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Practical insights into chronic management of hepatic Wilson’s disease

World Journal of Clinical Cases 2022年第14期10卷 4334-4347页

作者： Erica Nicola Lynch Claudia Campani Tommaso Innocenti Gabriele Dragoni paolo forte Andrea Galli Gastroenterology Research Unit Department of Experimental and Clinical Biomedical Sciences“Mario Serio”University of FlorenceFlorence 50134Italy Department of Experimental and Clinical Medicine University of FlorenceFlorence 50134Italy Department of Medical Biotechnologies University of SienaSiena 53100Italy Division of Gastroenterology University Hospital“Careggi”Florence 50134Italy

Wilson’s disease(WD)is a rare inherited disorder of human copper metabolism,with an estimated prevalence of 1:30000-1:50000 and a broad spectrum of hepatic and neuropsychiatric *** healthy individuals,the bile is the main route of elimination of *** WD patients,copper accumulates in the liver,it is released into the bloodstream,and is excreted in *** can also be accumulated in the brain,kidneys,heart,and osseous matter and causes damage due to direct toxicity or oxidative *** WD is commonly but not exclusively diagnosed in childhood or young ***,non-cirrhotic WD patients seem to have a normal life ***,chronic management of patients with Wilson’s disease is challenging,as available biochemical tests have many limitations and do not allow a clear identification of non-compliance,overtreatment,or treatment *** provide optimal care,clinicians should have a complete understanding of these limitations and counterbalance them with a thorough clinical *** aim of this review is to provide clinicians with practical tools and suggestions which may answer doubts that can arise during chronic management of patients with hepatic *** particular,it summarises current knowledge on Wilson’s disease clinical and biochemical monitoring and *** also analyses available evidence on pregnancy and the role of low-copper diet in *** research should focus on trying to provide new copper metabolism tests which could help to guide treatment adjustments.

关键词： Wilson’s disease Urinary copper excretion Non-ceruloplasmin-bound copper D-penicillamine Trientine Zinc salts

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Understanding fatigue in primary biliary cholangitis:From pathophysiology to treatment perspectives

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World Journal of Hepatology 2022年第6期14卷 1111-1119页

作者： Erica Nicola Lynch Claudia Campani Tommaso Innocenti Gabriele Dragoni Maria Rosa Biagini paolo forte Andrea Galli Gastroenterology Research Unit Department of Experimental and Clinical Biomedical Sciences“Mario Serio”University of FlorenceFlorence 50134Italy Department of Experimental and Clinical Medicine University of FlorenceFlorence 50134Italy Department of Medical Biotechnologies University of SienaSiena 53100Italy Division of Gastroenterology University Hospital“Careggi”Florence 50134Italy

Fatigue is considered one of the most frequent and debilitating symptoms in primary biliary cholangitis(PBC),affecting over 50%of PBC *** in five patients with PBC suffer from severe fatigue,which significantly impairs quality of *** is made up of a central and a peripheral component,whose pathophysiology is still greatly *** fatigue is characterised by a lack of self-motivation and can manifest both in physical and mental activities(lack of intention).Peripheral fatigue includes neuromuscular dysfunction and muscle weakness(lack of ability).Peripheral fatigue could be explained by an excessive deviation from aerobic to anaerobic metabolism leading to excessive lactic acid accumulation and therefore accelerated decline in muscle function and prolonged recovery *** opposed to itching,and with the exception of endstage liver disease,fatigue is not related to disease *** objective of this review is to outline current understanding regarding the pathophysiology of fatigue,the role of comorbidities and contributing factors,the main tools for fatigue assessment,the failed therapeutic options,and future treatment perspectives for this disabling *** fatigue is an extremely common and debilitating symptom and there is still no licensed therapy for fatigue in PBC patients,further research is warranted to understand its causative mechanisms and to find an effective treatment.

关键词： Fatigue Primary biliary cholangitis Treatment Pathophysiology Central fatigue Peripheral fatigue

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Predictors of survival in patients with established cirrhosis and hepatocellular carcinoma treated with sorafenib

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World Journal of Gastroenterology 2014年第3期20卷 786-794页

作者： Andrea L Inghilesi Donatella Gallori Lorenzo Antonuzzo paolo forte Daniela Tomcikova Umberto Arena Stefano Colagrande Silvia Pradella Bernardo Fani Elena Gianni Luca Boni Giacomo Laffi Francesco Di Costanzo Fabio Marra Dipartimento di Medicina Sperimentale e Clinica Università degli Studi di Firenze Oncologia Medica Azienda Ospedaliero-Universitaria Careggi Gastroenterologia 2 Azienda Ospedaliero-Universitaria Careggi Centro per il Coordinamento delle Sperimentazioni Cliniche Istituto Toscano Tumoriand Azienda Ospedaliero-Universitaria Careggi Dipartimento di Scienze Biomediche Sperimentali e ClinicheUniversità degli Studi di Firenze

AIM: To investigate in greater detail the efficacy and safety of sorafenib for the treatment of hepatocellular carcinoma (HCC) in patients with established cirrhosis.

关键词： Hepatocellular carcinoma Sorafenib Cirrhosis Adverse events Barcelona Clinic Liver Cancer

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Clinical epidemiology of chronic viral hepatitis B:A Tuscany real-world large-scale cohort study

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World Journal of Hepatology 2018年第5期10卷 409-416页

作者： Cristina Stasi Caterina Silvestri Roberto Berni Maurizia Rossana Brunetto Anna Linda Zignego Cristina Orsini Stefano Milani Liana Ricciardi Andrea De Luca Pierluigi Blanc Cesira Nencioni Donatella Aquilini Alessandro Bartoloni Giampaolo Bresci Santino Marchi Franco Filipponi Piero Colombatto paolo forte Andrea Galli Sauro Luchi Silvia Chigiotti Alessandro Nerli Giampaolo Corti Rodolfo Sacco Paola Carrai Angelo Ricchiuti Massimo Giusti paolo Almi Andrea Cozzi Silvia Carloppi Giacomo Laffi Fabio Voller Francesco Cipriani Observatory of Epidemiology Regional Health Agency of TuscanyFlorence 50141Italy Center for Systemic Manifestations of Hepatitis Viruses(MaSVE) Internal Medicine and Liver UnitDepartment of Experimental and Clinical MedicineCareggi University HospitalFlorence 50134Italy Web Solutions Data Visualization and Scientific DocumentationRegional Health Agency of TuscanyFlorence 50141Italy Hepatology Unit Department of Clinical and Experimental MedicineUniversity Hospital of PisaPisa 56100Italy Gastroenterology Research Unit Department of Experimental and Clinical Biomedical Sciences“Mario Serio”Careggi University HospitalFlorence 50134Italy Infectious Disease Unit Hospital of LuccaLucca 55100Italy Infectious Diseases Unit Department of Medical BiotechnologiesSiena University HospitalSiena 53100Italy Infectious Disease Unit “S.Maria Annunziata”HospitalPonte a Niccheri 50012Italy Infectious Disease Unit Hospital of GrossetoGrosseto 58100Italy Infectious Disease Unit Hospital of PratoPrato 59100Italy Infectious and Tropical Diseases Unit Department of Experimental and Clinical MedicineCareggi University HospitalFlorence 50134Italy Gastroenterology and Metabolic Disorders Department of SurgeryCisanello University HospitalPisa 56100Italy Gastroenterology Unit Department of Translational Research and New Technologies in Medicine and SurgeryCisanello University Hospital of PisaPisa 56100Italy Liver Surgery and Transplantation Unit Department of Surgical PathologyMedicineMolecular and Critical AreaCisanello University HospitalPisa 56100Italy Internal Medicine Unit “San Jacopo”HospitalPistoia 51100Italy Infectious Diseases and Hepatology Unit Department of Internal and Specialized MedicineUniversity Hospital of SienaSiena 53100Italy Gastroenterology Unit San Giuseppe HospitalEmpoli 50053Italy Internal Medicine and Liver Unit Department of Experimental and Clinical MedicineCareggi University HospitalFlorence 50135Italy Department of Prevention Central Tuscany Local UnitFlorence 5

AIM To build a regional database of chronic patients to define the clinical epidemiology of hepatitis B virus(HBV)-infected patients in the Tuscan public health care *** This study used a cross-sectional cohort design. We evaluated chronic viral hepatitis patients with HBV referred to the outpatient services of 16 hospital units. Information in the case report forms included main demographic data, blood chemistry data, viral hepatitis markers, instrumental evaluations, and eligibility for treatment or ongoing therapy and liver transplantation. RESULTS Of 4015 chronic viral hepatitis patients, 1096(27.3%) were HBV infected. The case report form was correctly completed for only 833 patients(64% males, 36% females; mean age 50.1 ± 15.4). Of these HBV-infected patients, 73% were Caucasian, 21% Asian, 4% Central African, 1% North African and 1% American. Stratifying patients by age and nationality, we found that 21.7% of HBV-infected patients were aged < 34 years(only 2.8% were Italian). The most represented routes of transmission were nosocomial/dental procedures(23%), mother-to-child(17%) and sexual transmission(12%). The most represented HBV genotypes were D(72%) and A(14%). Of the patients, 24.7% of patients were HBe Ag positive, and 75.3% were HBe Ag negative. Of the HBV patients 7% were anti-HDV positive. In the whole cohort, 26.9% were cirrhotic(35.8% aged < 45 years), and 47% were eligible for or currently undergoing treatment, of whom 41.9 % were cirrhotic. CONCLUSION Only 27.3% of chronic viral hepatitis patients were HBV infected. Our results provide evidence of HBV infection in people aged < 34 years, especially in the foreign population not protected by vaccination. In our cohort of patients, liver cirrhosis was also found in young adults.

关键词： Hepatitis B virus infection Liver fibrosis Cirrhosis Public health Epidemiology

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Single-cell pan-omics, environmental neurology, and artificial intelligence:the time for holistic brain health research

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Neural Regeneration Research 2025年第6期20卷 1703-1704页

作者： paolo Abondio Francesco Bruno IRCCS Istituto delle Scienze Neurologiche di Bologna BolognaItaly Association for Neurogenetic Research(ARN) Lamezia TermeCatanzaroItaly

The brain,with its trillions of neural connections,different cellular types,and molecular complexities,presents a formidable challenge for researchers aiming to comprehend the multifaceted nature of neural *** traditional methods have provided valuable insights,emerging technologies offer unprecedented opportunities to delve deeper into the underpinnings of brain *** the everevolving landscape of neuroscience,the quest to unravel the mysteries of the human brain is bound to take a leap forward thanks to new technological improvements and bold interpretative frameworks.

关键词： function artificial landscape

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Inclusion of infrared dielectric screening in the GW method from polaron energies to charge mobilities

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npj Computational Materials 2022年第1期8卷 1300-1307页

作者： paolo Umari Dipartimento di Fisica e Astronomia Universitàdi Padovavia Marzolo 8I-35131PadovaItaly CNR-IOM Istituto Officina Dei Materiali Consiglio Nazionale Delle RicercheArea Science ParkStrada Statale 14km 163.5I-34149TriesteItaly

We introduce in the many-body GW scheme the modulation of the screened Coulomb interaction W arising from the macroscopic dielectric response in the *** derive expressions for the polaron binding energies,the renormalization of the effective masses and for the electron and hole relaxation *** and hole mobilities are then obtained from the incorporation of appropriate scattering ***-blende GaN and orthorhombic MAPbI3 are used as test beds finding fair agreement with results from rigorous electron-phonon coupling *** limited to polar phonons,our method has a negligible computational cost.

关键词： dielectric polaron negligible

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Optimal weakening and damping using polynomial control for seismically excited nonlinear structures

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Earthquake Engineering and Engineering Vibration 2009年第4期8卷 607-616页

作者： Gian paolo Cimellaro Department of Structural & Geotechnical Engineering(DISTR)

This paper presents an approach for the optimal design of a new retrofit technique called weakening and damping that is valid for civil engineering inelastic structures. An alternative design methodology is developed with respect to the existing ones that is able to determine the locations and the magnitude of weakening and/or softening of structural elements and adding damping while insuring structural stability. An optimal polynomial controller that is a summation of polynomials in nonlinear states is used in Phase I of the method to reduce the peak response quantities of seismically excited nonlinear or hysteretic systems. The main advantage of the optimal polynomial controller is that it is able to automatically stabilize the structural system. The optimal design of a shear-type structure is used as an example to illustrate the feasibility of the proposed approach, which leads to a reduction of both peak inter-story drifts and peak total accelerations.

关键词： weakening and damping optimal design optimal polynomial controller inter-story drift acceleration

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Does divergence from normal patterns of integration increase as chromosomal fusions increase in number?A test on a house mouse hybrid zone

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Current Zoology 2020年第5期66卷 527-538页

作者： Carmelo FRuciANO paolo Colangelo Riccardo Castiglia paolo Franchini Institut de Biologie de KEcole Normale Superieure(IBENS) Ecole Normale SuperieureCNRSPSL Universite ParisParis75005France School of Biological Sciences University of PortsmouthPortsmouthP012DYUK National Research Council Research Institute on Terrestrial EcosystemsMontelibretti(RM)00010Italy Department of Biology and Biotechnology"Charles Darwin" "La Sapienza"University of RomeRome00161Italy Department of Biology Lehrstuhl fiir Zoologie und EvolutionsbiologieUniversity of KonstanzKonstanz78457Germany

Chromosomal evolution is widely considered an important driver of speciation because it can promote the establishment of reproductive *** reorganization is also expected to affect the mea n phe no type,as well as its developme nt and patter ns of phenotypic in tegrati on,through processes such as variation in genetic linkage between quantitative trait loci or between regulatory regions and their *** we explore the relationship between chromosomal evolution and phenotypic integration by analyzing a well-known house mouse parapatric contact zone between a highly derived Robertsonian(Rb)race(2n=22)and populations with standard karyotype(2n=40).Populations with hybrid karyotypes are scattered throughout the hybrid zone connecting the two parental *** mandible shape data and geometric morphometries,we test the hypothesis that patter ns of in tegration progressively diverge from the"normal"integration pattern observed in the standard race as they accumulate Rb *** find that the main pattern of integration observed between the posterior and anterior part of the mandible can be largely attributed to *** find no support for a gradual increase in divergence from normal patterns of integration as fusions ***,however,we find that the derived Rb race(2n=22)has a distinct allometric trajectory compared with the standard *** results suggest that either individual fusions disproportionately affect patterns of integration or that there are mechanisms which"purge"extreme variants in hybrids(*** fitness of hybrid shape).

关键词： chromosomal races geometric morphometries hybrid zone integration modularity Robertsonian fusions

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Experiments and modeling of discharge characteristics in water-mist sprays generated by pressure-swirl atomizers

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Journal of Thermal Science 2012年第6期21卷 539-548页

作者： paolo E.Santangelo Department of Fire Protection Engineering University of Maryland3106 J.M.Patterson BuildingCollege ParkMD 20742USA

Pressure-swirl atomizers are often employed to generate a water-mist spray,typically employed in fire *** the present study,an experimental characterization of dispersion(velocity and cone angle)and atomization(drop-size axial evolution)was carried out following a previously developed methodology,with specific reference to the initial region of the ***-based techniques were used to quantitatively evaluate the considered phenomena:velocity field was reconstructed through a Particle Image Velocimetry analysis;drop-size distribution was measured by a Malvern Spraytec device,highlighting secondary atomization and subsequent coalescence along the spray ***,a comprehensive set of relations was validated as predictive of the involved parameters,following an inviscid-fluid *** proposed model pertains to early studies on pressure-swirl atomizers and primarily yields to determine both initial velocity and cone *** spray thickness is also predicted and a classic correlation for Sauter Mean Diameter is shown to provide good agreement with experimental *** analysis was carried out at the operative pressure of 80 bar;two injectors were employed featuring different orifice diameters and flow numbers,as a sort of parametric approach to this spray typology.

关键词： Water mist Pressure-swirl atomizers Atomization Velocity Cone angle

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Methodology and application of Escherichia coli F4 and F18 encoding infection models in post-weaning pigs

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Journal of Animal Science and Biotechnology 2019年第3期10卷 559-578页

作者： Diana Luise Charlotte Lauridsen paolo Bosi paolo Trevisi Department of Agricultural and Food Sciences (DISTAL) Alma Mater Studiorum-University of BolognaBolognaItaly Faculty of Science and Technology Department of Animal ScienceAarhus UniversityTjeleDenmark

The enterotoxigenic Escherichia coli (ETEC) expressing F4 and F18 fimbriae are the two main pathogens associated with post-weaning diarrhea (PWD) in *** growing global concern regarding antimicrobial resistance (AMR) has encouraged research into the development of nutritional and feeding strategies as well as vaccination protocols in order to counteract the PWD due to ETEC.A valid approach to researching effective strategies is to implement piglet in vivo challenge models with ETEC ***,the proper application and standardization of ETEC F4 and F18 challenge models represent an urgent *** current review provides an overview regarding the current piglet ETEC F4 and F18 challenge models;it highlights the key points for setting the challenge protocols and the most important indicators which should be included in research studies to verify the effectiveness of the ETEC *** on the current review,it is recommended that the setting of the model correctly assesses the choice and preconditioning of pigs,and the timing and dosage of the ETEC ***,the evaluation of the ETEC challenge response should include both clinical parameters (such as the occurrence of diarrhea,rectal temperature and bacterial fecal shedding) and biomarkers for the specific expression of ETEC F4/F18 (such as antibody production,specific F4/F18 immunoglobulins (lgs),ETEC F4/F18 fecal enumeration and analysis of the F4/F18 receptors expression in the intestinal brush borders).On the basis of the review,the piglets' response upon F4 or F18 inoculation differed in terms of the timing and intensity of the diarrhea development,on ETEC fecal shedding and in the piglets' immunological antibody *** information was considered to be relevant to correctly define the experimental protocol,the data recording and the sample *** challenge settings and evaluation of the response parameters will allow future research studies to comply w

关键词： Biomarkers Challenge ETEC Piglet Post-weaning

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