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Chitosan tubes enriched with fresh skeletal muscle fibers for delayed repair of peripheral nerve defects

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Neural Regeneration Research 2019年第6期14卷 1079-1084页

作者： AlessANDro Crosio Benedetta Elena Fornasari Giovanna Gambarotta Stefano Geuna Stefania Raimondo Bruno Battiston pierluigi Tos Giulia Ronchi Department of Orthopedics and Traumatology II-Surgery for Hand and Upper Limb-AOU Città della Salute e della Scienza di Torino-CTO Hospital Department of Clinical and Biological Sciences University of Torino Neuroscience Institute Cavalieri Ottolenghi University of Torino UO Microchirurgia e Chirurgia della Mano Ospedale Gaetano Pini

Nerve regeneration after delayed nerve repair is often unsuccessful. Indeed, the expression of genes associated with regeneration, including neurotrophic and gliotrophic factors, is drastically reduced in the distal stump of chronically transected nerves; moreover, Schwann cells undergo atrophy, losing their ability to sustain regeneration. In the present study, to provide a three-dimensional environment and trophic factors supporting Schwann cell activity and axon re-growth, we combined the use of an effective conduit(a chitosan tube) with a promising intraluminal structure(fresh longitudinal skeletal muscle fibers). This enriched conduit was used to repair a 10-mm rat median nerve gap after 3-month delay and functional and morphometrical analyses were performed 4 months after nerve reconstruction. Our data show that the enriched chitosan conduit is as effective as the hollow chitosan conduit in promoting nerve regeneration,and its efficacy is not statistically different from the autograft, considered the "gold standard" technique for nerve reconstruction. Since hollow tubes not always lead to good results after long defects(> 20 mm), we believe that the conduit enriched with fresh muscle fibers could be a promising strategy to repair longer gaps, as muscle fibers create a favorable three-dimensional environment and release trophic factors. All procedures were approved by the Bioethical Committee of the University of Torino and by the Italian Ministry of Health(approval number: 864/2016/PR) on September 14, 2016.

关键词： tubulization Schwann cells scaffold tissue engineering nerve reconstruction morphometrical analyses grasping test secondary repair median nerve nerve regeneration

COVID-19 and pediatric fatty liver disease:Is there interplay?

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World Journal of Gastroenterology 2021年第22期27卷 3064-3072页

作者： Anna Di Sessa Francesca Lanzaro Sarah Zarrilli Vittorio Picone Stefano Guarino Emanuele Miraglia del Giudice pierluigi Marzuillo Department of Woman Childand General and Specialized SurgeryUniversity of Campania“Luigi Vanvitelli”Naples 80138Italy

The rapid global spread of coronavirus disease 2019(COVID-19)infection has become a major health issue with higher morbidity and mortality *** respiratory symptoms,a growing body of evidence indicates a variety of gastrointestinal manifestations including liver *** this regard,several data supported an association between COVID-19 infection and liver injury in adults,while in children there is compelling but currently limited *** particular,patients with COVID-19 have shown a higher risk of liver injury(mainly expressed as increased transaminase levels or hepatic steatosis).Conversely,a greater risk of more severe forms of COVID-19 infection has been observed in subjects with pre-existing chronic liver *** dramatic interplay between COVID-19 and liver damage has been related to the inflammatory pathways chronically active in patients with nonalcoholic fatty liver disease and acutely in those affected by COVID-19,but other different pathogenic mechanisms have also been *** note,patients with previous metabolic comorbidities also had a higher risk of severe COVID-19 *** emphasizes the pathogenic interrelation of the inflammatory pathways with a dysregulated metabolic milieu in COVID-19 *** into account the prognostic role of fatty liver in COVID-19 patients and its intrinsic relationship with metabolic abnormalities even in childhood,a strict monitoring of this condition is *** aimed to summarize the most recent evidence regarding the potential interplay between pediatric fatty liver and COVID-19.

关键词： COVID-19 Children Adults Nonalcoholic fatty liver disease

Novel mutation in the ligand-binding domain of the androgen receptor gene （1790p） associated with complete androgen insensitivity syndrome

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Asian Journal of Andrology 2008年第4期10卷 687-691页

作者： Florina Raicu Rossella Giuliani Valentina Gatta Chiara Palka Paolo Guanciali Franchi pierluigi Lelli-Chiesa Stefano Tumini Liborio Stuppia Department of Clinical Sciences and Imaging G. d^t Annunzio University Foundation Chieti-Pescara 66013 Italy Department of Biomedical Sciences G. d^t Annunzio University Foundation Chieti-Pescara 66013 Italy Aging Research Center G. d^t Annunzio University Foundation Chieti-Pescara 66013 Italy Division of Pediatric Surgery G. d^t Annunzio University Foundation Chieti-Pescara 66013 Italy Department of Pediatrics and Gynecology G. d^t Annunzio University Foundation Chieti-Pescara 66013 Italy Institute of Molecular Genetics National Research Council IGM-CNR Bologna 40100 Italy Carol Davila University of Medicine and Pharmacy Bucharest 020027 Romania

Mutations in the X-linked androgen receptor （AR） gene cause androgen insensitivity syndrome （AIS）, resulting in an impaired embryonic sex differentiation in 46,XY genetic men. Complete androgen insensitivity （CAIS） produces a female external phenotype, whereas cases with partial androgen insensitivity （PALS） have various ambiguities of the genitalia. Mild androgen insensitivity （MAIS） is characterized by undermasculinization and gynecomastia. Here we describe a 2-month-old 46,XY female patient, with all of the characteristics of CAIS. Defects in testosterone （T） and dihydrotestosterone （DHT） synthesis were excluded. Sequencing of the AR gene showed the presence in exon 6 of a T to C transition in the second base of codon 790, nucleotide position 2369, causing a novel missense Leu790Pro mutation in the ligand-binding domain of the AR protein. The identification of a novel AR mutation in a girl with CAIS provides significant information due to the importance of missense mutations in the ligand-binding domain of the AR, which are able to induce functional abnormalities in the androgen binding capability, stabilization of active conformation, or interaction with coactivators.

关键词： androgen receptor novel androgen receptor gene mutation complete androgen insensitivity syndrome

Orographic Effects on Extreme Rainfall at Different Durations: A Case Study in Campania Region (Southern Italy)

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Journal of Geoscience and Environment Protection 2018年第11期6卷 77-88页

作者： pierluigi Furcolo Anna Pelosi Department of Civil Engineering University of Salerno Fisciano (SA) Italy

Long-term probabilistic prediction of extreme rainfall at the regional scale is a significant tool in the mitigation of hydro-geological disasters: it actually provides the starting point in the design of strategic hydraulic infrastructures and emergency plans. A crucial task of regional estimation of extreme rainfall is how to include the complex effects of orographic barriers in a mathematical model for Intensity-Duration-Frequency (IDF) curves. Here, an analysis of how orography can affect extreme rainfall at different durations is presented for three orographic systems that are very relevant for hydrological risk assessment in the Campania Region in Southern Italy. Then, we introduce a power law model to link the amplification factor to the duration, thus allowing a simple and effective enhancement of the IDF model in mountainous areas.

关键词： Orography Extreme Rainfall Regional Models Orographic Amplification IDF Curves

Omics era in type 2 diabetes:From childhood to adulthood

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World Journal of Diabetes 2021年第12期12卷 2027-2035页

作者： Antonio Paride Passaro pierluigi Marzuillo Stefano Guarino Federica Scaglione Emanuele Miraglia del Giudice Anna Di Sessa Department of Woman Child and of General and Specialized SurgeryUniversitàdegli Studi della Campania“Luigi Vanvitelli”Napoli 80138Italy

Parallel to the dramatic rise of pediatric obesity, estimates reported an increasedprevalence of type 2 diabetes (T2D) already in childhood. The close relationshipbetween obesity and T2D in children is mainly sustained by insulin resistance(IR). In addition, the cardiometabolic burden of T2D including nonalcoholic fattyliver disease, cardiovascular disease and metabolic syndrome is also strictlyrelated to IR. Although T2D pathophysiology has been largely studied in anattempt to improve therapeutic options, molecular mechanisms are still not fullyelucidated. In this perspective, omics approaches (including lipidomics,metabolomics, proteomics and metagenomics) are providing the most attractivetherapeutic options for T2D. In particular, distinct both lipids and metabolites areemerging as potential therapeutic tools. Of note, among lipid classes, thepathogenic role of ceramides in T2D context has been supported by several ***, selective changes of ceramides expression might represent innovativetherapeutic strategies for T2D treatment. More, distinct metabolomics pathwayshave been also found to be associated with higher T2D risk, by providing novelpotential T2D biomarkers. Taken together, omics data are responsible for theexpanding knowledge of T2D pathophysiology, by providing novel insights toimprove therapeutic strategies for this tangled disease. We aimed to summarizethe most recent evidence in the intriguing field of the omics approaches in T2Dboth in adults and children.

关键词： Omics Diabetes Children Adults Type 2 diabetes

Relationship between nonalcoholic fatty liver disease and chronic kidney disease could start in childhood

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World Journal of Gastroenterology 2021年第34期27卷 5793-5795页

作者： Anna Di Sessa Stefano Guarino Rosa Melone Rossella Francesca De Simone pierluigi Marzuillo Emanuele Miraglia del Giudice Department of Woman Childand General and Specialized SurgeryUniversity of Campania Luigi VanvitelliNaples 80138Italy

The relationship between nonalcoholic fatty liver disease(NAFLD)and chronic kidney disease(CKD)has gained considerable scientific interest in adults over the past few ***,this association has recently emerged in *** published studies have suggested a role for NAFLD as a risk factor for CKD from the earliest age,with a potential influence of the major NAFLD risk polymorphisms,resulting in an increased risk of both cardiovascular and metabolic *** view of the progressive course and increased cardiometabolic risk closely related to NAFLD and CKD,we focused on the link between these diseases in childhood.

关键词： Nonalcoholic fatty liver disease Chronic kidney disease Children Liver

Telemedicine in the COVID-19 era:Taking care of children with obesity and diabetes mellitus

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World Journal of Diabetes 2021年第5期12卷 651-657页

作者： Giuseppina Rosaria Umano Anna Di Sessa Stefano Guarino Giuseppina Gaudino pierluigi Marzuillo Emanuele Miraglia del Giudice Department of Woman Childand of General and Specialized SurgeryUniversity of Campania“Luigi Vanvitelli”Naples 80138Italy

Severe acute respiratory syndrome coronavirus 2 infection was declared a pandemic in January *** then,several measures to limit virus transmission have been imposed;among them,home confinement has been the most severe,with drastic changes in the daily routines of the general ***“stay at home”rule has impaired healthcare service access,and patients with chronic conditions were the most exposed to the negative effects of this *** is strong evidence of the worsening of obesity and diabetes mellitus in children during this *** overcome these issues,healthcare providers have changed their clinical practice to ensure follow-up visits and medical consultation though the use of ***,including telephone calls,videocalls,data platforms of shared telemedicine data platforms mitigated the negative effect of pandemic *** evidence has documented good metabolic control and weight management outcomes in centers that performed extensive telemedicine services last year during the *** review discusses studies that investigated the use of telemedicine tools for the management of pediatric obesity and diabetes.

关键词： COVID-19 Pandemic Children and adolescents Obesity Diabetes Telemedicine

Dehydrated patient without clinically evident cause:A case report

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World Journal of Clinical Cases 2020年第20期8卷 4838-4843页

作者： Federica Palladino Maria Cristina Fedele Marianna Casertano Laura Liguori Tiziana Esposito Stefano Guarino Emanuele Miraglia del Giudice pierluigi Marzuillo Department of Woman Child and of General and Specialized SurgeryUniversitàdegli Studi della Campania“Luigi Vanvitelli”Naples 80138Italy

BACKGROUND Patients affected by cystic fibrosis can present with metabolic alkalosis such as Bartter's *** this case report we want to underline this differential diagnosis and we aimed focusing on the suspect of cystic fibrosis,also in case of a negative newborn *** SUMMARY In a hot August–with a mean environmental temperature of 36℃–an 8-mo-old female patient presented with severe dehydration complicated by hypokalemic metabolic alkalosis,in absence of fever,diarrhea and *** diagnosis between cystic fibrosis and tubulopathies causing metabolic alkalosis(Bartter's Syndrome)was *** started intravenous rehydration with subsequent improvement of clinical conditions and serum electrolytes *** diagnosed a mild form of cystic fibrosis(heterozygous mutations:G126 D and F508 del in the cystic fibrosis transmembrane conductance regulator gene).The trigger factor of this condition had been heat *** When facing a patient with hypokalemic metabolic alkalosis,cystic fibrosis presenting with Pseudo-Bartter's syndrome should be considered in the differential diagnosis,even if the newborn screening was negative.

关键词： Metabolic alkalosis Dehydration Cystic fibrosis Pseudo-Bartter syndrome Heat exposure Children Case report

Liver decompensation predicts ribavirin overexposure in hepatitis C virus patients treated with direct-acting antivirals

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World Journal of Hepatology 2017年第34期9卷 1270-1277页

作者： Viola Guardigni Lorenzo Badia Matteo Conti Matteo Rinaldi Rita Mancini pierluigi Viale Gabriella Verucchi Department of Medical and Surgical Sciences University of Bologna S.Orsola-Malpighi Hospital Research Centre for the Study of Hepatitis University of Bologna Metropolitan Laboratory Maggiore Hospital

AIM To determine whether ribavirin(RBV) concentrations differ according to cirrhosis stage among cirrhotic patients treated with interferon-free regimens. METHODS We included patients with hepatitis C virus and cirrhosis [Child-Pugh(CP) A or B], Glomerular Filtration Rate ≥ 60 mL/min, who started therapy with DAAs and weightbased RBV between October 2014 and February 2016. RBV plasma levels were assessed during the treatment. We focused our analysis on the first 8 wk of therapy. RESULTS We studied 68 patients: 54 with compensated(CP-B) and 14 with decompensated(CP-A) cirrhosis. Patients withdecompensated cirrhosis displayed significantly higher RBV concentrations than those with compensated cirrhosis at week 1, 2, 4 and 8(P < 0.035). RBV levels were positively correlated with Hb loss over the treatment(P < 0.04). Majority(71%) of CP-B patients required a RBV dosage reduction during the treatment. After adjustment for confounders, Child-Pugh class remained significantly associated(95%CI: 35, 348, P = 0.017) to RBV levels, independently from baseline per-Kg RBV dosage. CONCLUSION Liver decompensation might affect RBV clearance leading to an overexposure and increased related toxicities in decompensated cirrhosis. Our findings underscore the importance of an early ribavirin therapeutic drug monitoring and suggest that an initial lower RBV dose, rather than weight-based, might be considered in those with advanced liver disease(CP-B) treated with directacting antivirals.

关键词：丙肝直接行动的 antivirals Ribavirin 监视的治疗学的药患心脏代偿失调的肝硬化