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Aims: This review evaluates the mechanisms underlying red blood cell (RBC) membrane fluidity changes in diabetes mellitus (DM) and explores strategies to assess and address these alterations. Emphasis is placed on developing a comprehensive index for membrane fluidity to improve monitoring and management in diabetic patients., Materials and Methods: We reviewed current literature on RBC membrane fluidity, focussing on lipid composition, glycation, oxidative stress, and lipid transport alterations in diabetic patients. Key methodologies include lipidomics, multi-scale probe assessment, and machine learning integration for standardized fluidity measurement., Results: Diabetic RBCs exhibit increased membrane fluidity, primarily due to oxidative stress, increased glycation, and dysregulated lipid composition. These alterations contribute to vascular complications and impair RBC functionality. Assessing membrane composition as a nutritional marker provides insights into the metabolic impacts of glycaemic management., Conclusions: There is a critical need for a unified and comprehensive membrane fluidity index in DM, which could support personalised interventions through dietary, medicinal, and lifestyle modifications. Future research should prioritise standardising measurement techniques and integrating lipidomic data with machine learning for predictive modelling, aiming to enhance clinical outcomes for diabetic patients., (© 2024 The Author(s). Diabetes/Metabolism Research and Reviews published by John Wiley & Sons Ltd.)

Recent studies have shown a growing interest in the complex relationship between the human gut microbiota, metabolism, and overall health. This review aims to explore the gut microbiota-host association, focusing on its implications for precision nutrition and personalized medicine. The objective is to highlight how gut microbiota modulate metabolic and immune functions, contributing to disease susceptibility and wellbeing. The review synthesizes recent research findings, analyzing key studies on the influence of gut microbiota on lipid and carbohydrate metabolism, intestinal health, neurobehavioral regulation, and endocrine signaling. Data were drawn from both experimental and clinical trials examining microbiota-host interactions relevant to precision nutrition. Our findings highlight the essential role of gut microbiota-derived metabolites in regulating host metabolism, including lipid and glucose pathways. These metabolites have been found to influence immune responses and gut barrier integrity. Additionally, the microbiota impacts broader physiological processes, including neuroendocrine regulation, which could be crucial for dietary interventions. Therefore, understanding the molecular mechanisms of dietary-microbiota-host interactions is pivotal for advancing personalized nutrition strategies. Tailored dietary recommendations based on individual gut microbiota compositions hold promise for improving health outcomes, potentially revolutionizing future healthcare approaches across diverse populations.

Objective: Maintaining plasma glucose homeostasis is vital for mammalian survival, but the masticatory function, which influences glucose regulation, has, to our knowledge, been overlooked., Research Methods and Procedures: In this study, we investigated the relationship between the glycemic response curve and chewing performance in a group of 8 individuals who consumed 80 g of apple. A device called "Chewing" utilizing electromyographic (EMG) technology quantitatively assesses chewing pattern, while glycemic response is analyzed using continuous glucose monitoring. We assessed chewing pattern characterizing chewing time (t chew ), number of bites (n chew ), work (w), power (wr), and chewing cycles (t cyc ). Moreover, we measured the principal features of the glycemic response curve, including the area under the curve (α) and the mean time to reach the glycemic peak (t mean ). We used linear regression models to examine the correlations between these variables., Results: t chew , n chew , and wr were correlated with α (R 2 =  0.44,   P  <  0.05 for t chew and n chew , P  <  0.001 for wr), and t mean was correlated with t chew (R 2   =  0.25,  P  <  0.05). These findings suggest that increasing chewing time and power, while reducing the number of chews, resulted in a wider glycemic curve and an earlier attainment of the glycemic peak., Conclusions: These results emphasize the influence of proper chewing techniques on blood sugar levels. Implementing correct chewing habits could serve as an additional approach to managing the glycemic curve, particularly for individuals with diabetes., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Giuseppe Maulucci reports financial support was provided by Regione Lazio PO FSE 2014-2020. “Chewing Performance” was taken from the article by Alessia Riente et al. title “Evaluation of the masticatory pattern through an electromyographic device” by the same co-authors., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The rising obesity epidemic requires effective and sustainable weight loss intervention strategies that take into account both of individual preferences and environmental impact. This study aims to develop and evaluate the effectiveness of an innovative digital biohacking approach for dietary modifications in promoting sustainable weight loss and reducing carbon footprint impact. A pilot study was conducted involving four participants who monitored their weight, diet, and activities over the course of a year. Data on food consumption, carbon footprint impact, calorie intake, macronutrient composition, weight, and energy expenditure were collected. A digital replica of the metabolism based on nutritional information, the Personalized Metabolic Avatar (PMA), was used to simulate weight changes, plan, and execute the digital biohacking approach to dietary interventions. The dietary modifications suggested by the digital biohacking approach resulted in an average daily calorie reduction of 236.78 kcal (14.24%) and a 15.12% reduction in carbon footprint impact (-736.48 gCO 2 eq) per participant. Digital biohacking simulations using PMA showed significant differences in weight change compared to actual recorded data, indicating effective weight reduction with the digital biohacking diet. Additionally, linear regression analysis on real data revealed a significant correlation between adherence to the suggested diet and weight loss. In conclusion, the digital biohacking recommendations provide a personalized and sustainable approach to weight loss, simultaneously reducing calorie intake and minimizing the carbon footprint impact. This approach shows promise in combating obesity while considering both individual preferences and environmental sustainability.

The objective of this review was to critically examine existing digital applications, tailored for use by citizens and professionals, to provide diet monitoring, diet planning, and precision nutrition. We sought to identify the strengths and weaknesses of such digital applications, while exploring their potential contributions to enhancing public health, and discussed potential developmental pathways. Nutrition is a critical aspect of maintaining good health, with an unhealthy diet being one of the primary risk factors for chronic diseases, such as obesity, diabetes, and cardiovascular disease. Tracking and monitoring one's diet has been shown to help improve health and weight management. However, this task can be complex and time-consuming, often leading to frustration and a lack of adherence to dietary recommendations. Digital applications for diet monitoring, diet generation, and precision nutrition offer the promise of better health outcomes. Data on current nutrition-based digital tools was collected from pertinent literature and software providers. These digital tools have been designed for particular user groups: citizens, nutritionists, and physicians and researchers employing genetics and epigenetics tools. The applications were evaluated in terms of their key functionalities, strengths, and limitations. The analysis primarily concentrated on artificial intelligence algorithms and devices intended to streamline the collection and organization of nutrition data. Furthermore, an exploration was conducted of potential future advancements in this field. Digital applications designed for the use of citizens allow diet self-monitoring, and they can be an effective tool for weight and diabetes management, while digital precision nutrition solutions for professionals can provide scalability, personalized recommendations for patients, and a means of providing ongoing diet support. The limitations in using these digital applications include data accuracy, accessibility, and affordability, and further research and development are required. The integration of artificial intelligence, machine learning, and blockchain technology holds promise for improving the performance, security, and privacy of digital precision nutrition interventions. Multidisciplinarity is crucial for evidence-based and accessible solutions. Digital applications for diet monitoring and precision nutrition have the potential to revolutionize nutrition and health. These tools can make it easier for individuals to control their diets, help nutritionists provide better care, and enable physicians to offer personalized treatment., (© The Author(s) 2024. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aims: Improving the composition of circulating fatty acids (FA) leads to a reduction in cardiovascular diseases (CVD) in high-risk individuals. The membrane fluidity of red blood cells (RBC), which reflects circulating FA status, may be a valid biomarker of cardiovascular (CV) risk in type 2 diabetes (T2D)., Methods: Red blood cell membrane fluidity, quantified as general polarization (GP), was assessed in 234 subjects with T2D, 86 with prior major CVD. Based on GP distribution, a cut-off of .445 was used to divide the study cohort into two groups: the first with higher GP, called GEL, and the second, defined as lower GP (LGP). Lipidomic analysis was performed to evaluate FA composition of RBC membranes., Results: Although with comparable CV risk factors, the LGP group had a greater percentage of patients with major CVD than the GEL group (40% vs 24%, respectively, p < .05). Moreover, in a logistic regression analysis, a lower GP value was independently associated with the presence of macrovascular complications. Lipidomic analysis showed a clear shift of LGP membranes towards a pro-inflammatory condition due to higher content of arachidonic acid and increased omega 6/omega 3 index., Conclusions: Increased membrane fluidity is associated with a higher CV risk in subjects with T2D. If confirmed in prospective studies, membrane fluidity could be a new biomarker for residual CV risk assessment in T2D., (© 2023 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

The human gut microbiome, an intricate ecosystem housing trillions of microorganisms within the gastrointestinal tract, holds significant importance in human health and the development of diseases. Recent advances in technology have allowed for an in-depth exploration of the gut microbiome, shedding light on its composition and functions. Of particular interest is the role of diet in shaping the gut microbiome, influencing its diversity, population size, and metabolic functions. Precision nutrition, a personalized approach based on individual characteristics, has shown promise in directly impacting the composition of the gut microbiome. However, to fully understand the long-term effects of specific diets and food components on the gut microbiome and to identify the variations between individuals, longitudinal studies are crucial. Additionally, precise methods for collecting dietary data, alongside the application of machine learning techniques, hold immense potential in comprehending the gut microbiome's response to diet and providing tailored lifestyle recommendations. In this study, we investigated the complex mechanisms that govern the diverse impacts of nutrients and specific foods on the equilibrium and functioning of the individual gut microbiome of seven volunteers (four females and three males) with an average age of 40.9 ± 10.3 years, aiming at identifying potential therapeutic targets, thus making valuable contributions to the field of personalized nutrition. These findings have the potential to revolutionize the development of highly effective strategies that are tailored to individual requirements for the management and treatment of various diseases.

Chewing is essential in regulating metabolism and initiating digestion. Various methods have been used to examine chewing, including analyzing chewing sounds and using piezoelectric sensors to detect muscle contractions. However, these methods struggle to distinguish chewing from other movements. Electromyography (EMG) has proven to be an accurate solution, although it requires sensors attached to the skin. Existing EMG devices focus on detecting the act of chewing or classifying foods and do not provide self-awareness of chewing habits. We developed a non-invasive device that evaluates a personalized chewing style by analyzing various aspects, like chewing time, cycle time, work rate, number of chews and work. It was tested in a case study comparing the chewing pattern of smokers and non-smokers, as smoking can alter chewing habits. Previous studies have shown that smokers exhibit reduced chewing speed, but other aspects of chewing were overlooked. The goal of this study is to present the device and provide additional insights into the effects of smoking on chewing patterns by considering multiple chewing features. Statistical analysis revealed significant differences, as non-smokers had more chews and higher work values, indicating more efficient chewing. The device provides valuable insights into personalized chewing profiles and could modify unhealthy chewing habits.

Nutrition is a cross-cutting sector in medicine, with a huge impact on health, from cardiovascular disease to cancer. Employment of digital medicine in nutrition relies on digital twins: digital replicas of human physiology representing an emergent solution for prevention and treatment of many diseases. In this context, we have already developed a data-driven model of metabolism, called a "Personalized Metabolic Avatar" (PMA), using gated recurrent unit (GRU) neural networks for weight forecasting. However, putting a digital twin into production to make it available for users is a difficult task that as important as model building. Among the principal issues, changes to data sources, models and hyperparameters introduce room for error and overfitting and can lead to abrupt variations in computational time. In this study, we selected the best strategy for deployment in terms of predictive performance and computational time. Several models, such as the Transformer model, recursive neural networks (GRUs and long short-term memory networks) and the statistical SARIMAX model were tested on ten users. PMAs based on GRUs and LSTM showed optimal and stable predictive performances, with the lowest root mean squared errors (0.38 ± 0.16-0.39 ± 0.18) and acceptable computational times of the retraining phase (12.7 ± 1.42 s-13.5 ± 3.60 s) for a production environment. While the Transformer model did not bring a substantial improvement over RNNs in term of predictive performance, it increased the computational time for both forecasting and retraining by 40%. The SARIMAX model showed the worst performance in term of predictive performance, though it had the best computational time. For all the models considered, the extent of the data source was a negligible factor, and a threshold was established for the number of time points needed for a successful prediction.

Diabetes-induced oxidative stress induces the development of vascular complications, which are significant causes of morbidity and mortality in diabetic patients. Among these, diabetic retinopathy (DR) is often caused by functional changes in the blood-retinal barrier (BRB) due to harmful oxidative stress events in lipids, proteins, and DNA. Docosahexaenoic acid (DHA) has a potential therapeutic effect against hyperglycemia-induced oxidative damage and apoptotic pathways in the main constituents of BRB, retinal pigment epithelium cells (ARPE-19). Effective antioxidant response elicited by DHA is driven by the activation of the Nrf2/Nqo1 signaling cascade, which leads to the formation of NADH, a reductive agent found in the cytoplasm. Nrf2 also induces the expression of genes encoding enzymes involved in lipid metabolism. This study, therefore, aims at investigating the modulation of lipid metabolism induced by high-glucose (HG) on ARPE-19 cells through the integration of metabolic imaging and molecular biology to provide a comprehensive functional and molecular characterization of the mechanisms activated in the disease, as well the therapeutic role of DHA. This study shows that HG augments RPE metabolic processes by enhancing lipid metabolism, from fatty acid uptake and turnover to lipid biosynthesis and β-oxidation. DHA exerts its beneficial effect by ameliorating lipid metabolism and reducing the increased ROS production under HG conditions. This investigation may provide novel insight for formulating novel treatments for DR by targeting lipid metabolism pathways.

During exercise with increasing intensity, the human body transforms energy with mechanisms dependent upon actual requirements. Three phases of the body's energy utilization are recognized, characterized by different metabolic processes, and separated by two threshold points, called aerobic (AerT) and anaerobic threshold (AnT). These thresholds occur at determined values of exercise intensity(workload) and can change among individuals. They are considered indicators of exercise capacities and are useful in the personalization of physical activity plans. They are usually detected by ventilatory or metabolic variables and require expensive equipment and invasive measurements. Recently, particular attention has focused on AerT, which is a parameter especially useful in the overweight and obese population to determine the best amount of exercise intensity for weight loss and increasing physical fitness. The aim of study is to propose a new procedure to automatically identify AerT using the analysis of recurrences (RQA) relying only on Heart rate time series, acquired from a cohort of young athletes during a sub-maximal incremental exercise test (Cardiopulmonary Exercise Test, CPET) on a cycle ergometer. We found that the minima of determinism, an RQA feature calculated from the Recurrence Quantification by Epochs (RQE) approach, identify the time points where generic metabolic transitions occur. Among these transitions, a criterion based on the maximum convexity of the determinism minima allows to detect the first metabolic threshold. The ordinary least products regression analysis shows that values of the oxygen consumption VO 2 , heart rate (HR), and Workload correspondent to the AerT estimated by RQA are strongly correlated with the one estimated by CPET (r > 0.64). Mean percentage differences are <2% for both HR and VO 2 and <11% for Workload. The Technical Error for HR at AerT is <8%; intraclass correlation coefficients values are moderate (≥0.66) for all variables at AerT. This system thus represents a useful method to detect AerT relying only on heart rate time series, and once validated for different activities, in future, can be easily implemented in applications acquiring data from portable heart rate monitors.

Heart rate time series are widely used to characterize physiological states and athletic performance. Among the main indicators of metabolic and physiological states, the detection of metabolic thresholds is an important tool in establishing training protocols in both sport and clinical fields. This paper reviews the most common methods, applied to heart rate (HR) time series, aiming to detect metabolic thresholds. These methodologies have been largely used to assess energy metabolism and to identify the appropriate intensity of physical exercise which can reduce body weight and improve physical fitness. Specifically, we focused on the main nonlinear signal evaluation methods using HR to identify metabolic thresholds with the purpose of identifying a method which can represent a useful tool for the real-time settings of wearable devices in sport activities. While the advantages and disadvantages of each method, and the possible applications, are presented, this review confirms that the nonlinear analysis of HR time series represents a solid, robust and noninvasive approach to assess metabolic thresholds.

In this work, we will investigate if red blood cell (RBC) membrane fluidity, influenced by several hyperglycemia-induced pathways, could provide a complementary index of HbA1c to monitor the development of type 2 diabetes mellitus (T2DM)-related macroangiopathic complications such as Peripheral Artery Disease (PAD). The contextual liquid crystalline (LC) domain spatial organization in the membrane was analysed to investigate the phase dynamics of the transition. Twenty-seven patients with long-duration T2DM were recruited and classified in DM, including 12 non-PAD patients, and DM + PAD, including 15 patients in any stage of PAD. Mean values of RBC generalized polarization (GP), representative of membrane fluidity, together with spatial organization of LC domains were compared between the two groups; p-values < 0.05 were considered statistically significant. Although comparable for anthropometric characteristics, duration of diabetes, and HbA1c, RBC membranes of PAD patients were found to be significantly more fluid (GP: 0.501 ± 0.026) than non-PAD patients (GP: 0.519 ± 0.007). These alterations were shown to be triggered by changes in both LC microdomain composition and distribution. We found a decrease in Feret diameter from 0.245 ± 0.281 μm in DM to 0.183 ± 0.124 μm in DM + PAD, and an increase in circularity. Altered RBC membrane fluidity is correlated to a spatial reconfiguration of LC domains, which, by possibly altering metabolic function, are associated with the development of T2DM-related macroangiopathic complications.

Development of predictive computational models of metabolism through mechanistic models is complex and resource demanding, and their personalization remains challenging. Data-driven models of human metabolism would constitute a reliable, fast, and continuously updating model for predictive analytics. Wearable devices, such as smart bands and impedance balances, allow the real time and remote monitoring of physiological parameters, providing for a flux of data carrying information on user metabolism. Here, we developed a data-driven model of end-user metabolism, the Personalized Metabolic Avatar (PMA), to estimate its personalized reactions to diets. PMA consists of a gated recurrent unit (GRU) deep learning model trained to forecast personalized weight variations according to macronutrient composition and daily energy balance. The model can perform simulations and evaluation of diet plans, allowing the definition of tailored goals for achieving ideal weight. This approach can provide the correct clues to empower citizens with scientific knowledge, augmenting their self-awareness with the aim to achieve long-lasting results in pursuing a healthy lifestyle., Competing Interests: The authors declare no conflict of interest.

Diabetes-induced oxidative stress leads to the onset of vascular complications, which are major causes of disability and death in diabetic patients. Among these, diabetic retinopathy (DR) often arises from functional alterations of the blood-retinal barrier (BRB) due to damaging oxidative stress reactions in lipids, proteins, and DNA. This study aimed to investigate the impact of the ω3-polyunsaturated docosahexaenoic acid (DHA) on the regulation of redox homeostasis in the human retinal pigment epithelial (RPE) cell line (ARPE-19) under hyperglycemic-like conditions. The present results show that the treatment with DHA under high-glucose conditions activated erythroid 2-related factor Nrf2, which orchestrates the activation of cellular antioxidant pathways and ultimately inhibits apoptosis. This process was accompanied by a marked increase in the expression of NADH (Nicotinamide Adenine Dinucleotide plus Hydrogen) Quinone Oxidoreductase 1 (Nqo1), which is correlated with a contextual modulation and intracellular re-organization of the NAD+/NADH redox balance. This investigation of the mechanisms underlying the impairment induced by high levels of glucose on redox homeostasis of the BRB and the subsequent recovery provided by DHA provides both a powerful indicator for the detection of RPE cell impairment as well as a potential metabolic therapeutic target for the early intervention in its treatment.

VO 2 max index has a significant impact on overall health. Its estimation through wearables notifies the user of his level of fitness but cannot provide a detailed analysis of the time intervals in which heartbeat dynamics are changed and/or fatigue is emerging. Here, we developed a multiple modality biosignal processing method to investigate running sessions to characterize in real time heartbeat dynamics in response to external energy demand. We isolated dynamic regimes whose fraction increases with the VO 2 max and with the emergence of neuromuscular fatigue. This analysis can be extremely valuable by providing personalized feedback about the user's fitness level improvement that can be realized by developing personalized exercise plans aimed to target a contextual increase in the dynamic regime fraction related to VO 2 max increase, at the expense of the dynamic regime fraction related to the emergence of fatigue. These strategies can ultimately result in the reduction in cardiovascular risk.

Self-monitoring of weight, diet and physical activity is a valuable component of behavioral weight loss treatment. The validation and user-friendliness of this approach is not optimal since users are selected from homogeneous pools and rely on different applications, increasing the burden and achieving partial, generic and/or unrelated information about their metabolic state. Moreover, studies establishing type, time, duration, and adherence criteria for self-monitoring are lacking. In this study, we developed a digital web-based application (ArmOnIA), which integrates dietary, anthropometric, and physical activity data and provides a personalized estimation of energy balance. Moreover, we determined type, time, duration, and adherence criteria for self-monitoring to achieve significant weight loss in a highly heterogeneous group. A single-arm, uncontrolled prospective study on self-monitored voluntary adults for 7 months was performed. Hierarchical clustering of adherence parameters yielded three behavioral approaches: high (HA), low (LA), and medium (MA) adherence. Average BMI decrease is statistically significant between LA and HA. Moreover, we defined thresholds for the minimum frequencies and duration of dietary and weight self-monitoring. This approach can provide the correct clues to empower citizens with scientific knowledge, augmenting their self-awareness with the aim of achieving long-lasting results when pursuing a healthy lifestyle.

Rationale, Aims and Objectives: Early reperfusion is the key to therapeutic success in acute myocardial infarction (AMI). The duration of the process is influenced by various factors which in most of the cases are not easily modifiable. The aim of this study is to analyse AMI treatment process duration to identify determining factors. The objective is to better exploit time intervals imposed by spatial distance from the hospital., Method: One-year data regarding acute coronary syndromes with elevated ST segment for patients presenting to Policlinico teaching hospital (Modena, Italy) have been studied. Patients were divided into two groups for hospital access: A - ambulance access to Policlinico emergency room (ER); B - self-referral to ER., Results: A total of 141 patients have undergone percutaneous transluminal coronary angioplasty for AMI at Policlinico, 106 males, 35 females (58.1% males in group A, 82.7% in B, P 0.002), with an average age of 66.09 ± 14.30 years in group A and 60.90 ± 13.47 in B (P 0.047). Mean pre-hospital time for group A was 122.54 ± 130.69 minutes and B 171.49 ± 353.60 (P 0.25), mean hospital time in group A was 196.03 ± 67.66 and B 255.14 ± 113.16 (P<0.001), mean total time in group A was 318.56 ± 146.91 and B 426.63 ± 382.01 (P 0.02)., Discussion: Data show that group B suffered on average a 108-minute delay from symptoms insurgence to definitive treatment. The duration of hospital time plays more important role in this finding than distance from the medical facility. In fact, on the ambulance a medical crew starts the diagnostic and therapeutic process relieving ER from initial evaluation., (© 2010 Blackwell Publishing Ltd.)

The collagen, elastin and total sugar content was evaluated in 32 samples of saphenous varicose veins and in 34 controls. A significantly lower collagen and elastin content was found in the varicose samples. In addition, the total sugars and the soluble non-scleroproteins were found to be increased in varicose samples. The results are more significant when expressed as mg per unit surface of endothelium. Our findings support the hypothesis that the decrease in collagen and elastin content is a primary rather than a secondary change.