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Vertical hepatitis C virus transmission:Main questions and answers

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World Journal of Hepatology 2014年第8期6卷 538-548页

作者： Grazia Tosone alberto enrico maraolo Silvia Mascolo Giulia Palmiero Orsola Tambaro Raffaele Orlando Department of Clinical Medicine and Surgery Section of Infectious Diseases University of Naples Federico Ⅱ 80131 Napoli Italy

Hepatitis C virus(HCV) affects about 3% of the world's population and peaks in subjects aged over 40 years. Its prevalence in pregnant women is low(1%-2%) in most western countries but drastically increases in women in developing countries or with high risk behav-iors for blood-transmitted infections. Here we review clinical, prognostic and therapeutic aspects of HCV in-fection in pregnant women and their offspring infected through vertical transmission. Pregnancy-related im-mune weakness does not seem to affect the course of acute hepatitis C but can affect the progression of chronic hepatitis C. In fact, postpartum immune res-toration can exacerbate hepatic inflammation, thereby worsening the liver disease, particularly in patients with liver cirrhosis. HCV infection increases the risk of gestational diabetes in patients with excessive weight gain, premature rupture of membrane and caesarean delivery. Only 3%-5% of infants born to HCV-positive mothers have been infected by intrauterine or perinatal transmission. Maternal viral load, human immunode-ficiency virus coinfection, prolonged rupture of mem-branes, fetal exposure to maternal infected blood con-sequent to vaginal or perineal lacerations and invasive monitoring of fetus increase the risk of viral transmis-sion. Cesarean delivery and breastfeeding increases the transmission risk in HCV/human immunodeficiency virus coinfected women. The consensus is not to offer antivi-ral therapy to HCV-infected pregnant women because it is based on ribavirin(pregnancy category X) because of its embryocidal and teratogenic effects in animal spe-cies. In vertically infected children, chronic C hepatitis is often associated with minimal or mild liver disease and progression to liver cirrhosis and hepatocarcinoma is lower than in adults. Infected children may be treated after the second year of life, given the adverse effects of current antiviral agents.

关键词： Hepatitis C infection Pregnancy Vertical transmission Antiviral therapy Prevention

Nosocomial spontaneous bacterial peritonitis antibiotic treatment in the era of multi-drug resistance pathogens: A systematic review

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World Journal of Gastroenterology 2017年第25期23卷 4654-4660页

作者： Marco Fiore alberto enrico maraolo Ivan Gentile Guglielmo Borgia Sebastiano Leone Pasquale Sansone Maria Beatrice Passavanti Caterina Aurilio Maria Caterina Pace Department of Anaesthesiological Surgical and Emergency SciencesUniversity of Campania“Luigi Vanvitelli” Department of Clinical Medicine and Surgery Section of Infectious DiseasesUniversity of Naples Federico II Division of Infectious Diseases “San Giuseppe Moscati”Hospital

To systematically review literature upon aetiology of nosocomial spontaneous bacterial peritonitis (N-SBP) given the rising importance of multidrug-resistant (MDR) bacteria. METHODSA literature search was performed on MEDLINE and Google Scholar databases from 2000 to 15th of November 2016, using the following search strategy: “spontaneous” AND “peritonitis”. RESULTSThe initial search through electronic databases retrieved 2556 records. After removing duplicates, 1958 records remained. One thousand seven hundred and thirty-five of them were excluded on the basis of the screening of titles and abstract, and the ensuing number of remaining articles was 223. Of these records, after careful evaluation, only 9 were included in the qualitative analysis. The overall proportion of MDR bacteria turned out to be from 22% to 73% of cases across the studies. CONCLUSIONN-SBP is caused, in a remarkable proportion, by MDR pathogens. This should prompt a careful re-assessment of guidelines addressing the treatment of this clinical entity.

关键词： Hospital-acquired infections Nosocomial spontaneous bacterial peritonitis Multidrug resistant bacteria Cirrhosis Critically ill patient

Current concepts and future strategies in the antimicrobial therapy of emerging Gram-positive spontaneous bacterial peritonitis

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World Journal of Hepatology 2017年第30期9卷 1166-1175页

作者： Marco Fiore alberto enrico maraolo Ivan Gentile Guglielmo Borgia Sebastiano Leone Pasquale Sansone Maria Beatrice Passavanti Caterina Aurilio Maria Caterina Pace Department of Anesth-esiological Surgical and Emergency SciencesUniversity of Campania 'Luigi Vanvitelli' Department of Clinical Medicine and Surgery Section of Infectious DiseasesUniversity of Naples Federico Ⅱ Division of Infectious Diseases 'San Giuseppe Moscati' Hospital

Spontaneous bacterial peritonitis(SBP) is the most common infection in end-stage liver disease *** is defined as an ascitic fluid infection with a polymorphonuclear leucocyte count ≥ 250/mm^3 without an evident intra-abdominal surgically treatable *** mechanisms contribute to SBP occurrence,including translocation of gut bacteria and their products,reduced intestinal motility provoking bacterial overgrowth,alteration of the gut's barrier function and local immune ***,Gram-negative enteric bacteria have been the main causative agents of SBP,thereby guiding the empirical therapeutic ***,over the last decade,a worryingly increasing prevalence of Gram-positive and multi-drug resistant(MDR) SBP has been ***,the microbiological spectrum of SBP seems to have changed in Europe due to a high prevalence of Gram-positive bacteria(48%-62%).The overall proportion of MDR bacteria is up to 22%-73% of ***,empirical therapy based on thirdgeneration cephalosporins or amoxicillin/clavulanic acid,can no longer be considered the standard of care,as these drugs are associated with poor *** of this review is to describe,with an epidemiological focus,the evidence behind this rise in Gram-positive and MDR SBP from 2000 to present,and illustrate potential targeted therapeutic *** appropriate treatment protocol should include daptomycin plus ceftaroline and meropenem,with prompt stepdown to a narrower spectrum when cultures and sensitivity data are available in order to reduce both cost and potential antibiotic resistance development.

关键词： Spontaneous bacterial peritonitis Multi-drug resistant bacteria End-stage liver disease Cirrhosis Critically ill patient

Current evidence on the management of hepatitis B in pregnancy

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World Journal of Hepatology 2018年第9期10卷 585-594页

作者： alberto enrico maraolo Ivan Gentile Antonio Riccardo Buonomo Biagio Pinchera Guglielmo Borgia Section of Infectious Diseases Department of Clinical Medicine and SurgeryUniversity of Naples Federico Ⅱ

Hepatitis B virus(HBV) infection is one of the main public health problems across the globe,since almost one third of the world population presents serological markers of contact with the virus. A profound impact on the epidemiology has been exerted by universal vaccination programmes in many countries,nevertheless the infection is still widespread also in its active form. In the areas of high endemicity(prevalence of hepatitis B surface antigen positivity > 7%),mother-to-child transmission represents the main modality of infection spread. That makes the correct management of HBV in pregnancy a matter of utmost importance. Furthermore,the infection in pregnancy needs to be carefully assessed and handled not only with respect to the risk of vertical transmission but also with respect to gravid women health. Each therapeutic or preventive choice deserves to be weighed upon attentively. On many aspects evidence is scarce or controversial. This review will highlight the latest insights into the paramount steps in managing HBV in pregnancy,with particular attention to recommendations from recent guidelines and data from up-do-date research syntheses.

关键词： Pregnancy Hepatitis B immunoglobulin Hepatitis B Therapy Immunoprophylaxis Antiviral prophylaxis

Therapeutic targeting of cellular prion protein: toward the development of dual mechanism anti-prion compounds

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Neural Regeneration Research 2025年第4期20卷 1009-1014页

作者： Antonio Masone Chiara Zucchelli enrico Caruso Giovanna Musco Roberto Chiesa Laboratory of Prion Neurobiology Department of NeuroscienceIstituto di Ricerche Farmacologiche Mario Negri IRCCSMilanItaly Biomolecular NMR Unit Division of Genetics and Cell BiologyIRCCS Ospedale San RaffaeleMilanItaly Department of Biotechnology and Life Sciences University of InsubriaVareseItaly

PrPSc,a misfolded,aggregation-prone isoform of the cellular prion protein(PrPC),is the infectious prion agent responsible for fatal neurodegenerative diseases of humans and other *** adopt different pathogenic conformations(prion strains),which can be resistant to potential drugs,or acquire drug resistance,posing challenges for the development of effective *** PrPCis the obligate precursor of any prion strain and serves as the mediator of prion neurotoxicity,it represents an attractive therapeutic target fo r prion *** this minireview,we briefly outline the approaches to target PrPCand discuss our recent identification of Zn(Ⅱ)-Bn PyP,a PrPC-targeting porphyrin with an unprecedented bimodal mechanism of *** argue that in-depth understanding of the molecular mechanism by which Zn(Ⅱ)-Bn PyP targets PrPCmay lead toward the development of a new class of dual mechanism anti-prion compounds.

关键词： anti-prion drug anti-PrPC antibody antisense oligonucleotide neurodegeneration pharmacological chaperone porphyrin prion disease PrPC degrader PrPC shedding zinc finger repressor

Genetic signatures of ERCC1 and ERCC2 expression, along with SNPs variants, unveil favorable prognosis in SCLC patients undergoing platinum-based chemotherapy

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Oncology research 2025年第1期33卷 45-55页

作者： enrico Caliman Sara Fancelli Federico Scolari Adriano Pasqui Clara Manneschi Daniele Lavacchi Francesca Mazzoni Francesca Gensini Valeria Pasini Camilla Eva Comin Luca Voltolini Serena Pillozzi Lorenzo Antonuzzo Clinical Oncology Unit Careggi University Hospital Florence 50134 Italy. Department of Experimental and Clinical Medicine University of Florence Florence 50134 Italy. Department of Health Sciences University of Florence Florence 50134 Italy. Medical Oncology Unit Careggi University Hospital Florence 50134 Italy. Department of Experimental and Clinical Biomedical Sciences "Mario Serio" University of Florence Florence 50134 Italy. Section of Anatomic Pathology Department of Health Sciences University of Florence Florence 50139 Italy. Section of Surgery Histopathology and Molecular Pathology University of Florence Florence 50139 Italy. Thoracic Surgery Unit Careggi University Hospital Florence 50134 Italy.

Background:Platinum chemotherapy (CT) remains the backbone of systemic therapy for patients with small-cell lung cancer (SCLC). The nucleotide excision repair (NER) pathway plays a central role in the repair of the DNA damage exerted by platinum agents. Alteration in this repair mechanism may affect patients' survival.Materials and Methods:We conducted a retrospective analysis of data from 38 patients with extensive disease (ED)-SCLC who underwent platinum-CT at the Clinical Oncology Unit, Careggi University Hospital, Florence (Italy), from 2015 to 2020. mRNA expression analysis and single nucleotide polymorphism (SNP) characterization of three NER pathway genes-namely , , and -were performed on patient tumor samples.Results:Overall, elevated expression of genes was observed in SCLC patients compared to healthy controls. Patients with low and expression levels exhibited a better median progression-free survival (mPFS = 7.1 . 4.9 months, = 0.39 for and mPFS = 6.9 . 4.8 months, = 0.093 for ) and overall survival (mOS = 8.7 . 6.0 months, = 0.4 for and mOS = 7.2 . 6.2 months, = 0.13 for ). Genotyping analysis of five SNPs of genes showed a longer survival in patients harboring the wild-type genotype or the heterozygous variant of the rs11615 SNP ( = 0.24 for PFS and = 0.14 for OS) and of the rs13181 and rs1799793 SNPs ( = 0.43 and = 0.26 for PFS and = 0.21 and = 0.16 for OS, respectively) compared to patients with homozygous mutant genotypes.Conclusions:The comprehensive analysis of gene expression and SNP variants appears to identify patients who derive greater survival benefits from platinum-CT.

关键词： ERCC genes Nucleotide excision repair (NER) pathway Platinum-chemotherapy (CT) Single nucleotide polymorphisms (SNPs) Small cell lung cancer (SCLC)

Role of phosphoinositide 3-kinase in the pathogenesis of acute pancreatitis

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World Journal of Gastroenterology 2014年第41期20卷 15190-15199页

作者： enrico Lupia Luca Pigozzi alberto Goffi Emilio Hirsch Giuseppe Montrucchio Department of Medical Sciences University of Torino Emergency Medicine Unit "Città della Salute e della Scienza" Hospital Interdepartmental Division of Critical Care Medicine University of Toronto Molecular Biotechnology Center Department of Molecular Biotechnology and Health SciencesUniversity of Torino

A large body of experimental and clinical data supports the notion that inflammation in acute pancreatitis has a crucial role in the pathogenesis of local and systemic damage and is a major determinant of clinical severity. Thus, research has recently focused on molecules that can regulate the inflammatory processes, such as phosphoinositide 3-kinases (PI3Ks), a family of lipid and protein kinases involved in intracellular signal transduction. Studies using genetic ablation or pharmacologic inhibitors of different PI3K isoforms, in particular the class I PI3Kδ and PI3Kγ, have contributed to a greater understanding of the roles of these kinases in the modulation of inflammatory and immune responses. Recent data suggest that PI3Ks are also involved in the pathogenesis of acute pancreatitis. Activation of the PI3K signaling pathway, and in particular of the class IB PI3Kγ isoform, has a significant role in those events which are necessary for the initiation of acute pancreatic injury, namely calcium signaling alteration, trypsinogen activation, and nuclear factor-κB transcription. Moreover, PI3Kγ is instrumental in modulating acinar cell apoptosis, and regulating local neutrophil infiltration and systemic inflammatory responses during the course of experimental acute pancreatitis. The availability of PI3K inhibitors selective for specific isoforms may provide new valuable therapeutic strategies to improve the clinical course of this disease. This article presents a brief summary of PI3K structure and function, and highlights recent advances that implicate PI3Ks in the pathogenesis of acute pancreatitis.

关键词： Phosphoinositide 3-kinase Cell signaling Inflammation Pathogenesis Acute pancreatitis

Experimental rigs for testing components of advanced industrial applications

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Friction 2019年第1期7卷 59-73页

作者： enrico CIULLI Department of Civil and Industrial Engineering University of Pisa

This paper presents experimental rigs of the Research Centre for the Mechanics of Turbomachinery of the Department of Civil and Industrial Engineering of the University of Pisa. Most of them were designed and constructed to allow investigations of real machine components and to furnish more realistic results than basic tribological test rigs. Tilting pad journal bearings, as well as gears and complete gearboxes for advanced industrial applications, can be tested using the rigs described in the paper. A novel test rig with a power rating of approximately 1 MW allows investigations of the static and dynamic characteristics of high-performance tilting pad journal bearings for turbomachinery. A twin disc machine and closed loop gear test rig are used to investigate the different kinds of wear mechanisms occurring in gears. Functional and durability tests on planetary gearboxes for new turbo-fan engines could be performed using another novel large test rig. A circulating power configuration was adopted for most of the rigs so that only the power needed to cover the friction losses has to be supplied, while the circulating power can be more than 20 times higher. All the test rigs include very complex load applications and lubrication plants, as well as dedicated control and data acquisition systems. The rigs and related plants were designed and constructed through strong and fruitful collaborations between the university and some large and small–medium companies. Despite some limitations in the publication of the results as a result of the industrial sensitivity of the data, the synergy among these different actors was stimulating and fundamental for the realization of new advanced industrial applications.

关键词： experimental rigs tilting pad journal bearings twin disc machine gears gearboxes

PtRu nanoparticles supported on noble carbons for ethanol electrooxidation

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Journal of Energy Chemistry 2022年第3期31卷 168-180,I0006页

作者： alberto Rodríguez-Gómez enrico Lepre Luz Sánchez-Silva Nieves López-Salas Ana Raquel de la Osa Faculty of Chemical Sciences and Technologies University of Castilla-La ManchaEnrique Costa Novella Building.Avda.Camilo Jose Cela1213071 Ciudad RealSpain Colloid Chemistry Department Max Planck Institute of Colloids and InterfacesAm Mühlenberg 114476 PotsdamGermany

In this work,three cytosine derived nitrogen doped carbonaceous materials(noble carbons,NCs)with different atomic C/N ratios and porous networks have been synthesized and used as supports for Pt Ru electrocatalysts in the ethanol oxidation reaction(EOR)for clean hydrogen ***,the metal phase and the carbon support play critical roles in the electrocatalysts final *** NPs size distribution was obtained over supports with low atomic C/N ratios(i.e.,4 and 6)and defined porosity(i.e.,1701 m^(2)g^(-1)for Pt Ru/CNZ and 1834 m^(2)g^(-1)for Pt Ru/CLZ,respectively).In contrast,a lower C/N ratio and poor porous network(i.e.,65 m^(2)g^(-1),Pt Ru/CLK)led to the largest particle size and fostered an increase of the alloying degree between Pt and Ru NPs(i.e.,3%for C/N~6 and 28%for C/N~3).Electrochemical active surface area was found to increase with decreasing NPs size and the alloy extent,due to a higher availability of Pt active *** degradation tests showed that Pt Ru/NCs outperform similar to Pt Ru NPs on commercial carbon pointing at the stabilizing effect of *** Ru/CNZ exhibited the best electrochemical performance(i.e.,69.1 m A mgPt-1),outperforming Pt Ru/CLZ and Pt Ru/CLK by3-and 9-fold,respectively,due to a suitable compromise between particle sizes,degree of alloy,textural properties and elemental *** anodes were scaled-up to a proton exchange membrane cell and Pt Ru/CNZ was proved to provide the best electrocatalytic activity(262 m A cm^(-2)and low energy requirements),matching the values obtained by the state of the art of EOR electrocatalysts.

关键词： Noble carbon Cytosine H2 production Ethanol electrooxidation PtRu anode PEM cell