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The developing of antibacterial resistance is becoming in crisis. In this sense, natural products play a fundamental role in the discovery of antibacterial agents with diverse mechanisms of action. Phytochemical investigation of Cissus incisa leaves led to isolation and characterization of the ceramides mixture (1): (8E)-2-(tritriacont-9-enoyl amino)-1,3,4-octadecanetriol-8-ene (1-I); (8E)-2-(2',3'-dihydroxyoctacosanoyl amino)-1,3,4-octadecanetriol-8-ene (1-II); (8E)-2-(2'-hydroxyheptacosanoyl amino)-1,3,4-octadecanetriol-8-ene (1-III); and (8E)-2-(-2'-hydroxynonacosanoyl amino)-1,3,4-octadecanetriol-8-ene (1-IV). Until now, this is the first report of the ceramides (1-I), (1-II), and (1-IV). The structures were elucidated using NMR and mass spectrometry analyses. Antibacterial activity of ceramides (1) and acetylated derivates (2) was evaluated against nine multidrug-resistant bacteria by Microdilution method. (1) showed the best results against Gram-negatives, mainly against carbapenems-resistant Acinetobacter baumannii with MIC = 50 µg/mL. Structure-activity analysis and molecular docking revealed interactions between plant ceramides with membrane proteins, and enzymes associated with biological membranes of Gram-negative bacteria, through hydrogen bonding of functional groups. Vesicular contents release assay showed the capacity of (1) to disturb membrane permeability detected by an increase of fluorescence probe over time. The membrane disruption is not caused for ceramides lytic action on cell membranes, according in vitro hemolyticactivity results. Combining SAR analysis, bioinformatics and biophysical techniques, and also experimental tests, it was possible to explain the antibacterial action of these natural ceramides.
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Acinetobacter baumannii/efectos de los fármacos , Antibacterianos/farmacología , Ceramidas/farmacología , Cissus/química , Simulación del Acoplamiento Molecular , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Ceramidas/química , Ceramidas/aislamiento & purificación , Relación Dosis-Respuesta a Droga , Farmacorresistencia Bacteriana/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Relación Estructura-ActividadRESUMEN
Mobile health (mHealth) technologies are contributing to the increasing relevance of control engineering principles in understanding and improving health behaviors, such as physical activity. Social Cognitive Theory (SCT), one of the most influential theories of health behavior, has been used as the conceptual basis for behavioral interventions for smoking cessation, weight management, and other health-related outcomes. This paper presents a control-oriented dynamical systems model of SCT based on fluid analogies that can be used in system identification and control design problems relevant to the design and analysis of intensively adaptive interventions. Following model development, a series of simulation scenarios illustrating the basic workings of the model are presented. The model's usefulness is demonstrated in the solution of two important practical problems: 1) semiphysical model estimation from data gathered in a physical activity intervention (the MILES study) and 2) as a means for discerning the range of "ambitious but doable" daily step goals in a closed-loop behavioral intervention aimed at sedentary adults. The model is the basis for ongoing experimental validation efforts, and should encourage additional research in applying control engineering technologies to the social and behavioral sciences.
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BACKGROUND: Control systems engineering methods, particularly, system identification (system ID), offer an idiographic (i.e., person-specific) approach to develop dynamic models of physical activity (PA) that can be used to personalize interventions in a systematic, scalable way. The purpose of this work is to: (1) apply system ID to develop individual dynamical models of PA (steps/day measured using Fitbit Zip) in the context of a goal setting and positive reinforcement intervention informed by Social Cognitive Theory; and (2) compare insights on potential tailoring variables (i.e., predictors expected to influence steps and thus moderate the suggested step goal and points for goal achievement) selected using the idiographic models to those selected via a nomothetic (i.e., aggregated across individuals) approach. METHOD: A personalized goal setting and positive reinforcement intervention was deployed for 14â¯weeks. Baseline PA measured in weeks 1-2 was used to inform personalized daily step goals delivered in weeks 3-14. Goals and expected reward points (granted upon goal achievement) were pseudo-randomly assigned using techniques from system ID, with goals ranging from their baseline median steps/day up to 2.5× baseline median steps/day, and points ranging from 100 to 500 (i.e., $0.20-$1.00). Participants completed a series of daily self-report measures. Auto Regressive with eXogenous Input (ARX) modeling and multilevel modeling (MLM) were used as the idiographic and nomothetic approaches, respectively. RESULTS: Participants (Nâ¯=â¯20, mean ageâ¯=â¯47.25⯱â¯6.16â¯years, 90% female) were insufficiently active, overweight (mean BMIâ¯=â¯33.79⯱â¯6.82â¯kg/m2) adults. Results from ARX modeling suggest that individuals differ in the factors (e.g., perceived stress, weekday/weekend) that influence their observed steps/day. In contrast, the nomothetic model from MLM suggested that goals and weekday/weekend were the key variables that were predictive of steps. Assuming the ARX models are more personalized, the obtained nomothetic model would have led to the identification of the same predictors for 5 of the 20 participants, suggesting a mismatch of plausible tailoring variables to use for 75% of the sample. CONCLUSION: The idiographic approach revealed person-specific predictors beyond traditional MLM analyses and unpacked the inherent complexity of PA; namely that people are different and context matters. System ID provides a feasible approach to develop personalized dynamical models of PA and inform person-specific tailoring variable selection for use in adaptive behavioral interventions.
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Ejercicio Físico , Conductas Relacionadas con la Salud , Monitoreo Ambulatorio/instrumentación , Caminata , Adulto , Anciano , Teléfono Celular , Cognición , Femenino , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Aplicaciones Móviles , Monitoreo Ambulatorio/métodos , Motivación , Distribución Normal , Cooperación del Paciente , Reproducibilidad de los Resultados , Programas InformáticosRESUMEN
Adaptive interventions are an emerging class of behavioral interventions that allow for individualized tailoring of intervention components over time to a person's evolving needs. The purpose of this study was to evaluate an adaptive step goal + reward intervention, grounded in Social Cognitive Theory delivered via a smartphone application (Just Walk), using a mixed modeling approach. Participants (N = 20) were overweight (mean BMI = 33.8 ± 6.82 kg/m2), sedentary adults (90% female) interested in participating in a 14-week walking intervention. All participants received a Fitbit Zip that automatically synced with Just Walk to track daily steps. Step goals and expected points were delivered through the app every morning and were designed using a pseudo-random multisine algorithm that was a function of each participant's median baseline steps. Self-report measures were also collected each morning and evening via daily surveys administered through the app. The linear mixed effects model showed that, on average, participants significantly increased their daily steps by 2650 (t = 8.25, p < 0.01) from baseline to intervention completion. A non-linear model with a quadratic time variable indicated an inflection point for increasing steps near the midpoint of the intervention and this effect was significant (t2 = -247, t = -5.01, p < 0.001). An adaptive step goal + rewards intervention using a smartphone app appears to be a feasible approach for increasing walking behavior in overweight adults. App satisfaction was high and participants enjoyed receiving variable goals each day. Future mHealth studies should consider the use of adaptive step goals + rewards in conjunction with other intervention components for increasing physical activity.
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Terapia Conductista , Objetivos , Sobrepeso/psicología , Sobrepeso/terapia , Recompensa , Teléfono Inteligente , Caminata/psicología , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Aplicaciones Móviles , Motivación , Autoinforme , Teoría Social , TelemedicinaRESUMEN
BACKGROUND: Adaptive behavioral interventions are individualized interventions that vary support based on a person's evolving needs. Digital technologies enable these adaptive interventions to function at scale. Adaptive interventions show great promise for producing better results compared with static interventions related to health outcomes. Our central thesis is that adaptive interventions are more likely to succeed at helping individuals meet and maintain behavioral targets if its elements can be iteratively improved via data-driven testing (ie, optimization). Control systems engineering is a discipline focused on decision making in systems that change over time and has a wealth of methods that could be useful for optimizing adaptive interventions. OBJECTIVE: The purpose of this paper was to provide an introductory tutorial on when and what to do when using control systems engineering for designing and optimizing adaptive mobile health (mHealth) behavioral interventions. OVERVIEW: We start with a review of the need for optimization, building on the multiphase optimization strategy (MOST). We then provide an overview of control systems engineering, followed by attributes of problems that are well matched to control engineering. Key steps in the development and optimization of an adaptive intervention from a control engineering perspective are then summarized, with a focus on why, what, and when to do subtasks in each step. IMPLICATIONS: Control engineering offers exciting opportunities for optimizing individualization and adaptation elements of adaptive interventions. Arguably, the time is now for control systems engineers and behavioral and health scientists to partner to advance interventions that can be individualized, adaptive, and scalable. This tutorial should aid in creating the bridge between these communities.
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Terapia Conductista/métodos , Ingeniería Biomédica/métodos , Telemedicina/métodos , HumanosRESUMEN
Physical inactivity is a major contributor to morbidity and mortality worldwide. Many current physical activity behavioral interventions have shown limited success addressing the problem from a long-term perspective that includes maintenance. This paper proposes the design of a decision algorithm for a mobile and wireless health (mHealth) adaptive intervention that is based on control engineering concepts. The design process relies on a behavioral dynamical model based on Social Cognitive Theory (SCT), with a controller formulation based on hybrid model predictive control (HMPC) being used to implement the decision scheme. The discrete and logical features of HMPC coincide naturally with the categorical nature of the intervention components and the logical decisions that are particular to an intervention for physical activity. The intervention incorporates an online controller reconfiguration mode that applies changes in the penalty weights to accomplish the transition between the behavioral initiation and maintenance training stages. Controller performance is illustrated using an ARX model estimated from system identification data of a representative participant for Just Walk, a physical activity intervention designed on the basis of control systems principles.
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Hybrid Model Predictive Control (HMPC) is presented as a decision-making tool for novel behavioral interventions to increase physical activity in sedentary adults, such as Just Walk. A broad-based HMPC formulation for mixed logical dynamical (MLD) systems relevant to problems in behavioral medicine is developed and illustrated on a representative participant model arising from the Just Walk study. The MLD model is developed based on the requirement of granting points for meeting daily step goals and categorical input variables. The algorithm features three degrees-of-freedom tuning for setpoint tracking, measured and unmeasured disturbance rejection that facilitates controller robustness; disturbance anticipation further improves performance for upcoming events such as weekends and weather forecasts. To avoid the corresponding mixed-integer quadratic problem (MIQP) from becoming infeasible, slack variables are introduced in the objective function. Simulation results indicate that the proposed HMPC scheme effectively manages hybrid dynamics, setpoint tracking, disturbance rejection, and the transition between the two phases of the intervention (initiation and maintenance) and is suitable for evaluation in clinical trials.
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Social cognitive theory (SCT) is among the most influential theories of behavior change and has been used as the conceptual basis of health behavior interventions for smoking cessation, weight management, and other health behaviors. SCT and other behavior theories were developed primarily to explain differences between individuals, but explanatory theories of within-person behavioral variability are increasingly needed as new technologies allow for intensive longitudinal measures and interventions adapted from these inputs. These within-person explanatory theoretical applications can be modeled as dynamical systems. SCT constructs, such as reciprocal determinism, are inherently dynamical in nature, but SCT has not been modeled as a dynamical system. This paper describes the development of a dynamical system model of SCT using fluid analogies and control systems principles drawn from engineering. Simulations of this model were performed to assess if the model performed as predicted based on theory and empirical studies of SCT. This initial model generates precise and testable quantitative predictions for future intensive longitudinal research. Dynamic modeling approaches provide a rigorous method for advancing health behavior theory development and refinement and for guiding the development of more potent and efficient interventions.
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Cognición/fisiología , Simulación por Computador , Teoría Social , Conductas Relacionadas con la Salud/fisiología , Humanos , Intención , Modelos Teóricos , Cese del Hábito de Fumar/psicología , Análisis de SistemasRESUMEN
Evidence-based practice is important for behavioral interventions but there is debate on how best to support real-world behavior change. The purpose of this paper is to define products and a preliminary process for efficiently and adaptively creating and curating a knowledge base for behavior change for real-world implementation. We look to evidence-based practice suggestions and draw parallels to software development. We argue to target three products: (1) the smallest, meaningful, self-contained, and repurposable behavior change modules of an intervention; (2) "computational models" that define the interaction between modules, individuals, and context; and (3) "personalization" algorithms, which are decision rules for intervention adaptation. The "agile science" process includes a generation phase whereby contender operational definitions and constructs of the three products are created and assessed for feasibility and an evaluation phase, whereby effect size estimates/casual inferences are created. The process emphasizes early-and-often sharing. If correct, agile science could enable a more robust knowledge base for behavior change.
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Medicina Basada en la Evidencia/métodos , Algoritmos , Simulación por Computador , Práctica Clínica Basada en la Evidencia , Conductas Relacionadas con la Salud , Humanos , Programas InformáticosRESUMEN
Among health behaviors, physical activity has the most extensive record of research using passive sensors. Control systems and other system dynamic approaches have long been considered applicable for understanding human behavior, but only recently has the technology provided the precise and intensive longitudinal data required for these analytic approaches. Although sensors provide intensive data on the patterns and variations of physical activity over time, the influences of these variations are often unmeasured. Health behavior theories provide an explanatory framework of the putative mediators of physical activity changes. Incorporating the intensive longitudinal measurement of these theoretical constructs is critical to improving the fit of control system model of physical activity and for advancing behavioral theory. Theory-based control models also provide guidance on the nature of the controllers which serve as the basis for just-in-time adaptive interventions based on these control system models.
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Conductas Relacionadas con la Salud , Modelos Teóricos , Humanos , Actividad Motora , Índice de Severidad de la Enfermedad , Tuberculosis/patología , Tecnología InalámbricaRESUMEN
Behavioral scientists have historically relied on static modeling methodologies. The rise in mobile and wearable sensors has made intensive longitudinal data (ILD) -- behavioral data measured frequently over time -- increasingly available. Consequently, analytical frameworks are emerging that seek to reliably quantify dynamics reflected in these data. Employing an input-output perspective, dynamical systems models from engineering can characterize time-varying behaviors as processes of change. Specifically, ILD and parameter estimation routines from system identification can be leveraged together to offer parsimonious and quantitative descriptions of dynamic behavioral constructs. The utility of this approach for facilitating a better understanding of health behaviors is illustrated with two examples. In the first example, dynamical systems models are developed for Social Cognitive Theory (SCT), a prominent concept in behavioral science that considers interrelationships between personal factors, the environment, and behaviors. Estimated models are then obtained that explore the role of SCT in a physical activity intervention. The second example uses ILD to model day-to-day changes in smoking levels as a craving-mediated process of behavior change.