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Introducción: La necrólisis epidérmica tóxica es un cuadro agudo, frecuentemente mortal, con aparición rápida de bulas y desprendimiento masivo de la epidermis.  Desarrollo: Es una urgencia dermatológica con dos fases: prodrómica  y crítica semeja a un alto grado de quemadura, por el desprendimiento masivo de epidermis que descubre una dermis de color oscuro o rosado con una afectación mayor al 30 % de la superficie corporal. Si llega a afectar más del 60 % de dicha superficie, la mortalidad asciende a un 25-35 %. Se desencadena por una reacción antígeno-anticuerpo en cuestión de días, con la secreción de tres enzimas, y culmina con la liberación de células tóxicas, formación de ampollas intradérmicas y ruptura de estas, provocando desprendimiento epidérmico.  Aplicaciones prácticas: El uso cuidadoso de fármacos, sobre todo en pacientes hiperérgicos, es muy importante como profilaxis. Es fundamental identificarla precozmente para prescribir el tratamiento multidisciplinario que logre impedir la aparición de complicaciones y disminuya la mortalidad Conclusiones: Esta urgencia dermatológica es una condición clínica que, de no ser identificada a tiempo, resulta potencialmente mortal, al afectar un importante porcentaje de superficie corporal y dañar órganos internos vitales., Introducción: La necrólisis epidérmica tóxica es un cuadro agudo, frecuentemente mortal, con aparición rápida de bulas y desprendimiento masivo de la epidermis.  Desarrollo: Es una urgencia dermatológica con dos fases: prodrómica  y crítica semeja a un alto grado de quemadura, por el desprendimiento masivo de epidermis que descubre una dermis de color oscuro o rosado con una afectación mayor al 30 % de la superficie corporal. Si llega a afectar más del 60 % de dicha superficie, la mortalidad asciende a un 25-35 %. Se desencadena por una reacción antígeno-anticuerpo en cuestión de días, con la secreción de tres enzimas, y culmina con la liberación de células tóxicas, formación de ampollas intradérmicas y ruptura de estas, provocando desprendimiento epidérmico.  Aplicaciones prácticas: El uso cuidadoso de fármacos, sobre todo en pacientes hiperérgicos, es muy importante como profilaxis. Es fundamental identificarla precozmente para prescribir el tratamiento multidisciplinario que logre impedir la aparición de complicaciones y disminuya la mortalidad Conclusiones: Esta urgencia dermatológica es una condición clínica que, de no ser identificada a tiempo, resulta potencialmente mortal, al afectar un importante porcentaje de superficie corporal y dañar órganos internos vitales.

Rapid progress has recently been made in the elucidation of the genetic basis of childhood-onset inherited generalized dystonia (IGD) due to the implementation of genomic sequencing methodologies. We identified four patients with childhood-onset IGD harboring novel disease-causing mutations in lysine-specific histone methyltransferase 2B gene (KMT2B) by whole-exome sequencing. The main focus of this paper is to gain novel pathophysiological insights through understanding the molecular consequences of these mutations. The disease course is mostly progressive, evolving from lower limbs into generalized dystonia, which could be associated with dysarthria, dysphonia, intellectual disability, orofacial dyskinesia, and sometimes distinct dysmorphic facial features. In two patients, motor performances improved after bilateral implantation of deep brain stimulation in the globus pallidus internus (GPi-DBS). Pharmacotherapy with trihexyphenidyl reduced dystonia in two patients. We discovered three novel KMT2B mutations. Our analyses revealed that the mutation in patient 1 (c.7463A > G, p.Y2488C) is localized in the highly conserved FYRC domain of KMT2B. This mutation holds the potential to alter the inter-domain FYR interactions, which could lead to KMT2B instability. The mutations in patients 2 and 3 (c.3596_3697insC, p.M1202Dfs*22; c.4229delA, p.Q1410Rfs*12) lead to predicted unstable transcripts, likely to be subject to degradation by non-sense-mediated decay. Childhood-onset progressive dystonia with orofacial involvement is one of the main clinical manifestations of KMT2B mutations. In all, 26% (18/69) of the reported cases have T2 signal alterations of the globus pallidus internus, mostly at a younger age. Anticholinergic medication and GPi-DBS are promising treatment options and shall be considered early.

El semáforo nutricional o Traffic-Light, es un sistema ideado en Gran Bretaña para brindar información entendible y didáctica, utilizando códigos de colores para hacer referencia a los componentes presentes en los productos procesados y/o ultra procesados; este ayuda a determinar en qué categoría se encuentra la cantidad de los ingredientes de determinado producto, según la media de valores recomendados, ya sea con un porcentaje bajo, medio o alto, comúnmente estas categorías están asociadas a los colores verde, amarillo y rojo respectivamente. (Emrich, Qi, Lou y L'Abbe, 2017).

Sexual and Reproductive Health is presented as an important issue to be analyzed in the world society and particularly in ours. Its validity and implementation underpins the social and economic development of the peoples. The present study analyzes the Knowledge, Attitudes and Practices (KAP´s) that in this field wield university students. The objective is determine the relationship between KAP´s in Sexual and Reproductive Health with the Socioeconomic stratum of the students of the University of Cuenca. This is a quantitative, descriptive and transversal investigation of a universe of 15,653 students that attend the 12 faculties that make up the institution. A sample of 680 students was obtained. Error margin of 5% and confidence level of 99%. The survey developed by the National University of Costa Rica, which addresses the dimensions of Sexual Health, Reproductive Health, HIV-AIDS-ETS, and Use of the Condom, was applied. For socioeconomic stratification, the INEC survey was used. 73.9% of those investigated come from the Medium High and Medium Typical strata. From the Medium Low and Low strata they total 7.4%. The figures of "adequate" KAP´s are quite similar between women and men, 65.9% compared to 65.2%. Women show better figures of "adequate" KAP´s in the areas of Sexual Health and HIV / AIDS / STDs, while men show better averages in Reproductive Health and Use of Condom. The highest figures of "adequate" CAPs in SSR are observed in the High socio-economic stratum.

Rapid progress has recently been made in the elucidation of the genetic basis of childhood-onset inherited generalized dystonia (IGD) due to the implementation of genomic sequencing methodologies. We identified four patients with childhood-onset IGD harboring novel disease-causing mutations in lysine-specific histone methyltransferase 2B gene (KMT2B) by whole-exome sequencing. The main focus of this paper is to gain novel pathophysiological insights through understanding the molecular consequences of these mutations. The disease course is mostly progressive, evolving from lower limbs into generalized dystonia, which could be associated with dysarthria, dysphonia, intellectual disability, orofacial dyskinesia, and sometimes distinct dysmorphic facial features. In two patients, motor performances improved after bilateral implantation of deep brain stimulation in the globus pallidus internus (GPi-DBS). Pharmacotherapy with trihexyphenidyl reduced dystonia in two patients. We discovered three novel KMT2B mutations. Our analyses revealed that the mutation in patient 1 (c.7463A > G, p.Y2488C) is localized in the highly conserved FYRC domain of KMT2B. This mutation holds the potential to alter the inter-domain FYR interactions, which could lead to KMT2B instability. The mutations in patients 2 and 3 (c.3596_3697insC, p.M1202Dfs*22; c.4229delA, p.Q1410Rfs*12) lead to predicted unstable transcripts, likely to be subject to degradation by non-sense-mediated decay. Childhood-onset progressive dystonia with orofacial involvement is one of the main clinical manifestations of KMT2B mutations. In all, 26% (18/69) of the reported cases have T2 signal alterations of the globus pallidus internus, mostly at a younger age. Anticholinergic medication and GPi-DBS are promising treatment options and shall be considered early.

El semáforo nutricional o Traffic-Light, es un sistema ideado en Gran Bretaña para brindar información entendible y didáctica, utilizando códigos de colores para hacer referencia a los componentes presentes en los productos procesados y/o ultra procesados; este ayuda a determinar en qué categoría se encuentra la cantidad de los ingredientes de determinado producto, según la media de valores recomendados, ya sea con un porcentaje bajo, medio o alto, comúnmente estas categorías están asociadas a los colores verde, amarillo y rojo respectivamente. (Emrich, Qi, Lou y L'Abbe, 2017).

Sexual and Reproductive Health is presented as an important issue to be analyzed in the world society and particularly in ours. Its validity and implementation underpins the social and economic development of the peoples. The present study analyzes the Knowledge, Attitudes and Practices (KAP´s) that in this field wield university students. The objective is determine the relationship between KAP´s in Sexual and Reproductive Health with the Socioeconomic stratum of the students of the University of Cuenca. This is a quantitative, descriptive and transversal investigation of a universe of 15,653 students that attend the 12 faculties that make up the institution. A sample of 680 students was obtained. Error margin of 5% and confidence level of 99%. The survey developed by the National University of Costa Rica, which addresses the dimensions of Sexual Health, Reproductive Health, HIV-AIDS-ETS, and Use of the Condom, was applied. For socioeconomic stratification, the INEC survey was used. 73.9% of those investigated come from the Medium High and Medium Typical strata. From the Medium Low and Low strata they total 7.4%. The figures of "adequate" KAP´s are quite similar between women and men, 65.9% compared to 65.2%. Women show better figures of "adequate" KAP´s in the areas of Sexual Health and HIV / AIDS / STDs, while men show better averages in Reproductive Health and Use of Condom. The highest figures of "adequate" CAPs in SSR are observed in the High socio-economic stratum.

Sexual and Reproductive Health is presented as an important issue to be analyzed in the world society and particularly in ours. Its validity and implementation underpins the social and economic development of the peoples. The present study analyzes the Knowledge, Attitudes and Practices (KAP´s) that in this field wield university students. The objective is determine the relationship between KAP´s in Sexual and Reproductive Health with the Socioeconomic stratum of the students of the University of Cuenca. This is a quantitative, descriptive and transversal investigation of a universe of 15,653 students that attend the 12 faculties that make up the institution. A sample of 680 students was obtained. Error margin of 5% and confidence level of 99%. The survey developed by the National University of Costa Rica, which addresses the dimensions of Sexual Health, Reproductive Health, HIV-AIDS-ETS, and Use of the Condom, was applied. For socioeconomic stratification, the INEC survey was used. 73.9% of those investigated come from the Medium High and Medium Typical strata. From the Medium Low and Low strata they total 7.4%. The figures of "adequate" KAP´s are quite similar between women and men, 65.9% compared to 65.2%. Women show better figures of "adequate" KAP´s in the areas of Sexual Health and HIV / AIDS / STDs, while men show better averages in Reproductive Health and Use of Condom. The highest figures of "adequate" CAPs in SSR are observed in the High socio-economic stratum.

The majority of the eukaryotic genome is transcribed into noncoding RNAs (ncRNAs), which are important regulators of different nuclear processes by controlling chromatin structure. However, the full extent of ncRNA function has remained elusive. Here we deciphered the function of the microRNA Mirlet7d as a key regulator of bidirectionally transcribed genes. We found that nuclear Mirlet7d binds ncRNAs expressed from these genes. Mirlet7d-ncRNA duplexes are further bound by C1D, which in turn targets the RNA exosome complex and the polycomb repressive complex 2 (PRC2) to the bidirectionally active loci. The exosome degrades the ncRNAs, whereas PRC2 induces heterochromatin and transcriptional silencing through EZH2. Moreover, this multicomponent RNA-protein complex, which we named MiCEE, tethers the regulated genes to the perinucleolar region and thus is required for proper nucleolar organization. Our study demonstrates that the MiCEE complex mediates epigenetic silencing of bidirectionally expressed genes and global genome organization.

Duchenne muscular dystrophy is a fatal muscle disease, caused by mutations in DMD, leading to loss of dystrophin expression. Phosphorodiamidate morpholino splice-switching oligonucleotides (PMO-SSOs) have been used to elicit the restoration of a partially functional truncated dystrophin by excluding disruptive exons from the DMD messenger. The 30-mer PMO eteplirsen (EXONDYS51) developed for exon 51 skipping is the first dystrophin-restoring, conditionally FDA-approved drug in history. Clinical trials had shown a dose-dependent variable and patchy dystrophin restoration. The main obstacle for efficient dystrophin restoration is the inadequate uptake of PMOs into skeletal muscle fibers at low doses. The excessive cost of longer PMOs has limited the utilization of higher dosing. We designed shorter 25-mer PMOs directed to the same eteplirsen-targeted region of exon 51 and compared their efficacies in vitro and in vivo in the mdx52 murine model. Our results showed that skipped-dystrophin induction was comparable between the 30-mer PMO sequence of eteplirsen and one of the shorter PMOs, while the other 25-mer PMOs showed lower exon-skipping efficacies. Shorter PMOs would make higher doses economically feasible, and high dosing would result in better drug uptake into muscle, induce higher levels of dystrophin restoration in DMD muscle, and, ultimately, increase the clinical efficacy.

The majority of the eukaryotic genome is transcribed into noncoding RNAs (ncRNAs), which are important regulators of different nuclear processes by controlling chromatin structure. However, the full extent of ncRNA function has remained elusive. Here we deciphered the function of the microRNA Mirlet7d as a key regulator of bidirectionally transcribed genes. We found that nuclear Mirlet7d binds ncRNAs expressed from these genes. Mirlet7d-ncRNA duplexes are further bound by C1D, which in turn targets the RNA exosome complex and the polycomb repressive complex 2 (PRC2) to the bidirectionally active loci. The exosome degrades the ncRNAs, whereas PRC2 induces heterochromatin and transcriptional silencing through EZH2. Moreover, this multicomponent RNA-protein complex, which we named MiCEE, tethers the regulated genes to the perinucleolar region and thus is required for proper nucleolar organization. Our study demonstrates that the MiCEE complex mediates epigenetic silencing of bidirectionally expressed genes and global genome organization.

Duchenne muscular dystrophy is a fatal muscle disease, caused by mutations in DMD, leading to loss of dystrophin expression. Phosphorodiamidate morpholino splice-switching oligonucleotides (PMO-SSOs) have been used to elicit the restoration of a partially functional truncated dystrophin by excluding disruptive exons from the DMD messenger. The 30-mer PMO eteplirsen (EXONDYS51) developed for exon 51 skipping is the first dystrophin-restoring, conditionally FDA-approved drug in history. Clinical trials had shown a dose-dependent variable and patchy dystrophin restoration. The main obstacle for efficient dystrophin restoration is the inadequate uptake of PMOs into skeletal muscle fibers at low doses. The excessive cost of longer PMOs has limited the utilization of higher dosing. We designed shorter 25-mer PMOs directed to the same eteplirsen-targeted region of exon 51 and compared their efficacies in vitro and in vivo in the mdx52 murine model. Our results showed that skipped-dystrophin induction was comparable between the 30-mer PMO sequence of eteplirsen and one of the shorter PMOs, while the other 25-mer PMOs showed lower exon-skipping efficacies. Shorter PMOs would make higher doses economically feasible, and high dosing would result in better drug uptake into muscle, induce higher levels of dystrophin restoration in DMD muscle, and, ultimately, increase the clinical efficacy.

BACKGROUND & AIMS: Alagille syndrome is a genetic disorder characterized by cholestasis, ocular abnormalities, characteristic facial features, heart defects, and vertebral malformations. Most cases are associated with mutations in JAGGED1 (JAG1), which encodes a Notch ligand, although it is not clear how these contribute to disease development. We aimed to develop a mouse model of Alagille syndrome to elucidate these mechanisms.METHODS: Mice with a missense mutation (H268Q) in Jag1 (Jag1+/Ndr mice) were outbred to a C3H/C57bl6 background to generate a mouse model for Alagille syndrome (Jag1Ndr/Ndr mice). Liver tissues were collected at different timepoints during development, analyzed by histology, and liver organoids were cultured and analyzed. We performed transcriptome analysis of Jag1Ndr/Ndr livers and livers from patients with Alagille syndrome, cross-referenced to the Human Protein Atlas, to identify commonly dysregulated pathways and biliary markers. We used species-specific transcriptome separation and ligand-receptor interaction assays to measure Notch signaling and the ability of JAG1Ndr to bind or activate Notch receptors. We studied signaling of JAG1 and JAG1Ndr via NOTCH 1, NOTCH2, and NOTCH3 and resulting gene expression patterns in parental and NOTCH1-expressing C2C12 cell lines.RESULTS: Jag1Ndr/Ndr mice had many features of Alagille syndrome, including eye, heart, and liver defects. Bile duct differentiation, morphogenesis, and function were dysregulated in newborn Jag1Ndr/Ndr mice, with aberrations in cholangiocyte polarity, but these defects improved in adult mice. Jag1Ndr/Ndr liver organoids collapsed in culture, indicating structural instability. Whole-transcriptome sequence analyses of liver tissues from mice and patients with Alagille syndrome identified dysregulated genes encoding proteins enriched at the apical side of cholangiocytes, including CFTR and SLC5A1, as well as reduced expression of IGF1. Exposure of Notch-expr

BACKGROUND & AIMS: Alagille syndrome is a genetic disorder characterized by cholestasis, ocular abnormalities, characteristic facial features, heart defects, and vertebral malformations. Most cases are associated with mutations in JAGGED1 (JAG1), which encodes a Notch ligand, although it is not clear how these contribute to disease development. We aimed to develop a mouse model of Alagille syndrome to elucidate these mechanisms.METHODS: Mice with a missense mutation (H268Q) in Jag1 (Jag1+/Ndr mice) were outbred to a C3H/C57bl6 background to generate a mouse model for Alagille syndrome (Jag1Ndr/Ndr mice). Liver tissues were collected at different timepoints during development, analyzed by histology, and liver organoids were cultured and analyzed. We performed transcriptome analysis of Jag1Ndr/Ndr livers and livers from patients with Alagille syndrome, cross-referenced to the Human Protein Atlas, to identify commonly dysregulated pathways and biliary markers. We used species-specific transcriptome separation and ligand-receptor interaction assays to measure Notch signaling and the ability of JAG1Ndr to bind or activate Notch receptors. We studied signaling of JAG1 and JAG1Ndr via NOTCH 1, NOTCH2, and NOTCH3 and resulting gene expression patterns in parental and NOTCH1-expressing C2C12 cell lines.RESULTS: Jag1Ndr/Ndr mice had many features of Alagille syndrome, including eye, heart, and liver defects. Bile duct differentiation, morphogenesis, and function were dysregulated in newborn Jag1Ndr/Ndr mice, with aberrations in cholangiocyte polarity, but these defects improved in adult mice. Jag1Ndr/Ndr liver organoids collapsed in culture, indicating structural instability. Whole-transcriptome sequence analyses of liver tissues from mice and patients with Alagille syndrome identified dysregulated genes encoding proteins enriched at the apical side of cholangiocytes, including CFTR and SLC5A1, as well as reduced expression of IGF1. Exposure of Notch-expr

Violence in dating relationships is an important topic because it existence as well as the consequences that this entails, we have only empirically; that is why our research arises from the need to obtain data that allow us to demonstrate a clear and objective reality. The main objective of this research is to characterize the violence in dating relationships in university students in the city of Cuenca; which will allow us closer to knowing this reality linked to gender violence and violence in general, while verifying how common these practices are in a relationship. The research developed model is within the quantitative paradigm, with exploratory and descriptive scope, the same that was executed in the urban area, at the institutional level, the Faculty of Medicine of the University of Cuenca. 224 women whose age was between 18 to 25 years were studied. The responses were recorded using a Likert scale measuring violent behavior in dating. Finally the answers were grouped into three types of events: physical violence, psychological violence and coercive and controlling behaviors. Finally we could conclude that violence, one way or another, is present in some of the dating relationships of university students, turning into a situation that should generate concern necessary and appropriate by the entities related to the topic of violence, because it constitutes a fundamental step in the socio-emotional development in humans, as a way to implement loving interactions that subsequently give rise to the formation of families, it is essential that they are as healthy as possible.

Violence in dating relationships is an important topic because it existence as well as the consequences that this entails, we have only empirically; that is why our research arises from the need to obtain data that allow us to demonstrate a clear and objective reality. The main objective of this research is to characterize the violence in dating relationships in university students in the city of Cuenca; which will allow us closer to knowing this reality linked to gender violence and violence in general, while verifying how common these practices are in a relationship. The research developed model is within the quantitative paradigm, with exploratory and descriptive scope, the same that was executed in the urban area, at the institutional level, the Faculty of Medicine of the University of Cuenca. 224 women whose age was between 18 to 25 years were studied. The responses were recorded using a Likert scale measuring violent behavior in dating. Finally the answers were grouped into three types of events: physical violence, psychological violence and coercive and controlling behaviors. Finally we could conclude that violence, one way or another, is present in some of the dating relationships of university students, turning into a situation that should generate concern necessary and appropriate by the entities related to the topic of violence, because it constitutes a fundamental step in the socio-emotional development in humans, as a way to implement loving interactions that subsequently give rise to the formation of families, it is essential that they are as healthy as possible.

Violence in dating relationships is an important topic because it existence as well as the consequences that this entails, we have only empirically; that is why our research arises from the need to obtain data that allow us to demonstrate a clear and objective reality. The main objective of this research is to characterize the violence in dating relationships in university students in the city of Cuenca; which will allow us closer to knowing this reality linked to gender violence and violence in general, while verifying how common these practices are in a relationship. The research developed model is within the quantitative paradigm, with exploratory and descriptive scope, the same that was executed in the urban area, at the institutional level, the Faculty of Medicine of the University of Cuenca. 224 women whose age was between 18 to 25 years were studied. The responses were recorded using a Likert scale measuring violent behavior in dating. Finally the answers were grouped into three types of events: physical violence, psychological violence and coercive and controlling behaviors. Finally we could conclude that violence, one way or another, is present in some of the dating relationships of university students, turning into a situation that should generate concern necessary and appropriate by the entities related to the topic of violence, because it constitutes a fundamental step in the socio-emotional development in humans, as a way to implement loving interactions that subsequently give rise to the formation of families, it is essential that they are as healthy as possible.

The selection of plant growth-promoting rhizobacteria (PGPR) can be based on the in vitro analysis of their auxin-producing and growth-promoting capabilities. This study determined the intrinsic production of indole acetic acid (IAA) by rhizobacteria isolated from petroleum-contaminated soil and tested its potential for growth promotion. The three isolated rhizobacteria (I, II and III) were high producers of indole acetic acid in vitro. Cynodon dactylon L. was inoculated with these isolates in hydroponic systems. The Rhizobacterium spp. strains I and II showed plant growth promotion without the addition of Trp (a common precursor in the biosynthesis of IAA), whereas strain III required the addition of Trp to promote foliar development in C. dactylon., El analizar rizobacterias por su potencial in vitro de producción de auxinas puede proveer de una base rentable para la selección de cepas efectivas, particularmente si esta capacidad se emplea en combinación con el análisis de su actividad promotora del crecimiento. Este estudio consistió en la caracterización de la producción intrínseca de rizobacterias aisladas de un suelo contaminado con hidrocarburos derivados del petróleo de producir ácido indolacético y el efecto de éstas sobre el crecimiento in vitro de Cynodon dactylon L, inoculada con estas rizobacterias en sistemas hidropónicos. Las rizobacterias aisladas I, II y III resultaron altas productoras in vitro de ácido indolacético. Se evidenció también la promoción del crecimiento de las plantas de Cynodon dactylon L. con la inoculación de las rizobacterias I y II. En experimentos con la adición de triptofano al medio y la inoculación con la rizobacteria III se observó la acción directa de la presencia del precursor en la biosíntesis de ácido indolacético que favoreció el desarrollo radical y foliar de las plantas.