Automatic Control of General Anesthesia: New Developments and Clinical Experiments

L’anestesia generale è uno stato di coma farmacologicamente indotto, temporaneo e reversibile. Il suo obiettivo consiste nel provocare la perdita totale della coscienza e nel sopprimere la percezione del dolore. Essa costituisce un aspetto fondamentale per la medicina moderna in quanto consente di praticare interventi chirurgici invasivi senza causare ansia e dolore al paziente. Nella pratica clinica dell’anestesia totalmente endovenosa questi effetti vengono generalmente ottenuti mediante la somministrazione simultanea del farmaco ipnotico propofol e del farmaco analgesico remifentanil. Il dosaggio di questi farmaci viene gestito dal medico anestesista basandosi su linee guida farmacologiche e monitorando la risposta clinica del paziente. Recenti sviluppi nelle tecniche di elaborazione dei segnali fisiologici hanno consentito di ottenere degli indicatori quantitativi dello stato anestetico del paziente. Tali indicatori possono essere utilizzati come segnali di retroazione per sistemi di controllo automatico dell'anestesia. Lo sviluppo di questi sistemi ha come obiettivo quello di fornire uno strumento di supporto per l'anestesista. Il lavoro presentato in questa tesi è stato svolto nell'ambito del progetto di ricerca riguardante il controllo automatico dell'anestesia attivo presso l'Università degli Studi di Brescia. Esso è denominato ACTIVA (Automatic Control of Total IntraVenous Anesthesia) ed è il risultato della collaborazione tra il Gruppo di Ricerca sui Sistemi di Controllo dell’Università degli Studi di Brescia e l’Unità Operativa Anestesia e Rianimazione 2 degli Spedali Civili di Brescia. L’obiettivo del progetto ACTIVA consiste nello sviluppo teorico, nell’implementazione e nella validazione clinica di strategie di controllo innovative per il controllo automatico dell’anestesia totalmente endovenosa. Nel dettaglio, in questa tesi vengono inizialmente presentati i risultati sperimentali ottenuti con strutture di controllo basate sull'algoritmo PID e PID ad eventi per la somministrazione di propofol e remifentanil. Viene poi presentato lo sviluppo teorico e la validazione clinica di strutture di controllo predittivo basate su modello. Successivamente vengono presentati i risultati di uno studio in simulazione riguardante una soluzione di controllo innovativa che consente all'anestesista di regolare esplicitamente il bilanciamento tra propofol e remifentanil. Infine, vengono presentati gli sviluppi teorici ed i relativi studi in simulazione riguardanti soluzioni di controllo personalizzate per le fasi di induzione e mantenimento dell'anestesia.General anesthesia is a state of pharmacologically induced, temporary and reversible coma. Its goal is to cause total loss of consciousness and suppress the perception of pain. It constitutes a fundamental aspect of modern medicine as it allows invasive surgical procedures to be performed without causing anxiety and pain to the patient. In the clinical practice of total intravenous anesthesia, these effects are generally obtained by the simultaneous administration of the hypnotic drug propofol and of the analgesic drug remifentanil. The dosing of these drugs is managed by the anesthesiologist on the basis of pharmacological guidelines and by monitoring the patient's clinical response. Recent developments in physiological signal processing techniques have introduced the possibility to obtain quantitative indicators of the patient's anesthetic state. These indicators can be used as feedback signals for automatic anesthesia control systems. The development of these systems aims to provide a support tool for the anesthesiologist. The work presented in this thesis has been carried out in the framework of the research project concerning the automatic control anesthesia at the University of Brescia. The project is called ACTIVA (Automatic Control of Total IntraVenous Anesthesia) and is the result of the collaboration between the Research Group on Control Systems of the University of Brescia and the Anesthesia and Intensive Care Unit 2 of the Spedali Civili di Brescia. The objective of the ACTIVA project consists in the theoretical development, implementation, and clinical validation of innovative control strategies for the automatic control of total intravenous anesthesia. In detail, in this thesis the experimental results obtained with control structures based on the PID and on event-based PID controllers for the administration of propofol and remifentanil are initially presented. The theoretical development and clinical validation of model predictive control strategies is then proposed. Next, the results of a simulation study regarding an innovative control solution that allows the anesthesiologist to explicitly adjust the balance between propofol and remifentanil are given. Finally, the theoretical developments and the relative simulation studies concerning personalized control solutions for induction and maintenance phases of anesthesia are explained

Event-based MPC for propofol administration in anesthesia

Background and Objective : The automatic control of anesthesia is a demanding task mostly due to the presence of nonlinearities, intra- and inter-patient variability and specific clinical requirements to be meet. The traditional approach to achieve the desired depth of hypnosis level is based on knowledge and experience of the anesthesiologist. In contrast to a typical automatic control system, their actions are based on events that are related to the effect of the administrated drug. Thus, it is interesting to build a control system that will be able to mimic the behavior of the human way of actuation, simultaneously keeping the advantages of an automatic system.Methods : In this work, an event-based model predictive control system is proposed and analyzed. The nonlinear patient model is used to form the predictor structure and its linear part is exploited to design the predictive controller, resulting in an individualized approach. In such a scenario, the BIS is the controlled variable and the propofol infusion rate is the control variable. The event generator governs the computation of control action applying a dead-band sampling technique. The proposed control architecture has been tested in simulation considering process noise and unmeasurable disturbances. The evaluation has been made for a set of patients using nonlinear pharmacokinetic/pharmacodynamic models allowing realistic tests scenarios, including inter- and intra-patient variability.Results For the considered patients dataset the number of control signal changes has been reduced of about 55% when compared to the classical control system approach and the drug usage has been reduced of about 2%. At the same time the control performance expressed by the integrated absolute error has been degraded of about 11%.Conclusions : The event-based MPC control system meets all the clinical requirements. The robustness analysis also demonstrates that the event-based architecture is able to satisfy the specifications in the presence of significant process noise and modelling errors related to inter- and intra-patient variability, providing a balanced solution between complexity and performance. (c) 2022 Elsevier B.V. All rights reserved

MPC for Propofol Anesthesia: the Noise Issue

The design of automatic control systems for general anesthesia is a challenging task due to the severe safety requirements and process constraints. This is even more complex when model-based control techniques are used due to the significant variability of the process model. Additionally, issues like noisy measurements and interference also influence the control system overall performance. In this context, adequate filtering and control system sampling period selection should be analyzed to test their influence on the controller. In this paper, an MPC system for the depth of hypnosis, where the BIS signal is used as a controlled variable, is analyzed. The main purpose is to test and evaluate how the process noise affects the performance of the control system. The analysis is performed in a simulation study using a dataset of virtual patients representative of a wide population. Results show that a satisfactory performance is obtained when the noise is explicitly taken into account in the controller tuning procedure for a specific sampling period

Genomic diversity and signatures of selection in meat and fancy rabbit breeds based on high-density marker data

open6noThe study was funded by the PSRN (Programma di Sviluppo Rurale Nazionale) Cun-Fu and Cun-Fu 2 projects (co-funded by the European Agricultural Fund for Rural Development of the European Union and by the Italian Ministry of Agriculture, Food and Forestry—MiPAAF) and by the University of Bologna RFO 2019 programme.Background: Domestication of the rabbit (Oryctolagus cuniculus) has led to a multi-purpose species that includes many breeds and lines with a broad phenotypic diversity, mainly for external traits (e.g. coat colours and patterns, fur structure, and morphometric traits) that are valued by fancy rabbit breeders. As a consequence of this human-driven selection, distinct signatures are expected to be present in the rabbit genome, defined as signatures of selection or selective sweeps. Here, we investigated the genome of three Italian commercial meat rabbit breeds (Italian Silver, Italian Spotted and Italian White) and 12 fancy rabbit breeds (Belgian Hare, Burgundy Fawn, Champagne d’Argent, Checkered Giant, Coloured Dwarf, Dwarf Lop, Ermine, Giant Grey, Giant White, Rex, Rhinelander and Thuringian) by using high-density single nucleotide polymorphism data. Signatures of selection were identified based on the fixation index (FST) statistic with different approaches, including single-breed and group-based methods, the latter comparing breeds that are grouped based on external traits (different coat colours and body sizes) and types (i.e. meat vs. fancy breeds). Results: We identified 309 genomic regions that contained signatures of selection and that included genes that are known to affect coat colour (ASIP, MC1R and TYR), coat structure (LIPH), and body size (LCORL/NCAPG, COL11A1 and HOXD) in rabbits and that characterize the investigated breeds. Their identification proves the suitability of the applied methodologies for capturing recent selection events. Other regions included novel candidate genes that might contribute to the phenotypic variation among the analyzed breeds, including genes for pigmentation-related traits (EDNRA, EDNRB, MITF and OCA2) and body size, with a strong candidate for dwarfism in rabbit (COL2A1). Conclusions: We report a genome-wide view of genetic loci that underlie the main phenotypic differences in the analyzed rabbit breeds, which can be useful to understand the shift from the domestication process to the development of breeds in O. cuniculus. These results enhance our knowledge about the major genetic loci involved in rabbit external traits and add novel information to understand the complexity of the genetic architecture underlying body size in mammals.openBallan, Mohamad; Bovo, Samuele; Schiavo, Giuseppina; Schiavitto, Michele; Negrini, Riccardo; Fontanesi, LucaBallan, Mohamad; Bovo, Samuele; Schiavo, Giuseppina; Schiavitto, Michele; Negrini, Riccardo; Fontanesi, Luc

Comparative analysis of genomic inbreeding parameters and runs of homozygosity islands in several fancy and meat rabbit breeds

Runs of homozygosity (ROH) are defined as long stretches of DNA homozygous at each polymorphic position. The proportion of genome covered by ROH and their length are indicators of the level and origin of inbreeding. In this study, we analysed SNP chip datasets (obtained using the Axiom OrcunSNP Array) of a total of 702 rabbits from 12 fancy breeds and four meat breeds to identify ROH with different approaches and calculate several genomic inbreeding parameters. The highest average number of ROH per animal was detected in Belgian Hare (~150) and the lowest in Italian Silver (~106). The average length of ROH ranged from 4.001 ± 0.556 Mb in Italian White to 6.268 ± 1.355 Mb in Ermine. The same two breeds had the lowest (427.9 ± 86.4 Mb, Italian White) and the highest (921.3 ± 179.8 Mb, Ermine) average values of the sum of all ROH segments. More fancy breeds had a higher level of genomic inbreeding (as defined by ROH) than meat breeds. Several ROH islands contain genes involved in body size, body length, pigmentation processes, carcass traits, growth, and reproduction traits (e.g.: AOX1, GPX5, IFRD1, ITGB8, NELL1, NR3C1, OCA2, TRIB1, TRIB2). Genomic inbreeding parameters can be useful to overcome the lack of information in the management of rabbit genetic resources. ROH provided information to understand, to some extent, the genetic history of rabbit breeds and to identify signatures of selection in the rabbit genome

Long-term outcome of low-activity radioiodine administration preceded by adjuvant recombinant human TSH pretreatment in elderly subjects with multinodular goiter

<p>Abstract</p> <p>Background</p> <p>Large multinodular goiter (MNG) in elderly people is a common finding which can require intervention. The long-term effect of radioiodine therapy on thyroid volume (TV) and function after recombinant human (rh) TSH pre-treatment was evaluated.</p> <p>Methods</p> <p>After baseline evaluation, 40 subjects over 60 years old with a large MNG were treated with ¹³¹I up to the activity of 600 MBq. Nineteen patients were pretreated with rhTSH (0.1 mg on 2 consecutive days; group 1) while 21 subjects underwent treatment without rhTSH pretreatment (group 2). TV was monitored every 6–12 months by ultrasonography. The median follow-up period was 36 months.</p> <p>Results</p> <p>At the baseline, the groups matched in terms of TV, 24-h radioiodine uptake (RAIU), urinary iodine and neck complaints. The number of subjects pretreated with anti-thyroid drugs was significantly (P = 0.01) greater in group 2 than in group 1; TSH was more suppressed (P = 0.003) and f-T3 was more elevated (P = 0.005) in group 2 than in group 1 patients. RhTSH increased 24-h RAIU in group 1 up to the baseline level observed in group 2. The ¹³¹I activity administered was similar in both groups. Adverse events were slight and similar in both groups. A permanent post-radioiodine toxic condition was reported only in 2 patients in group 2. After radioiodine therapy, hypothyroidism was observed in significantly more group 1 patients than group 2 patients (P = 0.002). While TV was reduced in both groups, the percentage TV reduction recorded at the last examination was significantly higher (P = 0.03) in group 1 than in group 2. MNG-related complaints were significantly reduced in both group 1 (P = 0.0001 vs baseline) and group 2 (P = 0.001) patients.</p> <p>Conclusion</p> <p>Low radioiodine activities after pretreatment with low-dosage rhTSH are able to reduce TV and improve MNG-related symptoms in elderly subjects.</p

Ab initio Study of Anchoring Groups for CuGaO2 Delafossite-Based p-Type Dye Sensitized Solar Cells

Here we report the first theoretical characterization of the interface between the CuGaO2 delafossite oxide and the carboxylic (–COOH) and phosphonic acid (–PO3H2) anchoring groups. The promising use of delafossites as effective alternative to nickel oxide in p-type DSSC is still limited by practical difficulties in sensitizing the delafossite surface. Thus, this work provides atomistic insights on the structure and energetics of all the possible interactions between the anchoring functional groups and the CuGaO2 surface species, including the effects of the Mg doping and of the solvent medium. Our results highlight the presence of a strong selectivity toward the monodentate binding mode on surface Ga atoms for both the carboxylic and phosphonic acid groups. Since the binding modes have a strong influence on the hole injection thermodynamics, these findings have direct implications for further development of delafossite based p-type DSSCs

SARS-CoV-2 infection predicts larger infarct volume in patients with acute ischemic stroke

Background and purpose: Acute ischemic stroke (AIS) is a fearful complication of Coronavirus Disease-2019 (COVID-19). Aims of this study were to compare clinical/radiological characteristics, endothelial and coagulation dysfunction between acute ischemic stroke (AIS) patients with and without COVID-19 and to investigate if and how the SARS-CoV-2 spike protein (SP) was implicated in triggering platelet activation. Methods: We enrolled AIS patients with COVID-19 within 12 h from onset and compared them with an age- and sex-matched cohort of AIS controls without COVID-19. Neuroimaging studies were performed within 24 h. Blood samples were collected in a subset of 10 patients. Results: Of 39 AIS patients, 22 had COVID-19 and 17 did not. Admission levels of Factor VIII and von Willebrand factor antigen were significantly higher in COVID-19 patients and positively correlated with the infarct volume. In multivariate linear regression analyses, COVID-19 was an independent predictor of infarct volume (B 20.318, Beta 0.576, 95%CI 6.077-34.559; p = 0.011). SP was found in serum of 2 of the 10 examined COVID-19 patients. Platelets from healthy donors showed a similar degree of procoagulant activation induced by COVID-19 and non-COVID-19 patients' sera. The anti-SP and anti-FcγRIIA blocking antibodies had no effect in modulating platelet activity in both groups. Conclusions: SARS-CoV-2 infection seems to play a major role in endothelium activation and infarct volume extension during AIS

Profile of the nutritional intake of patients with decreased bone mass

Osteoporosis is a systemic disorder in which there is bone fragility and an increase in susceptibility to fractures. A balanced diet that provides sufficient quantities of proteins, vitamins, and minerals has a positive influence on bone health. The aim of this study was to determine the profile of consumption of the main nutrients involved in bone health, in order to optimize their ingestion, in patients with low bone mass. The progress of the patients was followed at the calcium disorders outpatients unit of the Clinical Hospital of Botucatu Medical School (UNESP). Forty-five patients with low bone mass were invited to participate in this study. Of these, 15 women, with an average age of 60.7 years, accepted and concluded the project. 24-h food recollections were performed and nutritional education activities (NEA) were organized based on an information leaflet, with the aim of optimizing the consumption of calcium (Ca), vitamin D, phosphorus (P), magnesium (Mg), and other nutrients involved in bone health. There was also tasting of dietary preparations rich in Ca. The average consumption of the nutrients was evaluated before and after the end of the activities, using the program DietPro 5i®. The median ingestion of energy (1096.8 Kcal) and macronutrients (carbohydrates: 127.2 g; proteins: 40.4 g; lipids: 20.4 g) was below the levels recommended according to the Dietary Reference Intakes (DRI). The consumption of energy and the nutrients showed no significant changes after the NEA (energy: 1120.8 Kcal; carbohydrates: 164.8 g; proteins: 60.5 g; lipids: 29.9 g; p&gt;0.05). The median ingestion of micronutrients was also below the levels recommended by DRI/Institute of Medicine (IOM) (Ca: 661.57 mg; vitamin D: 0.64 µg; Mg: 292.71 mg; P: 1214.00 mg). The consumption of such nutrients did not present significant changes after the NEA (Ca: 619.57 mg; vitamin D: 0.73 µg; Mg: 212.15 mg; P: 821.24 mg; p&gt;0.05). The percentage deficiencies for Ca, vitamin D and Mg were elevated (81.7%, 99.8%, and 100%, respectively). The percentage deficiency for P was 36%. In this group of female patients with low bone mass, there was an unsatisfactory ingestion profile for the main nutrients related to bone health. The nutritional guidance provided during the 8-month period was not effective in optimizing such ingestion. This finding highlights the importance of establishing new strategies in order to optimize the consumption of these nutrients.</p

Perfil de la ingestión nutricional de los pacientes con masa ósea disminuida

A osteoporose é uma desordem sistêmica na qual é observada a fragilidade óssea e o aumento da susceptibilidade às fraturas. Uma alimentação balanceada que forneça quantidades suficientes de proteínas, vitaminas e minerais, influencia positivamente a saúde dos ossos. Desse modo, este estudo objetivou traçar o perfil do consumo dos principais nutrientes envolvidos com a saúde óssea, procurando otimizar esta ingestão, nos pacientes portadores de baixa massa óssea, acompanhados no Ambulatório de Distúrbios do Cálcio (ADC) do Hospital das Clínicas da Faculdade de Medicina de Botucatu – UNESP. Foram convidados a participar do estudo 45 pacientes com baixa massa óssea, acompanhados no ADC. Destes, 15 pacientes do sexo feminino, com idade média de 60,7 anos, aceitaram e concluíram o projeto. Foram realizados recordatórios de 24 horas e desenvolvidas Atividades de Educação Nutricional (AEN), baseadas em um livreto informativo, objetivando a otimização do consumo de cálcio (Ca), vitamina D, fósforo (P), magnésio (Mg) e demais nutrientes envolvidos na saúde óssea. Foram ainda realizadas degustações de preparações dietéticas, ricas em Ca. O consumo médio dos nutrientes, foi avaliado antes e após o final das atividades, por meio do Programa.DietPro 5i®. A ingestão mediana de energia (1096,8 Kcal) e macronutrientes (carboidratos: 127,2g; proteínas: 40,4g; lipídeos: 20,4g) esteve abaixo do recomendado pelas Dietary References Intakes-DRI. O consumo desses nutrientes não apresentou alterações significativas após as AEN (energia: 1120,8 Kcal; carboidratos: 164,8; proteínas: 60,5 g; lipídeos: 29,9 g/ p> 0,05). A ingestão mediana de micronutrientes esteve abaixo do recomendado pelas DRI/Institute of Medicine-IOM (Ca: 661,57 mg; vitamina D: 0,64 µg; Mg: 292,71 mg; P: 1214,00 mg). O consumo desses nutrientes não apresentou alterações significativas após as AEN (Ca: 619,57 mg; vitamina D: 0,73 µg; Mg: 212,15 mg; P: 821,24 mg; p> 0,05). Os percentuais de inadequação para cálcio, vitamina D e magnésio foram elevados (81,7%, 99,8% e 100%, respectivamente). O percentual de inadequação para o fósforo foi de 36%. Neste grupo de pacientes portadoras de baixa massa óssea, observou-se um perfil de ingestão inadequado em relação aos principais nutrientes relacionados a saúde óssea. A orientação nutricional durante o período de oito meses não se mostrou eficiente na otimização desta ingestão. Este achado ressalta a importância do estabelecimento de novas estratégias que otimizem o consumo destes nutrientes.Osteoporosis is a systemic disorder in which there is bone fragility and an increase in susceptibility to fractures. A balanced diet that provides sufficient quantities of proteins, vitamins, and minerals has a positive influence on bone health. The aim of this study was to determine the profile of consumption of the main nutrients involved in bone health, in order to optimize their ingestion, in patients with low bone mass. The progress of the patients was followed at the calcium disorders outpatients unit of the Clinical Hospital of Botucatu Medical School (UNESP). Forty-five patients with low bone mass were invited to participate in this study. Of these, 15 women, with an average age of 60.7 years, accepted and concluded the project. 24-h food recollections were performed and nutritional education activities (NEA) were organized based on an information leaflet, with the aim of optimizing the consumption of calcium (Ca), vitamin D, phosphorus (P), magnesium (Mg), and other nutrients involved in bone health. There was also tasting of dietary preparations rich in Ca. The average consumption of the nutrients was evaluated before and after the end of the activities, using the program DietPro 5i®. The median ingestion of energy (1096.8 Kcal) and macronutrients (carbohydrates: 127.2 g; proteins: 40.4 g; lipids: 20.4 g) was below the levels recommended according to the Dietary Reference Intakes (DRI). The consumption of energy and the nutrients showed no significant changes after the NEA (energy: 1120.8 Kcal; carbohydrates: 164.8 g; proteins: 60.5 g; lipids: 29.9 g; p>0.05). The median ingestion of micronutrients was also below the levels recommended by DRI/Institute of Medicine (IOM) (Ca: 661.57 mg; vitamin D: 0.64 µg; Mg: 292.71 mg; P: 1214.00 mg). The consumption of such nutrients did not present significant changes after the NEA (Ca: 619.57 mg; vitamin D: 0.73 µg; Mg: 212.15 mg; P: 821.24 mg; p>0.05). The percentage deficiencies for Ca, vitamin D and Mg were elevated (81.7%, 99.8%, and 100%, respectively). The percentage deficiency for P was 36%. In this group of female patients with low bone mass, there was an unsatisfactory ingestion profile for the main nutrients related to bone health. The nutritional guidance provided during the 8-month period was not effective in optimizing such ingestion. This finding highlights the importance of establishing new strategies in order to optimize the consumption of these nutrients.La osteoporosis es una enfermedad sistémica en la cual se observa fragilidad ósea y aumento de la susceptibilidad a las fracturas. Una alimentación equilibrada, que proporcione cantidades suficientes de proteínas, vitaminas y minerales, influye positivamente en la salud de los huesos. Así, el objetivo del estudio fue delinear el perfil de consumo de los principales nutrientes implicados en la salud ósea, con la finalidad de mejorar esta ingestión en pacientes con baja masa ósea, fueron acompañados en la enfermería de Trastornos de calcio del Hospital de las Clínicas de la Facultad de Medicina de Botucatu – UNESP. Fueron llamados a participar del estudio 45 pacientes con baja masa ósea, seguidos en el ADC. De éstos, 15 pacientes del sexo femenino, con edad media de 60,7 años, aceptaron y concluyeron el proyecto. Se registraron históricos alimenticios de 24 horas y se  desarollaron actividades de educación nutricional (AEN), basadas en un folleto informativo, apuntando la optimización del consumo de calcio (Ca), vitamina D, fósforo (P), magnesio (Mg) y otros nutrientes implicados en la salud ósea. Fueron también realizadas degustaciones de preparaciones alimenticias, ricas en Ca. El consumo medio de los nutrientes fue evaluado antes y después de las actividades, a través del programa DietPro 5i®. La ingesta mediana de energía (1096,8 Kcal) y de macronutrientes (hidratos de carbono: 127,2g; proteínas: 40,4g; lípidos: 20,4g) estaba debajo de lo recomendado por las Dietary References Intakes-DRI.. El consumo de éstos nutrientes no presentó cambios significativos después de las AEN (energía: 1120,8 Kcal; hidratos de carbono: 164,8; proteínas: 60,5 g; lípidos: 29,9 g/ p> 0,05). La ingestión mediana de micronutrientes también estaba debajo de lo recomendado por DRI/Institute of Medicine-IOM (Ca: 661,57 mg; vitamina D: 0,64 µg; Mg: 292,71 mg; P: 1214,00 mg). El consumo de éstos nutrientes no ha presentado cambios significativos después de las AEN (Ca: 619,57 mg; vitamina D: 0,73 µg; Mg: 212,15 mg; P: 821,24 mg; p> 0,05). Los porcentajes de inadecuación para el Ca, vitamina D y Mg fueron elevados (81,7%, 99,8% y 100%, respectivamente). El porcentaje de inadecuación para el P fue de 36%. En este grupo de pacientes femeninos con baja masa ósea, se observó un perfil de ingestión inadecuada en relación a los principales nutrientes implicados en la salud ósea. La orientación nutricional no se mostró eficiente en la optimización de esta ingestión. Esta constatación destaca la importancia de establecer nuevas estrategias que optimicen el consumo de estos nutrientes