Molecular Dynamic Simulations for Biopolymers with Biomedical Applications.

Computational modeling (CM) is a versatile scientific methodology used to examine the properties and behavior of complex systems, such as polymeric materials for biomedical bioengineering. CM has emerged as a primary tool for predicting, setting up, and interpreting experimental results. Integrating in silico and in vitro experiments accelerates scientific advancements, yielding quicker results at a reduced cost. While CM is a mature discipline, its use in biomedical engineering for biopolymer materials has only recently gained prominence. In biopolymer biomedical engineering, CM focuses on three key research areas: (A) Computer-aided design (CAD/CAM) utilizes specialized software to design and model biopolymers for various biomedical applications. This technology allows researchers to create precise three-dimensional models of biopolymers, taking into account their chemical, structural, and functional properties. These models can be used to enhance the structure of biopolymers and improve their effectiveness in specific medical applications. (B) Finite element analysis, a computational technique used to analyze and solve problems in engineering and physics. This approach divides the physical domain into small finite elements with simple geometric shapes. This computational technique enables the study and understanding of the mechanical and structural behavior of biopolymers in biomedical environments. (C) Molecular dynamics (MD) simulations involve using advanced computational techniques to study the behavior of biopolymers at the molecular and atomic levels. These simulations are fundamental for better understanding biological processes at the molecular level. Studying the wide-ranging uses of MD simulations in biopolymers involves examining the structural, functional, and evolutionary aspects of biomolecular systems over time. MD simulations solve Newton's equations of motion for all-atom systems, producing spatial trajectories for each atom. This provides valuable insights into properties such as water absorption on biopolymer surfaces and interactions with solid surfaces, which are crucial for assessing biomaterials. This review provides a comprehensive overview of the various applications of MD simulations in biopolymers. Additionally, it highlights the flexibility, robustness, and synergistic relationship between in silico and experimental techniques.

In Silico Approach: Anti-Tuberculosis Activity of Caespitate in the H37Rv Strain.

Tuberculosis is a highly lethal bacterial disease worldwide caused by Mycobacterium tuberculosis (Mtb). Caespitate is a phytochemical isolated from Helichrysum caespititium, a plant used in African traditional medicine that shows anti-tubercular activity, but its mode of action remains unknown. It is suggested that there are four potential targets in Mtb, specifically in the H37Rv strain: InhA, MabA, and UGM, enzymes involved in the formation of Mtb's cell wall, and PanK, which plays a role in cell growth. Two caespitate conformational structures from DFT conformational analysis in the gas phase (GC) and in solution with DMSO (CS) were selected. Molecular docking calculations, MM/GBSA analysis, and ADME parameter evaluations were performed. The docking results suggest that CS is the preferred caespitate conformation when interacting with PanK and UGM. In both cases, the two intramolecular hydrogen bonds characteristic of caespitate's molecular structure were maintained to achieve the most stable complexes. The MM/GBSA study confirmed that PanK/caespitate and UGM/caespitate were the most stable complexes. Caespitate showed favorable pharmacokinetic characteristics, suggesting rapid absorption, permeability, and high bioavailability. Additionally, it is proposed that caespitate may exhibit antibacterial and antimonial activity. This research lays the foundation for the design of anti-tuberculosis drugs from natural sources, especially by identifying potential drug targets in Mtb.

Exploring the enzymatic repertoires of Bacteria and Archaea and their associations with metabolic maps.

The evolution, survival, and adaptation of microbes are consequences of gene duplication, acquisition, and divergence in response to environmental challenges. In this context, enzymes play a central role in the evolution of organisms, because they are fundamental in cell metabolism. Here, we analyzed the enzymatic repertoire in 6,467 microbial genomes, including their abundances, and their associations with metabolic maps. We found that the enzymes follow a power-law distribution, in relation to the genome sizes. Therefore, we evaluated the total proportion enzymatic classes in relation to the genomes, identifying a descending-order proportion: transferases (EC:2.-), hydrolases (EC:3.-), oxidoreductases (EC:1.-), ligases (EC:6.-), lyases (EC:4.-), isomerases (EC:5.-), and translocases (EC:7-.). In addition, we identified a preferential use of enzymatic classes in metabolism pathways for xenobiotics, cofactors and vitamins, carbohydrates, amino acids, glycans, and energy. Therefore, this analysis provides clues about the functional constraints associated with the enzymatic repertoire of functions in Bacteria and Archaea.

Influencia de la sensibilidad, la calidad y la empatía en la satisfacción de proveedores de servicios de Internet

Este trabajo proporciona elementos para el desarrollo de un modelo conceptual del efecto que presentan la sensibilidad y la empatía sobre la percepción de calidad y la satisfacción, al momento de contratar a proveedores de servicios de internet en el sur del Estado de Quintana Roo, México. El objetivo del estudio es comprender cómo afecta la sensibilidad, la empatía y la calidad sobre la satisfacción de los clientes de los proveedores de servicios de Internet. Se utilizó la técnica de muestreo no probabilístico "bola de nieve" para integrar una muestra de 384 usuarios que proporcionaron información mediante la técnica de encuesta. Se desarrolló un modelo probado empíricamente utilizando el modelo de ecuaciones estructurales para analizar el impacto de las variables en la satisfacción. Los resultados muestran que la calidad del proveedor de internet se encuentra altamente influenciada por la empatía del personal y por la sensibilidad, todos estos factores inciden de manera directa y positiva en la satisfacción del cliente, siendo más importante el valor percibido de la empatía que puede afectar en la opinión del usuario, lo que es relevante porque ayuda a comprender por qué los clientes se quedan con un proveedor de servicios en particular. CLASIFICACIÓN JEL M31, L86

This research provides elements for the development of a conceptual model of the effect that sensitivity and empathy have on the perception of quality and satisfaction, when hiring internet service providers in the south of the State of Quintana Roo, Mexico. The objective of the study is to understand how sensitivity empathy and quality affect the satisfaction of customers of Internet service providers. The non-probabilistic "snowball" sampling technique was used to integrate a sample of 384 users who provided information through the survey technique. An empirically tested model was developed using the structural equation model to analyze the impact of variables on satisfaction. The results show that the quality of the Internet provider is highly influenced by the empathy of the staff and by the sensitivity all these factors directly and positively affect customer satisfaction, being more important the perceived value of empathy that can affect the opinion of the user which is relevant because it helps to understand why customers stay with a particular service provider. JEL CLASSIFICATION M3I, L86

Este artigo fornece elementos para o desenvolvimento de um modelo conceitual do efeito da sensibilidade e da empatia na percepção da qualidade e da satisfação ao contratar provedores de serviços de Internet no sul do estado de Quintana Roo, México. O objetivo do estudo é entender como a sensibilidade, a empatia e a qualidade afetam a satisfação do cliente com os provedores de serviços de Internet. A técnica de amostragem não probabilística "bola de neve" foi usada para integrar uma amostra de 384 usuários que forneceram informações por meio da técnica de pesquisa. Um modelo testado empiricamente foi desenvolvido usando modelagem de equação estrutural para analisar o impacto das variáveis na satisfação. Os resultados mostram que a qualidade do provedor de Internet é altamente influenciada pela empatia e pela capacidade de resposta da equipe, todas com impacto direto e positivo na satisfação do cliente, sendo que o valor percebido da empatia é mais importante e pode afetar a opinião do usuário, o que é relevante porque ajuda a entender por que os clientes permanecem com um determinado provedor de serviços. CLASSIFICAÇÃO JEL M31, L86

Rendimiento en los juegos panamericanos de Santiago 2023: predicción mediante método de suavización exponencial simple / Performance at the Santiago 2023 pan american games: prediction using a simple exponential smoothing method / Desempenho nos jogos pan-americanos de Santiago 2023: predição usando o método de suavização exponencial simples

El objetivo del presente trabajo es analizar el desempeño deportivo de la delegación chilena en los Juegos Panamericanos celebrados entre los años 1951 y 2023, haciendo uso de datos retrospectivos y proyectivos a través de series temporales de tiempo. Para esto se empleó un diseño cuantitativo, no experimental y longitudinal de tendencias y un método de suavización exponencial simple, que utiliza promedios históricos y que permite realizar una predicción o comportamiento futuro basado en una media ponderada de los valores actuales y de los pasados. A partir de los resultados obtenidos, fue posible concluir que, en las últimas décadas, la ubicación de Chile en el ranking de los Juegos Panamericanos se ha estabilizado en torno a un onceavo lugar, posición pronosticada para Santiago 2023. Manteniéndose condiciones similares, el desempeño deportivo general y específico no tendría un quiebre exponencial de la tendencia y los resultados no resultan favorables, específicamente en lo que respecta a la obtención de medallas de oro y la posición general de la delegación.

The objective of this paper is to analyze the sports performance of the Chilean delegation in the Pan American Games held between 1951 and 2023, using retrospective and projective data through time series. For this purpose, a quantitative, non-experimental and longitudinal design of trends and a simple exponential smoothing method was used, which uses historical averages and allows a prediction or future behavior based on a weighted average of current and past values. From the results obtained, it was possible to conclude that, in recent decades, Chile's position in the Pan American Games ranking has stabilized around eleventh place, a position predicted for Santiago 2023. Maintaining similar conditions, the general and specific sporting performance would not have an exponential break in the trend and the results are not favorable, specifically in terms of obtaining gold medals and the overall position of the delegation.

O objetivo deste artigo é analisar o desempenho esportivo da delegação chilena nos Jogos Pan-Americanos realizados entre 1951 e 2023, usando dados retrospectivos e projetivos por meio de séries temporais. Para isso, foi utilizado um desenho quantitativo, não experimental e longitudinal de tendências e um método de suavização exponencial simples, que utiliza médias históricas e permite uma previsão do comportamento futuro com base em uma média ponderada dos valores atuais e passados. Com base nos resultados obtidos, foi possível concluir que, nas últimas décadas, a posição do Chile no ranking dos Jogos Pan-Americanos se estabilizou em torno do 11º lugar, posição prevista para Santiago 2023. Mantendo-se condições semelhantes, o desempenho esportivo geral e específico não teria uma quebra exponencial na tendência e os resultados não são favoráveis, especificamente em termos de conquista de medalhas de ouro e posição geral da delegação.

Case studies of clinical decision-making through prescriptive models based on machine learning.

BACKGROUND: The development of computational methodologies to support clinical decision-making is of vital importance to reduce morbidity and mortality rates. Specifically, prescriptive analytic is a promising area to support decision-making in the monitoring, treatment and prevention of diseases. These aspects remain a challenge for medical professionals and health authorities. MATERIALS AND METHODS: In this study, we propose a methodology for the development of prescriptive models to support decision-making in clinical settings. The prescriptive model requires a predictive model to build the prescriptions. The predictive model is developed using fuzzy cognitive maps and the particle swarm optimization algorithm, while the prescriptive model is developed with an extension of fuzzy cognitive maps that combines them with genetic algorithms. We evaluated the proposed approach in three case studies related to monitoring (warfarin dose estimation), treatment (severe dengue) and prevention (geohelminthiasis) of diseases. RESULTS: The performance of the developed prescriptive models demonstrated the ability to estimate warfarin doses in coagulated patients, prescribe treatment for severe dengue and generate actions aimed at the prevention of geohelminthiasis. Additionally, the predictive models can predict coagulation indices, severe dengue mortality and soil-transmitted helminth infections. CONCLUSIONS: The developed models performed well to prescribe actions aimed to monitor, treat and prevent diseases. This type of strategy allows supporting decision-making in clinical settings. However, validations in health institutions are required for their implementation.

Dental restoration operative time and analysis of the internal gap of conventional resins (Incremental Technique) vs. Bulk Fill (Single-Increment Technique): In vitro study.

Background: To determine the operative time and the internal restoration gap in the restoration-tooth interface in the cavity floor using an incremental technique for conventional resins and the single-increment technique for the bulk fill resin. Material and Methods: In this in vitro experimental study, the internal gaps of the restoration-tooth interfaces in the cavity floors of two conventional resins and two bulk fill resins were microscopically analyzed, and the restoration times of the single-increment technique and the incremental technique were determined. Results: Bulk fill resins had smaller internal gap (63.31 µm) than conventional resins (333.14 µm). Regarding the restoration time, the single-increment technique obtained the best results in operative time (3.52 minutes), with significant differences relative to the incremental technique. Conclusions: The Tetric N-Ceram bulk fill resin presented better performance than conventional resins relative to the internal gap of the restoration-tooth interface in the cavity floor. In addition, the single-increment technique presented a short clinical restoration time. Key words:Composite, internal gap, restoration technique.

Evidence of resistance to ivermectin in the gastrointestinal nematodes of horses from Mexican southeast.

Gastrointestinal nematodes (GIN) are a major impediment to breeding and exploitation of horses. Traditional control of GIN has generated resistance to main anthelmintics, including ivermectin. An analysis of five ranches with a history of IVM use was done to determine the efficacy and resistance of GIN to IVM treatment in horses from the Mexican southeast. Predesigned questionnaires were applied to collect information on previous treatment protocols. The fecal egg count reduction test (FECRT) was applied to determine resistance. Before IVM application, a McMaster test was used to diagnose GIN infection in horses, and feces cultures were done to identify L3 larvae for Strongylida eggs. Pre-treatment samples showed that 72.7% (80/110) of horses were GIN positive, with cyathostomins being the most frequent (91.8%), followed by Oxyuris equi (7.0%), Parascaris equorum (1.0%), and Strongylus vulgaris (0.2%). Based on the results, the horses at each ranch were divided in control (CG) and experimental (EG) groups with similar eggs per gram of feces (EPG). The EG (40/80) was dewormed with IVM (0.2 mg/kg orally) and the CG (40/80) remained untreated. After 14 days, EPG were measured, and feces cultures were done again to identify L3 larvae. After treatment of EG, 40% (16/40) of horses were positive, the most frequently identified GIN were cyathostomins (98.6%), followed by P. equorum (1.0%) and S. vulgaris (0.2%). Three of the five ranches were classified as resistant, according to the FECRT, with a percentage of reduction from 53 to 68%, all of which used IVM ≥4 times annually. This is the first evidence of resistance in cyathostomins to IVM treatment in horses from the Mexican southeast, adding to the current problem of anthelmintic resistance in equine GIN.

Multifaceted Nature of Lipid Droplets in Viral Interactions and Pathogenesis.

Once regarded as inert organelles with limited and ill-defined roles, lipid droplets (LDs) have emerged as dynamic entities with multifaceted functions within the cell. Recent research has illuminated their pivotal role as primary energy reservoirs in the form of lipids, capable of being metabolized to meet cellular energy demands. Their high dynamism is underscored by their ability to interact with numerous cellular organelles, notably the endoplasmic reticulum (the site of LD genesis) and mitochondria, which utilize small LDs for energy production. Beyond their contribution to cellular bioenergetics, LDs have been associated with viral infections. Evidence suggests that viruses can co-opt LDs to facilitate their infection cycle. Furthermore, recent discoveries highlight the role of LDs in modulating the host's immune response. Observations of altered LD levels during viral infections suggest their involvement in disease pathophysiology, potentially through production of proinflammatory mediators using LD lipids as precursors. This review explores these intriguing aspects of LDs, shedding light on their multifaceted nature and implications in viral interactions and disease development.

Reversible Thermo-Optical Response Nanocomposites Based on RAFT Symmetric Triblock Copolymers (ABA) of Acrylamide and N-Isopropylacrylamide and Gold Nanoparticles.

The development of composite materials with thermo-optical properties based on smart polymeric systems and nanostructures have been extensively studied. Due to the fact of its ability to self-assemble into a structure that generates a significant change in the refractive index, one of most attractive thermo-responsive polymers is poly(N-isopropylacrylamide) (PNIPAM), as well as its derivatives such as multiblock copolymers. In this work, symmetric triblock copolymers of polyacrylamide (PAM) and PNIPAM (PAMx-b-PNIPAMy-b-PAMx) with different block lengths were prepared by reversible addition-fragmentation chain-transfer polymerization (RAFT). The ABA sequence of these triblock copolymers was obtained in only two steps using a symmetrical trithiocarbonate as a transfer agent. The copolymers were combined with gold nanoparticles (AuNPs) to prepare nanocomposite materials with tunable optical properties. The results show that copolymers behave differently in solution due to the fact of variations in their composition. Therefore, they have a different impact on the nanoparticle formation process. Likewise, as expected, an increase in the length of the PNIPAM block promotes a better thermo-optical response.

Circulating Nrf2, Glutathione, and Malondialdehyde Correlate with Disease Severity in Duchenne Muscular Dystrophy.

Oxidative stress (OS) plays an essential role in the pathophysiology of Duchenne muscular dystrophy (DMD). However, the actors that regulate OS need to be better studied. We aimed to evaluate whether NFE2-like bZIP transcription factor 2 (Nrf2), glutathione, malondialdehyde (MDA), and protein carbonyl concentrations change according to the disease severity in DMD patients. Moreover, we assessed whether OS correlated with muscle injury, clinical characteristics, physical activity, and antioxidant food consumption (AFC). A total of 28 DMD patients participated in this study. OS markers, metabolic indicators, and enzymatic markers of muscle injury were measured in circulation. Muscle injury was measured with clinical scales, and physical activity and AFC were evaluated with questionnaires. Nrf2 concentration was lower (p ≤ 0.01), and malondialdehyde concentration was higher (p < 0.05) in non-ambulatory patients than in ambulatory patients. Nrf2 correlated with age (rho = -0.387), Vignos scale (rho = -0.328), GMFCS scale (rho = -0.399), and Brooke scale scores (rho = -0.371) (p < 0.05). MDA correlated with Vignos (rho = 0.317) and Brooke scale scores (rho = 0.414) (p ≤ 0.05). In conclusion, DMD patients with the worst muscle function had more significant oxidative damage and lower antioxidant function than DMD patients with better muscle function.

Structural Basis of the Binding Mode of the Antineoplastic Compound Motixafortide (BL-8040) in the CXCR4 Chemokine Receptor.

Modulation of the CXCL12-CXCR4 signaling axis is of the utmost importance due to its central involvement in several pathological disorders, including inflammatory diseases and cancer. Among the different currently available drugs that inhibit CXCR4 activation, motixafortide-a best-in-class antagonist of this GPCR receptor-has exhibited promising results in preclinical studies of pancreatic, breast, and lung cancers. However, detailed information on the interaction mechanism of motixafortide is still lacking. Here, we characterize the motixafortide/CXCR4 and CXCL12/CXCR4 protein complexes by using computational techniques including unbiased all-atom molecular dynamics simulations. Our microsecond-long simulations of the protein systems indicate that the agonist triggers changes associated with active-like GPCR conformations, while the antagonist favors inactive conformations of CXCR4. Detailed ligand-protein analysis indicates the importance of motixafortide's six cationic residues, all of which established charge-charge interactions with acidic CXCR4 residues. Furthermore, two synthetic bulky chemical moieties of motixafortide work in tandem to restrict the conformations of important residues associated with CXCR4 activation. Our results not only elucidate the molecular mechanism by which motixafortide interacts with the CXCR4 receptor and stabilizes its inactive states, but also provide essential information to rationally design CXCR4 inhibitors that preserve the outstanding pharmacological features of motixafortide.

Hydrolyzed Polyacrylamide as an In Situ Assistant in the Nucleation and Growth of Gold Nanoparticles.

The modulation of nanoparticles' size, shape, and dispersion by polymers has attracted particular attention in different fields. Nevertheless, there is a lack of information regarding the use of charged macromolecules as assistants in the nanostructures' nucleation and growth processes. Prompted by this, the in situ synthesis of gold nanoparticles (AuNPs) aided by hydrolyzed polyacrylamides (HPAM), with different chemical structures, was developed. In contrast to the conventional synthesis of nanostructures assisted by polyacrylamide, here, the polymerization, hydrolysis, and nanostructure formation processes were carried out simultaneously in the same milieu. Likewise, the growing chains acted as a template for the nanoparticles' growth, so their conformations and chemical structure, especially the amount of charges along the chain, played an important role in the AuNPs' morphology, size, and some of the final composite features. The nanocomposite was thoroughly characterized with appropriate techniques, including ATR-FTIR, GPC, UV-Vis, and SEM.

Single-Step Protocol for Isolating the Recombinant Extracellular Domain of the Luteinizing Hormone Receptor from the Ovis aries Testis.

The luteinizing hormone receptor (LHR) is a glycoprotein member of the G protein-coupled receptors superfamily. It participates in corpus luteum formation and ovulation in females and acts in testosterone synthesis and spermatogenesis in males. In this study, we extracted RNA from sheep testicles and synthetized the cDNA to amplify the gene lhr-bed. This gene consists of 762 bp and encodes 273 amino acids of the extracellular domain of LHR. The lhr-bed was cloned into pJET1.2/blunt, then subcloned into pCOLD II, and finally, transformed in E. coli BL21 (DE3) cells. Because the induced rLHR-Bed protein was found in the insoluble fraction, we followed a modified purification protocol involving induction at 25 °C, subjection to denaturing conditions, and on-column refolding to increase solubility. We confirmed rLHR-Bed expression by means of Western blot and mass spectrometry analysis. It is currently known that the structure stem-loop 5'UTR on pCOLD II vector is stable at 15 °C. We predicted and obtained RNAfold stability at 25 °C. We successfully obtained the recombinant LHR extracellular domain, with protein yields of 0.2 mg/L, and purity levels of approximately 90%, by means of a single chromatographic purification step. The method described here may be used to obtain large quantities of rLHR-Bed in the future.

An autonomous cycle of data analysis tasks for the clinical management of dengue.

Dengue is the most widespread vector-borne disease worldwide. Timely diagnosis and treatment of dengue is the main objective of medical professionals to decrease mortality rates. In this paper, we propose an autonomous cycle that integrates data analysis tasks to support decision-making in the clinical management of dengue. Particularly, the autonomous cycle supports dengue diagnosis and treatment. The proposed system was built using machine learning techniques for classification tasks (artificial neural networks and support vector machines) and evolutionary techniques (a genetic algorithm) for prescription tasks (treatment). The system was quantitatively evaluated using dengue-patient datasets reported by healthcare institutions. Our system was compared with previous works using qualitative criteria. The proposed system has the ability to classify a patient's clinical picture and recommend the best treatment option. In particular, the classification of dengue was done with 98% accuracy and a genetic algorithm recommends treatment options for particular patients. Finally, our system is flexible and easily adaptable, which will allow the addition of new tasks for dengue analysis.

A Comparison of Surrogate Behavioral Models for Power Amplifier Linearization under High Sparse Data.

A good approximation to power amplifier (PA) behavioral modeling requires precise baseband models to mitigate nonlinearities. Since digital predistortion (DPD) is used to provide the PA linearization, a framework is necessary to validate the modeling figures of merit support under signal conditioning and transmission restrictions. A field-programmable gate array (FPGA)-based testbed is developed to measure the wide-band PA behavior using a single-carrier 64-quadrature amplitude modulation (QAM) multiplexed by orthogonal frequency-division multiplexing (OFDM) based on long-term evolution (LTE) as a stimulus, with different bandwidths signals. In the search to provide a heuristic target approach modeling, this paper introduces a feature extraction concept to find an appropriate complexity solution considering the high sparse data issue in amplitude to amplitude (AM-AM) and amplitude to phase AM-PM models extraction, whose penalties are associated with overfitting and hardware complexity in resulting functions. Thus, experimental results highlight the model performance for a high sparse data regime and are compared with a regression tree (RT), random forest (RF), and cubic-spline (CS) model accuracy capabilities for the signal conditioning to show a reliable validation, low-complexity, according to the peak-to-average power ratio (PAPR), complementary cumulative distribution function (CCDF), coefficients extraction, normalized mean square error (NMSE), and execution time figures of merit. The presented models provide a comparison with original data that aid to compare the dimension and robustness for each surrogate model where (i) machine learning (ML)-based and (ii) CS interpolate-based where high sparse data are present, NMSE between the CS interpolated based are also compared to demonstrate the efficacy in the prediction methods with lower convergence times and complexities.

Critical values for automated hemograms and peripheral blood smears / Valores críticos para hemogramas automatizados y frotis de sangre periférica

The report of critical values ​​is considered a necessary practice in clinical pathology laboratories, since its immediate communication determines therapeutic decisions that can save lives. The choice of critical values ​​and the way in which they are reported must be a joint decision between the laboratory specialists and the clinical professionals of each health facility, since they must be integrated into the dynamics of the services involved. Among the critical values ​​that have been chosen for this review, we have included quantitative parameters, whose processing is carried out in automated hematology analyzers, and morphological findings in peripheral blood smears, which are evaluated by trained professionals.

El reporte de valores críticos se considera una práctica necesaria en los laboratorios de patología clínica, pues su comunicación inmediata determina decisiones terapéuticas que pueden salvar vidas. La elección de los valores críticos y el modo en que son reportados debe ser una decisión conjunta entre los especialistas del laboratorio y los profesionales clínicos de cada establecimiento de salud, ya que deben integrarse a la dinámica de los servicios involucrados. Entre los valores críticos que se han escogido para esta revisión hemos incluido parámetros cuantitativos, cuyo procesamiento se ejecuta en analizadores hematológicos automatizados, y hallazgos morfológicos en los frotis de sangre periférica, lo cuales son evaluados por profesionales capacitados.