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Introduction Infants born preterm usually show a Preterm Behavioural Phenotype, which includes mixed symptomatology characterized by lack of attention, anxiety and social difficulties, with a 3-4 times greater risk of disorders in further childhood. Critically, this behavioural pattern is also observed in infants born after a threated preterm labour (TPL), regardless of the presence of prematurity. It is known that the course of this Preterm Behavioural Phenotype shows high variability. Nevertheless, the predictors of this Preterm Behavioural Phenotype prognosis remain unknown. Objectives This study aimed to explore the predictors of change of Preterm Behavioural Phenotype symptomatology during preschool ages in order to improve prognosis. Methods In this prospective cohort study, 117 mother–child pairs who experienced TPL were recruited. Preterm Behavioural Phenotype symptoms were assessed at age 2 and 6 using Child Behaviour Checklist. Gestational age at birth, maternal anxiety trait, maternal history of psychological traumas, prenatal and postnatal maternal depression, anxiety, and cortisol as well as parenting stress were included as predictors in a regression model. Results Whereas increased internalizing problems were associated with a previous trauma history (p = .003), increased externalizing symptoms were linked to prenatal and postnatal maternal anxiety (p = .004 and p = .018, respectively). Conclusions Identifying modifiable risk factors, such as the history of maternal traumas and anxiety at TPL diagnosis and postpartum is recommendable to enhance better prognosis of Preterm Behavioural Phenotype in the offspring. Disclosure of Interest None Declared

Introduction Emotional dysregulation are considered early manifestations of neuropsychiatric disorders. Recent research has shown that a threatened preterm labour (TPL) represents an adverse prenatal event that involves temperament disturbances, even in absence of prematurity. Thus, full-term TPL infants at 6 months of age are characterized by lower positive affect, higher negative affect, and worse emotional regulation relative to a full-term non-TPL control group. Objectives The aim of this study is to explore the predictors of change of emotional infant competences. Methods This prospective cohort study recruited mothers who suffered from a TPL. Infants’ temperament assessment was performed at 6 and 30 months of age using the Rothbart Behaviour Questionnaires, examining positive affectivity/surgency, negative emotionality, and orienting and emotional regulatory capacity. A regression model was carried out, including gestational age at birth, maternal anxiety trait, maternal history of psychological traumas, prenatal and postnatal maternal depression, anxiety, and cortisol as well as parenting stress as predictors. Results Increased positive affectivity was related with lower paternal stress (p = .044). Maternal history of trauma and parenting stress was associated with increased negative emotionality (p = .037 and p = .045, respectively). Increased emotional regulation disturbance was linked to low gestational age at birth (p < .001), higher postnatal depression (p = .002), higher prenatal anxiety at TPL diagnosis (p = .039) and higher postnatal anxiety (p = .008). Conclusions Therefore, maternal previous traumas, maternal psychopathology from pregnancy to postpartum as well as parenting stress should be considered in psychological treatment to improve infant’s emotional competences and prevent subsequent neuropsychiatric disorders. Disclosure of Interest None Declared

Introduction Threatened preterm labour (TPL) is associated with long-lasting neurodevelopmental challenges, independent of prematurity. For instance, it is known that infants born a TPL show delayed communication and socio-individual skills, regardless of the gestational age at birth. Furthermore, TPL constitutes an adverse prenatal event that can induce maternal anxiety or depression, even during postpartum period, which can produce a deleterious effect of the prognosis of infant’s psychomotor development. Objectives This study aimed to explore the influence of maternal psychopathology as well as other peripartum variables on the course of psychomotor development in children born after a TPL between the ages of 2 and 6. Methods In this prospective cohort study, 117 mother–child pairs who experienced TPL were recruited. Psychomotor development was assessed using the Ages & Stages Questionnaires-Third edition at age 2 and 6. A regression model was carried out, including gestational age at birth, maternal anxiety trait, maternal history of psychological traumas, prenatal and postnatal maternal depression, anxiety, and cortisol as well as parenting stress as predictors. Results Low gestational week at birth emerged as the most relevant factor in the course of increased communication delay (p

Introduction Threatened preterm labor (TPL) represents an adverse prenatal event that can impact maternal mental health in the long term. Additionally, this prenatal event can disrupt fetal neurodevelopment, primarily during the third trimester of pregnancy when neuronal connections in the fetus are established. Indeed, infants born following TPL exhibit delayed communication and socio-individual skills at 6 months of age, regardless of prematurity. Furthermore, maternal mental health during the postpartum period can also influence the offspring’s psychomotor development. Objectives The aim of this study is to examine the impact of maternal psychopathology on psychomotor development trajectories in infants born after a TPL from 6 to 30 months of age. Methods This prospective cohort study recruited 117 mother–child pairs who suffered from a TPL. Psychomotor assessment was performed at 6 and 30 months of age using the communication and socio-individual subscales of Ages & Stages Questionnaires for psychomotor development. A regression model was carried out, including gestational age at birth, maternal anxiety trait, maternal history of psychological traumas, prenatal and postnatal maternal depression, anxiety, and cortisol as well as parenting stress as predictors. Results Increased communication delays were associated with higher maternal anxiety levels (p

Introduction: Embolic stroke of undetermined source (ESUS) accounts for 25% of all cerebral infarcts; only 30% are associated with paroxysmal atrial fibrillation (AF). Various biochemical, electrocardiographic, and echocardiographic findings may suggest left atrial damage and increased risk of embolism in the absence of clinically documented AF or atrial flutter. In this review, we analyse the available evidence on atrial cardiopathy or atrial disease, its involvement in ESUS, and its identification through electrocardiographic, echocardiographic, and serum markers and its possible therapeutic implications. Development: A systematic search was conducted on MEDLINE (PubMed) using the following MeSH terms: MeSH [ESUS] + [atrial cardiopathy] + [atrial fibrillation] + [interatrial block] + [treatment]. We selected what we considered to be the most useful original prospective or retrospective studies and systematic reviews. We then read the full texts of the articles and checked the references cited in each article.We analyse epidemiological and demographic variables of patients with ESUS, as well as recent evidence related to presentation and prognosis and factors associated with recurrence and mortality. We review the contribution of atrial cardiopathy diagnosis prior to the detection of AF and the clinical, electrocardiographic, and echocardiographic variables and the biochemical markers associated with its development and its potential contribution to cerebral embolism. Conclusions: The systematic search of biochemical and electrocardiographic, and echocardiographic alterations can be useful to identify ESUS patients at higher risk of recurrence. Resumen: Introducción: El infarto cerebral embólico de origen no determinado (ESUS por sus siglas en inglés) representa el 25% de todos los infartos cerebrales y solo el 30% se asocia con fibrilación auricular (FA) paroxística. Existen diferentes hallazgos bioquímicos, electro y ecocardiográficos que sugieren daño auricular izquierdo y aumento del riesgo de embolismo en ausencia de FA o flutter auricular clínicamente documentados. En la presente revisión analizamos la evidencia disponible sobre cardiopatía atrial o enfermedad auricular, su implicación en el ESUS y su identificación mediante marcadores electrocardiográficos, ecocardiográficos y séricos y sus posibles implicaciones terapéuticas. Desarrollo: Se realizó una búsqueda sistematizada a través de la fuente de información MEDLINE (PubMed), utilizando una estrategia diseñada con términos MeSH [ESUS] + [atrial cardiopathy] + [atrial fibrillation] + [interatrial block] + [treatment]. Se seleccionaron las publicaciones originales de estudios prospectivos, retrospectivos y de revisión consideradas como las más útiles. Se procedió a la lectura del texto completo y la bibliografía aportada en cada artículo.Se incluyeron los factores epidemiológicos y demográficos de los pacientes ESUS, así como la evidencia reciente relacionada con su forma de presentación, pronóstico y factores asociados con recurrencia y mortalidad. Se revisó la contribución de la presencia de cardiopatía auricular previo a la documentación de FA y las variables clínicas, electro y ecocardiográficas, así como los marcadores bioquímicos asociados con su desarrollo y su contribución como fuente potencial de embolismo cerebral. Conclusiones: La búsqueda sistemática de alteraciones bioquímicas, electro y ecocardiográficas pueden ser de utilidad para identificar pacientes ESUS con mayor riesgo de recurrencia.

Resumen: Introducción: El infarto cerebral embólico de origen no determinado (ESUS por sus siglas en inglés) representa el 25% de todos los infartos cerebrales y solo el 30% se asocia con fibrilación auricular (FA) paroxística. Existen diferentes hallazgos bioquímicos, electro y ecocardiográficos que sugieren daño auricular izquierdo y aumento del riesgo de embolismo en ausencia de FA o flutter auricular clínicamente documentados. En la presente revisión analizamos la evidencia disponible sobre cardiopatía atrial o enfermedad auricular, su implicación en el ESUS y su identificación mediante marcadores electrocardiográficos, ecocardiográficos y séricos y sus posibles implicaciones terapéuticas. Desarrollo: Se realizó una búsqueda sistematizada a través de la fuente de información MEDLINE (PubMed), utilizando una estrategia diseñada con términos MeSH [ESUS] + [atrial cardiopathy] + [atrial fibrillation] + [interatrial block] + [treatment]. Se seleccionaron las publicaciones originales de estudios prospectivos, retrospectivos y de revisión consideradas como las más útiles. Se procedió a la lectura del texto completo y la bibliografía aportada en cada artículo.Se incluyeron los factores epidemiológicos y demográficos de los pacientes ESUS, así como la evidencia reciente relacionada con su forma de presentación, pronóstico y factores asociados con recurrencia y mortalidad. Se revisó la contribución de la presencia de cardiopatía auricular previo a la documentación de FA y las variables clínicas, electro y ecocardiográficas, así como los marcadores bioquímicos asociados con su desarrollo y su contribución como fuente potencial de embolismo cerebral. Conclusiones: La búsqueda sistemática de alteraciones bioquímicas, electro y ecocardiográficas pueden ser de utilidad para identificar pacientes ESUS con mayor riesgo de recurrencia. Abstract: Introduction: Embolic stroke of undetermined source (ESUS) accounts for 25% of all cerebral infarcts; only 30% are associated with paroxysmal atrial fibrillation (AF). Various biochemical, electrocardiographic, and echocardiographic findings may suggest left atrial damage and increased risk of embolism in the absence of clinically documented AF or atrial flutter. In this review, we analyse the available evidence on atrial cardiopathy or atrial disease, its involvement in ESUS, and its identification through electrocardiographic, echocardiographic, and serum markers and its possible therapeutic implications. Development: A systematic search was conducted on MEDLINE (PubMed) using the following MeSH terms: MeSH [ESUS] + [atrial cardiopathy] + [atrial fibrillation] + [interatrial block] + [treatment]. We selected what we considered to be the most useful original prospective or retrospective studies and systematic reviews. We then read the full texts of the articles and checked the references cited in each article.We analyse epidemiological and demographic variables of patients with ESUS, as well as recent evidence related to presentation and prognosis and factors associated with recurrence and mortality. We review the contribution of atrial cardiopathy diagnosis prior to the detection of AF and the clinical, electrocardiographic, and echocardiographic variables and the biochemical markers associated with its development and its potential contribution to cerebral embolism. Conclusions: The systematic search of biochemical and electrocardiographic, and echocardiographic alterations can be useful to identify ESUS patients at higher risk of recurrence.

Greenspaces within broader ecosystem-based disaster risk reduction (Eco-DRR) strategies provide multiple benefits to society, biodiversity, and addressing climate breakdown. In this study, we investigated urban growth, its intersection with hazards, and the availability of greenspace for disaster risk reduction (DRR) in the city of Quito, Ecuador, which experiences multiple hazards including landslides, floods, volcanoes, and earthquakes. We used satellite data to quantify urban sprawl and developed a workflow incorporating high-resolution digital elevation models (DEMs) to identify potential greenspaces for emergency refuge accommodation (DRR greenspace), for example, following an earthquake. Quito's historical urban growth totalled ∼ 192 km2 for 1986–2020 and was primarily on flatter land, in some cases crossed by steep ravines. By contrast, future projections indicate an increasing intersection between easterly urbanisation and steep areas of high landslide susceptibility. Therefore, a timely opportunity exists for future risk-informed planning. Our workflow identified 18.6 km2 of DRR greenspaces, of which 16.3 km2 intersected with potential sources of landslide and flood hazards, indicating that hazard events could impact potential “safe spaces”. These spaces could mitigate future risk if designated as greenspaces and left undeveloped. DRR greenspace overlapped 7 % (2.5 km2) with municipality-designated greenspace. Similarly, 10 % (1.7 km2) of municipality-designated “safe space” for use following an earthquake was classified as potentially DRR suitable in our analysis. For emergency refuge, currently designated greenspaces could accommodate ∼ 2 %–14 % (depending on space requirements) of Quito's population within 800 m. This increases to 8 %–40 % considering all the potential DRR greenspace mapped in this study. Therefore, a gap exists between the provision of DRR and designated greenspace. Within Quito, we found a disparity between access to greenspaces across socio-economic groups, with lower income groups having less access and further to travel to designated greenspaces. Notably, the accessibility of greenspaces was high overall with 98 % (2.3 million) of Quito's population within 800 m of a designated greenspace, of which 88 % (2.1 million) had access to potential DRR greenspaces. Our workflow demonstrates a citywide evaluation of DRR greenspace potential and provides the foundation upon which to evaluate these spaces with local stakeholders. Promoting equitable access to greenspaces, communicating their multiple benefits, and considering their use to restrict propagating development into hazardous areas are key themes that emerge for further investigation.

Introduction Preterm infants are at high-risk of developing autism spectrum disorders (ASD). The underlying mechanisms that explain the link between prematurity and ASD are unclear. Perinatal environmental factors may disrupt the gut-brain communication, when the gut microbiome composition is established and brain programming occurs. Therefore, the disruption of the gut-brain axis communication in response to perinatal environmental events may shed light on the association between prematurity and ASD. Objectives To describe a new research project protocol which aim is to develop a dynamic model of gut microbiota variation in response to environmental factors that modulate the ASD risk in preterm infants. Methods A two-year prospective observational study will be carried out, in which preterm infants will be assessed at birth, 40th postmenstrual week, at 6, 12, and 24 months of corrected age. Two-hundred preterm infants will be recruited. A comprehensive assessment will be conducted by collecting data on sociodemographic characteristics, medical history, family functioning, neurodevelopment, ASD screening, and diagnosis. Microbiome composition and microbial activity will be determined from feces. Results The expected results are: i) to characterize ASD since its early manifestations in an at-risk population, allowing an early diagnosis and intervention to improve clinical outcomes; ii) to identify early microbiota biomarkers in order to find potential pathophysiological pathways; iii) to understand the protective and risk factors associated to ASD since perinatal period. Conclusions A two-year predictive model will be generated based on environmental and gut microbiota variables. This predictive model of ASD would allow prevention, early diagnosis, improvement of prognosis, and personalized treatments in preterm infants. Disclosure No significant relationships.

Energy metabolism is dysregulated in obesity, and some if these changes persist after weight loss and may contribute to weight regain. Here the authors report that a vacuolar-type H+ ATPase, ATP6v0a1, is induced in adipocytes during obesity and persists after weight loss, and regulates food intake and weight gain in C. elegans and mice.

Abstract Although antipsychotics, such as olanzapine, are effective in the management of psychiatric conditions, some patients experience excessive antipsychotic-induced weight gain (AIWG). To illuminate pathways underlying AIWG, we compared baseline blood gene expression profiles in two cohorts of mice that were either prone (AIWG-P) or resistant (AIWG-R) to weight gain in response to olanzapine treatment for two weeks. We found that transcripts elevated in AIWG-P mice relative to AIWG-R are enriched for high-confidence transcriptional targets of numerous inflammatory and immunomodulatory signaling nodes. Moreover, these nodes are themselves enriched for genes whose disruption in mice is associated with reduced body fat mass and slow postnatal weight gain. In addition, we identified gene expression profiles in common between our mouse AIWG-P gene set and an existing human AIWG-P gene set whose regulation by immunomodulatory transcription factors is highly conserved between species. Finally, we identified striking convergence between mouse AIWG-P transcriptional regulatory networks and those associated with body weight and body mass index in humans. We propose that immunomodulatory transcriptional networks drive AIWG, and that these networks have broader conserved roles in whole body-metabolism.

Phosphine is now well-established as a biosignature, which has risen to prominence with its recent tentative detection on Venus. To follow up this discovery and related future exoplanet biosignature detections, it is important to spectroscopically detect the presence of phosphorus-bearing atmospheric molecules that could be involved in the chemical networks producing, destroying or reacting with phosphine. We start by enumerating phosphorus-bearing molecules (P-molecules) that could potentially be detected spectroscopically in planetary atmospheres and collecting all available spectral data. Gaseous P-molecules are rare, with speciation information scarce. Very few molecules have high accuracy spectral data from experiment or theory; instead, the best current spectral data was obtained using a high-throughput computational algorithm, RASCALL, relying on functional group theory to efficiently produce approximate spectral data for arbitrary molecules based on their component functional groups. Here, we present a high-throughput approach utilizing established computational quantum chemistry methods (CQC) to produce a database of approximate infrared spectra for 958 P-molecules. These data are of interest for astronomy and astrochemistry (importantly identifying potential ambiguities in molecular assignments), improving RASCALL's underlying data, big data spectral analysis and future machine learning applications. However, this data will probably not be sufficiently accurate for secure experimental detections of specific molecules within complex gaseous mixtures in laboratory or astronomy settings. We chose the strongly performing harmonic ωB97X-D/def2-SVPD model chemistry for all molecules and test the more sophisticated and time-consuming GVPT2 anharmonic model chemistry for 250 smaller molecules. Limitations to our automated approach, particularly for the less robust GVPT2 method, are considered along with pathways to future improvements. Our CQC calculations significantly improve on existing RASCALL data by providing quantitative intensities, new data in the fingerprint region (crucial for molecular identification) and higher frequency regions (overtones, combination bands), and improved data for fundamental transitions based on the specific chemical environment. As the spectroscopy of most P-molecules have never been studied outside RASCALL and this approach, the new data in this paper is the most accurate spectral data available for most P-molecules and represent a significant advance in the understanding of the spectroscopic behavior of these molecules.

This article investigates the results of a book sprint experience whose main objective was the development of instructional modules for an open textbook for the teaching of Spanish as a second language. Six graduate students at a public American university participated in the project for a week, working in pairs in the creation of activities that required the incorporation of the tenets of the dual pedagogical frameworks of performance- and literacy-based instruction (as realized through learning by design). Data were collected through both an opinion survey and the assessment of samples of the participants’ products. The results of the survey showed that graduate students felt that being part of the book sprint had been beneficial both at the professional and personal levels, but they had also experienced difficulties similar to those reported in previous studies. The products analyzed pointed to a lack of connection between the required pedagogical tenets and the materials developed, which has also been reported in existing works on pre- and in-service teachers as materials developers. The article discusses how these results could have been a consequence of the structure of the book sprint, and it offers recommendations for future activities of this kind.

Antecedentes: estudios previos reportan la presencia de grasas saturadas y grasas trans en productos de panadería, relacionadas con enfermedades crónicas no transmisibles. Sin embargo, se desconoce la procedencia y calidad de las materias primas grasas utilizadas por los panaderos en Medellín. Objetivo: caracterizar las materias primas grasas utilizadas para la preparación de productos de panadería. Materiales y métodos: estudio descriptivo transversal, de tipo exploratorio, con 24 muestras. Por cada muestra se realizó una encuesta a los panaderos para evaluar la calidad de las grasas y un análisis por cromatografía de gases para cuantificar 17 grasas saturadas y grasas trans. Resultados: el promedio de grasas trans en las materias primas grasas fue de 0,46 g en 100 g, mientras la normatividad permite 5 g en 100 g (Resolución 2508 de 2012, del Ministerio de Salud y Protección Social); el 42,1 % del contenido graso proviene de grasas saturadas; y algunas materias primas grasas no cumplen con la normatividad vigente para el etiquetado de alimentos envasados, pues no tienen rotulado nutricional. Conclusiones: en ninguna de las 24 materias primas grasas evaluadas cromatográficamente se cuantificó un contenido de grasas trans superior a lo permitido por la Resolución 2508, lo cual evidencia el esfuerzo de la industria de alimentos. Es necesario mantener la vigilancia del etiquetado para asegurar su cumplimiento.

Abstract Background Dyslipidemia, dysregulated adipokine secretion and alteration in glucagon and adropin concentrations are important obesity-related factors in the pathophysiology of human Type 2 diabetes; however, their roles in the pathophysiology of feline diabetes mellitus are relatively unknown. Here, we determined the concentrations of circulating leptin, adiponectin, pro-inflammatory cytokines, glucagon, adropin, triglycerides, and cholesterol, in non-diabetic lean and overweight cats and newly diagnosed diabetic cats. Client-owned cats were recruited and assigned into 3 study groups: lean, overweight and diabetic. Fasting blood samples were analyzed in lean, overweight and diabetic cats at baseline and 4 weeks after consumption of high protein/low carbohydrate standardized diet. Results Serum concentrations of triglycerides were greater in diabetics at baseline and were increased in both diabetic and overweight cats at 4 weeks. Plasma leptin concentrations were greater in diabetic and overweight at baseline and 4 weeks, whereas adiponectin was lower in diabetics compared to lean and overweight cats at baseline and 4 weeks. Diabetics had greater baseline plasma glucagon concentrations compared to lean, lower adropin than overweight at 4 weeks, and lower IL-12 concentrations at 4 weeks than baseline. Conclusions Our results suggest that feline obesity and diabetes mellitus are characterized by hypertriglyceridemia and hyperleptinemia; however, diabetic cats have significantly lower adiponectin and adropin compared to overweight cats. Thus, despite having similar body condition, overweight and diabetic cats have differential circulating concentrations of adiponectin and adropin.

Dentro de las actividades que alteran la composición del suelo está la minería, que causa el aumento de daños visibles al suelo mediante la creación de minas a cielo abierto, escombreras, estanques de residuos y otras instalaciones de minas. El objetivo principal de este trabajo fue evaluar el efecto de la lombriz roja californiana sobre el crecimiento de microorganismos en suelos contaminados con mercurio en el municipio de Segovia, Antioquia. Estos suelos representan una problemática importante debido a la acumulación de mercurio en exceso que ocasiona la pérdida de la calidad del suelo. Para este estudio se tomaron cuatro tratamientos en diferentes concentraciones de mercurio y un tratamiento más como blanco con lombrices rojas californianas (Eisenia foetida). Para esto, se evaluó el crecimiento de microorganismos a través de diferentes cultivos en el laboratorio, encontrando un crecimiento satisfactorio de los mismos luego de 25 y 90 días de tratamiento. De acuerdo al comportamiento observado, se evidencia una inmovilización del mercurio y una adaptación de los microorganismos al suelo contaminado, mostrando un aumento significativo de estos con el transcurso del tiempo.

Dengue is a major public health problem in hyperendemic countries like Colombia, the understanding of the epidemiological trends is important for the development of efficient public health policies. We conducted a systematic review of the epidemiologic data on dengue in Colombia from 1971 to 2020. A total of 375 relevant citations were identified, 36 of which fulfilled the inclusion criteria. The data of dengue and severe dengue cases, infection fatality rate, and serotype distribution were used to understand and identify gaps in the epidemiological knowledge in Colombia. The epidemiology of dengue in this country was characterized by five main outbreaks in 1998, 2002, 2010, 2013, and 2019 with high fatality rates in comparison with the average values reported in the Americas. The case fatality rate of severe dengue exceeded 2% and all four serotypes co-circulate throughout the country with some regional variations. Overall, the behavior of dengue in Colombia is influenced by multiple factors including seasonal temperature variation and socioeconomic conditions. Additionally, the most important barriers in the epidemiological surveillance of dengue may be due to the insufficient notification rate in some regions and the low active search for the circulation of different serotypes.

Dengue virus (DENV) is an arbovirus of the Flaviviridae family and is an enveloped virion containing a positive sense single-stranded RNA genome. DENV causes dengue fever (DF) which is characterized by an undifferentiated syndrome accompanied by fever, fatigue, dizziness, muscle aches, and in severe cases, patients can deteriorate and develop life-threatening vascular leakage, bleeding, and multi-organ failure. DF is the most prevalent mosquito-borne disease affecting more than 390 million people per year with a mortality rate close to 1% in the general population but especially high among children. There is no specific treatment and there is only one licensed vaccine with restricted application. Clinical and experimental evidence advocate the role of the humoral and T-cell responses in protection against DF, as well as a role in the disease pathogenesis. A lot of pro-inflammatory factors induced during the infectious process are involved in increased severity in dengue disease. The advances in DF research have been hampered by the lack of an animal model that recreates all the characteristics of this disease. Experiments in nonhuman primates (NHP) had failed to reproduce all clinical signs of DF disease and during the past decade, humanized mouse models have demonstrated several benefits in the study of viral diseases affecting humans. In DENV studies, some of these models recapitulate specific signs of disease that are useful to test drugs or vaccine candidates. However, there is still a need for a more complete model mimicking the full spectrum of DENV. This review focuses on describing the advances in this area of research.