One in five deaths worldwide is associated with sepsis, which is defined as organ dysfunction caused by a dysregulated host response to infection. An increased understanding of the pathophysiology of sepsis could provide improved approaches for early detection and treatment. Here we describe the development and validation of a mechanistic mathematical model of the inflammatory response, making use of a combination of in vitro and human in vivo data obtained from experiments where bacterial lipopolysaccharide (LPS) was used to induce an inflammatory response.
View Article and Find Full Text PDFComput Methods Programs Biomed
December 2024
Background And Objective: Patients who underwent Roux-en-Y Gastric Bypass surgery for treatment of obesity or diabetes can suffer from post-bariatric hypoglycemia (PBH). It has been assumed that PBH is caused by increased levels of the hormone GLP-1. In this research, we elucidate the role of GLP-1 in PBH with a physiology-based mathematical model.
View Article and Find Full Text PDFThe global rise in diabetes prevalence poses a significant challenge to healthcare providers, stimulating interest in digital interventions such as educational games. However, the impact and availability of research-developed diabetes games remain uncertain. This scoping review aimed to provide a comprehensive overview of serious games for diabetes, encompassing their availability, characteristics and health effects.
View Article and Find Full Text PDFCell-free systems have emerged as a versatile platform in synthetic biology, finding applications in various areas such as prototyping synthetic circuits, biosensor development, and biomanufacturing. To streamline the prototyping process, cell-free systems often incorporate a modeling step that predicts the outcomes of various experimental scenarios, providing a deeper insight into the underlying mechanisms and functions. There are two recognized approaches for modeling these systems: mechanism-based modeling, which models the underlying reaction mechanisms; and data-driven modeling, which makes predictions based on data without preconceived interactions between system components.
View Article and Find Full Text PDFContinuous glucose monitoring (CGM) is a promising, minimally invasive alternative to plasma glucose measurements for calibrating physiology-based mathematical models of insulin-regulated glucose metabolism, reducing the reliance on in-clinic measurements. However, the use of CGM glucose, particularly in combination with insulin measurements, to develop personalized models of glucose regulation remains unexplored. Here, we simultaneously measured interstitial glucose concentrations using CGM as well as plasma glucose and insulin concentrations during an oral glucose tolerance test (OGTT) in individuals with overweight or obesity to calibrate personalized models of glucose-insulin dynamics.
View Article and Find Full Text PDFThe manifestation of metabolic deteriorations that accompany overweight and obesity can differ greatly between individuals, giving rise to a highly heterogeneous population. This inter-individual variation can impede both the provision and assessment of nutritional interventions as multiple aspects of metabolic health should be considered at once. Here, we apply the Mixed Meal Model, a physiology-based computational model, to characterize an individual's metabolic health A population of 342 personalized models were generated using data for individuals with overweight and obesity from three independent intervention studies, demonstrating a strong relationship between the model-derived metric of insulin resistance (ρ = 0.
View Article and Find Full Text PDFThe liver is the primary site for the metabolism and detoxification of many compounds, including pharmaceuticals. Consequently, it is also the primary location for many adverse reactions. As the liver is not readily accessible for sampling in humans; rodent or cell line models are often used to evaluate potential toxic effects of a novel compound or candidate drug.
View Article and Find Full Text PDFObesity is a major risk factor for the development of type 2 diabetes (T2D), where a sustained weight loss may result in T2D remission in individuals with obesity. To design effective and feasible intervention strategies to prevent or reverse T2D, it is imperative to study the progression of T2D and remission together. Unfortunately, this is not possible through experimental and observational studies.
View Article and Find Full Text PDFPurpose: This study aimed to describe the 24-hour cycle of wearable sensor-obtained heart rate in patients with deterioration-free recovery and to compare it with patients experiencing postoperative deterioration.
Methods: A prospective observational trial was performed in patients following bariatric or major abdominal cancer surgery. A wireless accelerometer patch (Healthdot) continuously measured postoperative heart rate, both in the hospital and after discharge, for a period of 14 days.
Computational models of human glucose homeostasis can provide insight into the physiological processes underlying the observed inter-individual variability in glucose regulation. Modelling approaches ranging from "bottom-up" mechanistic models to "top-down" data-driven techniques have been applied to untangle the complex interactions underlying progressive disturbances in glucose homeostasis. While both approaches offer distinct benefits, a combined approach taking the best of both worlds has yet to be explored.
View Article and Find Full Text PDFAssessing post-operative recovery is a significant component of perioperative care, since this assessment might facilitate detecting complications and determining an appropriate discharge date. However, recovery is difficult to assess and challenging to predict, as no universally accepted definition exists. Current solutions often contain a high level of subjectivity, measure recovery only at one moment in time, and only investigate recovery until the discharge moment.
View Article and Find Full Text PDFMicrobial cell factories face changing environments during industrial fermentations. Kinetic metabolic models enable the simulation of the dynamic metabolic response to these perturbations, but their development is challenging due to model complexity and experimental data requirements. An example of this is the well-established microbial cell factory Saccharomyces cerevisiae, for which no consensus kinetic model of central metabolism has been developed and implemented in industry.
View Article and Find Full Text PDFCurrent computational models of whole-body glucose homeostasis describe physiological processes by which insulin regulates circulating glucose concentrations. While these models perform well in response to oral glucose challenges, interaction with other nutrients that impact postprandial glucose metabolism, such as amino acids (AAs), is not considered. Here, we developed a computational model of the human glucose-insulin system, which incorporates the effects of AAs on insulin secretion and hepatic glucose production.
View Article and Find Full Text PDFJMIR Perioper Med
February 2023
Background: Postoperative deterioration is often preceded by abnormal vital parameters. Therefore, vital parameters of postoperative patients are routinely measured by nursing staff. Wrist-worn sensors could potentially provide an alternative tool for the measurement of vital parameters in low-acuity settings.
View Article and Find Full Text PDFMicrobial metabolism is strongly dependent on the environmental conditions. While these can be well controlled under laboratory conditions, large-scale bioreactors are characterized by inhomogeneities and consequently dynamic conditions for the organisms. How response to frequent perturbations in industrial bioreactors is still not understood mechanistically.
View Article and Find Full Text PDFBackground: Heart failure (HF) biomarkers have prognostic value. The aim of this study was to combine HF biomarkers into an objective classification system for risk stratification of patients with HF.
Methods: HF biomarkers were analyzed in a population of HF outpatients and expressed relative to their cut-off values (N-terminal pro-B-type natriuretic peptide [NT-proBNP] >1,000 pg/mL, soluble suppression of tumorigenesis-2 [ST2] >35 ng/mL, growth differentiation factor-15 [GDF-15] >2,000 pg/mL, and fibroblast growth factor-23 [FGF-23] >95.
Within the human population, considerable variability exists between individuals in their susceptibility to develop obesity and dyslipidemia. In humans, this is thought to be caused by both genetic and environmental variation. APOE*3-Leiden.
View Article and Find Full Text PDFDespite the pivotal role played by elevated circulating triglyceride levels in the pathophysiology of cardio-metabolic diseases many of the indices used to quantify metabolic health focus on deviations in glucose and insulin alone. We present the Mixed Meal Model, a computational model describing the systemic interplay between triglycerides, free fatty acids, glucose, and insulin. We show that the Mixed Meal Model can capture deviations in the post-meal excursions of plasma glucose, insulin, and triglyceride that are indicative of features of metabolic resilience; quantifying insulin resistance and liver fat; validated by comparison to gold-standard measures.
View Article and Find Full Text PDFIntroduction: The shift toward remote patient monitoring methods to detect clinical deterioration requires testing of wearable devices in real-life clinical settings. This study aimed to develop a remote early warning scoring (REWS) system based on continuous measurements using a wearable device, and compare its diagnostic performance for the detection of deterioration to the diagnostic performance of the conventional modified early warning score (MEWS).
Materials And Methods: The study population of this prospective, single center trial consisted of patients who underwent major abdominal cancer surgery and were monitored using routine in-hospital spotcheck measurements of the vital parameters.
Objectives: Identifying patients with a possible SARS-CoV-2 infection in the emergency department (ED) is challenging. Symptoms differ, incidence rates vary and test capacity may be limited. As PCR-testing all ED patients is neither feasible nor effective in most centres, a rapid, objective, low-cost early warning score to triage ED patients for a possible infection is developed.
View Article and Find Full Text PDFBackground: The left atrium (LA) is a key player in the pathophysiology of systolic and diastolic heart failure (HF). Speckle tracking derived LA reservoir strain (LAS) can be used as a prognostic surrogate for elevated left ventricular filling pressure similar to NT-proBNP. The aim of the study is to investigate the correlation between LAS and NT-proBNP and its prognostic value with regards to the composite endpoint of HF hospitalization and all-cause mortality within 1 year.
View Article and Find Full Text PDFCentral carbon metabolism comprises the metabolic pathways in the cell that process nutrients into energy, building blocks and byproducts. To unravel the regulation of this network upon glucose perturbation, several metabolic models have been developed for the microorganism . These dynamic representations have focused on glycolysis and answered multiple research questions, but no commonly applicable model has been presented.
View Article and Find Full Text PDFIntroduction: Recent advances in wearable technology allow for the development of wirelessly connected sensors to continuously measure vital parameters in the general ward or even at home. The present study assesses the accuracy of a wearable patch (Healthdot) for continuous monitoring of heartrate (HR) and respiration rate (RR).
Materials And Methods: The Healthdot measures HR and RR by means of chest accelerometry.
Metabolic flexibility is the ability of an organism to adapt its energy source based on nutrient availability and energy requirements. In humans, this ability has been linked to cardio-metabolic health and healthy aging. Genome-scale metabolic models have been employed to simulate metabolic flexibility by computing the Respiratory Quotient (RQ), which is defined as the ratio of carbon dioxide produced to oxygen consumed, and varies between values of 0.
View Article and Find Full Text PDFPlasma glucose and insulin responses following an oral glucose challenge are representative of glucose tolerance and insulin resistance, key indicators of type 2 diabetes mellitus pathophysiology. A large heterogeneity in individuals' challenge test responses has been shown to underlie the effectiveness of lifestyle intervention. Currently, this heterogeneity is overlooked due to a lack of methods to quantify the interconnected dynamics in the glucose and insulin time-courses.
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