Non-invasive Focal Mechanical Vibrations Delivered by Wearable Devices: An Open-Label Pilot Study in Childhood Ataxia.

Non-invasive focal mechanical vibrations (NIFMV) now represent a strategy of increasing interest to improve motor control in different neurological diseases. Nanotechnology allowed the creation of wearable devices transforming thermal variations into mechanical energy with focal vibrations. This kind of wearable stimulators (WS) has produced encouraging preliminary results when used in the treatment of movement disorders and ataxia in adults.

Comparison of standard versus orthogonal ECG leads for T-wave alternans identification.

T-wave alternans (TWA), an electrophysiologic phenomenon associated with ventricular arrhythmias, is usually detected from selected ECG leads. TWA amplitude measured in the 12-standard and the 3-orthogonal (vectorcardiographic) leads were compared here to identify which lead system yields a more adequate detection of TWA as a noninvasive marker for cardiac vulnerability to ventricular arrhythmias. Our adaptive match filter (AMF) was applied to exercise ECG tracings from 58 patients with an implanted cardiac defibrillator, 29 of which had ventricular tachycardia or fibrillation during follow-up (cases), while the remaining 29 were used as controls.

Repolarization alternans heterogeneity in healthy subjects and acute myocardial infarction patients.

An association between heterogeneity of repolarization alternans (RA) and cardiac electrical instability has been reported. Characterization of RA in health and identification of physiological RA heterogeneity may help discrimination of abnormal RA cases more likely associated to arrhythmic events. Thus, aim of the present study was the identification of a physiological RA region in terms of mean temporal location (MRAD) with respect to the T apex, and mean amplitude (MRAA), by application of our heart-rate adaptive match filter method to clinical ECG recordings from 51 control healthy (CH) subjects and 43 acute myocardial infarction (AMI) patients.

Identification of an integrated mathematical model of standard oral glucose tolerance test for characterization of insulin potentiation in health.

Two new formulations, respectively denominated INT_M1 and INT_M2, of an integrated mathematical model to describe the glycemic and insulinemic responses to a 75 g oral glucose tolerance test (OGTT) are proposed and compared. The INT_M1 assumes a single compartment for the intestine and the derivative of a power exponential function for the gastric emptying rate, while, in the INT_M2, a nonlinear three-compartment system model is adopted to produce a more realistic, multiphase gastric emptying rate. Both models were implemented in a Matlab-based, two-step procedure for estimation of seven adjustable coefficients characterizing the gastric emptying rate and the incretin, insulin and glucose kinetics.

Predictive power of T-wave alternans and of ventricular gradient hysteresis for the occurrence of ventricular arrhythmias in primary prevention cardioverter-defibrillator patients.

Background And Purpose: Left ventricular ejection fraction lacks specificity to predict sudden cardiac death in heart failure. T-wave alternans (TWA; beat-to-beat T-wave instability, often measured during exercise) is deemed a promising noninvasive predictor of major cardiac arrhythmic event. Recently, it was demonstrated that TWA during recovery from exercise has additional predictive value.

Dynamics of insulin action in hypertension: assessment from minimal model interpretation of intravenous glucose tolerance test data.

Based on glucose kinetics minimal model (GKMM) interpretation of frequently sampled intravenous glucose tolerance test (FSIGTT), the aim was to broaden the characterization of insulin-mediated glucose disposal in hypertension by aid of a dynamic insulin sensitivity index, S(D)(I), and the related efficiency, η = S(D)(I) / S(I), of the metabolic system to convert the maximal individual response capacity, measured by S (I), into an effective insulin control on glucose. The C-peptide minimal model (CPMM) was used to interpret the role of β-cell function. Plasma glucose, insulin, and C-peptide concentrations were measured, during a 5-h FSIGTT, in eighteen normoglycemic individuals: ten hypertensive patients (H-group) and eight normotensive subjects (N-group) with no metabolic syndrome.

Physiological interpretation of inductance and low-resistance terms in four-element windkessel models: assessment by generalized sensitivity function analysis.

Physiological relevance of parameters of three arterial models, denominated W4P, W4S and IVW, was assessed by computation of parameter-related generalized sensitivity functions (GSFs), which allow the definition of heart-cycle time intervals where the information content of experimental data, useful for estimation of each model parameter, is concentrated. The W4P and W4S are derived from the three-element windkessel by connecting an inductance, L, in parallel or in series, respectively, with aortic characteristic impedance, R(c). In the IVW, L is placed in series at the input of a viscoelastic windkessel, incorporating a Voigt cell (a resistor, R(d), in series with a capacitor, C).

Identification of gender-related normality regions for T-wave alternans.

Background: T-wave alternans (TWA), a harbinger of sudden cardiac death, associates to a broad variety of pathologies. In a previous study, we observed the presence of unstable and low-amplitude TWA also in healthy subjects, and considered it as "physiological TWA." The possible existence of different TWA characteristics between males and female is investigated in the present work.

Automatic microvolt T-wave alternans identification in relation to ECG interferences surviving preprocessing.

The aim was to investigate the effect of interferences surviving preprocessing (residual noise, baseline wanderings, respiration modulation, replaced beats, missed beats and T-waves misalignment) on automatic identification of T-wave alternans (TWA), an ECG index of risk for sudden cardiac death. The procedures denominated fast-Fourier-transform spectral method (FFTSM), complex-demodulation method (CDM), modified-moving-average method (MMAM), Laplacian-likelihood-ratio method (LLRM), and adaptive-match-filter method (AMFM) were applied to interferences-corrupted synthetic ECG tracings and Holter ECG recordings from control-healthy subjects (CH-group; n=25) and acute-myocardial-infarction patients (AMI group; n=25). The presence of interferences in simulated data caused detection of false-positive TWA by all techniques but the FFTSM and AMFM.

Correlation method versus enhanced modified moving average method for automatic detection of T-wave alternans.

Enhanced modified moving average method (EMMAM) and correlation method (CM) for microvolt TWA identification are compared by aid of simulated ECG tracings (cases of absence of TWA and presence of stationary or time-varying TWA) and ECG recordings from healthy subjects (H-group) and patients who survived an acute myocardial infarction (AMI-group). The two competing methods were found to be equivalent when analyzing clean ECGs affected by stationary TWA. Non-stationary TWA is correctly tracked by the CM, whereas it is identified as stationary by the EMMAM.

Assessment of physiological amplitude, duration, and magnitude of ECG T-wave alternans.

Background: An association between T-wave alternans (TWA) and malignant ventricular arrhythmias is generally recognized. Because relatively low levels of TWA have also been observed in healthy (H) subjects, the question arises as to whether these are ascribable to noise and artifacts, or can be given the relevance of a physiological phenomenon characterizing a preclinical condition.

Methods: To answer this question, in the present study 20-minute not noisy, sinus ECG recordings, from 138 H-subjects and 148 coronary artery diseased (CAD) patients, were submitted to our adaptive match filter (AMF) procedure to identify and parameterize TWA in terms of duration (TWAD), amplitude (TWAA), and magnitude (TWAM, defined as the product of TWAD times TWAA).

Assessment of hepatic insulin degradation, in normoglycemic hypertensive patients, by minimal modelling of standard intravenous glucose tolerance test data.

Role of hepatic insulin degradation in modulating insulin delivery to peripheral circulation, in insulin-resistant hypertensive patients, is not yet fully understood. This issue was investigated here by a novel application to hypertension of a previously proposed minimal modelling of insulin and C-peptide data, using population values for insulin and C-peptide kinetics parameters. Data, from frequently sampled intravenous glucose tolerance test (FSIGTT), were analysed in ten normoglycemic, hypertensive patients (H-group), compared with eight normoglycemic, normotensive subjects (N-group), matched for age, gender and body mass index.

Comparative analysis of methods for automatic detection and quantification of microvolt T-wave alternans.

Microvolt T-wave alternans (TWA), consisting of every-other-beat changes in ECG T-wave morphology, is an index of susceptibility to malignant ventricular arrhythmias, requiring automatic techniques to be identified. Five of these, namely, fast-Fourier-transform spectral method (FFTSM), complex-demodulation method (CDM), modified-moving-average method (MMAM), Laplacian-likelihood-ratio method (LLRM) and adaptive-match-filter method (AMFM), were applied here to simulated and sample clinical data. The aim was to compare individual methods ability to properly identify stationary and time-varying TWA, avoiding false-positive detections.

Insulin action and secretion in hypertension in the absence of metabolic syndrome: model-based assessment from oral glucose tolerance test.

Relationship between insulin action and secretion was analyzed in 10 hypertensive patients (H group; 5 male, 5 female; 56.9 +/- 2.5 years) compared with 10 normotensive subjects (N group; 5 male, 5 female; 51.

Age-related analysis of insulin resistance, body weight and arterial pressure in the Zucker fatty rat.

The evolution with ageing of insulin resistance, body weight (BW) and mean arterial pressure (MAP) was studied in a group of Zucker fatty rats (ZFRs, n = 22), between 7 and 16 weeks of age, compared with an age-matched control group of Zucker lean rats (ZLRs, n = 22). The minimal model of glucose kinetics was applied to estimate glucose effectiveness, S(G), and insulin sensitivity, S(I), from insulinaemia and glycaemia measured during a 70 min intravenous glucose tolerance test. No correlation was found between S(G) and age in both ZFR and ZLR groups.

Adaptive match filter based method for time vs. amplitude characterization of microvolt ECG T-wave alternans.

To develop a new method for non-invasive identification of patients prone to ventricular tachyarrhythmia and sudden cardiac death, an adaptive match-filter (AMF) was applied to detect and characterize T-wave alternans (TWA) in 200 coronary artery diseased (CAD) patients compared with 176 healthy (H) subjects. TWA was characterized in terms of duration (TWAD), amplitude (TWAA), and magnitude (TWAM, defined as the product of TWAD times TWAA). A criterion derived from these parameters, estimated over the H-population, allowed discrimination between a risk (TWA+) and a normality (NO TWA) zone in the TWAD-TWAA plane.

Insulin secretion rate and beta-cell sensitivity from oral glucose tolerance test in normotensive and normoglycemic humans.

Aim of the study was to test the reproducibility of estimates of static, Phi s, and dynamic, Phi d, beta-cell sensitivity to glucose, and predictions of the insulin secretion rate, SR(t), provided by the C-peptide oral minimal model (COMM) applied to oral glucose tolerance tests (OGTT) of various complexity. The study involved six volunteer, normotensive and normoglycemic subjects who underwent a 300-minute OGTT. Results from a full 22-sampling schedule (OGTT300/22), were compared with those from two reduced schedules consisting of 11 samples in 300 min (OGTT300/11) and 7 samples in 120 min (OGTT120/7).

Development of systemic arterial mechanical properties from infancy to adulthood interpreted by four-element windkessel models.

Aortic impedance data of infants, children and adults (age range 0.8-54 yr), previously reported by others, were interpreted by means of three alternative four-element windkessel models: W4P, W4S, and IVW. The W4P and W4S are derived from the three-element windkessel (W3) by connecting an inertance (L) in parallel or in series, respectively, with the aortic characteristic resistance (Rc).

Enhanced sympathetic reactivity associates with insulin resistance in the young Zucker rat.

Somatosympathetic reflexes were studied in young hyperinsulinemic, insulin-resistant (Zucker fatty) rats (ZFR) and a related control (Zucker lean) strain (ZLR). Glucose metabolism was characterized by minimal model analysis of intravenous glucose tolerance test data. Seven-week-old ZFR (n=18) and ZLR (n=17) were studied under pentobarbital anesthesia.

Deterioration of insulin sensitivity and glucose effectiveness with age and hypertension.

Background: This study examined the relative role of age and hypertension in deterioration of insulin-dependent (insulin sensitivity, S(I)) and insulin-independent (glucose effectiveness, S(G)) actions on glucose tolerance.

Methods: We applied the minimal model of glucose kinetics to estimate S(I) and S(G) indexes from insulinemia and glycemia data detected during a frequently sampled intravenous glucose tolerance test performed in 21 normoglycemic subjects who were not affected by the metabolic syndrome (MS): seven young normotensive subjects (YN; mean age 29.3 +/- 1.

Insulin resistance in hypertension quantified by oral glucose tolerance test: comparison of methods.

Four methods reported in the literature for evaluation of insulin sensitivity indexes from oral glucose tolerance tests (OGTTs) were analyzed and compared in order to test their ability to discriminate the insulin-resistant state in hypertension. To this aim, 15 normoglycemic subjects, not affected by metabolic syndrome, underwent a 22-sample, 300-minute OGTT. Eight subjects were normotensive (mean age, 47.

The baroreflex is counteracted by autoregulation, thereby preventing circulatory instability.

The aims of this study were (a) to apply in the animal with intact baroreflex a two-point method for estimation of overall, effective open-loop gain, G0e, which results from the combined action of baroregulation and total systemic autoregulation on peripheral resistance; (b) to predict specific baroreflex gain by correcting the effective gain for the autoregulation gain; and (c) to discuss why the effective gain is usually as low as 1-2 units. G0e was estimated from two measurements of both cardiac output, Q, and mean systemic arterial pressure, P: one in the reference state (set-point) and the other in a steady-state reached 1-3 min after a small cardiac output perturbation. In anaesthetized cats and dogs a cardiac output perturbation was accomplished by partial occlusion of the inferior vena cava and by cardiac pacing, respectively.

Age-related analysis of glucose metabolism in spontaneously hypertensive and normotensive rats.

This study was designed to investigate the effect of both hypertension and ageing on the efficiency of glucose metabolism. A 12-sample, 120 min intravenous glucose tolerance test (IVGTT) was applied to 36 rats: two groups of nine young (12 weeks) spontaneously hypertensive and Wistar Kyoto rats (Y-SHR and Y-WKY group, respectively) and two groups of nine old (40 weeks) SHR and WKY rats (O-SHR and O-WKY group, respectively). Insulinaemia and glycaemia data were interpreted in terms of estimates of glucose effectiveness, S(G), and insulin sensitivity, S(I), provided by the minimal model of glucose kinetics.

Interaction between glucose metabolism and endogenous insulin release in hypertension.

The minimal model approach was applied to examine the dynamic interaction between glucose metabolism and endogenous insulin release during an intravenous glucose tolerance test (IVGTT) in a group of hypertensive patients (H group) compared with a group of normotensive subjects (N group). A modified version of the classical minimal model of C-peptide kinetics and secretion was used to evaluate the total amount of insulin secretion per unit of distribution volume (TIS) together with 3 indexes of beta-cell function (the basal, Phi(b), first, Phi1, and second phase, Phi2, beta-cell sensitivity to glucose). These indexes were associated with estimates of glucose effectiveness (S(G)) and insulin sensitivity (S(I)) provided by the classical minimal model of glucose kinetics.

Comparative analysis of aortic impedance and wave reflection in ferrets and dogs.

Our modified version of the T-tube arterial model (consisting of two parallel, loss-free transmission paths terminating in lumped loads of complex and frequency-dependent nature) was applied to experimental measurements of ascending aortic pressure and of ascending and descending aortic flows taken from dogs and ferrets. Our aim was to provide quantitative evaluation of the aortic pressure and flow pulse wave components as they relate to the distribution of arterial properties and relate to wave travel and reflection in mammalians of consistently different size and shape. Estimated effective lengths (distances to effective reflection sites) of the head-end (d(h)) and body-end (d(b)) transmission paths were approximately 12 and 30 cm, respectively, in the dog and 6.