Zika virus infection suppresses CYP24A1 and CAMP expression in human monocytes.

Monocytes are the primary targets of Zika virus (ZIKV) and are associated with ZIKV pathogenesis. Currently, there is no effective treatment for ZIKV infection. It is known that 1,25-dihydroxy vitamin D3 (VitD3) has strong antiviral activity in dengue virus-infected macrophages, but it is unknown whether VitD3 inhibits ZIKV infection in monocytes. We investigated the relationship between ZIKV infection and the expression of genes of the VitD3 pathway, as well as the inflammatory response of infected monocytes in vitro. ZIKV replication was evaluated using a plaque assay, and VitD3 pathway gene expression was analyzed by RT-qPCR. Pro-inflammatory cytokines/chemokines were quantified using ELISA. We found that VitD3 did not suppress ZIKV replication. The results showed a significant decrease in the expression of vitamin D3 receptor (VDR), cytochrome P450 family 24 subfamily A member 1 (CYP24A1), and cathelicidin antimicrobial peptide (CAMP) genes upon ZIKV infection. Treatment with VitD3 was unable to down-modulate production of pro-inflammatory cytokines, except TNF-α, and chemokines. This suggests that ZIKV infection inhibits the expression of VitD3 pathway genes, thereby preventing VitD3-dependent inhibition of viral replication and the inflammatory response. This is the first study to examine the effects of VitD3 in the context of ZIKV infection, and it has important implications for the role of VitD3 in the control of viral replication and inflammatory responses during monocyte infection.

Interleukin 27, Similar to Interferons, Modulates Gene Expression of Tripartite Motif (TRIM) Family Members and Interferes with Mayaro Virus Replication in Human Macrophages.

BACKGROUND: The Tripartite motif (TRIM) family includes more than 80 distinct human genes. Their function has been implicated in regulating important cellular processes, including intracellular signaling, transcription, autophagy, and innate immunity. During viral infections, macrophages are key components of innate immunity that produce interferons (IFNs) and IL27. We recently published that IL27 and IFNs induce transcriptional changes in various genes, including those involved in JAK-STAT signaling. Furthermore, IL27 and IFNs share proinflammatory and antiviral pathways in monocyte-derived macrophages (MDMs), resulting in both common and unique expression of inflammatory factors and IFN-stimulated genes (ISGs) encoding antiviral proteins. Interestingly, many TRIM proteins have been recognized as ISGs in recent years. Although it is already very well described that TRIM expression is induced by IFNs, it is not fully understood whether TRIM genes are induced in macrophages by IL27. Therefore, in this study, we examined the effect of stimulation with IL27 and type I, II, and III IFNs on the mRNA expression profiles of TRIM genes in MDMs. METHODS: We used bulk RNA-seq to examine the TRIM expression profile of MDMs treated with IFNs or IL27. Initially, we characterized the expression patterns of different TRIM subfamilies using a heatmap. Subsequently, a volcano plot was employed to identify commonly differentially expressed TRIM genes. Additionally, we conducted gene ontology analysis with ClueGO to explore the biological processes of the regulated TRIMs, created a gene-gene interaction network using GeneMANIA, and examined protein-protein interactions with the STRING database. Finally, RNA-seq data was validated using RT-qPCR. Furthermore, the effect of IL27 on Mayaro virus replication was also evaluated. RESULTS: We found that IL27, similar to IFNs, upregulates several TRIM genes' expression in human macrophages. Specifically, we identified three common TRIM genes (TRIM19, 21, and 22) induced by IL27 and all types of human IFNs. Additionally, we performed the first report of transcriptional regulation of TRIM19, 21, 22, and 69 genes in response to IL27. The TRIMs involved a broad range of biological processes, including defense response to viruses, viral life cycle regulation, and negative regulation of viral processes. In addition, we observed a decrease in Mayaro virus replication in MDMs previously treated with IL27. CONCLUSIONS: Our results show that IL27, like IFNs, modulates the transcriptional expression of different TRIM-family members involved in the induction of innate immunity and an antiviral response. In addition, the functional analysis demonstrated that, like IFN, IL27 reduced Mayaro virus replication in MDMs. This implies that IL27 and IFNs share many similarities at a functional level. Moreover, identifying distinct TRIM groups and their differential expressions in response to IL27 provides new insights into the regulatory mechanisms underlying the antiviral response in human macrophages.

Interleukin 27, like interferons, activates JAK-STAT signaling and promotes pro-inflammatory and antiviral states that interfere with dengue and chikungunya viruses replication in human macrophages.

Interferons (IFNs) are a family of cytokines that activate the JAK-STAT signaling pathway to induce an antiviral state in cells. Interleukin 27 (IL-27) is a member of the IL-6 and/or IL-12 family that elicits both pro- and anti-inflammatory responses. Recent studies have reported that IL-27 also induces a robust antiviral response against diverse viruses, both in vitro and in vivo, suggesting that IFNs and IL-27 share many similarities at the functional level. However, it is still unknown how similar or different IFN- and IL-27-dependent signaling pathways are. To address this question, we conducted a comparative analysis of the transcriptomic profiles of human monocyte-derived macrophages (MDMs) exposed to IL-27 and those exposed to recombinant human IFN-α, IFN-γ, and IFN-λ. We utilized bioinformatics approaches to identify common differentially expressed genes between the different transcriptomes. To verify the accuracy of this approach, we used RT-qPCR, ELISA, flow cytometry, and microarrays data. We found that IFNs and IL-27 induce transcriptional changes in several genes, including those involved in JAK-STAT signaling, and induce shared pro-inflammatory and antiviral pathways in MDMs, leading to the common and unique expression of inflammatory factors and IFN-stimulated genes (ISGs)Importantly, the ability of IL-27 to induce those responses is independent of IFN induction and cellular lineage. Additionally, functional analysis demonstrated that like IFNs, IL-27-mediated response reduced chikungunya and dengue viruses replication in MDMs. In summary, IL-27 exhibits properties similar to those of all three types of human IFN, including the ability to stimulate a protective antiviral response. Given this similarity, we propose that IL-27 could be classified as a distinct type of IFN, possibly categorized as IFN-pi (IFN-π), the type V IFN (IFN-V).

Mayaro virus infection elicits a robust pro-inflammatory and antiviral response in human macrophages.

Mayaro virus (MAYV), the etiological agent of Mayaro fever (MAYF), is an emergent arbovirus pathogen belonging to Togaviridae family. MAYF is characterized by high inflammatory component that can cause long-lasting arthralgia that persists for months. Macrophages are viral targets and reservoirs, key components of innate immunity and host response. Given the importance of this pathogen, our aim was to determine the inflammatory and antiviral response of human monocyte-derived macrophages (MDMs) infected with MAYV. First, we established the replication kinetics of the virus. Thereafter, we determined the expression of pattern recognition receptors, NF-ĸB complex, interferons (IFNs), two interleukin 27 (IL27) subunits, IFN-stimulated genes (ISGs), and the production of cytokines/chemokines. We found that human MDMs are susceptible to MAYV infection in vitro, with a peak of viral particles released between 24- and 48-hours post-infection (h.p.i) at MOI 0.5, and between 12 and 24 h.p.i at MOI 1. Interestingly, we observed a significant decline in the production of infectious viral particles at 72 h.p.i that was associated with the induction of antiviral response and high cytotoxic effect of MAYV infection in MDMs. We observed modulation of several genes after MAYV infection, as well, we noted the activation of antiviral detection and response pathways (Toll-like receptors, RIG-I/MDA5, and PKR) at 48 h.p.i but not at 6 h.p.i. Furthermore, MAYV-infected macrophages express high levels of the three types of IFNs and the two IL27 subunits at 48 h.p.i. Moreover, we found higher production of IL6, IL1ß, CXCL8/IL8, CCL2, and CCL5 at 48 h.p.i as compared to 6 h.p.i. A robust antiviral response (ISG15, APOBEC3A, IFITM1, and MX2) was observed at 48 but not at 6 h.p.i. The innate and antiviral responses of MAYV-infected MDMs differ at 6 and 48 h.p.i. We conclude that MAYV infection induces robust pro-inflammatory and antiviral responses in human primary macrophages.

Protective Effects of Caffeine on Chikungunya and Zika Virus Infections: An in Vitro and in Silico Study.

Infection by viruses Chikungunya (CHIKV) and Zika (ZIKV) continue to be serious problems in tropical and subtropical areas of the world. Here, we evaluated the antiviral and virucidal activity of caffeine against CHIKV and ZIKV in Vero, A549, and Huh-7 cell lines. Results showed that caffeine displays antiviral properties against both viruses. By pre-and post-infection treatment, caffeine significantly inhibited CHIKV and ZIKV replication in a dose-dependent manner. Furthermore, caffeine showed a virucidal effect against ZIKV. Molecular docking suggests the possible binding of caffeine with envelope protein and RNA-dependent RNA polymerase of CHIKV and ZIKV. This is the first study that showed an antiviral effect of caffeine against CHIKV and ZIKV. Although further studies are needed to better understand the mechanism of caffeine-mediated repression of viral replication, caffeine appears to be a promising compound that could be used for in vivo studies, perhaps in synergy with other compounds present in daily beverages.

Antiviral response and immunopathogenesis of interleukin 27 in COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with a high mortality rate. The clinical course is attributed to the severity of pneumonia and systemic complications. In COVID-19 patients and murine models of SARS-CoV-2 infection, the disease may be accompanied by excessive production of cytokines, leading to an accumulation of immune cells in affected organs such as lungs. Previous reports have shown that SARS-CoV-2 infection antagonizes interferon (IFN)-dependent antiviral response, thereby preventing the expression of IFN-stimulated genes (ISGs). Lower IFN levels have been linked to more-severe COVID-19. Interleukin 27 (IL27) is a heterodimeric cytokine composed of IL27p28 and EBI3 subunits, which induce both pro- and anti-inflammatory responses. Recently, we and others have reported that IL27 also induces a strong antiviral response in an IFN-independent manner. Here, we investigated transcription levels of both IL27 subunits in COVID-19 patients. The results show that SARS-CoV-2 infection modulates TLR1/2-MyD88 signaling in PBMCs and monocytes and induces NF-κB activation and expression of NF-κB-target genes that are dependent on a robust pro-inflammatory response, including EBI3; and activates IRF1 signaling which induces IL27p28 mRNA expression. The results suggest that IL27 induces a robust STAT1-dependent pro-inflammatory and antiviral response in an IFN-independent manner in COVID-derived PBMCs and monocytes as a function of a severe clinical course of COVID-19. Similar results were observed in macrophages stimulated with the SARS-CoV-2 spike protein. Thus, IL27 can trigger an antiviral response in the host, suggesting the possibility of novel therapeutics against SARS-CoV-2 infection in humans.

Immunoglobulin E and G autoantibodies against eosinophil proteins in children and adults with asthma and healthy subjects.

Background: Autoimmune IgG response has been described in the pathogenesis of asthma in adults, but IgE autoimmunity has been little explored. Considering high levels of blood eosinophils and immunoglobulin E in asthmatic patients, the possibility of IgE autoantibody response to eosinophil proteins arises. Objective: To explore the presence of IgE and IgG autoantibodies against Eosinophil peroxidase (EPX) and Eosinophil cationic protein (ECP). Methods: Three steps were followed: 1) The frequency of IgE and IgG autoantibodies against EPX and ECP was investigated among asthmatic and healthy subjects. 2) The ability of IgE autoantibodies to induce an inflammatory response (basophil activation) was performed. 3) The capacity of autoantibodies to identify patients with severe asthma was evaluated. Results: Asthmatic and healthy subjects had IgE and IgG autoantibodies against EPX and ECP. Anti-EPX IgE was significantly higher in asthmatic patients. Severe asthmatic patients had a higher frequency and higher levels of IgE and IgG autoantibodies compared to healthy subjects. There was not a correlation between autoantibodies and blood eosinophils. Children younger than 14 years of age had IgE and IgG autoantibodies against to EPX and ECP. IgE autoantibodies to EPX and ECP induced basophil activation in asthmatic patients. Conclusion: In this study, we identify for the first time IgE autoantibodies against EPX and ECP in adults and children patients with asthma; IgE and IgG autoantibodies against EPX and ECP could serve as a predictive biomarker of the clinical severity.

American-Asian- and African lineages of Zika virus induce differential pro-inflammatory and Interleukin 27-dependent antiviral responses in human monocytes.

Zika virus (ZIKV) is an arbovirus that belongs to the Flaviviridae family and inflammatory responses play a critical role in ZIKV pathogenesis. As a first-line defense, monocytes are key components of innate immunity and host response to viruses. Monocytes are considered the earliest blood cell type to be infected by ZIKV and have been shown to be associated with ZIKV pathogenesis. The first ZIKV epidemic was reported in Africa and Asia although, it is less well known whether African- and Asian- lineages of ZIKV have different impacts on host immune response. We studied the pro-inflammatory and antiviral response of ZIKV-infected monocytes using publicly available RNA-seq analysis (GSE103114). We compared the transcriptomic profiles of human monocytes infected with ZIKV Puerto Rico strain (PRVABC59), American-Asian lineage, and ZIKV Nigeria strain (IBH30656), African lineage. We validated RNA-seq results by ELISA or RT-qPCR, in human monocytes infected with a clinical isolate of ZIKV from Colombia (American-Asian lineage), or with ZIKV from Dakar (African lineage). The transcriptomic analysis showed that ZIKV Puerto Rico strain promotes a higher pro-inflammatory response through TLR2 signaling and NF-kB activation and induces a strong IL27-dependent antiviral activity than ZIKV Nigeria strain. Furthermore, human monocytes are more susceptible to infection with ZIKV from Colombia than ZIKV from Dakar. Likewise, Colombian ZIKV isolate activated IL27 signaling and induced a robust antiviral response in an IFN-independent manner. Moreover, we show that treatment of monocytes with IL27 results in decreased release of ZIKV particles in a dose-dependent manner with an EC50 =2.870 ng/mL for ZIKV from Colombia and EC50 =10.23 ng/mL to ZIKV from Dakar. These findings highlight the differential inflammatory response and antiviral activity of monocytes infected with different lineages of ZIKV and may help better management of ZIKV-infected patients.

Environmental contributions to the interactions of COVID-19 and asthma: A secondary publication and update.

An outbreak of coronavirus disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) started in Wuhan, Hubei Province, China and quickly spread around the world. Current evidence is contradictory on the association of asthma with COVID-19 and associated severe outcomes. Type 2 inflammation may reduce the risk for severe COVID-19. Whether asthma diagnosis may be a risk factor for severe COVID-19, especially for those with severe disease or non-allergic phenotypes, deserves further attention and clarification. In addition, COVID-19 does not appear to provoke asthma exacerbations, and asthma therapeutics should be continued for patients with exposure to COVID-19. Changes in the intensity of pollinization, an earlier start and extension of the pollinating season, and the increase in production and allergenicity of pollen are known direct effects that air pollution has on physical, chemical, and biological properties of the pollen grains. They are influenced and triggered by meteorological variables that could partially explain the effect on COVID-19. SARS-CoV-2 is capable of persisting in the environment and can be transported by bioaerosols which can further influence its transmission rate and seasonality. The COVID-19 pandemic has changed the behavior of adults and children globally. A general trend during the pandemic has been human isolation indoors due to school lockdowns and loss of job or implementation of virtual work at home. A consequence of this behavior change would presumably be changes in indoor allergen exposures and reduction of inhaled outdoor allergens. Therefore, lockdowns during the pandemic might have improved some specific allergies, while worsening others, depending on the housing conditions.

Diagnostic Performance of IgE Anti-Der p 10 to Identify Patients with Shrimp Allergy.

BACKGROUND: Patients with allergic rhinitis to house dust mites have an increased risk of shrimp allergy. Der p 10 is a candidate biomarker to predict the risk of shrimp allergy among allergic rhinitis patients. OBJECTIVES: The aim of this study was to evaluate the diagnostic performance of anti-Der p 10 IgE as a predictor of shrimp allergy. METHODS: A nested case-control study was carried out with eighty-six allergic rhinitis patients sensitized to mite (Dermatophagoides pteronyssinus) and shrimp (Litopenaeu vannamei). Cases and controls were defined by anti-Der p 10 IgE results. Oral challenge with shrimp was used as the gold standard for the evaluation of diagnostic performance. RESULTS: All shrimp oral challenge test (OCT)-positive patients were positive for IgE against Der p 10. The level of anti-Der p 10 IgE >1.2 kUA/mL had the best diagnostic performance (sensitivity 100%, specificity 65%) Conclusion: Anti-Der p 10 IgE is useful for predicting shrimp allergy diagnosis and could reduce the requirement of an OCT.

Synergistic Effects of Toll-Like Receptor 1/2 and Toll-Like Receptor 3 Signaling Triggering Interleukin 27 Gene Expression in Chikungunya Virus-Infected Macrophages.

Chikungunya virus (CHIKV) is the etiological agent of chikungunya fever (CHIKF), a self-limiting disease characterized by myalgia and severe acute or chronic arthralgia. CHIKF is associated with immunopathology and high levels of pro-inflammatory factors. CHIKV is known to have a wide range of tropism in human cell types, including keratinocytes, fibroblasts, endothelial cells, monocytes, and macrophages. Previously, we reported that CHIKV-infected monocytes-derived macrophages (MDMs) express high levels of interleukin 27 (IL27), a heterodimeric cytokine consisting of IL27p28 and EBI3 subunits, that triggers JAK-STAT signaling and promotes pro-inflammatory and antiviral response, in interferon (IFN)-independent manner. Based on the transcriptomic analysis, we now report that induction of IL27-dependent pro-inflammatory and antiviral response in CHIKV-infected MDMs relies on two signaling pathways: an early signal dependent on recognition of CHIKV-PAMPs by TLR1/2-MyD88 to activate NF-κB-complex that induces the expression of EBI3 mRNA; and second signaling dependent on the recognition of intermediates of CHIKV replication (such as dsRNA) by TLR3-TRIF, to activate IRF1 and the induction of IL27p28 mRNA expression. Both signaling pathways were required to produce a functional IL27 protein involved in the induction of ISGs, including antiviral proteins, cytokines, CC- and CXC- chemokines in an IFN-independent manner in MDMs. Furthermore, we reported that activation of TLR4 by LPS, both in human MDMs and murine BMDM, results in the induction of both subunits of IL27 that trigger strong IL27-dependent pro-inflammatory and antiviral response independent of IFNs signaling. Our findings are a significant contribution to the understanding of molecular and cellular mechanisms of CHIKV infection.

Presence of IgE Autoantibodies Against Eosinophil Peroxidase and Eosinophil Cationic Protein in Severe Chronic Spontaneous Urticaria and Atopic Dermatitis.

PURPOSE: Eosinophils are frequently found in atopic dermatitis (AD) and chronic spontaneous urticaria (CSU) that release eosinophil peroxidase (EPX) and eosinophil cationic protein (ECP). Continuous exposure to these proteins could trigger an autoimmune response which may contribute to the pathogenesis and severity of skin inflammation. In this study, we investigate the immunoglobulin E (IgE) response against eosinophil proteins in CSU and AD. METHODS: We recruited patients with severe AD, severe CSU and healthy subjects to explore the presence of IgE autoantibodies and cross-reactivity against EPX, ECP and thyroid peroxidase (TPO). The potential cross-reactive epitopes among the peroxidase family were determined using in silico tools. RESULTS: The frequencies of anti-EPX IgE (28.8%) and anti-ECP IgE (26.6%) were higher in the AD group, and anti-TPO IgE was higher in the CSU group (27.2%). In the CSU group, there was a correlation between the anti-EPX IgE and anti-TPO IgE levels (r = 0.542, P < 0.001); TPO inhibited 42% of IgE binding to EPX, while EPX inhibited 59% of IgE binding to TPO, suggesting a cross-reactivity with EPX as a primary sensitizer. There was greater inhibition when we used a pool of sera CSU and AD, TPO inhibited 52% of IgE binding to EPX, while EPX inhibited 78% of IgE binding to TPO. In silico analysis showed a possible shared epitope in the peroxidase protein family. CONCLUSIONS: IgE against eosinophil proteins may contribute to chronic inflammation in patients with AD and CSU. Cross-reactivity between EPX and TPO could explain thyroid problems in CSU patients.

Perinatal and Early-Life Nutrition, Epigenetics, and Allergy.

Epidemiological studies have shown a dramatic increase in the incidence and the prevalence of allergic diseases over the last several decades. Environmental triggers including risk factors (e.g., pollution), the loss of rural living conditions (e.g., farming conditions), and nutritional status (e.g., maternal, breastfeeding) are considered major contributors to this increase. The influences of these environmental factors are thought to be mediated by epigenetic mechanisms which are heritable, reversible, and biologically relevant biochemical modifications of the chromatin carrying the genetic information without changing the nucleotide sequence of the genome. An important feature characterizing epigenetically-mediated processes is the existence of a time frame where the induced effects are the strongest and therefore most crucial. This period between conception, pregnancy, and the first years of life (e.g., first 1000 days) is considered the optimal time for environmental factors, such as nutrition, to exert their beneficial epigenetic effects. In the current review, we discussed the impact of the exposure to bacteria, viruses, parasites, fungal components, microbiome metabolites, and specific nutritional components (e.g., polyunsaturated fatty acids (PUFA), vitamins, plant- and animal-derived microRNAs, breast milk) on the epigenetic patterns related to allergic manifestations. We gave insight into the epigenetic signature of bioactive milk components and the effects of specific nutrition on neonatal T cell development. Several lines of evidence suggest that atypical metabolic reprogramming induced by extrinsic factors such as allergens, viruses, pollutants, diet, or microbiome might drive cellular metabolic dysfunctions and defective immune responses in allergic disease. Therefore, we described the current knowledge on the relationship between immunometabolism and allergy mediated by epigenetic mechanisms. The knowledge as presented will give insight into epigenetic changes and the potential of maternal and post-natal nutrition on the development of allergic disease.

Prácticas sobre cuidado de niños con discapacidad construidas por cuidadores del Instituto de Capacitación Los Álamos

Introducción:La labor de cuidado de niños con discapacidad en primera infancia está mediada por muchos elementos, entre ellos, las prácticas. Dada la discapacidad y la edad de los niños, es habitual que sean sus cuidadores los responsables de su bienestar. Comprender las prácticas de los cuidadores permite optimizar e implementar rutinas funcionales, que propendan al bienestar y la calidad de vida de los niños y sus cuidadores. Objetivo: Comprender las prácticas de personas encargadas del cuidado a niños con discapacidad, de 1 a 6 años de edad, en el Instituto de Capacitación Los Álamos (Itagüí, Colombia). Método: Estudio cualitativo enfocado en la teoría fundamentada. Se invitó a participar 12 madres sustitutas del instituto, se realizó un muestreo a conveniencia hasta la saturación teórica. Resultados: Las prácticas se constituyen en rutinas de cuidado que incluyen actividades que son específicas para los niños con discapacidad, tales como masajes, terapias, adaptaciones del espacio para el posicionamiento y la participación, entre otros. Actividades como la alimentación y el masaje son igual de importantes a la hora del cuidado de un niño con discapacidad. Conclusión: El cuidado de niños con discapacidad supone la realización de múltiples actividades y diferentes prácticas específicas para la condición del niño. A pesar de lo difíciles que son, terminan estando inmersas en un compilado de rutinas que se incorporan al día a día de la familia.

Introdução: O trabalho de cuidar de crianças com deficiência na primeira infância é mediado por muitos elementos, incluindo práticas. Dada a deficiência e a idade das crianças, é comum que seus cuidadores sejam responsáveis por seu bem-estar. A compreensão das práticas dos cuidadores permite otimizar e implementar rotinas funcionais que promovam o bem-estar e a qualidade de vida da criança e de seus cuidadores. Objetivo: Compreender as práticas sobre o cuidado de crianças com deficiência física na primeira infância, construídas por cuidadores pertencentes ao Instituto de Capacitación Los Álamos. Método: Estudo qualitativo com foco na teoria fundamentada. Doze mães de aluguel foram convidadas a participar, sendo realizada uma amostragem por conveniência até a saturação teórica. Resultados: As práticas se constituem em rotinas de cuidado, que incluem atividades específicas para crianças com deficiência, como massagens, terapias, adaptações do espaço para posicionamento e participação, entre outras. Atividades como alimentação e massagem são tão importantes quanto ao cuidar de uma criança com deficiência. Conclusão: Cuidar de crianças com deficiência envolve a realização de múltiplas atividades e diferentes práticas específicas à condição da criança. Por mais difíceis que sejam, acabam imersos em uma compilação de rotinas que se incorporam ao dia a dia da família.

Introduction: Many elements, including practices, mediate the work of caring for children with disabilities in early childhood. As a result of the disability and age of the children, their caregivers commonly become responsible for their well-being. Understanding the practices of caregivers allows optimizing and implementing functional routines that promote the well-being and quality of life of children and their caregivers. Objective: To understand the practices of caregivers of children aged 1-6 years with disabilities at the Instituto de Capacitación Los Álamos (Itagüí, Colombia). Method: Qualitative study focused on grounded theory. The participants were twelve surrogate mothers from the institute; a convenience sampling was carried out until theoretical saturation. Results: The practices consisted of care routines, including activities specifically for children with disabilities such as massages, therapies, adaptations of the space for postural control and participation. Moreover, activities such as feeding and massages are equally important when caring for a child with a disability. Conclusion: Caring for children with disabilities involves multiple activities and practices specific to the child's condition. Despite their difficulty, they become immersed in a compilation of routines incorporated into the family's daily life.

Chikungunya Virus and Zika Virus, Two Different Viruses Examined with a Common Aim: Role of Pattern Recognition Receptors on the Inflammatory Response.

Chikungunya virus (CHIKV) and Zika virus (ZIKV) are 2 reemerging arboviruses that have been the focus of public health institutions worldwide, since the last decades and following a spate of outbreaks in tropical and subtropical areas. The disease caused by both viruses manifests itself first as an acute stage of severe inflammation into the infected tissues, which later progresses to arthritis and chronic polyarthralgia in the case of CHIKV or congenital microcephaly and neurological disorders such as Guillain-Barré syndrome in the case of ZIKV. This review aims to summarize on current knowledge of the role of different pattern recognition receptors that leads to an elevated production and secretion of antiviral response (interferon) and severe inflammation in response to CHIKV and ZIKV infection.

Papular urticaria: A review of causal agents in Colombia.

Papular urticaria is a chronic allergic reaction induced by insect bites, which is common in the tropics. The objective of this review was to deepen on epidemiological and immunological aspects of this disease, focused on data published in Latin American countries.We conducted a non-systematic review of the literature through electronic search on the epidemiology of papular urticaria, the entomological characteristics of the causative agents and associated immunological mechanisms.Several reports from medical centers suggest that papular urticaria is common in Latin America. Only one epidemiological survey designed to estimate prevalence of papular urticaria has been published, reporting that about a quarter of children under six years of age is affected by this condition in Bogotá. There is evidence on the causal relationship among exposure to indoor fleas, poverty and papular urticaria in Bogotá, a representative city of the Andean altitudes. Information about causal insects in tropical warmer areas is scarce, although from clinical reports Aedes aegypti and Culex quienquefasciatus appear to be the most common. Th2 cellular-mediated mechanisms are involved in its pathogenesis, which explains its delayed hypersensitivity. The role of immunoglobulin E is not clear in this disease. Insect-derived antigens directly involved in papular urticaria etiology are unknown. However, it is possible that common molecules among causal insects mediate cross-reactive reactions, such as Cte f 2 allergen, found in cat fleas, and its counterparts in mosquitoes.Papular urticaria is a frequent disease in Latin America that should be further investigated. Immunological characterization of the molecular components that cause this condition may solve questions about its pathogenesis.