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Parazzini M.,CNR Institute of Biomedical Engineering | Fiocchi S.,CNR Institute of Biomedical Engineering | Fiocchi S.,Polytechnic of Milan | Ravazzani P.,CNR Institute of Biomedical Engineering
Bioelectromagnetics | Year: 2012

Tinnitus is considered an auditory phantom percept. Recently, transcranial direct current stimulation (tDCS) has been proposed as a new approach for tinnitus treatment including, as potential targets of interest, either the temporal and temporoparietal cortex or prefrontal areas. This study investigates and compares the spatial distribution of the magnitude of the electric field and the current density in the brain tissues during tDCS of different brain targets. A numerical method was applied on a realistic human head model to calculate these field distributions in different brain structures, such as the cortex, white matter, cerebellum, hippocampus, medulla oblongata, pons, midbrain, thalamus, and hypothalamus. Moreover, the same distributions were evaluated along the auditory pathways. Results of this study show that tDCS of the left temporoparietal cortex resulted in a widespread diffuse distribution of the magnitude of the electric fields (and also of the current density) on an area of the cortex larger than the target brain region. On the contrary, tDCS of the dorsolateral prefrontal cortex resulted in a stimulation mainly concentrated on the target itself. Differences in the magnitude distribution were also found on the structures along the auditory pathways. A sensitivity analysis was also performed, varying the electrode position and the human head models. Accurate estimation of the field distribution during tDCS in different regions of the head could be valuable to better determine and predict efficacy of tDCS for tinnitus suppression. © 2012 Wiley Periodicals, Inc.

Clemente F.,CNR Institute of Biomedical Engineering | Arpaia P.,University of Sannio | Cimmino P.,CNR Institute of Biomedical Engineering
Physiological Measurement | Year: 2010

A non-invasive piezo-film-based measurement method for haemodynamic assessment is proposed. The design of a system, able to reconstruct the blood pressure waveform online by dealing with problems arising from the piezo-film capacitive nature in the targeted frequency range (from quasi-dc up to 12 Hz), is illustrated. The system is based on a commercial piezo-film placed easily on the radial artery with a special brace without any discomfort for the patient. The analogical conditioning circuit and digital signal processing are continuously tuned with the signal from the sensor to reconstruct the blood pressure signal online. Diagnostic schema, based on physio-pathological models, have been implemented in order to compute online trends of max[dP(t)/d(t)] and volemic status highly useful for the intensivist and anaesthesiologist. The system was characterized by numerical simulation and experimental in vivo comparison to the traditional reference system. © 2010 Institute of Physics and Engineering in Medicine.

Ferrannini E.,University of Pisa | Mari A.,CNR Institute of Biomedical Engineering | Nofrate V.,CNR Institute of Biomedical Engineering | Sosenko J.M.,University of Miami | Skyler J.S.,University of Miami
Diabetes | Year: 2010

OBJECTIVE - Relatives of type 1 diabetic patients are at enhanced risk of developing diabetes. We investigated the mode of onset of hyperglycemia and how insulin sensitivity and β-cell function contribute to the progression to the disease. RESEARCH DESIGN AND METHODS - In 328 islet cell autoantibody-positive, nondiabetic relatives from the observational arms of the Diabetes Prevention Trial-1 Study (median age 11 years [interquartile range 8], sequential OGTTs (2,143 in total) were performed at baseline, every 6 months, and 2.7 years [2.7] later, when 115 subjects became diabetic. β-Cell glucose sensitivity (slope of the insulin-secretion/plasma glucose dose-response function) and insulin sensitivity were obtained by mathematical modeling of the OGTT glucose/C-peptide responses. RESULTS - In progressors, baseline insulin sensitivity, fasting insulin secretion, and total postglucose insulin output were similar to those of nonprogressors, whereas β-cell glucose sensitivity was impaired (median 48 pmol/min per m2 per mmol/l [interquartile range 36] vs. 87 pmol/min per m2 per mmol/l [67]; P < 0.0001) and predicted incident diabetes (P < 0.0001) independently of sex, age, BMI, and clinical risk. In progressors, 2-h glucose levels changed little until 0.78 years before diagnosis, when they started to rise rapidly (∼13 mmol · l-1 · year-1); glucose sensitivity began to decline significantly (P < 0.0001) earlier (1.45 years before diagnosis) than the plasma glucose surge. During this anticipation phase, both insulin secretion and insulin sensitivity were essentially stable. CONCLUSIONS - In high-risk relatives, β-cell glucose sensitivity is impaired and is a strong predictor of diabetes progression. The time trajectories of plasma glucose are frequently biphasic, with a slow linear increase followed by a rapid surge, and are anticipated by a further deterioration of β-cell glucose sensitivity. © 2010 by the American Diabetes Association.

Michaliszyn S.F.,University of Pittsburgh | Mari A.,CNR Institute of Biomedical Engineering | Lee S.,University of Pittsburgh | Bacha F.,Baylor College of Medicine | And 5 more authors.
Diabetes | Year: 2014

Using the hyperglycemic and euglycemic clamp, we demonstrated impaired β-cell function in obese youth with increasing dysglycemia. Herein we describe oral glucose tolerance test (OGTT)-modeled β-cell function and incretin effect in obese adolescents spanning the range of glucose tolerance. β-Cell function parameters were derived from established mathematical models yielding β-cell glucose sensitivity (bCGS), rate sensitivity, and insulin sensitivity in 255 obese adolescents (173 with normal glucose tolerance [NGT], 48 with impaired glucose tolerance [IGT], and 34 with type 2 diabetes [T2D]). The incretin effect was calculated as the ratio of the OGTT-bCGS to the 2-h hyperglycemic clamp-bCGS. Incretin and glucagon concentrations were measured during the OGTT. Compared with NGT, βCGS was 30 and 65% lower in youth with IGT and T2D, respectively; rate sensitivity was 40% lower in T2D. Youth with IGT or T2D had 32 and 38% reduced incretin effect compared with NGT in the face of similar changes in GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) in response to oral glucose. We conclude that glucose sensitivity deteriorates progressively in obese youth across the spectrum of glucose tolerance in association with impairment in incretin effect without reduction in GLP-1 or GIP, similar to that seen in adult dysglycemia. © 2014 by the American Diabetes Association.

Stazi A.V.,Instituto Superiore Of Sanita | Trinti B.,CNR Institute of Biomedical Engineering
Annali dell'Istituto Superiore di Sanita | Year: 2010

In celiac disease (CD), for its multifactorial nature, the target organs are not limited to the gut, but include thyroid, liver, skin and reproductive and nervous systems. Between the extraintestinal symptoms associated with CD, autoimmune thyroid diseases (AITDs) are more evident, underlining as CD-related autoimmune alterations can be modulated not only by gluten but also by various concurrent endogenous (genetic affinity, over-expression of cytokines) and exogenous (environment, nutritional deficiency) factors. In their pathogenesis a central role for over-expression of interleukin-15 (IL-15) is shown, by inhibiting apoptosis, leading to the perpetuation of inflammation and tissue destruction. Thyroid is particularly sensitive to selenium deficiency because selenoproteins are significant in biosynthesis and activity of thyroid hormones; besides, some selenoproteins as glutathione peroxidase are involved in inhibiting apoptosis. Thus, selenium malabsorption in CD can be thought as a key factor directly leading to thyroid and intestinal damage. Considering the complexity of this interaction and on the basis of available evidence, the aim of this review is to assess as preventive and therapeutic target the role of IL-15 and selenium in the pathogeneses of both CD and AITD.

Giorgino T.,University Pompeu Fabra | Giorgino T.,CNR Institute of Biomedical Engineering | Buch I.,University Pompeu Fabra | De Fabritiis G.,University Pompeu Fabra
Journal of Chemical Theory and Computation | Year: 2012

Approximately 100 proteins in the human genome contain an SH2 domain recognizing small flexible phosphopeptides. It is therefore important to understand in atomistic detail the way these peptides bind and the conformational changes that take place upon binding. Here, we obtained several spontaneous binding events between the p56 lck SH2 domain and the pYEEI peptide within 2 Å RMSD from the crystal structure and with kinetic rates compatible with experiments using high-throughput molecular dynamics simulations. Binding is achieved in two phases, fast contacts of the charged phospho-tyrosine and then rearrangement of the ligand involving the stabilization of two important loops in the SH2 domain. These observations provide insights into the binding pathways and induced conformations of the SH2-phosphopeptide complex which, due to the characteristics of SH2 domains, should be relevant for other SH2 recognition peptides. © 2012 American Chemical Society.

Finesso L.,CNR Institute of Biomedical Engineering | Grassi A.,CNR Institute of Biomedical Engineering | Spreij P.,University of Amsterdam
Mathematics of Control, Signals, and Systems | Year: 2010

Stochastic realization is still an open problem for the class of hidden Markov models (HMM): given the law Q of an HMM find a finite parametric description of it. Fifty years after the introduction of HMMs, no computationally effective realization algorithm has been proposed. In this paper we direct our attention to an approximate version of the stochastic realization problem for HMMs. We aim at the realization of an HMM of assigned complexity (number of states of the underlying Markov chain) which best approximates, in Kullback Leibler divergence rate, a given stationary law Q. In the special case of Q being the law of an HMM this corresponds to solving the approximate realization problem for HMMs. In general there is no closed form expression of the Kullback Leibler divergence rate, therefore we replace it, as approximation criterion, with the informational divergence between the Hankel matrices of the processes. This not only has the advantage of being easy to compute, while providing a good approximation of the divergence rate, but also makes the problem amenable to the use of nonnegative matrix factorization (NMF) techniques. We propose a three step algorithm, based on the NMF, which realizes an optimal HMM. The viability of the algorithm as a practical tool is tested on a few examples of HMM order reduction. © 2010 The Author(s).

Marchesi S.,CNR Institute of Biomedical Engineering | Tognola G.,CNR Institute of Biomedical Engineering | Paglialonga A.,CNR Institute of Biomedical Engineering
IEEE Transactions on Biomedical Circuits and Systems | Year: 2013

A new approach to study nonlinearity in cochlear active mechanisms, as evaluated in transient evoked otoacoustic emissions (TEOAEs), is presented. TEOAEs are signals generated in the cochlea by a mix of linear and nonlinear mechanisms. This new approach was designed to complement the traditional TEOAE analysis performed by currently available systems used in objective hearing screening and assessment. Nonlinearity of TEOAEs was studied by means of the bispectrum, which is able to find out quadratic frequency couplings (QFCs) that occur when a frequency is not only generated by an independent cochlear source, but it is the result of the interaction among a number of cochlear sources. To fit with the technical constraints of currently available TEOAE systems, the bispectrum was estimated by the third-order scaled polyperiodogram. The proposed method was characterized with synthesized TEOAEs as a function of the main TEOAE parameters and then used to analyze TEOAEs recorded in normal hearing adults and full-term neonates. Results revealed the presence of QFCs in both adult and neonatal TEOAEs, with peculiar patterns and significantly different frequency content in the two groups: adults had QFCs mainly around 2 kHz and neonates had QFCs mainly in the range 3.5-4 kHz. © 2007-2012 IEEE.

Giorgino T.,CNR Institute of Biomedical Engineering
Computer Physics Communications | Year: 2014

Molecular dynamics simulations have a prominent role in biophysics and drug discovery due to the atomistic information they provide on the structure, energetics and dynamics of biomolecules. Specialized software packages are required to analyze simulated trajectories, either interactively or via scripts, to derive quantities of interest and provide insight for further experiments. This paper presents the Density Profile Tool, a package that enhances the Visual Molecular Dynamics environment with the ability to interactively compute and visualize 1-D projections of various density functions of molecular models. We describe how the plugin is used to perform computations both via a graphical interface and programmatically. Results are presented for realistic examples, all-atom bilayer models, showing how mass and electron densities readily provide measurements such as membrane thickness, location of structural elements, and how they compare to X-ray diffraction experiments. © 2013 Elsevier B.V. All rights reserved.

Giorgino T.,CNR Institute of Biomedical Engineering
Computer Physics Communications | Year: 2014

PLUMED-GUI is an interactive environment to develop and test complex PLUMED scripts within the Visual Molecular Dynamics (VMD) environment. Computational biophysicists can take advantage of both PLUMED's rich syntax to define collective variables (CVs) and VMD's chemically-aware atom selection language, while working within a natural point-and-click interface. Pre-defined templates and syntax mnemonics facilitate the definition of well-known reaction coordinates. Complex CVs, e.g. involving reference snapshots used for RMSD or native contacts calculations, can be built through dialogs that provide a synoptic view of the available options. Scripts can be either exported for use in simulation programs, or evaluated on the currently loaded molecular trajectories. Script development takes place without leaving VMD, thus enabling an incremental try-see-modify development model for molecular metrics. © 2014 Published by Elsevier B.V.

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