Publications by authors named "Francesco Valentini"

14 Publications

  • Page 1 of 1

Gut microbiota composition in children with obstructive sleep apnoea syndrome: a pilot study.

Sleep Med 2020 12 17;76:140-147. Epub 2020 Oct 17.

Pediatric Sleep Disease Center, Child Neurology, NESMOS Dept, School of Medicine and Psychology, Sapienza University of Rome, S. Andrea Hospital, Rome, Italy. Electronic address:

Background: Obstructive Sleep Apnoea syndrome (OSAS) is considered a systemic inflammatory disease and is characterized by intermittent hypoxia that can damage the integrity of intestinal barrier and alter gut microbiota composition in adults and animal models. To date there is only one study on snoring children and microbiota but no studies are present on paediatric OSAS related dysbiosis.

Study Objectives: To evaluate gut microbiota composition in OSAS children in respect to healthy subjects and investigate the role of sleep parameters in changing gut microbiome.

Methods: Sixteen children divided in OSAS and healthy groups. Stool samples were collected from both the two groups to assess gut microbiota composition using 16S rRNA sequencing and a nocturnal pulsossimetry and polysomnography were performed in OSAS children.

Results: OSAS children showed a decreased microbial diversity in respect to healthy subjects in terms of number of observed species and Chao1 index (p = 0,01). Firmicutes/Bacteroidetes ratio was directly correlated to Sleep Clinical Record (p = 0,03). The abundance of several inflammation-related strains (Proteobacteria, Clostridiaceae, Oscillospiraceae, Klebsiella) were found significantly modified in relation to sleep parameters. Bacteria implied in the gut barrier integrity (Desulfovibrionaceae, Bacteroides fragilis and Faecalibacterium prausnitzii) were found significantly different in the two study groups and correlated with sleep parameters.

Conclusions: OSAS children showed a lower microbiota diversity in respect to heathy subjects and an increase of inflammation and gut barrier disruptors-related strains probably induced by intermittent hypoxia. Further studies should be conducted to understand the role of gut microbiota in OSAS physiopathology and comorbidities in children.
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http://dx.doi.org/10.1016/j.sleep.2020.10.017DOI Listing
December 2020

An overview of deregulated lipid metabolism in nonalcoholic fatty liver disease with special focus on lysosomal acid lipase.

Am J Physiol Gastrointest Liver Physiol 2020 10 19;319(4):G469-G480. Epub 2020 Aug 19.

Unit of Internal Medicine and Hepatology, University Campus Bio-Medico, Rome, Italy.

Obesity and type 2 diabetes are frequently complicated by excess fat accumulation in the liver, which is known as nonalcoholic fatty liver disease (NAFLD). In this context, liver steatosis develops as a result of the deregulation of pathways controlling de novo lipogenesis and fat catabolism. Recent evidences suggest the clinical relevance of a reduction in the activity of lysosomal acid lipase (LAL), which is a key enzyme for intracellular fat disposal, in patients with NAFLD. In this review, we provided a comprehensive overview of the critical steps in hepatic fat metabolism and alterations in these pathways in NAFLD, with a special focus on lipophagy and LAL activity. During NAFLD, hepatic fat metabolism is impaired at several levels, which is significantly contributed to by impaired lipophagy, in which reduced LAL activity may play an important role. For further research and intervention in NAFLD, targeting LAL activity may provide interesting perspectives.
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http://dx.doi.org/10.1152/ajpgi.00049.2020DOI Listing
October 2020

Lipophagy Impairment Is Associated With Disease Progression in NAFLD.

Front Physiol 2020 17;11:850. Epub 2020 Jul 17.

Internal Medicine, Geriatrics, and Hepatology Unit, University Campus Bio-Medico, Rome, Italy.

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in Western countries and is associated with aging and features of metabolic syndrome. Lipotoxicity and oxidative stress are consequent to dysregulation of lipid metabolism and lipid accumulation, leading to hepatocyte injury and inflammation. Lipophagy consists in selective degradation of intracellular lipid droplets by lysosome and mounting evidence suggests that lipophagy is dysregulated in NAFLD. Here we demonstrate lipophagy impairment in experimental models of NAFLD and in a NAFLD patient cohort by histomorphological and molecular analysis. High fat diet-fed C57BL/6J male mice and high-fat/high-glucose cultured Huh7 cells showed accumulation of both p62/SQSTM1 and LC3-II protein. In 59 NAFLD patients, lipid droplet-loaded lysosomes/lipolysosomes and p62/SQSTM1 clusters correlated with NAFLD activity score (NAS) and with NAS and fibrosis stage, respectively, and levels of expression of lysosomal genes, as well as autophagy-related genes, correlated with NAS and fibrosis stage. An increased amount of lipid droplets, lipolysosomes and autophagosomes was found in subjects with NAFLD compared to healthy subjects at ultrastructural level. In conclusion, here we observed that NAFLD is characterized by histological, ultrastructural and molecular features of altered autophagy that is associated with an impaired lipid degradation. Impaired autophagy is associated with features of advanced disease. Lipopolysosomes, as individuated with light microscopy, should be further assessed as markers of disease severity in NAFLD patients.
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http://dx.doi.org/10.3389/fphys.2020.00850DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7380071PMC
July 2020

Turbulence-Driven Ion Beams in the Magnetospheric Kelvin-Helmholtz Instability.

Phys Rev Lett 2019 Jan;122(3):035102

Swedish Institute of Space Physics, Uppsala SE-751 05, Sweden.

The description of the local turbulent energy transfer and the high-resolution ion distributions measured by the Magnetospheric Multiscale mission together provide a formidable tool to explore the cross-scale connection between the fluid-scale energy cascade and plasma processes at subion scales. When the small-scale energy transfer is dominated by Alfvénic, correlated velocity, and magnetic field fluctuations, beams of accelerated particles are more likely observed. Here, for the first time, we report observations suggesting the nonlinear wave-particle interaction as one possible mechanism for the energy dissipation in space plasmas.
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http://dx.doi.org/10.1103/PhysRevLett.122.035102DOI Listing
January 2019

Combining Genetic Variants to Improve Risk Prediction for NAFLD and Its Progression to Cirrhosis: A Proof of Concept Study.

Can J Gastroenterol Hepatol 2018 14;2018:7564835. Epub 2018 Mar 14.

Internal Medicine, Geriatrics, and Hepatology Unit, University Campus Bio-Medico, Rome, Italy.

Background & Aims: Identifying NAFLD patients at risk of progression is crucial to orient medical care and resources. We aimed to verify if the effects determined by different single nucleotide polymorphisms (SNPs) could add up to multiply the risk of NAFLD and NASH-cirrhosis.

Methods: Three study populations, that is, patients diagnosed with NASH-cirrhosis or with noncirrhotic NAFLD and healthy controls, were enrolled. PNPLA3 rs738409, TM6SF2 rs58542926, KLF6 rs3750861, SOD2 rs4880, and LPIN1 rs13412852 were genotyped.

Results: One hundred and seven NASH-cirrhotics, 93 noncirrhotic NAFLD, and 90 controls were enrolled. At least one difference in allele frequency between groups was significant, or nearly significant, for the PNPLA3, TM6SF2, and KLF6 variants ( < 0.001, < 0.05, and = 0.06, resp.), and a risk score based on these SNPs was generated. No differences were observed for SOD2 and LPIN1 SNPs. When compared to a score of 0, a score of 1-2 quadrupled, and a score of 3-4 increased 20-fold the risk of noncirrhotic NAFLD; a score of 3-4 quadrupled the risk of NASH-cirrhosis.

Conclusions: The effects determined by disease-associated variants at different can add up to multiply the risk of NAFLD and NASH-cirrhosis. Combining different disease-associated variants may represent the way for genetics to keep strength in NAFLD diagnostics.
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http://dx.doi.org/10.1155/2018/7564835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5872672PMC
March 2019

Impairment of GH/IGF-1 Axis in the Liver of Patients with HCV-Related Chronic Hepatitis.

Horm Metab Res 2018 02 18;50(2):145-151. Epub 2017 Sep 18.

Unit of Microscopic and Ultrastructural Anatomy, University Campus Bio-Medico, Rome, Italy.

Resistance to the action of growth hormone (GH) frequently complicates liver cirrhosis, while, physiologically, the activation of GH receptor (GHR) determines phosphorylation of signal transducer and activator of transcription (STAT)-5 and the consequent induction of insulin-like growth factor-1 (IGF-1) expression. The suppressor of cytokine signaling (SOCS)-3 negatively regulates this intracellular cascade. We aimed to evaluate the hepatic expression of the GH/IGF-1 axis components in the liver of patients with HCV-related chronic hepatitis at different fibrosis stages. The expression of GH/IGF-1 axis components, such as GHR, IGF-1, STAT5-p, and SOCS-3, was assessed by immunohistochemistry at the lobular level in 61 patients with HCV-related hepatitis. At the hepatocyte level, IGF-1 and nuclear STAT5-p positivity scores showed negative correlations with fibrosis stage, while SOCS-3 score a positive one (p<0.05 for all). Furthermore, the reduction of hepatocyte score of IGF-1 expression was associated with the serological parameters of liver damage (p<0.05) and with the increase of the score of IGF-1 expression by hepatic stellate cells (p<0.05). IGF-1 expression by hepatocytes was reduced with fibrosis progression, probably due to the impairment of GHR intracellular cascade by the SOCS-3 activation already in pre-cirrhotic stages. The inverse correlation between IGF-1 expressed by hepatocytes and by hepatic stellate cells suggests that IGF-1 may exert specific functions in different hepatic cells.
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http://dx.doi.org/10.1055/s-0043-118911DOI Listing
February 2018

Platelet count may impact on lysosomal acid lipase activity determination in dried blood spot.

Clin Biochem 2017 Aug 24;50(12):726-728. Epub 2017 Feb 24.

Internal Medicine and Hepatology Unit, University Campus Bio-Medico, Rome, Italy.

Background: We aimed to evaluate the influence of white blood cell (WBC) and platelet (PLT) counts on dried blood spot (DBS)-determined lysosomal acid lipase (LAL) activity in a large group of healthy subjects.

Methods: One-hundred-and-seventy-two healthy subjects aged ≥18 were enrolled. Complete clinical biochemistry and LAL activity in DBS were determined. In 35 subjects, WBCs and PLTs were isolated, and LAL activity was measured in both blood cell populations. Univariate and multivariate analyses to DBS-LAL activity were performed.

Results: Mean age of subjects was 44.8±17.2years, 43.6% were males, and mean DBS-LAL activity was normal (1.0±0.3nmol/spot/h). LAL activity in WBCs was significantly higher than in PLTs (458.9±133.6 vs 235.0±88.3nmol/mg/h, p<0.001). However, LAL activity in DBS correlated more strongly with that in PLTs (r=0.65, p<0.001) than with that in WBCs (r=0.49, p<0.01). Consistently, in the multivariate model, DBS-LAL activity was independently associated only with PLT count (β=0.39, p<0.001).

Conclusions: PLT number may impact on the result of the DBS-LAL test, and a consideration of PLT count is recommended before interpreting LAL activity in DBS.
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http://dx.doi.org/10.1016/j.clinbiochem.2017.02.013DOI Listing
August 2017

Collisional Relaxation of Fine Velocity Structures in Plasmas.

Phys Rev Lett 2016 04 5;116(14):145001. Epub 2016 Apr 5.

Dipartimento di Fisica, Università della Calabria, 87036 Rende (CS), Italy.

The existence of several characteristic times during the collisional relaxation of fine velocity structures is investigated by means of Eulerian numerical simulations of a spatially homogeneous force-free weakly collisional plasma. The effect of smoothing out velocity gradients on the evolution of global quantities, such as temperature and entropy, is discussed, suggesting that plasma collisionality can locally increase due to velocity space deformations of the particle velocity distribution function. These results support the idea that high-resolution measurements of the particle velocity distribution function are crucial for an accurate description of weakly collisional systems, such as the solar wind, in order to answer relevant scientific questions, related, for example, to particle heating and energization.
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http://dx.doi.org/10.1103/PhysRevLett.116.145001DOI Listing
April 2016

Turbulent dynamo in a collisionless plasma.

Proc Natl Acad Sci U S A 2016 Apr 29;113(15):3950-3. Epub 2016 Mar 29.

Dipartimento di Fisica, Universitá della Calabria, I-87036 Rende (CS), Italy.

Magnetic fields pervade the entire universe and affect the formation and evolution of astrophysical systems from cosmological to planetary scales. The generation and dynamical amplification of extragalactic magnetic fields through cosmic times (up to microgauss levels reported in nearby galaxy clusters, near equipartition with kinetic energy of plasma motions, and on scales of at least tens of kiloparsecs) are major puzzles largely unconstrained by observations. A dynamo effect converting kinetic flow energy into magnetic energy is often invoked in that context; however, extragalactic plasmas are weakly collisional (as opposed to magnetohydrodynamic fluids), and whether magnetic field growth and sustainment through an efficient turbulent dynamo instability are possible in such plasmas is not established. Fully kinetic numerical simulations of the Vlasov equation in a 6D-phase space necessary to answer this question have, until recently, remained beyond computational capabilities. Here, we show by means of such simulations that magnetic field amplification by dynamo instability does occur in a stochastically driven, nonrelativistic subsonic flow of initially unmagnetized collisionless plasma. We also find that the dynamo self-accelerates and becomes entangled with kinetic instabilities as magnetization increases. The results suggest that such a plasma dynamo may be realizable in laboratory experiments, support the idea that intracluster medium turbulence may have significantly contributed to the amplification of cluster magnetic fields up to near-equipartition levels on a timescale shorter than the Hubble time, and emphasize the crucial role of multiscale kinetic physics in high-energy astrophysical plasmas.
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http://dx.doi.org/10.1073/pnas.1525194113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4839418PMC
April 2016

Mapping City Accessibility: Review and Analysis.

Stud Health Technol Inform 2015 ;217:325-31

CRAiS, Italy.

The paper presents an analysis of prototypes, studies, and applications for the mapping of city accessibility, focusing mainly on sidewalks accessibility. Moreover, it presents the results of two focus groups that we organized both with electric and with manual wheelchairs to attain requirements and insights to design a user-friendly app for the collection and visualization of information about the accessibility of urban pedestrian pathways.
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April 2017

New ion-wave path in the energy cascade.

Phys Rev Lett 2011 Apr 18;106(16):165002. Epub 2011 Apr 18.

Dipartimento di Fisica and CNISM, Università della Calabria, Rende (CS), Italy.

We present the results of kinetic numerical simulations that demonstrate the existence of a novel branch of electrostatic nonlinear waves driven by particle trapping processes. These waves have an acoustic-type dispersion with phase speed comparable to the ion thermal speed and would thus be heavily Landau damped in the linear regime. At variance with the ion-acoustic waves, this novel electrostatic branch can exist at a small but finite amplitude even for low values of the electron to ion temperature ratio. Our results provide a new interpretation of observations in space plasmas, where a significant level of electrostatic activity is observed in the high frequency region of the solar-wind turbulent spectra.
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http://dx.doi.org/10.1103/PhysRevLett.106.165002DOI Listing
April 2011

Electrostatic short-scale termination of solar-wind turbulence.

Phys Rev Lett 2009 Jun 1;102(22):225001. Epub 2009 Jun 1.

Dipartimento di Fisica and CNISM, Universitá della Calabria, 87036 Rende (CS), Italy.

Recent hybrid Vlasov simulations [F. Valentini, Phys. Rev. Lett. 101, 025006 (2008)10.1103/PhysRevLett.101.025006] have shown that the short-scale termination of solar-wind turbulence is characterized by the occurrence of longitudinal electrostatic fluctuations. Beside the ion-acoustic branch, in agreement with solar-wind observations, a novel branch of acoustic-like waves, with phase velocity close to the ion thermal speed, has been recovered in the simulations. In this Letter, we show that these waves turn out to be Bernstein-Greene-Kruskal-like solutions of the hybrid Vlasov-Maxwell equations, driven by kinetic effects of resonant particle trapping. We also discuss the development of the solar-wind turbulent spectra across the ion inertial length and especially stress the fact that turbulence privileges acoustic paths to develop towards short wavelengths.
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http://dx.doi.org/10.1103/PhysRevLett.102.225001DOI Listing
June 2009

Self-consistent Lagrangian study of nonlinear Landau damping.

Phys Rev E Stat Nonlin Soft Matter Phys 2005 Jan 10;71(1 Pt 2):017402. Epub 2005 Jan 10.

Dipartimento di Fisica, Istituto Nazionale di Fisica della Materia, Unità di Cosenza, Università della Calabria, I-87030 Arcavacata di Rende, Italy.

The electric field computed by numerically solving the one-dimensional Vlasov-Poisson system is used to calculate Lagrangian trajectories of particles in the wave-particle resonance region. The analysis of these trajectories shows that, when the initial amplitude of the electric field is above some threshold, two populations of particles are present: a first one located near the separatrix, which performs flights in the phase space and whose trajectories become ergodic and chaotic, and a second population of trapped particles, which displays a nonergodic dynamics. The complex, nonlinear interaction between these populations determines the oscillating long-time behavior of solutions.
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http://dx.doi.org/10.1103/PhysRevE.71.017402DOI Listing
January 2005