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Background: Deep-learning applications in cardiology typically perform trivial binary classification and are able to discriminate between subjects affected or not affected by a specific cardiac disease. However, this working scenario is very different from the real one, where clinicians are required to recognize the occurrence of one cardiac disease among the several possible ones, performing a multiclass classification. The present work aims to create a new interpretable deep-learning tool able to perform a multiclass classification and, thus, discriminate among several different cardiac diseases. Methods: The “China Physiological Signal Challenge in 2018” Physionet database was used to develop a multiclass neural network, constructed by the Advanced Repeated Structuring & Learning Procedure (AdvRS&LP). Data, consisting of 6877 12-lead 10-second electrocardiograms, was processed to obtain 252 electrocardiographic and vectorcardiographic input features, used to classify the data into eight classes (normal sinus rhythm, atrial fibrillation, first-degree atrioventricular block, left bundle branch block, right bundle branch block, premature atrial contraction, premature ventricular contraction, and unknown). Classification performance was evaluated by the area under the curve of the receiver operating characteristics. Clinical interpretability was assessed by standard statistical analysis and the local interpretable model-agnostic explainer algorithm. Results: Performance ranged from 89.88% to 90.10% (95.98 ± 3.32%) in the learning dataset and from 69.15% to 91.14% (83.65 ± 8.24%) in the testing dataset. These results are good considering the difficult, realistic multiclass classification task. Conclusions: The proposed multiclass neural network constructed using the AdvRS&LP represents a promising deep-learning tool for discriminating several cardiac diseases while ensuring clinical interpretability.

Abstract The aim of this study was to develop a dynamic model-based approach to separately quantify the exogenous and endogenous contributions to total plasma insulin concentration and to apply it to assess the effects of inhaled-insulin administration on endogenous insulin secretion during a meal test. A three-step dynamic in-silico modeling approach was developed to estimate the two insulin contributions of total plasma insulin in a group of 21 healthy subjects who underwent two equivalent standardized meal tests on separate days, one of which preceded by inhalation of a Technosphere® Insulin dose (22U or 20U). In the 30–120 min test interval, the calculated endogenous insulin component showed a divergence in the time course between the test with and without inhaled insulin. Moreover, the supra-basal area-under-the-curve of endogenous insulin in the test with inhaled insulin was significantly lower than that in the test without (2.1 ± 1.7 × 104 pmol·min/L vs 4.2 ± 1.8 × 104 pmol·min/L, p

The database is constituted by 50 datasets containing cardiorespiratory signals acquired from 50 healthy volunteer subjects (one dataset for each subject; 23 males and 27 females; age: 23±5 years) while performing normal breathing, deep breathing, and breath holding, and two spreadsheet files, namely the “SubjectsInfo.xlsx” and “DBInfo.xlsx” containing the metadata of subjects (including demographic data) and of acquired signals, respectively.Cardiorespiratory signals consisted in simultaneously recorded 12-lead electrocardiograms acquired by the clinical M12 Global InstrumentationⓇ digital Holter ECG recorder, and single-lead electrocardiograms and respiration signals acquired by the wearable chest strap BioHarness 3.0 by Zephyr.The database may be useful to: (1) validate the use of wearable sensors in the acquisition of cardiorespiratory data during different respiration kinds, including apnea; (2) investigate the physiological association between cardiovascular and respiratory systems; (3) validate algorithms able to indirectly extract the respiration signal from the electrocardiogram; (4) study the fatigue level induced by a series ofcontrolled respiration patterns; and (5) investigate the effect of COVID-19 infection on the cardiorespiratory system.

Changes in cardiac function and morphology are reflected in variations in the electrocardiogram (ECG) and, in turn, in the cardiac risk indices derived from it. These variations have led to the introduction of normalization as a step to compensate for possible biasing factors responsible for inter- and intra-subject differences, which can affect the accuracy of ECG-derived risk indices in assessing cardiac risk. The aim of this work is to perform a scoping review to provide a comprehensive collection of open-access published research that examines normalized ECG-derived parameters used as markers of cardiac anomalies or instabilities. The literature search was conducted from February to July 2024 in the major global electronic bibliographic repositories. Overall, 39 studies were selected. Results suggest extensive use of normalization on heart rate variability-related indices (49% of included studies), QT-related indices (18% of included studies), and T-wave alternans (5% of included studies), underscoring their recognized importance and suggesting that normalization may enhance their role as clinically useful risk markers. However, the primary objective of the included studies was not to evaluate the effect of normalization itself; thus, further research is needed to definitively assess the impact and advantages of normalization across various ECG-derived parameters.

Background/ObjectivesGlucagon is important in the maintenance of glucose homeostasis, with also effects on lipids. In this study, we aimed to apply a recently developed model of glucagon kinetics to determine the sensitivity of glucagon variations (especially, glucagon inhibition) to insulin levels (“alpha-cell insulin sensitivity”), during oral glucose administration.Subjects/MethodsWe studied 50 participants (spanning from normal glucose tolerance to type 2 diabetes) undergoing frequently sampled 5-hr oral glucose tolerance test (OGTT). The alpha-cell insulin sensitivity and the glucagon kinetics were assessed by a mathematical model that we developed previously.ResultsThe alpha-cell insulin sensitivity parameter (named SGLUCA; “GLUCA”: “glucagon”) was remarkably variable among participants (CV=221%). SGLUCA was found inversely correlated with the mean glycemic values, as well as with 2-hr glycemia of the OGTT. When stratifying participants into two groups (normal glucose tolerance, NGT, N=28, and impaired glucose regulation/type 2 diabetes, IGR_T2D, N=22), we found that SGLUCA was lower in the latter (1.50 ± 0.50·10-2vs. 0.26 ± 0.14·10-2 ng·L-1GLUCA/pmol·L-1INS, in NGT and IGR_T2D, respectively, p=0.009; “INS”: “insulin”).ConclusionsThe alpha-cell insulin sensitivity is highly variable among subjects, and it is different in groups at different glucose tolerance. This may be relevant for defining personalized treatment schemes, in terms of dietary prescriptions but also for treatments with glucagon-related agents.

Electroencephalography (EEG) wearable devices are particularly suitable for monitoring a subject’s engagement while performing daily cognitive tasks. EEG information provided by wearable devices varies with the location of the electrodes, the suitable location of which can be obtained using standard multi-channel EEG recorders. Cognitive engagement can be assessed during working memory (WM) tasks, testing the mental ability to process information over a short period of time. WM could be impaired in patients with epilepsy. This study aims to evaluate the cognitive engagement of nine patients with epilepsy, coming from a public dataset by Boran et al., during a verbal WM task and to identify the most suitable location of the electrodes for this purpose. Cognitive engagement was evaluated by computing 37 engagement indexes based on the ratio of two or more EEG rhythms assessed by their spectral power. Results show that involvement index trends follow changes in cognitive engagement elicited by the WM task, and, overall, most changes appear most pronounced in the frontal regions, as observed in healthy subjects. Therefore, involvement indexes can reflect cognitive status changes, and frontal regions seem to be the ones to focus on when designing a wearable mental involvement monitoring EEG system, both in physiological and epileptic conditions.

Introduction: Maternal overweight is a risk factor for Gestational Diabetes Mellitus (GDM). However, emerging evidence suggests that an increased maternal body mass index (BMI) promotes the development of perinatal complications even in women who do not develop GDM. This study aims to assess physiological glucometabolic changes associated with increased BMI. Methods: 21 women with overweight and 21 normal weight controls received a metabolic assessment at 13 weeks of gestation, including a 60 min frequently sampled intravenous glucose tolerance test. A further investigation was performed between 24 and 28 weeks in women who remained normal glucose tolerant. Results: At baseline, mothers with overweight showed impaired insulin action, whereby the calculated insulin sensitivity index (CSI) was lower as compared to normal weight controls (3.5 vs. 6.7 10-4 min-1 [microU/ml]-1, p=0.025). After excluding women who developed GDM, mothers with overweight showed higher average glucose during the oral glucose tolerance test (OGTT) at third trimester. Moreover, early pregnancy insulin resistance and secretion were associated with increased placental weight in normal glucose tolerant women. Conclusion: Mothers with overweight or obesity show an unfavourable metabolic environment already at the early stage of pregnancy, possibly associated with perinatal complications in women who remain normal glucose tolerant.

Despite hand gesture recognition is a widely investigated field, the design of myoelectric architectures for detecting finer motor task, like the handwriting, is less studied. However, writing tasks involving cognitive loads represent an important aspect toward the generalization of myoelectric-based human-machine interfaces (HMI), and also for many rehabilitative tasks. In this study, the handwriting recognition of the ten digits was faced under the myoelectric control perspective, considering the probes setup and the feature extraction step. Time and frequency domain features were extracted from surface electromyography (sEMG) signals of 11 subjects who wrote the ten digits following a standardized template and 8 sEMG probes were equally distributed between forearm and wrist. Feature class separability was investigated and an aggregated feature set was built to train pattern recognition architectures, i.e. linear discriminant analysis (LDA) and quadratic support vector machine (QSVM). Also, four reduced probes setups were investigated. LDA and QSVM showed mean accuracy of about 97%, with all the forearm and wrist sEMG information. A significant reduction of performances was observed considering the wrist or the forearm only ( $\leq 92$ %) and when LDA and QSVM were trained with two electrodes information ( $\leq 90$ %). For the reliable classification performances in a motor task involving high cognitive demands, like the handwriting, it is required the use of probes fully covering forearm and wrist. Outcomes support the methodological transfer from myoelectric hand gesture to the handwriting recognition, which represents a key aspect in the development of new HMI for rehabilitation tasks.

Goal: To evaluate suitability of respiratory signals derived from clinical 12-lead electrocardiograms (ECGs) and wearable 1-lead ECG to identify different respiration types. Methods: ECGs were simultaneously acquired through the M12R ECG Holter by Global Instrumentation and the chest strap BioHarness 3.0 by Zephyr from 42 healthy subjects alternating normal breathing, breath holding, and deep breathing. Respiration signals were derived from the ECGs through the Segmented-Beat Modulation Method (SBMM)-based algorithm and the algorithms by Van Gent, Charlton, Soni and Sarkar, and characterized in terms of breathing rate and amplitude. Respiration classification was performed through a linear support vector machine and evaluated by F1 score. Results: Best F1 scores were 86.59%(lead V2) and 80.57%, when considering 12-lead and 1-lead ECGs, respectively, and using SBMM-based algorithm. Conclusion: ECG-derived respiratory signals allow reliable identification of different respiration types even when acquired through wearable sensors, if associated to appropriate processing algorithms, such as the SBMM-based algorithm.

Timely and reliable fetal monitoring is crucial to prevent adverse events during pregnancy and delivery. Fetal phonocardiography, i.e., the recording of fetal heart sounds, is emerging as a novel possibility to monitor fetal health status. Indeed, due to its passive nature and its noninvasiveness, the technique is suitable for long-term monitoring and for telemonitoring applications. Despite the high share of literature focusing on signal processing, no previous work has reviewed the technological hardware solutions devoted to the recording of fetal heart sounds. Thus, the aim of this scoping review is to collect information regarding the acquisition devices for fetal phonocardiography (FPCG), focusing on technical specifications and clinical use. Overall, PRISMA-guidelines-based analysis selected 57 studies that described 26 research prototypes and eight commercial devices for FPCG acquisition. Results of our review study reveal that no commercial devices were designed for fetal-specific purposes, that the latest advances involve the use of multiple microphones and sensors, and that no quantitative validation was usually performed. By highlighting the past and future trends and the most relevant innovations from both a technical and clinical perspective, this review will represent a useful reference for the evaluation of different acquisition devices and for the development of new FPCG-based systems for fetal monitoring.

Abstract Background The triglyceride-glucose index (TyG) has been proposed as a surrogate marker of insulin resistance, which is a typical trait of pregnancy. However, very few studies analyzed TyG performance as marker of insulin resistance in pregnancy, and they were limited to insulin resistance assessment at fasting rather than in dynamic conditions, i.e., during an oral glucose tolerance test (OGTT), which allows more reliable assessment of the actual insulin sensitivity impairment. Thus, first aim of the study was exploring in pregnancy the relationships between TyG and OGTT-derived insulin sensitivity. In addition, we developed a new version of TyG, for improved performance as marker of insulin resistance in pregnancy. Methods At early pregnancy, a cohort of 109 women underwent assessment of maternal biometry and blood tests at fasting, for measurements of several variables (visit 1). Subsequently (26 weeks of gestation) all visit 1 analyses were repeated (visit 2), and a subgroup of women (84 selected) received a 2 h-75 g OGTT (30, 60, 90, and 120 min sampling) with measurement of blood glucose, insulin and C-peptide for reliable assessment of insulin sensitivity (PREDIM index) and insulin secretion/beta-cell function. The dataset was randomly split into 70% training set and 30% test set, and by machine learning approach we identified the optimal model, with TyG included, showing the best relationship with PREDIM. For inclusion in the model, we considered only fasting variables, in agreement with TyG definition. Results The relationship of TyG with PREDIM was weak. Conversely, the improved TyG, called TyGIS, (linear function of TyG, body weight, lean body mass percentage and fasting insulin) resulted much strongly related to PREDIM, in both training and test sets (R2 > 0.64, p

COVID-19 is an infectious disease that has greatly affected worldwide healthcare systems, due to the high number of cases and deaths. As COVID-19 patients may develop cardiac comorbidities that can be potentially fatal, electrocardiographic monitoring can be crucial. This work aims to identify electrocardiographic and vectorcardiographic patterns that may be related to mortality in COVID-19, with the application of the Advanced Repeated Structuring and Learning Procedure (AdvRS&LP). The procedure was applied to data from the “automatic computation of cardiovascular arrhythmic risk from electrocardiographic data of COVID-19 patients” (COVIDSQUARED) project to obtain neural networks (NNs) that, through 254 electrocardiographic and vectorcardiographic features, could discriminate between COVID-19 survivors and deaths. The NNs were validated by a five-fold cross-validation procedure and assessed in terms of the area under the curve (AUC) of the receiver operating characteristic. The features’ contribution to the classification was evaluated through the Local-Interpretable Model-Agnostic Explanations (LIME) algorithm. The obtained NNs properly discriminated between COVID-19 survivors and deaths (AUC = 84.31 ± 2.58% on hold-out testing datasets); the classification was mainly affected by the electrocardiographic-interval-related features, thus suggesting that changes in the duration of cardiac electrical activity might be related to mortality in COVID-19 cases.

Posttransplant diabetes mellitus (PTDM) is a common complication after kidney transplantation. Pathophysiologically, whether beta-cell dysfunction rather than insulin resistance may be the predominant defect in PTDM has been a matter of debate. The aim of the present analysis was to compare glucometabolism in kidney transplant recipients with and without PTDM. To this aim, we included 191 patients from a randomized controlled trial who underwent oral glucose tolerance tests (OGTTs) 6 months after transplantation. We derived several basic indices of beta-cell function and insulin resistance as well as variables from mathematical modeling for a more robust beta-cell function assessment. Mean ± standard deviation of the insulin sensitivity parameter PREDIM was 3.65 ± 1.68 in PTDM versus 5.46 ± 2.57 in NON-PTDM. Model-based glucose sensitivity (indicator of beta-cell function) was 68.44 ± 57.82 pmol∙min−1∙m−2∙mM−1 in PTDM versus 143.73 ± 112.91 pmol∙min−1∙m−2∙mM−1 in NON-PTDM, respectively. Both basic indices and model-based parameters of beta-cell function were more than 50% lower in patients with PTDM, indicating severe beta-cell impairment. Nonetheless, some defects in insulin sensitivity were also present, although less marked. We conclude that in PTDM, the prominent defect appears to be beta-cell dysfunction. From a pathophysiological point of view, patients at high risk for developing PTDM may benefit from intensive treatment of hyperglycemia over the insulin secretion axis.

Amino acids (AAs) are well known to be involved in the regulation of glucose metabolism and, in particular, of insulin secretion. However, the effects of different AAs on insulin release and kinetics have not been completely elucidated. The aim of this study was to propose a mathematical model that includes the effect of AAs on insulin kinetics during a mixed meal tolerance test. To this aim, five different models were proposed and compared. Validation was performed using average data, derived from the scientific literature, regarding subjects with normal glucose tolerance (CNT) and with type 2 diabetes (T2D). From the average data of the CNT and T2D people, data for two virtual populations (100 for each group) were generated for further model validation. Among the five proposed models, a simple model including one first-order differential equation showed the best results in terms of model performance (best compromise between model structure parsimony, estimated parameters plausibility, and data fit accuracy). With regard to the contribution of AAs to insulin appearance/disappearance (kAA model parameter), model analysis of the average data from the literature yielded 0.0247 (confidence interval, CI: 0.0168 – 0.0325) and -0.0048 (CI: -0.0281 – 0.0185) μU·ml-1/(μmol·l-1·min), for CNT and T2D, respectively. This suggests a positive effect of AAs on insulin secretion in CNT, and negligible effect in T2D. In conclusion, a simple model, including single first-order differential equation, may help to describe the possible AAs effects on insulin kinetics during a physiological metabolic test, and provide parameters that can be assessed in the single individuals.

Abstract Background Stroke is a leading cause of disability, injury, and death in elderly people and represents a major public health problem with substantial medical and economic consequences. The incidence of stroke rapidly increases with age, doubling for each decade after age 55 years. Gait impairment is one of the most important problems after stroke, and improving walking function is often a key component of any rehabilitation program. To achieve this goal, a robotic gait trainer seems to be promising. In fact, some studies underline the efficacy of robotic gait training based on end-effector technology, for different diseases, in particular in stroke patients. In this randomized controlled trial, we verify the efficacy of the robotic treatment in terms of improving the gait and reducing the risk of falling and its long-term effects. Methods In this single-blind randomized controlled trial, we will include 152 elderly subacute stroke patients divided in two groups to receive a traditional rehabilitation program or a robotic rehabilitation using G-EO system, an end-effector device for the gait rehabilitation, in addition to the traditional therapy. Twenty treatment sessions will be conducted, divided into 3 training sessions per week, for 7 weeks. The control group will perform traditional therapy sessions lasting 50 min. The technological intervention group, using the G-EO system, will carry out 30 min of traditional therapy and 20 min of treatment with a robotic system. The primary outcome of the study is the evaluation of the falling risk. Secondary outcomes are the assessment of the gait improvements and the fear of falling. Further evaluations, such as length and asymmetry of the step, walking and functional status, and acceptance of the technology, will be carried. Discussion The final goal of the present study is to propose a new approach and an innovative therapeutic plan in the post-stroke rehabilitation, focused on the use of a robotic device, in order to obtain the beneficial effects of this treatment. Trial registration ClinicalTrials.gov NCT04087083 . Registered on September 12, 2019

Background: This review systematically examined the scientific literature about electroencephalogram-derived ratio indexes used to assess human mental involvement, in order to deduce what they are, how they are defined and used, and what their best fields of application are. (2) Methods: The review was carried out according to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. (3) Results: From the search query, 82 documents resulted. The majority (82%) were classified as related to mental strain, while 12% were classified as related to sensory and emotion aspects, and 6% to movement. The electroencephalographic electrode montage used was low-density in 13%, high-density in 6% and very-low-density in 81% of documents. The most used electrode positions for computation of involvement indexes were in the frontal and prefrontal cortex. Overall, 37 different formulations of involvement indexes were found. None of them could be directly related to a specific field of application. (4) Conclusions: Standardization in the definition of these indexes is missing, both in the considered frequency bands and in the exploited electrodes. Future research may focus on the development of indexes with a unique definition to monitor and characterize mental involvement.

Acute Ischemic Stroke (AIS) is defined as the acute condition of occlusion of a cerebral artery and is often caused by a Hypertensive Condition (HC). Due to its sudden occurrence, AIS is not observable the right moment it occurs, thus information about instantaneous changes in hemodynamics is limited. This study aimed to propose an integrated Lumped Parameter (LP) model of the cardiovascular system to simulate an AIS and describe instantaneous changes in hemodynamics. In the integrated LP model of the cardiovascular system, heart chambers have been modelled with elastance systems with controlled pressure inputs; heart valves have been modelled with static open/closed pressure-controlled valves; eventually, the vasculature has been modelled with resistor-inductor-capacitor (RLC) direct circuits and have been linked to the rest of the system through a series connection. After simulating physiological conditions, HC has been simulated by changing pressure inputs and constant RLC parameters. Then, AIS occurring in arteries of different sizes have been simulated by considering time-dependent RLC parameters due to the elimination from the model of the occluding artery; instantaneous changes in hemodynamics have been evaluated by Systemic Arteriolar Flow (Qa) and Systemic Arteriolar Pressure (Pa) drop with respect to those measured in HC. Occlusion of arteries of different sizes leaded to an average Qa drop of 0.38 ml/s per cardiac cycle (with minimum and maximum values of 0.04 ml/s and 1.93 ml/s) and average Pa drop of 0.39 mmHg, (with minimum and maximum values of 0.04 mmHg and 1.98 mmHg). In conclusion, hemodynamic variations due to AIS are very small with respect to HC. A direct relation between the inverse of the length of the artery in which the occlusion occurs and the hemodynamic variations has been highlighted; this may allow to link the severity of AIS to the length of the interested artery.

BackgroundThis study aimed to design a simple surrogate marker (i.e., predictor) of the minimal model glucose effectiveness (SG), namely calculated SG (CSG), from a short insulin-modified intravenous glucose tolerance test (IM-IVGTT), and then to apply it to study women with previous gestational diabetes mellitus (pGDM).MethodsCSG was designed using the stepwise model selection approach on a population of subjects (n=181) ranging from normal tolerance to type 2 diabetes mellitus (T2DM). CSG was then tested on a population of women with pGDM (n=57). Each subject underwent a 3-hour IM-IVGTT; women with pGDM were observed early postpartum and after a follow-up period of up to 7 years and classified as progressors (PROG) or non-progressors (NONPROG) to T2DM. The minimal model analysis provided a reference SG.ResultsCSG was described as CSG=1.06×10−2+5.71×10−2×KG/Gpeak, KG being the mean slope (absolute value) of loge glucose in 10–25- and 25–50-minute intervals, and Gpeak being the maximum of the glucose curve. Good agreement between CSG and SG in the general population and in the pGDM group, both at baseline and follow-up (even in PROG and NONPROG subgroups), was shown by the Bland-Altman plots (

Knowledge about the anatomical structures of the left heart, specifically the atrium (LA) and ventricle (i.e., endocardium—Vendo—and epicardium—LVepi) is essential for the evaluation of cardiac functionality. Manual segmentation of cardiac structures from echocardiography is the baseline reference, but results are user-dependent and time-consuming. With the aim of supporting clinical practice, this paper presents a new deep-learning (DL)-based tool for segmenting anatomical structures of the left heart from echocardiographic images. Specifically, it was designed as a combination of two convolutional neural networks, the YOLOv7 algorithm and a U-Net, and it aims to automatically segment an echocardiographic image into LVendo, LVepi and LA. The DL-based tool was trained and tested on the Cardiac Acquisitions for Multi-Structure Ultrasound Segmentation (CAMUS) dataset of the University Hospital of St. Etienne, which consists of echocardiographic images from 450 patients. For each patient, apical two- and four-chamber views at end-systole and end-diastole were acquired and annotated by clinicians. Globally, our DL-based tool was able to segment LVendo, LVepi and LA, providing Dice similarity coefficients equal to 92.63%, 85.59%, and 87.57%, respectively. In conclusion, the presented DL-based tool proved to be reliable in automatically segmenting the anatomical structures of the left heart and supporting the cardiological clinical practice.

The brain is the organ most studied using Magnetic Resonance (MR). The emergence of 7T scanners has increased MR imaging resolution to a sub-millimeter level. However, there is a lack of automatic segmentation techniques for 7T MR volumes. This research aims to develop a novel deep learning-based algorithm for on-cloud brain extraction and multi-structure segmentation from unenhanced 7T MR volumes. To this aim, a double-stage 3D U-Net was implemented in a cloud service, directing its first stage to the automatic extraction of the brain and its second stage to the automatic segmentation of the grey matter, basal ganglia, white matter, ventricles, cerebellum, and brain stem. The training was performed on the 90% (the 10% of which served for validation) and the test on the 10% of the Glasgow database. A mean test Dice Similarity Coefficient (DSC) of 96.33% was achieved for the brain class. Mean test DSCs of 90.24%, 87.55%, 93.82%, 85.77%, 91.53%, and 89.95% were achieved for the brain structure classes, respectively. Therefore, the proposed double-stage 3D U-Net is effective in brain extraction and multi-structure segmentation from 7T MR volumes without any preprocessing and training data augmentation strategy while ensuring its machine-independent reproducibility.

Wearable and portable devices capable of acquiring cardiac signals are at the frontier of the sport industry. They are becoming increasingly popular for monitoring physiological parameters while practicing sport, given the advances in miniaturized technologies, powerful data, and signal processing applications. Data and signals acquired by these devices are increasingly used to monitor athletes’ performances and thus to define risk indices for sport-related cardiac diseases, such as sudden cardiac death. This scoping review investigated commercial wearable and portable devices employed for cardiac signal monitoring during sport activity. A systematic search of the literature was conducted on PubMed, Scopus, and Web of Science. After study selection, a total of 35 studies were included in the review. The studies were categorized based on the application of wearable or portable devices in (1) validation studies, (2) clinical studies, and (3) development studies. The analysis revealed that standardized protocols for validating these technologies are necessary. Indeed, results obtained from the validation studies turned out to be heterogeneous and scarcely comparable, since the metrological characteristics reported were different. Moreover, the validation of several devices was carried out during different sport activities. Finally, results from clinical studies highlighted that wearable devices are crucial to improve athletes’ performance and to prevent adverse cardiovascular events.

American football is the sport with the highest rates of concussion injuries. Biomedical engineering applications may support athletes in monitoring their injuries, evaluating the effectiveness of their equipment, and leading industrial research in this sport. This literature review aims to report on the applications of biomedical engineering research in American football, highlighting the main trends and gaps. The review followed the PRISMA guidelines and gathered a total of 1629 records from PubMed (n = 368), Web of Science (n = 665), and Scopus (n = 596). The records were analyzed, tabulated, and clustered in topics. In total, 112 studies were selected and divided by topic in the biomechanics of concussion (n = 55), biomechanics of footwear (n = 6), biomechanics of sport-related movements (n = 6), the aerodynamics of football and catch (n = 3), injury prediction (n = 8), heat monitoring of physiological parameters (n = 8), and monitoring of the training load (n = 25). The safety of players has fueled most of the research that has led to innovations in helmet and footwear design, as well as improvements in the understanding and prevention of injuries and heat monitoring. The other important motivator for research is the improvement of performance, which has led to the monitoring of training loads and catches, and studies on the aerodynamics of football. The main gaps found in the literature were regarding the monitoring of internal loads and the innovation of shoulder pads.

Gestational diabetes mellitus (GDM) is a type of diabetes that usually resolves at the end of the pregnancy but exposes to a higher risk of developing type 2 diabetes mellitus (T2DM). This study aimed to unravel the factors, among those that quantify specific metabolic processes, which determine progression to T2DM by using machine-learning techniques. Classification of women who did progress to T2DM (labeled as PROG, n = 19) vs. those who did not (labeled as NON-PROG, n = 59) progress to T2DM has been performed by using Orange software through a data analysis procedure on a generated data set including anthropometric data and a total of 34 features, extracted through mathematical modeling/methods procedures. Feature selection has been performed through decision tree algorithm and then Naïve Bayes and penalized (L2) logistic regression were used to evaluate the ability of the selected features to solve the classification problem. Performance has been evaluated in terms of area under the operating receiver characteristics (AUC), classification accuracy (CA), precision, sensitivity, specificity, and F1. Feature selection provided six features, and based on them, classification was performed as follows: AUC of 0.795, 0.831, and 0.884; CA of 0.827, 0.813, and 0.840; precision of 0.830, 0.854, and 0.834; sensitivity of 0.827, 0.813, and 0.840; specificity of 0.700, 0.821, and 0.662; and F1 of 0.828, 0.824, and 0.836 for tree algorithm, Naïve Bayes, and penalized logistic regression, respectively. Fasting glucose, age, and body mass index together with features describing insulin action and secretion may predict the development of T2DM in women with a history of GDM.

Women with a previous history of gestational diabetes mellitus (GDM) have increased risk of developing GDM in future pregnancies (i.e. recurrent GDM) and also Type 2 Diabetes (T2D). Insulin clearance represents one of the processes regulating glucose tolerance but has been scarcely investigated for its possible impairment in high-risk subjects. The aim of this study was to identify possible determinants of insulin clearance in women with a previous history of GDM. A detailed model-based analysis of a regular 3-hour, insulin-modified intravenous glucose tolerance test (IM-IVGTT) has been performed in women with a previous history of GDM (pGDM, n = 115) and in women who had a healthy pregnancy (CNT, n = 41) to assess total, first-phase and second-phase insulin clearance (ClINS-TOT, ClINS-FP and ClINS-SP) and other metabolic parameters (insulin sensitivity SI, glucose effectiveness SG, beta-cell function and disposition index DI). CLINS-SP was found increased in pGDM with respect to CNT and was found significantly inversely linearly correlated with SG (r = -0.20, p = 0.03, slope: -16.2, 95% CI -30.9 to -1.4, intercept: 1.1, 95% CI 0.7–1.4) and also with DI (r = -0.22, p = 0.02, slope: -10.0, 95% CI -18.5 to -1.6, intercept: 0.9, 95% CI 0.7–1.3). Disposition index, accounting for the combined contribution of insulin sensitivity and beta-cell function, and glucose effectiveness were identified as possible determinants of insulin clearance in women with a previous history of GDM. This may be of relevance for more accurate estimation and prevention of the risk for recurrent GDM and T2D.

Fetal heart rate (FHR) monitoring can serve as a benchmark to identify high-risk fetuses. Fetal phonocardiogram (FPCG) is the recording of the fetal heart sounds (FHS) by means of a small acoustic sensor placed on maternal abdomen. Being heavily contaminated by noise, FPCG processing implies mandatory filtering to make FPCG clinically usable. Aim of the present study was to perform a comparative analysis of filters based on Wavelet transform (WT) characterized by different combinations of mothers Wavelet and thresholding settings. By combining three mothers Wavelet (4th-order Coiflet, 4th-order Daubechies and 8th-order Symlet), two thresholding rules (Soft and Hard) and three thresholding algorithms (Universal, Rigorous and Minimax), 18 different WT-based filters were obtained and applied to 37 simulated and 119 experimental FPCG data (PhysioNet/PhysioBank). Filters performance was evaluated in terms of reliability in FHR estimation from filtered FPCG and noise reduction quantified by the signal-to-noise ratio (SNR). The filter obtained by combining the 4th-order Coiflet mother Wavelet with the Soft thresholding rule and the Universal thresholding algorithm was found to be optimal in both simulated and experimental FPCG data, since able to maintain FHR with respect to reference (138.7[137.7; 140.8] bpm vs. 140.2[139.7; 140.7] bpm, P > 0.05, in simulated FPCG data; 139.6[113.4; 144.2] bpm vs. 140.5[135.2; 146.3] bpm, P > 0.05, in experimental FPCG data) while strongly incrementing SNR (25.9[20.4; 31.3] dB vs. 0.7[-0.2; 2.9] dB, P < 10-14, in simulated FPCG data; 22.9[20.1; 25.7] dB vs. 15.6[13.8; 16.7] dB, P < 10-37, in experimental FPCG data). In conclusion, the WT-based filter obtained combining the 4th-order Coiflet mother Wavelet with the thresholding settings constituted by the Soft rule and the Universal algorithm provides the optimal WT-based filter for FPCG filtering according to evaluation criteria based on both noise and clinical features.

Diabetic foot syndrome is a multifactorial pathology with at least three main etiological factors, i.e., peripheral neuropathy, peripheral arterial disease, and infection. In addition to complexity, another distinctive trait of diabetic foot syndrome is its insidiousness, due to a frequent lack of early symptoms. In recent years, it has become clear that the prevalence of diabetic foot syndrome is increasing, and it is among the diabetes complications with a stronger impact on patient’s quality of life. Considering the complex nature of this syndrome, artificial intelligence (AI) methodologies appear adequate to address aspects such as timely screening for the identification of the risk for foot ulcers (or, even worse, for amputation), based on appropriate sensor technologies. In this review, we summarize the main findings of the pertinent studies in the field, paying attention to both the AI-based methodological aspects and the main physiological/clinical study outcomes. The analyzed studies show that AI application to data derived by different technologies provides promising results, but in our opinion future studies may benefit from inclusion of quantitative measures based on simple sensors, which are still scarcely exploited.

Glucagon is secreted from the pancreatic alpha cells and plays an important role in the maintenance of glucose homeostasis, by interacting with insulin. The plasma glucose levels determine whether glucagon secretion or insulin secretion is activated or inhibited. Despite its relevance, some aspects of glucagon secretion and kinetics remain unclear. To gain insight into this, we aimed to develop a mathematical model of the glucagon kinetics during an oral glucose tolerance test, which is sufficiently simple to be used in the clinical practice. The proposed model included two first-order differential equations -one describing glucagon and the other describing C-peptide in a compartment remote from plasma - and yielded a parameter of possible clinical relevance (i.e., SGLUCA(t), glucagon-inhibition sensitivity to glucose-induced insulin secretion). Model was validated on mean glucagon data derived from the scientific literature, yielding values for SGLUCA(t) ranging from -15.03 to 2.75 (ng of glucagon·nmol of C-peptide-1). A further validation on a total of 100 virtual subjects provided reliable results (mean residuals between -1.5 and 1.5 ng·L-1) and a negative significant linear correlation (r = -0.74, p < 0.0001, 95% CI: -0.82 – -0.64) between SGLUCA(t) and the ratio between the areas under the curve of suprabasal remote C-peptide and glucagon. Model reliability was also proven by the ability to capture different patterns in glucagon kinetics. In conclusion, the proposed model reliably reproduces glucagon kinetics and is characterized by sufficient simplicity to be possibly used in the clinical practice, for the estimation in the single individual of some glucagon-related parameters.

The proposed dataset provides annotations for the 552 cardiotocographic (CTG) recordings included in the publicly available “CTU-CHB intra-partum CTG database” from Physionet (https://physionet.org/content/ctu-uhb-ctgdb/1.0.0/). Each CTG recording is composed by two simultaneously acquired signals: i) the fetal heart rate (FHR) and ii) the maternal tocogram (representing uterine activity). Annotations consist in the detection of starting and ending points of specific CTG events on both FHR signal and maternal tocogram. Annotated events for the FHR signal are the bradycardia, tachycardia, acceleration and deceleration episodes. Annotated events for the maternal tocogram are the uterine contractions. The dataset also reports classification of each deceleration as early, late, variable or prolonged, in relation to the presence of a uterine contraction. Annotations were obtained by an expert gynecologist with the support of CTG Analyzer, a dedicated software application for automatic analysis of digital CTG recordings. These annotations can be useful in the development, testing and comparison of algorithms for the automatic analysis of digital CTG recordings, which can make CTG interpretation more objective and independent from clinician's experience.

The database here described contains data of integrated surveillance for the “Coronavirus disease 2019” (abbreviated as COVID-19 by the World Health Organization) in Italy, caused by the novel coronavirus SARS-CoV-2. The database, included in a main folder called COVID-19, has been designed and created by the Italian Civil Protection Department, which currently manages it. The database consists of six folders called ‘aree’ (containing charts of geographical areas interested by containment measures), ‘dati-andamento-nazionale’ (containing data relating to the national trend of SARS-CoV-2 spread), ‘dati-json’ (containing data that summarize the national, provincial and regional trends of SARS-CoV-2 spread), ‘dati-province’ (containing data relating to the provincial trend of SARS-CoV-2 spread), ‘dati-regioni’ (containing data relating to the regional trend of SARS-CoV-2 spread) and ‘schede-riepilogative’ (containing summary sheets relating to the provincial and regional trends of SARS-CoV-2 spread). The Italian Civil Protection Department daily receives data by the Italian Ministry of Health, analyzes them and updates the database. Thus, the database is subject to daily updates and integrations. The database is freely accessible (CC-BY-4.0 license) at https://github.com/pcm-dpc/COVID-19. This database is useful to provide insight on the spread mechanism of SARS-CoV-2, to support organizations in the evaluation of the efficiency of current prevention and control measures, and to support governments in the future prevention decisions.

Tidal volume (TV), defined as the amount of air that moves in or out of the lungs with each respiratory cycle, is important in evaluating the respiratory function. Although TV can be reliably measured in laboratory settings, this information is hardly obtainable under everyday living conditions. Under such conditions, wearable devices could provide valuable support to monitor vital signs, such as heart rate (HR) and breathing rate (BR). The aim of this study was to develop a model to estimate TV from wearable-device measures of HR and BR during exercise. HR and BR were acquired through the Zephyr Bioharness 3.0 wearable device in nine subjects performing incremental cycling tests. For each subject, TV during exercise was obtained with a metabolic cart (Cosmed). A stepwise regression algorithm was used to create the model using as possible predictors HR, BR, age, and body mass index; the model was then validated using a leave-one-subject-out cross-validation procedure. The performance of the model was evaluated using the explained variance (R2), obtaining values ranging from 0.65 to 0.72. The proposed model is a valid method for TV estimation with wearable devices and can be considered not subject-specific and not instrumentation-specific.

Background: Surface electromyography (SEMG) is widely used in clinics for assessing muscle functionality. All procedures proposed for noise reduction alter SEMG spectrum, especially in the low-frequency band (below 30 Hz). Indeed, low-frequency band is generally addressed to motion artifacts and electrocardiogram (ECG) interference without any further investigation on the possibility of SEMG having significant spectral content. The aim of the present study was evaluating SEMG frequency content to understand if low-frequency spectral content is negligible or, on the contrary, represents a significant SEMG portion potentially providing relevant clinical information. Method: Isometric recordings of five muscles (sternocleidomastoideus, erectores spinae at L4, rectus abdominis, rectus femoris and tibialis anterior) were acquired in 10 young healthy voluntary subjects. These recordings were not affected by motion artifacts by construction and were pre-processed by the Segmented-Beat Modulation Method for ECG deletion before performing spectral analysis. Results: Results indicated that SEMG frequency content is muscle and subject dependent. Overall, the 50th[25th;75th] percentiles spectrum median frequency and spectral power below 30 Hz were 74[54; 87] Hz and 18[10; 31] % of total (0–450 Hz) spectral power. Conclusions: Low-frequency spectral content represents a significant SEMG portion and should not be neglected. Keywords: Surface electromyographic signal, Electromyographic spectrum, Segmented-Beat Modulation Method, Non-linear filtering, Spectral analysis

Sport Database is a collection of 126 cardiorespiratory data, acquired through wearable sensors from 81 subjects while practicing 10 different sports. Each cardiorespiratory dataset consists of demographic info (gender, age, weight, height, smoking habit, alcohol consumption and weekly training rate), cardiorespiratory signals (electrocardiogram, heart-rate series, RR-interval series and breathing-rate series) and training notes. Demographic info was collected by survey. Cardiorespiratory signals were acquired through the chest strap BioHarness 3.0 by Zephyr. Eventually, training notes including the sport-dependent training protocol, were manually annotated. Sport Database may be useful to support: 1) the investigation of cardiorespiratory system adaptations to different types of physical exercise; 2) the development of automatic algorithms finalized to real-time health monitoring of athletes and preventive identification of subjects at increased risk of sport-related sudden cardiac death; and, 3) clinical testing of the BioHarness 3.0 by Zephyr. Further acquisitions could involve other sports, other cardiovascular signals and/or parameters, data from different biological systems, and other acquisition devices. Keywords: Sport acquisition, Exercise, Electrocardiogram, Heart-rate series, Breathing-rate series

The proposed dataset provides a complete set of simultaneously acquired data from contactless and wearable devices for direct and indirect heart-rate measurement. Data were acquired on a total of 20 healthy white Caucasian subjects wearing no makeup (10 males and 10 females; age: 22.50 ± 1.57 years; height: 173 ± 10 cm; weight: 62.80 ± 9.52 kg) and consisted of: i) videos of the subject's face acquired by a RGB-D (Red, Green, Blue and Depth) camera (Microsoft Kinect v2), which is a contactless device; ii) electrocardiographic (ECG) recordings acquired by a clinical Holter ECG recorder (Global Instrumentation's M12R Holter), which is a wearable device; and iii) heart-rate measurements acquired from a commercial smartwatch (Moto 360 smartwatch by Motorola), which is also a wearable device. ECG recordings were processed to extract the R-peaks position and obtain a reference indirect measurement of the heart rate. A direct measurement of the heart rate was provided by the commercial smartwatch. The dataset here presented could be useful to develop new algorithms for heart-rate detection from contactless devices and to validate contactless heart-rate estimation in comparison to reference heart rate from clinical wearable devices and to heart rate from commercial wearable devices. Keywords: Heart-rate measurement, Contactless sensing, RGB-D sensors, Holter electrocardiography, Wearable sensor

This paper describes a dataset acquired on 8 subjects while simulating 13 types of falls and 5 types of Activities of Daily Living (ADL), each repeated 3 times. In details, data includes 4 simulated falls forward (falling on knees ending up lying, ending in lateral position, ending up lying, ending up lying with recovery), 4 backward (falling sitting ending up lying, ending in lateral position, ending up lying, ending up lying with recovery), 2 lateral right (ending up lying, ending up lying with recovery), 2 lateral left (ending up lying, ending up lying with recovery), and 1 syncope. Simulated ADL are: lying on a bed then standing; walking a few meters; sitting on a chair then standing; go up or down three steps; and standing after picking something. Data were acquired using a MARG sensor, a wearable multisensory device tied to the subject's waist, that recorded time-variations of the subject's acceleration and orientation (expressed through the yaw, pitch and roll angles). These data can be useful in the development and test of algorithms to automatically identify and classify fall events. Fall detection systems are particularly useful when a subject is alone and not able to stand up after a fall, since an automatic alarm can be sent remotely to receive proper help. Keywords: Human fall, Fall detection, MARG (Magnetic Angular Rate and Gravity) sensor, Wearable device

The aim of this study was to investigate whether incretins, at physiological levels, affect hepatic and/or extrahepatic insulin clearance. Hepatic and extrahepatic insulin clearance was studied in 31 double incretin receptor knockout (DIRKO) and 45 wild-type (WT) mice, which underwent an Intravenous Glucose Tolerance Test (IVGTT). A novel methodology based on mathematical modeling was designed to provide two sets of values (FEL-P1, CLP-P1; FEL-P2, CLP-P2) accounting for hepatic and extrahepatic clearance in the IVGTT first and second phases, respectively, plus the respective total clearances, CLT-P1 and CLT-P2. A statistically significant difference between DIRKO and WT was found in CLT-P1 (0.61 [0.48–0.82] vs. 0.51 [0.46–0.65] (median [interquartile range]); p = 0.02), which was reflected in the peripheral component, CLP-P1 (0.18 [0.13–0.27] vs. 0.15 [0.11–0.22]; p = 0.04), but not in the hepatic component, FEL-P1 (29.7 [26.7–34.9] vs. 28.9 [25.7–32.0]; p = 0.18). No difference was detected between DIRKO and WT in CLT-P2 (1.38 [1.13–1.75] vs. 1.69 [1.48–1.87]; p = 0.10), neither in CLP-P2 (0.72 [0.64–0.81] vs. 0.79 [0.69–0.87]; p = 0.27) nor in FEL-P2 (37.8 [35.1–43.1] vs. 39.8 [35.8–44.2]; p = 0.46). In conclusion, our findings suggest that the higher insulin clearance observed in DIRKO compared with WT during the IVGTT first phase may be due to its extrahepatic component.

A new surgical procedure for the treatment of primary bladder neck obstruction with maintenance of anterograde ejaculation is proposed. In place of monolateral or bilateral bladder neck incision, associated with a loss of ejaculation rate of up to 30%, the new surgical procedure consists of laser drilling the bladder neck with a number of holes and without muscle fiber disruption. The effect of this novel procedure has been studied numerically, with a simplified two-dimensional numerical model of the internal urethral sphincter, varying the position and the number of holes in the fibrotic region of the urethral tissue. Results show an improvement of the urethral sphincter opening by increasing the number of holes, ranging from about 6% to 16% of recovery. Moreover, a non-aligned position of holes positively influences the opening recovery. The concentrations of maximum principal strain and stress have been registered in the proximity of the interface between the physiologic and diseased sphincter, and in those regions where the radial thickness is significantly thinner. The effects on the first five patients have been included in the study, showing improvement in micturition, lower urinary tract symptoms, sustained ejaculatory function, and quality of life.

Atrial fibrillation (AF) is a common cardiac disorder that can cause severe complications. AF diagnosis is typically based on the electrocardiogram (ECG) evaluation in hospitals or in clinical facilities. The aim of the present work is to propose a new artificial neural network for reliable AF identification in ECGs acquired through portable devices. A supervised fully connected artificial neural network (RSL_ANN), receiving 19 ECG features (11 morphological, 4 on F waves and 4 on heart-rate variability (HRV)) in input and discriminating between AF and non-AF classes in output, was created using the repeated structuring and learning (RSL) procedure. RSL_ANN was created and tested on 8028 (training: 4493; validation: 1125; testing: 2410) annotated ECGs belonging to the “AF Classification from a Short Single Lead ECG Recording” database and acquired with the portable KARDIA device by AliveCor. RSL_ANN performance was evaluated in terms of area under the curve (AUC) and confidence intervals (CIs) of the received operating characteristic. RSL_ANN performance was very good and very similar in training, validation and testing datasets. AUC was 91.1% (CI: 89.1–93.0%), 90.2% (CI: 86.2–94.3%) and 90.8% (CI: 88.1–93.5%) for the training, validation and testing datasets, respectively. Thus, RSL_ANN is a promising tool for reliable identification of AF in ECGs acquired by portable devices.

The beneficial effects of physical activity for the prevention and management of several chronic diseases are widely recognized. Mathematical modeling of the effects of physical exercise in body metabolism and in particular its influence on the control of glucose homeostasis is of primary importance in the development of eHealth monitoring devices for a personalized medicine. Nonetheless, to date only a few mathematical models have been aiming at this specific purpose. We have developed a whole-body computational model of the effects on metabolic homeostasis of a bout of physical exercise. Built upon an existing model, it allows to detail better both subjects' characteristics and physical exercise, thus determining to a greater extent the dynamics of the hormones and the metabolites considered.

Objective: Inflammatory cytokines released by hypertrophic adipocytes contribute to low-grade inflammation, a characteristic of Type 2 Diabetes. Skeletal muscle contraction during physical activity stimulates the secretion of anti-inflammatory cytokines able to counteract this inflammatory status. The aim of this study was to review the evidence of the effectiveness of walking as a physical activity intervention to reduce inflammation. The interplay between adipose tissue and skeletal muscle contributions was also investigated. Method: A structured literature review of papers available up to December 2014 was carried out within the PubMed, Scopus and ISI Web of Science databases using the keywords “walking” and “inflammation” in order to identify the studies involving healthy subjects and subjects diagnosed with, or at increased risk of, Type 2 Diabetes. Results: Thirty-two studies were reviewed, five investigating the acute effects of walking and twenty-seven its chronic effects (n = 21 interventional and n = 6 observational). Acute effects of walking bouts led to an increase of interleukin-6 in one study, although without any increase in the concentration of the anti-inflammatory marker interleukin-1 receptor antagonist. Eight interventional studies showed a significant reduction of inflammation. A reduction in tumour necrosis factor-α concentration was often associated with an adiposity reduction. The observational studies showed that individuals who walk more present a lower inflammatory status. Conclusion: There is no consensus regarding the efficacy of walking in the reduction of low-grade systemic inflammation, even though a relationship cannot be excluded. In each walking bout, no anti-inflammatory effect due to the IL-6-stimulated myokine cascade can be demonstrated.

Interleukin-6 (IL-6) has been recently shown to play a central role in glucose homeostasis, since it stimulates the production and secretion of Glucagon-like Peptide-1 (GLP-1) from intestinal L-cells and pancreas, leading to an enhanced insulin response. In resting conditions, IL-6 is mainly produced by the adipose tissue whereas, during exercise, skeletal muscle contractions stimulate a marked IL-6 secretion as well. Available mathematical models describing the effects of exercise on glucose homeostasis, however, do not account for this IL-6 contribution. This study aimed at developing and validating a system model of exercise's effects on plasma IL-6 dynamics in healthy humans, combining the contributions of both adipose tissue and skeletal muscle. A two-compartment description was adopted to model plasma IL-6 changes in response to oxygen uptake's variation during an exercise bout. The free parameters of the model were estimated by means of a cross-validation procedure performed on four different datasets. A low coefficient of variation (

For the assessment of glucose tolerance from IVGTT data in Zucker rat, minimal model methodology is reliable but time- and money-consuming. This study aimed to validate for the first time in Zucker rat, simple surrogate indexes of insulin sensitivity and secretion against the glucose-minimal-model insulin sensitivity index (SI) and against first- (Φ1) and second-phase (Φ2) β-cell responsiveness indexes provided by C-peptide minimal model. Validation of the surrogate insulin sensitivity index (ISI) and of two sets of coupled insulin-based indexes for insulin secretion, differing from the cut-off point between phases (FPIR3-SPIR3, t = 3 min and FPIR5-SPIR5, t = 5 min), was carried out in a population of ten Zucker fatty rats (ZFR) and ten Zucker lean rats (ZLR). Considering the whole rat population (ZLR+ZFR), ISI showed a significant strong correlation with SI (Spearman's correlation coefficient, r = 0.88; P

A C-peptide-based assessment of β-cell function was performed here in the Zucker fatty rat, a suitable animal model of human metabolic syndrome. To this aim, a 90-min intravenous glucose tolerance test (IVGTT) was performed in seven Zucker fatty rats (ZFR), 7-to-9 week-old, and seven age-matched Zucker lean rats (ZLR). The minimal model of C-peptide (CPMM), originally introduced for humans, was adapted to Zucker rats and then applied to interpret IVGTT data. For a comprehensive evaluation of glucose tolerance in ZFR, CPMM was applied in combination with the minimal model of glucose kinetics (GKMM). Our results showed that the present CPMM-based interpretation of data is able to: 1) provide a suitable fit of C-Peptide data; 2) achieve a satisfactory estimation of parameters of interest 3) quantify both insulin secretion by estimating the time course of pre-hepatic secretion rate, SR(t), and total insulin secretion, TIS, and pancreatic sensitivity by means of three specific indexes of β-cell responsiveness to glucose stimulus (first-phase, Ф(1), second-phase, Ф(2), and steady-state, Ф(ss), never assessed in Zucker rats before; 4) detect the significant enhancement of insulin secretion in the ZFR, in face of a severe insulin-resistant state, previously observed only using a purely experimental approach. Thus, the methodology presented here represents a reliable tool to assess β-cell function in the Zucker rat, and opens new possibilities for the quantification of further processes involved in glucose homeostasis such as the hepatic insulin degradation.