50. doi: 10.1111/aor.12407.
  
  Fresiello Libera, Trivella Maria Giovanna, Di Molfetta Arianna, Ferrari Gianfranco, Bernini Fabio, Meste Olivier
  
  Abstract
  
  The current use of left ventricular assist devices (LVADs) as destination therapy is associated with the clinical need of monitoring patient-pump interaction. To this aim, the present work investigated the possibility of getting useful information about the status of the assisted left ventricle using electrocardiographic (ECG) data. A total of six animals, undergoing Gyro Centrifugal Pump 2 implantation (a new version of Gyro Centrifugal Pump C1E3 [Kyocera Corporation, Kyoto, Japan]) and CircuLite Synergy Micropump (CircuLite, Inc., Saddlebrooke, NJ, USA) in atrio-aortic connection, were analyzed. Data refer to different LVAD speeds with consequently different levels of ventricular unloading. From ECG signal, the R wave peak was individuated together with the corresponding left ventricular volume. Then on both signals, a moving average analysis was performed to reduce the effect of the ventilation. A regression and correlation analysis performed on the two resulting signals evidenced that the R wave peak and the ventricular volume are strictly related. Specifically, any change of LVAD speed, inducing a change in ventricular volume, is associated with a change in R wave peak value. The present work is a first step in investigating the usefulness of the ECG signal during LVAD therapy, for the monitoring of mechanical parameters of the heart such as the ventricular volumes. The correlation found between the ECG and the ventricular volume can be a promising starting point for possible future noninvasive LVAD patient monitoring.
  
  Copyright © 2014 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.
  
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• An innovative adaptive control strategy for sensorized left ventricular assist devices.
  IEEE Trans Biomed Circuits Syst

  2014 Oct;8(5):660-8. doi: 10.1109/TBCAS.2014.2346015.
  
  Verbeni Antonella, Fontana Rossella, Silvestri Michele, Tortora Giuseppe, Vatteroni Monica, Trivella Maria Giovanna, Dario Paolo
  
  Abstract
  
  Nowadays advanced heart failure is mainly treated through heart transplantation. However, the low availability of donors makes the research of alternative therapies urgent. Continuous-flow left ventricular assist devices (LVADs) are going to assume a more significant role in assisting the failing heart. A recent challenge in clinical practice is the possibility to use LVAD as long-term therapy rather than as a bridge to transplantation. For this reason, more comfortable devices, able to dynamically adapt to the physiological cardiac demand in relation to the patient activity level, are needed in order to improve the life quality of patients with implants. Nevertheless, no control system has been developed yet for this purpose. This work proposes an innovative control strategy for a novel sensorized LVAD, based on the continuous collection of physical and functional parameters coming from implantable sensors and from the LVAD itself. Thanks to the proposed system, both the patient and the LVAD conditions are continuously monitored and the LVAD activity regulated accordingly. Specifically, a Proportional Integrative (PI) and a threshold control algorithms have been implemented, respectively based on flow and pressure feedbacks collected from the embedded sensors. To investigate the feasibility and applicability of this control strategy, an on-bench platform for LVADs sensing and monitoring has been developed and tested.
  
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• Caspase-1 transcripts in failing human heart after mechanical unloading.
  Cardiovasc Pathol

  ;24(1):11-8. doi: 10.1016/j.carpath.2014.08.002.
  
  Prescimone Tommaso, D'Amico Andrea, Caselli Chiara, Cabiati Manuela, Viglione Federica, Caruso Raffaele, Verde Alessandro, Del Ry Silvia, Trivella Maria Giovanna, Giannessi Daniela
  
  Abstract
  
  BACKGROUND:
  Caspase (Casp)-1 has been indicated as a molecular target capable of preventing the progression of cardiovascular diseases, including heart failure (HF), due to its central role in promoting inflammation and cardiomyocyte loss. The aim of this study was to assess whether Left Ventricular Assist Device (LVAD) implantation modifies the inflammatory and apoptotic profile in the heart through the modulation of Casp-1 expression level.
  
  METHODS:
  Cardiac tissue was collected from end-stage HF patients before LVAD implant (pre-LVAD group, n=22) and at LVAD removal (post-LVAD, n=6), and from stable HF patients on medical therapy without prior circulatory support (HTx, n=7) at heart transplantation, as control. The cardiac expression of Casp-1, of its inhibitors caspase recruitment domain (CARD) only protein (COP) and CARD family, member 18 (ICEBERG), was evaluated by real-time PCR in the three groups of patients.
  
  RESULTS:
  Casp-1 was increased in the pre-LVAD group compared to HTx (p=0.006), while on the contrary the ICEBERG level was significantly decreased in pre-LVAD with respect to HTx patients (p<0.001); no difference in COP expression level was found.
  
  CONCLUSIONS:
  This study describes a specific pattern of the Casp-1 system associated with inflammation and apoptosis markers in patients who require LVAD insertion. The inflammation could be the key process regulating, in a negative loop, Casp-1 signaling and its down-stream effects, apoptosis included.
  
  Copyright © 2014 Elsevier Inc. All rights reserved.
  
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• A novel three-dimensional biosensor based on aluminum oxide: application for early-stage detection of human interleukin-10.
  Methods Mol Biol

  2014 ;1172():49-64. doi: 10.1007/978-1-4939-0928-5_5.
  
  Lee Michael, Baraket Abdoullatif, Zine Nadia, Zabala Miguel, Campabadal Francesca, Caruso Raffaele, Trivella Maria Giovanna, Jaffrezic-Renault Nicole, Errachid Abdelhamid
  
  Abstract
  
  Immunosensors based on electrolyte-oxide-semiconductors (EOS) have been extensively researched over the last few decades. By electrochemical impedance spectroscopy (EIS) the specific molecular biorecognition of the antibody-antigen (Ab-Ag) can be detected providing an alternative quantitative system to immunoassay techniques. The electrochemical variations from a fabricated immunosensor can provide quantitative values for the analyte of interest at reduced costs and analysis time. In this context, a novel EOS substrate based on aluminum oxide (Al2O3) grown by atomic layer deposition on silicon was applied. The interaction between recombinant human (rh) interleukin-10 (IL-10) with the corresponding monoclonal antibody (mAb) for early cytokine detection of an anti-inflammatory response due to left ventricular assisted device implantation was studied. For this purpose, a 3D biosensor was composed of multi-walled carbon nanotubes with carboxylic acid functionalities (multi-walled carbon nanotubes-COOH) to increase the surface area for the range of human IL-10 detection. These were activated with N-hydroxysuccinimide and N-(3-dimethylaminopropyl)-N'-ethyl-carbodiimide hydrochloride for the immobilization of the anti-human IL-10 mAb. First, the interaction between the Ab and Ag was observed by fluorescence patterning to ensure that the biorecognition event was achievable. Then, EIS is explained for the quantification of commercial human IL-10 on this capacitance-based EOS macroimmuno-FET sensor.
  
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• Modeling and simulation of speed selection on left ventricular assist devices.
  Comput Biol Med

  2014 Aug;51():128-39. doi: 10.1016/j.compbiomed.2014.04.013.
  
  Tzallas Alexandros T, Katertsidis Nikolaos S, Karvounis Evaggelos C, Tsipouras Markos G, Rigas George, Goletsis Yorgos, Zielinski Krzysztof, Fresiello Libera, Molfetta Arianna Di, Ferrari Gianfranco, Terrovitis John V, Trivella Maria Giovanna, Fotiadis Dimitrios I
  
  Abstract
  
  The control problem for LVADs is to set pump speed such that cardiac output and pressure perfusion are within acceptable physiological ranges. However, current technology of LVADs cannot provide for a closed-loop control scheme that can make adjustments based on the patient's level of activity. In this context, the SensorART Speed Selection Module (SSM) integrates various hardware and software components in order to improve the quality of the patients' treatment and the workflow of the specialists. It enables specialists to better understand the patient-device interactions, and improve their knowledge. The SensorART SSM includes two tools of the Specialist Decision Support System (SDSS); namely the Suction Detection Tool and the Speed Selection Tool. A VAD Heart Simulation Platform (VHSP) is also part of the system. The VHSP enables specialists to simulate the behavior of a patient?s circulatory system, using different LVAD types and functional parameters. The SDSS is a web-based application that offers specialists with a plethora of tools for monitoring, designing the best therapy plan, analyzing data, extracting new knowledge and making informative decisions. In this paper, two of these tools, the Suction Detection Tool and Speed Selection Tool are presented. The former allows the analysis of the simulations sessions from the VHSP and the identification of issues related to suction phenomenon with high accuracy 93%. The latter provides the specialists with a powerful support in their attempt to effectively plan the treatment strategy. It allows them to draw conclusions about the most appropriate pump speed settings. Preliminary assessments connecting the Suction Detection Tool to the VHSP are presented in this paper.
  
  Copyright © 2014 Elsevier Ltd. All rights reserved.
  
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• [Telemedicine and wireless devices in heart failure].
  Recenti Prog Med

  2014 May;105(5):210-6. doi: 10.1701/1493.16457.
  
  Billeci Lucia, Guerriero Lorenzo, L'Abbate Antonio, Pioggia Giovanni, Tartarisco Gennaro, Trivella Maria Giovanna
  
  Abstract
  
  Telemedicine has the potential to constitute the central element of the future primary care and become an effective means of prevention and early warning of acute exacerbation of chronic diseases. Up to now, the application of telemedicine has found a variety of difficulties, regarding the types and methods of acquisition and transmission of biological signals, the acceptance and cooperation of the patient, etc. The latest technological developments involve the combined use of wireless technologies and smartphones, for the collection and the transmission of data, and specific softwares for their automatic analysis. This paper examines some of the critical aspects in the application of new technologies for heart failure remote management.
  
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• Inflammation blood and tissue factors of plaque growth in an experimental model evidenced by a systems approach.
  Front Genet

  2014 ;5():70. doi: 10.3389/fgene.2014.00070.
  
  Pelosi Gualtiero, Rocchiccioli Silvia, Cecchettini Antonella, Viglione Federica, Puntoni Mariarita, Parodi Oberdan, Capobianco Enrico, Trivella Maria G
  
  Abstract
  
  PURPOSE:
  The multifactorial pathogenesis of coronary atherosclerotic lesion formation has been investigated in a swine model of high cholesterol diet induced atherogenesis and data processed by a systems approach.
  
  METHODS:
  Farm pigs were fed on standard or high cholesterol diet of 8 and 16 weeks duration. Plasma assessment of total cholesterol, HDL, LDL, and ELISA of some cytokines and ICAM-1 were performed on baseline and end-diet samples. Segments of the right coronary artery were incubated for 24 h in serum-free medium to collect secreted proteins and their expression analyzed by mass spectrometry. Data of plasma and tissue factors were processed by a statistical systems inference approach: both histologic parameters of coronary intimal thickness (IT) and of lesion area (LA) were chosen as dependent variables (coronary atherosclerotic burden).
  
  RESULTS:
  Relations among plasma adhesion molecules, cytokines, lipoproteins, tissue proteins and histology indexes were integrated in a model regression scheme. Bayesian model averaging (BMA) variable selection was chosen as a method to identify relevant factors associated to atherosclerotic burden: TNF? was identified as an associated plasma marker, oxLDL and HDL as relevant lipoproteins; macrophage function related antioxidant Catalase enzyme, lysosome associated Cathepsin D, S100-A10, and Transforming growth factor-beta-induced protein ig-h3 were identified and selected as associated to atherogenesis outcome.
  
  CONCLUSIONS:
  The results of this systems approach are consistent with the hypothesis that, in high cholesterol diet-induced experimental atherogenesis, the interaction between plasma cytokines, lipoproteins and artery-specific proteins, influences lesion initiation and growth. In particular, some macrophage function related proteins are found significantly and positively associated to atherosclerotic burden, suggesting a novel molecular framework into the atherogenesis-inflammatory disorder.
  
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• Simulation of apical and atrio-aortic VAD in patients with transposition or congenitally corrected transposition of the great arteries.
  Int J Artif Organs

  2014 Jan;37(1):58-70. doi: 10.5301/ijao.5000264.
  
  Di Molfetta Arianna, Jacobs Steven, Fresiello Libera, Verbelen Tom, Trivella Maria G, Meyns Bart, Ferrari Gianfranco
  
  Abstract
  
  PURPOSE:
  VADs could be used for transportation of the great arteries (TGA) and for congenitally corrected transposition (ccTGA) treatment. A cardiovascular numerical model (NM) may offer a useful clinical support in these complex physiopathologies. This work aims at developing and preliminarily verifying a NM of ccTGA and TGA interacting with VADs.
  
  METHODS:
  Hemodynamic data were collected at the baseline (BL) and three months (FUP) after apical (atrio-aortic) VAD implantation in a TGA (ccTGA) patient and used in a lumped parameter NM to simulate the patient's physiopathology. Measured (MS) and simulated (SIM) data were compared.
  
  RESULTS:
  MS and SIM data are in accordance at the BL and at FUP. Cardiac output (l/min): BL_m = 2.9 ± 0.4, BL_s = 3.0 ± 0.3; FUP_m = 4.2 ± 0.2, FUP_s = 4.1 ± 0.1. Right atrial pressure (mmHg): BL_m = 21.4 ± 4.1, BL_s = 18.5 ± 4.5; FUP_m = 13 ± 4, FUP_s = 14.8 ± 3.6. Pulmonary arterial pressure (mmHg): BL_m = 56 ± 6.3,BL_s = 57 ± 2, FUP_m = 37.5 ± 7.5, FUP_s = 35.5 ± 5.9. Systemic arterial pressure (mmHg): BL_m = 71 ± 2, BL_s = 74.6 ± 2.1; FUP_m = 84 ± 9, FUP_s = 81.9 ± 9.8.
  
  CONCLUSIONS:
  NM can simulate the effect of a VAD in complex physiopathologies, with the inclusion of changes in circulatory parameters during the acute phase and at FUP. The simulation of differently assisted physiopathologies offers a useful support for clinicians.
  
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• Characterization of secreted vesicles from vascular smooth muscle cells.
  Mol Biosyst

  2014 May;10(5):1146-52. doi: 10.1039/c3mb70544g.
  
  Comelli Laura, Rocchiccioli Silvia, Smirni Salvatore, Salvetti Alessandra, Signore Giovanni, Citti Lorenzo, Trivella Maria Giovanna, Cecchettini Antonella
  
  Abstract
  
  The artery medial layer is mainly composed of vascular smooth muscle cells (VSMCs). These cells contribute to the formation of neointima and atherosclerotic plaques by switching from the quiescent-contractile to migratory-activated state. Apoptotic blebs, microvesicles and exosomes are secreted vesicles, with differences in composition and size, involved in cellular communication at multiple levels. In this article, an untargeted, proteomics approach was exploited to characterise VSMC released vesicles and a preliminary protein profile for microvesicles and exosomes of different cell phenotypes was obtained. Enriched samples of vesicles from serum-free and serum-activated VSMCs were analysed by a LC-MS/MS strategy leading to the identification of 349 proteins. In microvesicles, the most abundant classes of identified proteins were cytoplasmic or organelle associated, house keeping and metabolic factors. Otherwise, exosomes from different phenotypes revealed a sharper peculiarity thus, as suggested by the high percentage of ECM and ECM related proteins and cell adhesion molecules, they seem to play an important role in outward or cell-to-cell signalling. Comparison between exosomes or microvesicles from quiescent and activated VSMCs evidenced 29 differentially expressed proteins. Among these, in microvesicles there are several proteins that are involved in vesicle trafficking while in exosomes focal adhesion and ECM related factors are the most interesting. These data, although preliminary, are promising for a possible identification of potential circulating markers of a cell state.
  
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• Relationship between pre-implant interleukin-6 levels, inflammatory response, and early outcome in patients supported by left ventricular assist device: a prospective study.
  PLoS One

  2014 ;9(3):e90802. doi: 10.1371/journal.pone.0090802.
  
  Caruso Raffaele, Botta Luca, Verde Alessandro, Milazzo Filippo, Vecchi Irene, Trivella Maria Giovanna, Martinelli Luigi, Paino Roberto, Frigerio Maria, Parodi Oberdan
  
  Abstract
  
  PURPOSE:
  The immune response is crucial in the development of multi-organ failure (MOF) and complications in end-stage heart failure patients supported by left ventricular assist device (LVAD). However, at pre-implant, the association between inflammatory state and post-LVAD outcome is not yet clarified. Aim of the study was to assess the relationship among pre-implant levels of immune-related cytokines, postoperative inflammatory response and 3-month outcome in LVAD-patients.
  
  METHODS:
  In 41 patients undergoing LVAD implantation, plasma levels of interleukin (IL)-6, IL-8, crucial for monocyte modulation, and urine neopterin/creatinine ratio (Neo/Cr), marker of monocyte activation, were assessed preoperatively, at 3 days, 1 and 4 weeks post-LVAD. MOF was evaluated by total sequential organ failure assessment (tSOFA) score. Intensive care unit (ICU)-death and/or post-LVAD tSOFA ?11 was considered as main adverse outcome. Length of ICU-stay, 1 week-tSOFA score, hospitalisation and 3-month survival were considered additional end-points.
  
  RESULTS:
  During ICU-stay, 8 patients died of MOF, while 8 of the survivors experienced severe MOF with postoperative tSOFA score ?11. Pre-implant level of IL-6 ? 8.3 pg/mL was identified as significant marker of discrimination between patients with or without adverse outcome (OR 6.642, 95% CI 1.201-36.509, p?=?0.030). Patients were divided according to pre-implant IL-6 cutoff of 8.3 pg/ml in A [3.5 (1.2-6.1) pg/mL] and B [24.6 (16.4-38.0) pg/mL] groups. Among pre-implant variables, only white blood cells count was independently associated with pre-implant IL-6 levels higher than 8.3 pg/ml (OR 1.491, 95% CI 1.004-2.217, p?=?0.048). The ICU-stay and hospitalisation resulted longer in B-group (p?=?0.001 and p?=?0.030, respectively). Postoperatively, 1 week-tSOFA score, IL-8 and Neo/Cr levels were higher in B-group.
  
  CONCLUSIONS:
  LVAD-candidates with elevated pre-implant levels of IL-6 are associated, after intervention, to higher release of monocyte activation related-markers, a clue for the development of MOF, longer clinical course and poor outcome.
  
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• Secreted proteins from carotid endarterectomy: an untargeted approach to disclose molecular clues of plaque progression.
  J Transl Med

  2013 Oct;11():260. doi: 10.1186/1479-5876-11-260.
  
  Rocchiccioli Silvia, Pelosi Gualtiero, Rosini Silvia, Marconi Michele, Viglione Federica, Citti Lorenzo, Ferrari Mauro, Trivella Maria Giovanna, Cecchettini Antonella
  
  Abstract
  
  BACKGROUND:
  Atherosclerosis is the main cause of morbidity and mortality in Western countries and carotid plaque rupture is associated to acute events and responsible of 15-20% of all ischemic strokes. Several proteomics approaches have been up to now used to elucidate the molecular mechanisms involved in plaque formation as well as to identify markers of pathology severity for early diagnosis or target of therapy. The aim of this study was to characterize the plaque secretome. The advantage of this approach is that secretome mimics the in vivo condition and implies a reduced complexity compared to the whole tissue proteomics allowing the detection of under-represented potential biomarkers.
  
  METHODS:
  Secretomes from carotid endarterectomy specimens of 14 patients were analyzed by a liquid chromatography approach coupled with label free mass spectrometry. Differential expression of proteins released from plaques and from their downstream distal side segments were evaluated in each specimen. Results were validated by Western blot analysis and ELISA assays. Histology and immunohistochemistry were performed to characterize plaques and to localise the molecular factors highlighted by proteomics.
  
  RESULTS:
  A total of 463 proteins were identified and 31 proteins resulted differentially secreted from plaques and corresponding downstream segments. A clear-cut distinction in the distribution of cellular- and extracellular-derived proteins, evidently related to the higher cellularity of distal side segments, was observed along the longitudinal axis of carotid endarterectomy samples. The expressions of thrombospondin-1, vitamin D binding protein, and vinculin, as examples of extracellular and intracellular proteins, were immunohistologically compared between adjacent segments and validated by antibody assays. ELISA assays of plasma samples from 34 patients and 10 healthy volunteers confirmed a significantly higher concentration of thrombospondin-1 and vitamin D binding protein in atherosclerotic subjects.
  
  CONCLUSIONS:
  Taking advantage of the optimized workflow, a detailed protein profile related to carotid plaque secretome has been produced which may assist and improve biomarker discovery of molecular factors in blood. Distinctive signatures of proteins secreted by adjacent segments of carotid plaques were evidenced and they may help discriminating markers of plaque complication from those of plaque growth.
  
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• Reproduction of continuous flow left ventricular assist device experimental data by means of a hybrid cardiovascular model with baroreflex control.
  Artif Organs

  2014 Jun;38(6):456-68. doi: 10.1111/aor.12178.
  
  Fresiello Libera, Zieli?ski Krzysztof, Jacobs Steven, Di Molfetta Arianna, Pa?ko Krzysztof Jakub, Bernini Fabio, Martin Michael, Claus Piet, Ferrari Gianfranco, Trivella Maria Giovanna, Górczy?ska Krystyna, Darowski Marek, Meyns Bart, Kozarski Maciej
  
  Abstract
  
  Long-term mechanical circulatory assistance opened new problems in ventricular assist device-patient interaction, especially in relation to autonomic controls. Modeling studies, based on adequate models, could be a feasible approach of investigation. The aim of this work is the exploitation of a hybrid (hydronumerical) cardiovascular simulator to reproduce and analyze in vivo experimental data acquired during a continuous flow left ventricular assistance. The hybrid cardiovascular simulator embeds three submodels: a computational cardiovascular submodel, a computational baroreflex submodel, and a hydronumerical interface submodel. The last one comprises two impedance transformers playing the role of physical interfaces able to provide a hydraulic connection with specific cardiovascular sites (in this article, the left atrium and the ascending/descending aorta). The impedance transformers are used to connect a continuous flow pump for partial left ventricular support (Synergy Micropump, CircuLite, Inc., Saddlebrooke, NJ, USA) to the hybrid cardiovascular simulator. Data collected from five animals in physiological, pathological, and assisted conditions were reproduced using the hybrid cardiovascular simulator. All parameters useful to characterize and tune the hybrid cardiovascular simulator to a specific hemodynamic condition were extracted from experimental data. Results show that the simulator is able to reproduce animal-specific hemodynamic status both in physiological and pathological conditions, to reproduce cardiovascular left ventricular assist device (LVAD) interaction and the progressive unloading of the left ventricle for different pump speeds, and to investigate the effects of the LVAD on baroreflex activity. Results in chronic heart failure conditions show that an increment of LVAD speed from 20?000 to 22?000?rpm provokes a decrement of left ventricular flow of 35% (from 2 to 1.3?L/min). Thanks to its flexibility and modular structure, the simulator is a platform potentially useful to test different assist devices, thus providing clinicians additional information about LVAD therapy strategy.
  
  Copyright © 2013 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.
  
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• Adverse event prediction in patients with left ventricular assist devices.
  Annu Int Conf IEEE Eng Med Biol Soc

  2013 ;2013():1314-7. doi: 10.1109/EMBC.2013.6609750.
  
  Tsipouras Markos G, Karvounis Evaggelos C, Tzallas Alexandros T, Katertsidis Nikolaos S, Goletsis Yorgos, Frigerio Maria, Verde Alessandro, Trivella Maria G, Fotiadis Dimitrios I
  
  Abstract
  
  This work presents the Treatment Tool, which is a component of the Specialist's Decision Support Framework (SDSS) of the SensorART platform. The SensorART platform focuses on the management of heart failure (HF) patients, which are treated with implantable, left ventricular assist devices (LVADs). SDSS supports the specialists on various decisions regarding patients with LVADs including decisions on the best treatment strategy, suggestion of the most appropriate candidates for LVAD weaning, configuration of the pump speed settings, while also provides data analysis tools for new knowledge extraction. The Treatment Tool is a web-based component and its functionality includes the calculation of several acknowledged risk scores along with the adverse events appearance prediction for treatment assessment.
  
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• Effects of amlodipine and adenosine on coronary haemodynamics: in vivo study and numerical simulation.
  Comput Methods Biomech Biomed Engin

  2014 Nov;17(15):1642-52. doi: 10.1080/10255842.2012.761691.
  
  De Lazzari Claudio, L'Abbate Antonio, Micalizzi Mauro, Trivella Maria Giovanna, Neglia Danilo
  
  Abstract
  
  Amlodipine (AMLO) is a calcium channel blocker with vasodilating properties, in which the specific effects on the coronary circulation are not fully known. Coronary flow velocity-pressure (F/P) curves were obtained at rest and during administration of AMLO (10 mg to 20 mg iv) or adenosine (ADO, 1 mg ic) in 10 normal subjects (six women, age 48 ± 14 years). F/P curves were reproduced in a numerical simulator of systemic and coronary circulations (CARDIOSIM(©)) by adjustment of coronary resistance ( > or < 100 ?m diameter vessels) and extravascular resistance applied to smaller vessels at endocardial (ENDO), middle and epicardial (EPI) myocardial layers. Best matching of in silico to in vivo curves was achieved by trial and error approach. ADO induced 170% and 250% increase in coronary flow velocity CFV and F/P diastolic slope as compared to 80% and 25-30% increase induced by AMLO, respectively. In the cardiovascular model, AMLO effects were predicted by progressive reduction of>100 ?m vessels resistance from EPI to ENDO. ADO effects were mimicked by reducing resistance of both>100 ?m and < 100 ?m vessels, progressively from EPI to ENDO in the latter. Additional reduction in extravascular resistance avoided to impose a transmural gradient of vasodilating effect for both drugs. Numerical simulation predicts vasodilating effects of AMLO mainly on larger arteries and of ADO on both>and < 100 ?m vessels. In vivo F/P loops could be completely reproduced in silico by adding extravascular resistance reduction for both drugs. Numerical simulator is useful tool for exploring the coronary effects of cardioactive drugs.
  
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• Automated knowledge-based fuzzy models generation for weaning of patients receiving ventricular assist device (VAD) therapy.
  Annu Int Conf IEEE Eng Med Biol Soc

  2012 ;2012():2206-9. doi: 10.1109/EMBC.2012.6346400.
  
  Tsipouras Markos G, Karvounis Evaggelos C, Tzallas Alexandros T, Goletsis Yorgos, Fotiadis Dimitrios I, Adamopoulos Stamatis, Trivella Maria G
  
  Abstract
  
  The SensorART project focus on the management of heart failure (HF) patients which are treated with implantable ventricular assist devices (VADs). This work presents the way that crisp models are transformed into fuzzy in the weaning module, which is one of the core modules of the specialist's decision support system (DSS) in SensorART. The weaning module is a DSS that supports the medical expert on the weaning and remove VAD from the patient decision. Weaning module has been developed following a "mixture of experts" philosophy, with the experts being fuzzy knowledge-based models, automatically generated from initial crisp knowledge-based set of rules and criteria for weaning.
  
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• Knowledge Editor and execution engine development for optimal ventricular assist device weaning.
  Annu Int Conf IEEE Eng Med Biol Soc

  2012 ;2012():1262-5. doi: 10.1109/EMBC.2012.6346167.
  
  Karvounis Evaggelos C, Tsipouras Markos G, Tzallas Alexandros T, Goletsis Yorgos, Fotiadis Dimitrios I, Terrovitis John, Trivella Maria G
  
  Abstract
  
  In this work, the weaning module of the SensorART specialist decision support system (SDSS) is presented. SensorART focuses on the treatment of patients suffering from end-stage heart failure (HF). The use of a ventricular assist device (VAD) is the main treatment for HF patients. However in certain cases, myocardial function recovers and VADs can be explanted after the patient is weaned. In that framework an efficient module is developed responsible for the selection of the most suitable candidates for VAD weaning. In this study we describe all technical specifications concerning its two main sub-modules of the weaning module, of the Clinical Knowledge Editor and the Knowledge Execution Engine.
  
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• Innovative erythrocyte-based carriers for gene delivery in porcine vascular smooth muscle cells: basis for local therapy to prevent restenosis.
  Cardiovasc Hematol Disord Drug Targets

  2012 Sep;12(1):68-75.
  
  Lande Caterina, Cecchettini Antonella, Tedeschi Lorena, Taranta Monia, Naldi Ilaria, Citti Lorenzo, Trivella Maria Giovanna, Grimaldi Settimio, Cinti Caterina
  
  Abstract
  
  Vascular restenosis is affecting 30-40% of patients treated by percutaneous coronary angioplasty (PTCA). The advent of stenting reduced but not abolished restenosis. The introduction of drug eluting stent (DES) further reduced restenosis, but impaired endothelization exposed to intracoronary thrombosis as late adverse event. It is widely accepted that the endothelial denudation and coronary wall damages expose Vascular Smooth Muscle Cells (VSMC) to multiple growth factors and plasma circulating agents thus activating migration and proliferative pathways leading to restenosis. Among the major players of this processes, phosphorylated Elk-1, forming the Elk-1/SRF transcription complex, controls the expression of a different set of genes responsible for cell proliferation. Therefore, it is feasible that gene-specific oligonucleotide therapy targeting VSMC migration and proliferation genes can be a promising therapeutic approach. While a plethora of vehicles is suitably working in static in vitro cultures, methods for in vivo delivery of oligonucleotides are still under investigation. Recently, we have patented a novel erythrocyte-based drug delivery system with high capability to fuse with targeted cells thus improving drug bioavailability at the site of action. Here, the potential of these engineered porcine erythrocytes to deliver a synthetic DNA Elk-1 decoy inside syngenic porcine VSMC was tested. The results of this study indicate that Elk-1 decoy is actually able to inhibit cell proliferation and migration of VSMC. Our data also suggest that erythrocyte-based carriers are more efficient in delivering these oligonucleotides in comparison to conventional vehicles. As a consequence, a lower dose of Elk-1 decoy, delivered by engineered erythrocytes, was sufficient to inhibit cell growth and migration. This approach represents the translational step to reach in vivo experiments in pigs after PTCA and/or stent implantation where oligonucleotide drugs will be site-specific administered by using erythrocyte-based carriers to prevent restenosis.
  
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• Ribozyme-mediated gene knock down strategy to dissect the consequences of PDGF stimulation in vascular smooth muscle cells.
  BMC Res Notes

  2012 Jul;5():268. doi: 10.1186/1756-0500-5-268.
  
  Lande Caterina, Boccardi Claudia, Citti Lorenzo, Mercatanti Alberto, Rizzo Milena, Rocchiccioli Silvia, Tedeschi Lorena, Trivella Maria Giovanna, Cecchettini Antonella
  
  Abstract
  
  BACKGROUND:
  Vascular Smooth Muscle Cells (VSMCs), due to their plasticity and ability to shift from a physiological contractile-quiescent phenotype to a pathological proliferating-activated status, play a central role in the onset and progression of atherosclerosis and cardiovascular diseases. PDGF-BB, among a series of cytokines and growth factors, has been identified as the critical factor in this phenotypic switch. In order to obtain new insights on the molecular effects triggered by PDGF-BB, a hammerhead ribozyme targeting the membrane receptor PDGFR-? was applied to inhibit PDGF pathway in porcine VSMCs.
  
  FINDINGS:
  Ribozymes, loaded on a cationic polymer-based vehicle, were delivered into cultured VSMCs. A significant impairment of the activation mechanisms triggered by PDGF-BB was demonstrated since cell migration decreased after treatments. In order to functionally validate the effects of PDGFR-? partial knock down we focused on the phosphorylation status of two proteins, protein disulfide isomerase-A3 (PDI-A3) and heat shock protein-60 (HSP-60), previously identified as indicative of VSMC phenotypic switch after PDGF-BB stimulation. Interestingly, while PDI-A3 phosphorylation was counteracted by the ribozyme administration indicating that PDI-A3 is a factor downstream the receptor signalling cascade, the HSP-60 phosphorylation status was greatly increased by the ribozyme administration.
  
  CONCLUSION:
  These contradictory observations suggested that PDGF-BB might trigger different parallel pathways that could be modulated by alternative isoforms of the receptors for the growth factor. In conclusion the knock down strategy here described enables to discriminate between two tightly intermingled pathways. Moreover it opens new attractive perspectives in functional investigations where combined gene knock down and proteomic technologies would allow the identification of key factors and pathways involved in VSMC-linked pathological disorders.
  
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• Proteomics changes in adhesion molecules: a driving force for vascular smooth muscle cell phenotypic switch.
  Mol Biosyst

  2012 Apr;8(4):1052-9. doi: 10.1039/c2mb05470a.
  
  Rocchiccioli Silvia, Ucciferri Nadia, Comelli Laura, Trivella Maria Giovanna, Citti Lorenzo, Cecchettini Antonella
  
  Abstract
  
  Vascular smooth muscle cells (VSMCs), if activated by growth factors as a consequence of vessel injuries, acquire the ability to proliferate and migrate thus contributing to the formation of neointima and atherosclerotic plaque. In this study, a gel-free and label-free proteomic approach was proposed to highlight factors modulated during VSMC activation. Twenty proteins, differentially expressed between quiescent and activated cells, were identified. A constellation of elements, that move together and are closely and functionally related, was visualized. The great majority of them are involved in cell migration and in adhesion formation, suggesting a pivotal role of these protein complexes on the phenotypic modulation. This study represents a first step to ascertain the precise actors of cell activation, their roles and interactions.
  
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• Measurement of warfarin in the oral fluid of patients undergoing anticoagulant oral therapy.
  PLoS One

  2011 ;6(12):e28182. doi: 10.1371/journal.pone.0028182.
  
  Ghimenti Silvia, Lomonaco Tommaso, Onor Massimo, Murgia Laura, Paolicchi Aldo, Fuoco Roger, Ruocco Lucia, Pellegrini Giovanni, Trivella Maria Giovanna, Di Francesco Fabio
  
  Abstract
  
  BACKGROUND:
  Patients on warfarin therapy undergo invasive and expensive checks for the coagulability of their blood. No information on coagulation levels is currently available between two controls.
  
  METHODOLOGY:
  A method was developed to determine warfarin in oral fluid by HPLC and fluorimetric detection. The chromatographic separation was performed at room temperature on a C-18 reversed-phase column, 65% PBS and 35% methanol mobile phase, flow rate 0.7 mL/min, injection volume 25 µL, excitation wavelength 310 nm, emission wavelength 400 nm.
  
  FINDINGS:
  The method was free from interference and matrix effect, linear in the range 0.2-100 ng/mL, with a detection limit of 0.2 ng/mL. Its coefficient of variation was <3% for intra-day measurements and <5% for inter-day measurements. The average concentration of warfarin in the oral fluid of 50 patients was 2.5±1.6 ng/mL (range 0.8-7.6 ng/mL). Dosage was not correlated to INR (r?=?-0.03, p?=?0.85) but positively correlated to warfarin concentration in the oral fluid (r?=?0.39, p?=?0.006). The correlation between warfarin concentration and pH in the oral fluid (r?=?0.37, p?=?0.009) confirmed the importance of pH in regulating the drug transfer from blood. A correlation between warfarin concentration in the oral fluid and INR was only found in samples with pH values ?7.2 (r?=?0.84, p?=?0.004).
  
  CONCLUSIONS:
  Warfarin diffuses from blood to oral fluid. The method allows to measure its concentration in this matrix and to analyze correlations with INR and other parameters.
  
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• A gel-free approach in vascular smooth muscle cell proteome: perspectives for a better insight into activation.
  Proteome Sci

  2010 Mar;8():15. doi: 10.1186/1477-5956-8-15.
  
  Rocchiccioli Silvia, Citti Lorenzo, Boccardi Claudia, Ucciferri Nadia, Tedeschi Lorena, Lande Caterina, Trivella Maria Giovanna, Cecchettini Antonella
  
  Abstract
  
  BACKGROUND:
  The use of chromatography coupled with mass spectrometry (MS) analysis is a powerful approach to identify proteins, owing to its capacity to fractionate molecules according to different chemical features. The first protein expression map of vascular smooth muscle cells (VSMC) was published in 2001 and since then other papers have been produced. The most detailed two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) map was presented by Mayr et al who identified 235 proteins, corresponding to the 154 most abundant unique proteins in mouse aortic VSMC. A chromatographic approach aimed at fractionating the VSMC proteome has never been used before.
  
  RESULTS:
  This paper describes a strategy for the study of the VSMC proteome. Our approach was based on pre-fractionation with ion exchange chromatography coupled with matrix assisted laser desorption-time of flight mass spectrometry analysis assisted by a liquid chromatography (LC-MALDI-TOF/TOF). Ion exchange chromatography resulted in a good strategy designed to simplify the complexity of the cellular extract and to identify a large number of proteins. Selectivity based on the ion-exchange chemical features was adequate if evaluated on the basis of protein pI. The LC-MALDI approach proved to be highly reproducible and sensitive since we were able to identify up to 815 proteins with a concentration dynamic range of 7 orders of magnitude.
  
  CONCLUSIONS:
  In our opinion, the large number of identified proteins and the promising quantitative reproducibility made this approach a powerful method to analyze complex protein mixtures in a high throughput way and to obtain statistical data for the discovery of key factors involved in VSMC activation and to analyze a label-free differential protein expression.
  
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• BIOTEX--biosensing textiles for personalised healthcare management.
  IEEE Trans Inf Technol Biomed

  2010 Mar;14(2):364-70. doi: 10.1109/TITB.2009.2038484.
  
  Coyle Shirley, Lau King-Tong, Moyna Niall, O'Gorman Donal, Diamond Dermot, Di Francesco Fabio, Costanzo Daniele, Salvo Pietro, Trivella Maria Giovanna, De Rossi Danilo Emilio, Taccini Nicola, Paradiso Rita, Porchet Jacque-André, Ridolfi Andrea, Luprano Jean, Chuzel Cyril, Lanier Thierry, Revol-Cavalier Frdéric, Schoumacker Sébastien, Mourier Véronique, Chartier Isabelle, Convert Reynald, De-Moncuit Henri, Bini Christina
  
  Abstract
  
  Textile-based sensors offer an unobtrusive method of continually monitoring physiological parameters during daily activities. Chemical analysis of body fluids, noninvasively, is a novel and exciting area of personalized wearable healthcare systems. BIOTEX was an EU-funded project that aimed to develop textile sensors to measure physiological parameters and the chemical composition of body fluids, with a particular interest in sweat. A wearable sensing system has been developed that integrates a textile-based fluid handling system for sample collection and transport with a number of sensors including sodium, conductivity, and pH sensors. Sensors for sweat rate, ECG, respiration, and blood oxygenation were also developed. For the first time, it has been possible to monitor a number of physiological parameters together with sweat composition in real time. This has been carried out via a network of wearable sensors distributed around the body of a subject user. This has huge implications for the field of sports and human performance and opens a whole new field of research in the clinical setting.
  
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• Ozone and cardiovascular injury.
  Cardiovasc Ultrasound

  2009 Jun;7():30. doi: 10.1186/1476-7120-7-30.
  
  Srebot Vera, Gianicolo Emilio A L, Rainaldi Giuseppe, Trivella Maria Giovanna, Sicari Rosa
  
  Abstract
  
  Air pollution is increasingly recognized as an important and modifiable determinant of cardiovascular diseases in urban communities. The potential detrimental effects are both acute and chronic having a strong impact on morbidity and mortality. The acute exposure to pollutants has been linked to adverse cardiovascular events such as myocardial infarction, heart failure and life-threatening arrhythmias. The long-terms effects are related to the lifetime risk of death from cardiac causes. The WHO estimates that air pollution is responsible for 3 million premature deaths each year. The evidence supporting these data is very strong nonetheless, epidemiologic and observational data have the main limitation of imprecise measurements. Moreover, the lack of clinical experimental models makes it difficult to demonstrate the individual risk. The other limitation is related to the lack of a clear mechanism explaining the effects of pollution on cardiovascular mortality. In the present review we will explore the epidemiological, clinical and experimental evidence of the effects of ozone on cardiovascular diseases. The pathophysiologic consequences of air pollutant exposures have been extensively investigated in pulmonary systems, and it is clear that some of the major components of air pollution (e.g. ozone and particulate matter) can initiate and exacerbate lung disease in humans 1. It is possible that pulmonary oxidant stress mediated by particulate matter and/or ozone (O3) exposure can result in downstream perturbations in the cardiovasculature, as the pulmonary and cardiovascular systems are intricately associated, and it is well documented that specific environmental toxins (such as tobacco smoke 2) introduced through the lungs can initiate and/or accelerate cardiovascular disease development. Indeed, several epidemiologic studies have proved that there is an association between PM and O3 and the increased incidence of cardiovascular morbidity and mortality 3. Most of the evidence comes from studies of ambient particles concentrations. However, in Europe and elsewhere, the air pollution profile has gradually changed toward a more pronounced photochemical component. Ozone is one of the most toxic components of the photochemical air pollution mixture. Indeed, the biological basis for these observations has not been elucidated. In the present review, the role of ozone as chemical molecule will be firstly considered. Secondly, pathogenetic mechanisms connecting the atmospheric ozone level and cardiovascular pathology will be examined. Thirdly, the literature relating hospitalization frequency, morbidity and mortality due to cardiovascular causes and ozone concentration will be studied. The correlation between ozone level and occurrence of acute myocardial infarction will be eventually discussed.
  
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• Personality traits and heart rate variability predict long-term cardiac mortality after myocardial infarction.
  Eur Heart J

  2005 Aug;26(16):1612-7.
  
  Carpeggiani Clara, Emdin Michele, Bonaguidi Franco, Landi Patrizia, Michelassi Claudio, Trivella Maria Giovanna, Macerata Alberto, L'Abbate Antonio
  
  Abstract
  
  AIMS:
  To investigate personality traits and sympatho-vagal modulation of heart rate variability (HRV) during acute myocardial infarction (AMI), assessing their relationships and their long-term prognostic value.
  
  METHODS AND RESULTS:
  Psychological traits and 24 h HRV were prospectively investigated in 246 patients at discharge of an AMI. Patients were followed-up to 8 years for the occurrence of cardiac death and non-fatal reinfarction. Low coping and anxiety traits associated with reduced HRV characterized the study population. At univariate analysis, low emotional sensitivity and insecurity, relative tachycardia, reduced high frequency (HF), and low frequency power and pNN50 were predictive of cardiac death at 8-year follow-up. At multivariable analysis, low emotional sensitivity and low HF power remained predictive, with a relative risk of 4.18 (P=0.003) and 2.76 (P=0.007), respectively; also the type of infarction (Q vs. non-Q) and hospital length of stay were independent predictive variables.
  
  CONCLUSION:
  Anxiety and emotional sensitivity were significant predictors of 8-year cardiac mortality after AMI. Reduced HF power, a recognized marker of vagal withdrawal, increased the risk.
  
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