Publications by authors named "Chiara Cardelli"

10 Publications

  • Page 1 of 1

Real life picture of the use of intravenous immunoglobulins in idiopathic inflammatory myopathies: Results of a multicentric study.

Autoimmun Rev 2021 Mar 18;20(3):102757. Epub 2021 Jan 18.

Rheumatology Unit, Pisa University Hospital, Italy.

Background: despite the absence of specific guidelines, the treatment with intravenous immunoglobulins (IvIg) is considered effective in patients with refractory idiopathic inflammatory myopathies (IIM). The aim of our study is to evaluate the effectiveness and the safety of IvIg and define the possible profile of IIM patients candidate to IvIg treatment.

Methods: we performed a retrospective study of IIM pts. treated with IvIg (2 g/kg/month). We collected demographic, epidemiological, laboratory and clinical data. Additionally, to evaluate the toxicity, the adverse events occurred during the treatment were collected.

Results: 123 patients with IIM were included in the study. The main indications for the prescription of IvIg were muscle (83.7% of patients) and esophageal involvement (45.5% of patients). IvIg were started mainly for refractory disease. At the end of treatment (mean duration 14 months), muscular necrosis enzymes decreased significantly and dysphagia VAS decreased significantly (p < 0.001), while MMT value increased (104.6 ± 24.2 vs. 127.0 ± 22.2 p < 0.001). Ninety-six pts. (78%) responded to IvIg. They had a shorter disease duration (p < 0.001), higher creatine kinase levels (p < 0.001), and higher prevalence of myalgias at the baseline (p = 0.023) compared to non-responders. The presence of Raynaud's phenomenon (p = 0.023-odds ratio 0.28 [0.11-0.72]) and skin involvement (p = 0.004, odds ratio 0.18 [0.06-0.55]), were associated to a worse response. Adverse events were mostly mild and transitory.

Conclusions: Despite their high cost, IvIg confirmed their effectiveness in refractory IIM pts., particularly in muscular and esophageal manifestations. Specific clinical characteristics at the baseline may identify the patients with higher probability of response to the treatment.
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http://dx.doi.org/10.1016/j.autrev.2021.102757DOI Listing
March 2021

Impact of first wave of SARS-CoV-2 infection in patients with Systemic Lupus Erythematosus: Weighting the risk of infection and flare.

PLoS One 2021 13;16(1):e0245274. Epub 2021 Jan 13.

Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.

Introduction: The aim of this study was to investigate the incidence and clinical presentation of SARS-CoV-2 infections in a Systemic Lupus Erythematosus (SLE) cohort; to assess correlations with disease characteristics and rheumatic therapy; and to evaluate the occurrence of treatment discontinuation and its impact on disease activity.

Materials And Methods: SLE patients monitored by a single Italian centre were interviewed between February and July 2020. Patients were considered to be positive for SARS-CoV-2 infections in case of 1) positive nasopharyngeal swab; 2) positive serology associated with COVID19 suggesting symptoms. The following data were also recorded: clinical symptoms, adoption of social distancing measures, disease activity and treatment discontinuation.

Results: 332 patients were enrolled in the study. Six patients (1.8%) tested positive for SARS-CoV-2 infection, with the incidence being significantly higher in the subgroup of patients treated with biological Disease-Modifying Anti-Rheumatic Drugs (p = 0.005), while no difference was observed for other therapies, age at enrollment, disease duration, type of cumulative organ involvement or adoption of social isolation. The course of the disease was mild. Thirty-six patients (11.1%) discontinued at least part of their therapy during this time period, and 27 (8.1%) cases of disease flare were recorded. Correlation between flare and discontinuation of therapy was statistically significant (p<0.001). No significant increase of rate of flare in a subgroup of the same patients during 2020 was observed.

Conclusion: Treatment discontinuation seems to be an important cause of disease flare. Our findings suggest that abrupt drug withdrawal should be avoided or evaluated with caution on the basis of individual infection risk and comorbidities.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0245274PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806138PMC
January 2021

Protein design under competing conditions for the availability of amino acids.

Sci Rep 2020 02 14;10(1):2684. Epub 2020 Feb 14.

Center for Cooperative Research in Biomaterials (CIC biomaGUNE), Basque Research and Technology Alliance (BRTA), Paseo Miramon 182, 20014, San Sebastian, Spain.

Isolating the properties of proteins that allow them to convert sequence into the structure is a long-lasting biophysical problem. In particular, studies focused extensively on the effect of a reduced alphabet size on the folding properties. However, the natural alphabet is a compromise between versatility and optimisation of the available resources. Here, for the first time, we include the impact of the relative availability of the amino acids to extract from the 20 letters the core necessary for protein stability. We present a computational protein design scheme that involves the competition for resources between a protein and a potential interaction partner that, additionally, gives us the chance to investigate the effect of the reduced alphabet on protein-protein interactions. We devise a scheme that automatically identifies the optimal reduced set of letters for the design of the protein, and we observe that even alphabets reduced down to 4 letters allow for single protein folding. However, it is only with 6 letters that we achieve optimal folding, thus recovering experimental observations. Additionally, we notice that the binding between the protein and a potential interaction partner could not be avoided with the investigated reduced alphabets. Therefore, we suggest that aggregation could have been a driving force in the evolution of the large protein alphabet.
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http://dx.doi.org/10.1038/s41598-020-59401-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7021711PMC
February 2020

Identification of Protein Functional Regions.

Chemphyschem 2020 02 16;21(4):335-347. Epub 2020 Jan 16.

CIC biomaGUNE, Paseo Miramon 182, 20014 San Sebastian, Spain, and IKERBASQUE, Basque Foundation for Science, 48013, Bilbao, Spain.

Protein sequence stores the information relative to both functionality and stability, thus making it difficult to disentangle the two contributions. However, the identification of critical residues for function and stability has important implications for the mapping of the proteome interactions, as well as for many pharmaceutical applications, e. g. the identification of ligand binding regions for targeted pharmaceutical protein design. In this work, we propose a computational method to identify critical residues for protein functionality and stability and to further categorise them in strictly functional, structural and intermediate. We evaluate single site conservation and use Direct Coupling Analysis (DCA) to identify co-evolved residues both in natural and artificial evolution processes. We reproduce artificial evolution using protein design and base our approach on the hypothesis that artificial evolution in the absence of any functional constraint would exclusively lead to site conservation and co-evolution events of the structural type. Conversely, natural evolution intrinsically embeds both functional and structural information. By comparing the lists of conserved and co-evolved residues, outcomes of the analysis on natural and artificial evolution, we identify the functional residues without the need of any a priori knowledge of the biological role of the analysed protein.
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http://dx.doi.org/10.1002/cphc.201900898DOI Listing
February 2020

Assessment of swallowing function with oro-pharyngeal-esophageal scintigraphy in patients with idiopathic inflammatory myopathies.

Neurogastroenterol Motil 2019 07 23;31(7):e13599. Epub 2019 Apr 23.

Rheumatology Unit, University of Pisa, Pisa, Italy.

Background: Swallowing impairment is frequently present in patients with idiopathic inflammatory myopathies (IIMs), and it represents an important cause of morbidity, dramatically reducing the quality of life of patients. Moreover, dysphagia is associated to a worst prognosis. Unfortunately, no standardized instrumental techniques for the assessment of the upper gastrointestinal tract in IIM patients are available. In this study, we explored the characteristics of the alterations in the upper gastrointestinal tract using oro-pharyngeal-esophageal scintigraphy (OPES) in a cohort of IIM patients and we correlated the alterations with clinical parameters.

Methods: A total of 51 IIM patients were examined with OPES, both with liquids and semisolids, and the data acquired were examined to compute the transit time and the percentage of retention at oral, pharyngeal, and esophageal level. Patient-reported outcome data (PRO) on dysphagia, disease activity, and clinical parameters were collected.

Key Results: Oro-pharyngeal-esophageal scintigraphy identified at least one alteration in all patients, particularly with the semisolid test and oral and pharyngeal levels presented a higher frequency of involvement compared to the esophageal tract (P < 0.05). A very good correlation between dysphagia severity assessed by PRO and many OPES results was identified. In patients with a shorter disease duration, there was a higher prevalence of alterations at the oral and pharyngeal level and they were correlated to higher swallowing difficulties and higher disease activity parameters.

Conclusions & Inferences: Our results showed that OPES may represent a novel reproducible tool to assess dysphagia in IIM patients, thus opening new possibilities to evaluate dysphagia in these patients.
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http://dx.doi.org/10.1111/nmo.13599DOI Listing
July 2019

Design of Protein-Protein Binding Sites Suggests a Rationale for Naturally Occurring Contact Areas.

J Chem Theory Comput 2019 Feb 26;15(2):1383-1392. Epub 2018 Dec 26.

CIC biomaGUNE, Paseo Miramon 182 , 20014 San Sebastian , Spain.

Molecular recognition is a critical process for many biological functions and consists in noncovalent binding of different molecules, such as protein-protein, antigen-antibody, and many others. The host-guest molecules involved often show a shape complementarity, and one of the leading specifications for molecular recognition is that the interaction should ideally be specific, i.e. the host should strongly bind exclusively to one selected guest. Our work focuses on the role played by the chemical heterogeneity and the steric compatibility on the specificity power of the binding site between two proteins. We tackle the problem computationally, reducing the complexity of the system by simulating a protein and a surface-like element, that shapes part of the protein and represents the binding site of an interaction partner. We investigate four systems, differing in terms of binding site size. A significant result is that, despite the fact that protein and surface chemical sequences are interdependent and simultaneously generated to stabilize the bound folded structure, the protein is stable in the folded conformation even in the absence of the surface-like partner for all investigated systems. We observe that an increase of the surface area results in a significant increase of the binding affinity. Interestingly, our data suggest the presence of upper and lower limits for the maximum and minimum area size available for a binding site. Our data match the experimental observation of such limits (750-1500 Å ( Arkin and Wells Nat. Rev. Drug Discov. 2004 , 3 , 301 - 317 ) and provide a rationale for them: the extent of the binding site area is limited by the value of the binding constant. For large contact areas, at physiological conditions, the binding is orders of magnitude stronger ( K > 10 L/mol) than what is typically observed in natural biological processes. Conversely, the smallest surface tested is just the minimal size to allow for specific binding.
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http://dx.doi.org/10.1021/acs.jctc.8b00667DOI Listing
February 2019

Lipid tempering simulation of model biological membranes on parallel platforms.

Biochim Biophys Acta Biomembr 2018 Jul 1;1860(7):1480-1488. Epub 2018 May 1.

Chemistry Dept., University of Florence, Via Lastruccia 3, Sesto Fiorentino 50019, Italy. Electronic address:

In this report we have tested a parallel implementation for the simulation of lipid bilayers at the atomistic level, based on a generalized ensemble protocol where only the torsional degrees of freedom of the alkyl chains of the lipids are heated. The results in terms of configurational sampling enhancement have been compared with a conventional simulation produced with a widespread molecular dynamics code. Results show that the proposed thermodynamic-based multiple trajectories parallel protocol for membrane simulations allows for an efficient use of CPU resources with respect to the conventional single trajectory, providing accurate results for area and volume per lipid, membrane thickness, undulation spectra and boosting significantly diffusion and mixing in lipid bilayers due to the sampling enhancement of gauche/trans ratios of the alkyl chain dihedral angles.
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http://dx.doi.org/10.1016/j.bbamem.2018.04.013DOI Listing
July 2018

Author Correction: The role of directional interactions in the designability of generalized heteropolymers.

Sci Rep 2018 Mar 12;8(1):4592. Epub 2018 Mar 12.

Faculty of Physics, University of Vienna, Boltzmanngasse 5, A-1090, Vienna, Austria.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
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http://dx.doi.org/10.1038/s41598-018-22649-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5847616PMC
March 2018

The role of directional interactions in the designability of generalized heteropolymers.

Sci Rep 2017 07 10;7(1):4986. Epub 2017 Jul 10.

Faculty of Physics, University of Vienna, Boltzmanngasse 5, A-1090, Vienna, Austria.

Heteropolymers are important examples of self-assembling systems. However, in the design of artificial heteropolymers the control over the single chain self-assembling properties does not reach that of the natural bio-polymers, and in particular proteins. Here, we introduce a sufficiency criterion to identify polymers that can be designed to adopt a predetermined structure and show that it is fulfilled by polymers made of monomers interacting through directional (anisotropic) interactions. The criterion is based on the appearance of a particular peak in the radial distribution function, that we show being a universal feature of all designable heteropolymers, as it is present also in natural proteins. Our criterion can be used to engineer new self-assembling modular polymers that will open new avenues for applications in materials science.
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http://dx.doi.org/10.1038/s41598-017-04720-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5504045PMC
July 2017

Fast Switching Alchemical Transformations in Molecular Dynamics Simulations.

J Chem Theory Comput 2014 Jul;10(7):2813-23

Dipartimento di Chimica, Università di Firenze , Via della Lastruccia 3, Sesto Fiorentino, Florence I-50019, Italy.

We present an efficient and rigorous implementation of the fast switching alchemical transformation for systems where electrostatic interactions are treated using the smooth particle mesh Ewald method. Free energies are computed using bidirectional nonequilibrium alchemical trajectories by applying the Crooks fluctuation theorem and the Bennett acceptance ratio to the collection of the final alchemical works. The technique is used for the evaluation of the 1-octanol/water partition coefficients for some selected organic molecules. Fast switching alchemical tranformations appear to be competitive, both in accuracy and in efficiency, with respect to the traditional methods based on independent equilibrium simulations of intermediate states.
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http://dx.doi.org/10.1021/ct500142cDOI Listing
July 2014
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