ZMYND8 Is a Regulator of Sonic Hedgehog Signaling in ATRA-Mediated Differentiation of Neuroblastoma Cells.

Zinc Finger MYND (Myeloid, Nervy, and DEAF-1) type containing 8 (ZMYND8) is a crucial epigenetic regulator that plays a multifaceted role in governing a spectrum of vital cellular processes, encompassing proliferation, apoptosis, migration, tumor suppression, and differentiation. It has emerged as a key player in neuronal differentiation by orchestrating the expression of neuronal lineage-committed genes. The present study uncovers the role of ZMYND8 in regulating the Sonic Hedgehog (SHH) signaling axis, which is crucial for neuronal differentiation. Genetic deletion of ZMYND8 leads to a significant reduction in SHH pathway genes, GLI1, and PTCH1 expression during all-trans-retinoic acid (ATRA)-induced differentiation. ZMYND8 and RNA pol II S5P are found to co-occupy the GLI1 and PTCH1 gene promoters, positively impacting their gene transcription upon ATRA treatment. Interestingly, ZMYND8 is found to counteract the inhibitory effects of Cyclopamine that block the upstream SHH pathway protein SMO, resulting in enhanced neurite formation in neuroblastoma cells following their treatment with ATRA. These results indicate that ZMYND8 is an epigenetic regulator of the SHH signaling pathway and has tremendous therapeutic potential in ATRA-mediated differentiation of neuroblastoma.

Pharmacogenetics May Prevent Psychotropic Adverse Events in Autism Spectrum Disorder: An Observational Pilot Study.

INTRODUCTION: Up to 73% of individuals with autism spectrum disorder (ASD) and intellectual disability (ID) currently have prescriptions for psychotropic drugs. This is explained by a higher prevalence of medical and psychiatric chronic comorbidities, which favors polypharmacy, increasing the probability of the appearance of adverse events (AEs). These could be a preventable cause of harm to patients with ASD and an unnecessary waste of healthcare resources. OBJECTIVE: To study the impact of pharmacogenetic markers on the prevention of AE appearance in a population with ASD and ID. METHODS: This is a cross-sectional, observational study (n = 118, 72 participants completed all information) in the ASD population. Sociodemographic and pharmacological data were gathered. The Udvalg for Kliniske Undersøgelser Scale (UKU Scale) was used to identify AEs related to the use of psychotropic medication. Polymorphisms of DOP2, ABCB1, and COMT were genotyped and correlated with the AE to find candidate genes. Furthermore, a review of all medications assessed in a clinical trial for adults with autism was performed to enrich the search for potential pharmacogenetic markers, keeping in mind the usual medications. RESULTS: The majority of the study population were men (75%) with multiple comorbidities and polypharmacy, the most frequently prescribed drugs were antipsychotics (69%); 21% of the participants had four or more AEs related to psychotropic drugs. The most common were "Neurological" and" Psychiatric" (both 41%). Statistical analysis results suggested a significant correlation between the neurological symptoms and the DOP2 genotype, given that they are not equally distributed among its allelic variants. The final review considered 19 manuscripts of medications for adults with ASD, and the confirmed genetic markers for those medications were consulted in databases. CONCLUSION: A possible correlation between neurologic AEs and polymorphisms of DOP2 was observed; therefore, studying this gene could contribute to the safety of this population's prescriptions. The following studies are underway to maximize statistical power and have a better representation of the population.

CYP2D6 Genotype and Pharmacovigilance Impact on Autism Spectrum Disorder: A Naturalistic Study with Extreme Phenotype Analysis.

The long-term use of psychopharmacology medications in autism spectrum disorder (ASD) hitherto remains controversial due to a lack of evidence about safety and tolerability. In this regard, genotyping the metabolizing enzyme cytochrome P450 (CYP) 2D6, especially its extreme phenotypes, could help to prevent drug-related adverse reactions or adverse events (AEs). There are several medications warranting CYP2D6 screening that are consumed by people with ASD, such as risperidone and aripiprazole to name a few. A naturalistic observational study was carried out in participants with ASD to analyze the influence of the CYP2D6 phenotype in drug tolerability using a local pharmacovigilance system created for this study. In this case, AEs were identified from participants' electronic health records (EHRs) and paper registries. Other variables were collected: socio-demographic information, comorbidities, and psychopharmacology prescriptions (polypharmacy defined as ≥4 simultaneous prescriptions) and doses. The genetic analysis included allelic discrimination (CYP2D6*1, *2, *3, *4, *5, *6, *10, *17, and *41) and copy number variations. All of these were used to determine theoretical phenotypes of the metabolic profiles: poor (PM); intermediate (IM); normal (NM); and ultra-rapid (UM). Sex differences were analyzed. A total of 71 participants (30 ± 10 years old, 82% male, 45% CYP2D6 NM phenotype (32 participants)) with a median of 3 (IQR 2-4) comorbidities per person, mainly urinary incontinence (32%) and constipation (22%), were included. CYP2D6 UM showed the highest rate of polypharmacy, whilst, IM participants had the highest rates of neurological and psychiatric AEs, even worse if a CYP2D6 inhibitor drug was prescribed simultaneously. CYP2D6 pharmacogenomics and the monitoring of new antipsychotic prescriptions may make a difference in medication safety in adults with ASD. Particularly in those with psychopharmacology polymedication, it can help with AE avoidance and understanding.

Funcionalidad del miembro inferior con exposición ósea con el uso de terapia con presión negativa VAC® vs. colgajo de gemelo medial

Objetivo: Comparar dos técnicas de cirugía reconstructiva para lesión en miembro inferior con exposición ósea y, a través de ella, diferenciar que la técnica de VAC® (Vacuum Assisted Closure, cierre asistido con presión negativa) es una alternativa con beneficio de recuperación potencial sin alteraciones significativas que pudieran llevar a un compromiso funcional. Materiales y métodos: Estudio de tipo analítico con corte prospectivo, cuantitativo y longitudinal, en el que se desarrolló la terapia con el uso del sistema de VAC® y de colgajo gemelar medial en todos los pacientes de la Clínica Stella Maris que presentaron heridas traumáticas de miembro inferior con exposición ósea de tercio medio tibial durante el periodo 2019. Resultados: Se evidenció que la medición con la escala funcional de la marcha (FAC, por sus siglas en inglés) fue mejor en los pacientes con la técnica de VAC® (dado que el 50 % tiene grado V) respecto a la técnica de colgajo (50 % en grado IV); las diferencias fueron estadísticamente significativas (p < 0,05). Se apreció que el tiempo de cierre fue mayor en la técnica de VAC® debido al proceso de regeneración progresiva hasta llenar o cubrir la zona completa de la lesión; por otro lado, se evidenció la diferencia de la intensidad del dolor posoperatorio entre las dos técnicas: de moderado a intenso con la técnica de colgajo y leve, en su mayoría, con la técnica de VAC®. Conclusiones: El sistema de aspiración VAC® es eficiente para la cobertura ósea en defectos traumáticos del tercio medio tibial anterior, por lo que constituye una alternativa con potencial beneficio de recuperación sin alteración de estructuras anatómicas, ya que brinda mejores resultados funcionales y menores complicaciones. Es una opción útil que actúa de forma segura porque estimula el cierre de la herida y minimiza las necesidades de un tratamiento quirúrgico.

Objective: To compare two reconstructive surgery techniques for lower limb injury with exposed bone and demonstrate that the VAC® (vacuum-assisted closure) negative pressure wound therapy is an alternative for potential recovery showing no significant changes that could lead to functional compromise. Materials and methods: An analytical, prospective, quantitative and longitudinal study conducted with all the patients of Clínica Stella Maris with traumatic injuries of the lower limb and exposure of the middle third of the tibia treated with the VAC® system and the medial calf flap in 2019. Results: The measurement obtained with the functional ambulation categories (FAC) scale showed better results among the patients treated with the VAC® technique (since 50 % got grade V) than those who underwent the flap technique (50 % got grade IV), being the differences statistically significant (p < 0.05). It was observed that the time to closure was longer with the VAC® technique due to the progressive regeneration process consisting of the complete filling or coverage of the lesion area. On the other hand, the difference in the postoperative pain intensity between the two techniques was evident, being moderate to intense with the flap technique and mild, for the most part, with the VAC® technique. Conclusions: The VAC® suction system is effective for bone coverage in traumatic defects of the anterior middle third of the tibia. It is an alternative for potential recovery that does not change the anatomical structures because it provides better functional results and fewer complications. It is a useful and safe option that stimulates wound closure and minimizes the need for surgical treatment.

Mycobacterium smegmatis secreting methionine sulfoxide reductase A (MsrA) modulates cellular processes in mouse macrophages.

Methionine sulfoxide reductase A (MsrA) is an antioxidant repair enzyme that reduces the oxidized methionine (Met-O) in proteins to methionine (Met). Its pivotal role in the cellular processes has been well established by overexpressing, silencing, and knocking down MsrA or deleting the gene encoding MsrA in several species. We are specifically interested in understanding the role of secreted MsrA in bacterial pathogens. To elucidate this, we infected mouse bone marrow-derived macrophages (BMDMs) with recombinant Mycobacterium smegmatis strain (MSM), secreting a bacterial MsrA or M. smegmatis strain (MSC) carrying only the control vector. BMDMs infected with MSM induced higher levels of ROS and TNF-α than BMDMs infected with MSC. The increased ROS and TNF-α levels in MSM-infected BMDMs correlated with elevated necrotic cell death in this group. Further, RNA-seq transcriptome analysis of BMDMs infected with MSC and MSM revealed differential expression of protein and RNA coding genes, suggesting that bacterial-delivered MsrA could modulate the host cellular processes. Finally, KEGG pathway enrichment analysis identified the down-regulation of cancer-related signaling genes in MSM-infected cells, indicating that MsrA can potentially regulate the development and progression of cancer.

ZMYND8 suppresses MAPT213 LncRNA transcription to promote neuronal differentiation.

Zinc Finger transcription factors are crucial in modulating various cellular processes, including differentiation. Chromatin reader Zinc Finger MYND (Myeloid, Nervy, and DEAF-1) type containing 8 (ZMYND8), an All-Trans Retinoic Acid (ATRA)-responsive gene, was previously shown to play a crucial role in promoting the expression of neuronal-lineage committed genes. Here, we report that ZMYND8 promotes neuronal differentiation by positively regulating canonical MAPT protein-coding gene isoform, a key player in the axonal development of neurons. Additionally, ZMYND8 modulates gene-isoform switching by epigenetically silencing key regulatory regions within the MAPT gene, thereby suppressing the expression of non-protein-coding isoforms such as MAPT213. Genetic deletion of ZMYND8 led to an increase in the MAPT213 that potentially suppressed the parental MAPT protein-coding transcript expression related to neuronal differentiation programs. In addition, ectopic expression of MAPT213 led to repression of MAPT protein-coding transcript. Similarly, ZMYND8-driven transcription regulation was also observed in other neuronal differentiation-promoting genes. Collectively our results elucidate a novel mechanism of ZMYND8-dependent transcription regulation of different neuronal lineage committing genes, including MAPT, to promote neural differentiation.

Hematologic evaluation of peripheral blood in Sprague Dawley rats by chronic exposure to aluminum chloride (AlCl3).

This study aimed to evaluate whether aluminum chloride (AlCl3) causes hematological changes in the peripheral blood of Sprague-Dawley (SD) rats. Five groups of female SD rats were intragastrically administered with 4 different concentrations of AlCl3 for 5 days a week for a total of 90 days. The aluminum concentration was determined via graphite furnace atomic absorption spectroscopy. Analysis of serum iron-kinetic profiles, blood cytometry outcomes, and blood smears of the blood samples. Scanning electron microscopy (SEM) and Raman spectroscopy were used to search for structural and ultrastructural changes, respectively. Blood aluminum concentration ranged 12.38-16.24 µg/L with no significant difference between experimental treatments. At the AlCl3 concentration of 40 mg Al/kg bw of rats/day, the mean ferritin value in the serum iron kinetic profile was 29.81±6.1 ng/mL, and this value showed a significant difference between experimental treatments. Blood cytometry revealed that there were 6.45-7.11×106 cells/µL erythrocytes, 8.91-9.32×103 cells/µL leukocytes, and 477.2-736.3×103 cells/µL platelets along with a hemoglobin of 37.38-41.93 g/dL and hematocrit level of 37.38-41.93%; the experimental treatments showed no significant differences. Erythrocyte structural analysis using SEM showed no differences between experimental treatments, whereas ultrastructural evaluation using Raman spectroscopy made it possible to identify the following bands: 741, 1123, 1350, 1578, and 1618 cm-1, which were respectively associated with the following vibrational modes and compounds: vibration of the tryptophan ring, asymmetric C-O-C stretching of glucose, C-H curve of tryptophan, C=C stretching of the heme group, and C-N stretching of the heme group, with no significant differences between experimental treatments. Therefore, AlCl3 administration does not induce ultrastructural changes in the erythrocyte membrane. This study revealed that serum ferritin concentration was the only parameter affected by AlCl3 exposure at 40 mg of Al/kg bw of rats/day.

Characterization of the Testis-specific LINC01016 Gene Reveals Isoform-specific Roles in Controlling Biological Processes.

Long noncoding RNAs (lncRNAs) have emerged as critical regulators of biological processes. However, the aberrant expression of an isoform from the same lncRNA gene could lead to RNA with altered functions due to changes in their conformations, leading to diseases. Here, we describe a detailed characterization of the gene that encodes long intergenic non-protein-coding RNA 01016 (LINC01016, also known as LncRNA1195) with a focus on its structure, exon usage, and expression in human and macaque tissues. In this study we show that it is among the highly expressed lncRNAs in the testis, exclusively conserved among nonhuman primates, suggesting its recent evolution and is processed into 12 distinct RNAs in testis, cervix, and uterus tissues. Further, we integrate de novo annotation of expressed LINC01016 transcripts and isoform-dependent gene expression analyses to show that human LINC01016 is a multiexon gene, processed through differential exon usage with isoform-specific roles. Furthermore, in cervical, testicular, and uterine cancers, LINC01016 isoforms are differentially expressed, and their expression is predictive of survival in these cancers. This study has revealed an essential aspect of lncRNA biology, rarely associated with coding RNAs, that lncRNA genes are precisely processed to generate isoforms with distinct biological roles in specific tissues.

Mycoplasma genitalium and M. pneumoniae Regulate a Distinct Set of Protein-Coding Genes in Epithelial Cells.

Mycoplasma genitalium and M. pneumoniae are two significant mycoplasmas that infect the urogenital and respiratory tracts of humans. Despite distinct tissue tropisms, they both have similar pathogenic mechanisms and infect/invade epithelial cells in the respective regions and persist within these cells. However, the pathogenic mechanisms of these species in terms of bacterium-host interactions are poorly understood. To gain insights on this, we infected HeLa cells independently with M. genitalium and M. pneumoniae and assessed gene expression by whole transcriptome sequencing (RNA-seq) approach. The results revealed that HeLa cells respond to M. genitalium and M. pneumoniae differently by regulating various protein-coding genes. Though there is a significant overlap between the genes regulated by these species, many of the differentially expressed genes were specific to each species. KEGG pathway and signaling network analyses revealed that the genes specific to M. genitalium are more related to cellular processes. In contrast, the genes specific to M. pneumoniae infection are correlated with immune response and inflammation, possibly suggesting that M. pneumoniae has some inherent ability to modulate host immune pathways.

TCF19 and p53 regulate transcription of TIGAR and SCO2 in HCC for mitochondrial energy metabolism and stress adaptation.

Alteration in glucose homeostasis during cancer metabolism is an important phenomenon. Though several important transcription factors have been well studied in the context of the regulation of metabolic gene expression, the role of epigenetic readers in this regard remains still elusive. Epigenetic reader protein transcription factor 19 (TCF19) has been recently identified as a novel glucose and insulin-responsive factor that modulates histone posttranslational modifications to regulate glucose homeostasis in hepatocytes. Here we report that TCF19 interacts with a non-histone, well-known tumor suppressor protein 53 (p53) and co-regulates a wide array of metabolic genes. Among these, the p53-responsive carbohydrate metabolic genes Tp53-induced glycolysis and apoptosis regulator (TIGAR) and Cytochrome C Oxidase assembly protein 2 (SCO2), which are the key regulators of glycolysis and oxidative phosphorylation respectively, are under direct regulation of TCF19. Remarkably, TCF19 can form different transcription activation/repression complexes which show substantial overlap with that of p53, depending on glucose-mediated variant stress situations as obtained from IP/MS studies. Interestingly, we observed that TCF19/p53 complexes either have CBP or HDAC1 to epigenetically program the expression of TIGAR and SCO2 genes depending on short-term high glucose or prolonged high glucose conditions. TCF19 or p53 knockdown significantly altered the cellular lactate production and led to increased extracellular acidification rate. Similarly, OCR and cellular ATP production were reduced and mitochondrial membrane potential was compromised upon depletion of TCF19 or p53. Subsequently, through RNA-Seq analysis from patients with hepatocellular carcinoma, we observed that TCF19/p53-mediated metabolic regulation is fundamental for sustenance of cancer cells. Together the study proposes that TCF19/p53 complexes can regulate metabolic gene expression programs responsible for mitochondrial energy homeostasis and stress adaptation.

Concordancia de tres escalas de riesgo cardiovascular en mujeres con diabetes mellitus tipo 2 / Concordance of three scales of cardiovascular risk in women with diabetes mellitus type 2

Resumen Introducción: establecer estimadores del riesgo cardiovasculares (RCV) que permitan tener igual concordancia dentro del subconjunto de la población es importante para diseñar terapias que briden ventajas a cada subpoblación. Objetivo: comparar las escalas Framingham, SCORE/REGICOR y ACC/AHA en una corte de mujeres con diabetes. Materiales y métodos: se realizó un estudio descriptivo transversal en donde se compararon las escalas Framingham, SCORE/REGICOR y ACC/AHA para identificar los niveles de riesgo cardiovascular en mujeres con diabetes mellitus tipo 2. Los datos se recopilaron entre 2014 y 2016 en pacientes del Centro Endocrinológico del Caribe ubicado en Barranquilla, Colombia. Se consideraron variables sociodemográficas, antropométricas y clínicas. Resultados: el 100% de la muestra (n=107) eran mujeres con una edad media de 58,5±13,646 años. Según la escala Framingham el 72,9% (n=78) se clasificó como de riesgo bajo; el 21,5% (23), intermedio, y el 5,6% (n=6), alto. Con la escala SCORE/REGICOR el 57,0% (n=61) estuvo en riesgo bajo; el 42,1% (n=45), en moderado, y el 0,9% (n=1), en alto. Finalmente, mediante la escala ACC/ AHA el 35,5% (n=38) se clasificó en riesgo bajo y el 64,5% (n=69), en elevado. Conclusiones: en el presente estudio se observó una baja concordancia al comparar las escalas de riesgo cardíaco analizadas (Framingham, SCORE/REGICOR y ACC/AHA) en mujeres colombianas con diabetes mellitus tipo dos y se observó además que la edad y el colesterol total fueron los valores que más afectaron la variación entre las escalas comparadas.

Abstract Introduction: Establishing cardiovascular risk (CVR) estimators that allow for equal concordance within the subset of the population is important for establishing therapy that provide advantages for each subpopulation. In this article we focus on buying CVR scale in women with type 2 diabetes mellitus. Objective: Compare between the Framingham, SCORE/REGICOR and ACC/AHA scales in a court of women with diabetes. Methods: The data collected were between 2014 and 2016 from the population of the Caribbean Endocrinological Center, Barranquilla, Colombia, considering the sociodemographic, anthropometric, and clinical variables. In this study, it was possible to establish comparisons between the Framingham, SCORE/REGICOR and ACC/AHA scales to identify cardiovascular risk levels in women with T2DM. Results: 100% of the sample (n = 107) were women with a mean age of 58.5 ± 13,646 years, 78 (72.9%) were classified as low risk, 23 (21.5%) intermediate and 6 ( 5.6%) high with the scale The SCORE/REGICOR scale showed 61 (57.0%) at low risk, 45 (42.1%) moderate and 1 (0.9%) high; while ACC / AHA 38 (35.5%) is classified as low risk and 69 (64.5%) as high. Conclusions: In the present study, a low concordance was observed when comparing the cardiac risk scales (Framingham, SCORE/REGICOR and ACC/AHA) in Colombian women with type two diabetes and it was also observed that age and total cholesterol were the values that more affected variation between the comparative cardiovascular risk scale.

Endometritis granulomatosa por tuberculosis en mujer postmenopaúsica / Granulomatous tuberculosis endometritis in a posmenopausal woman

INTRODUCCIÓN: La tuberculosis (TBC) genital es una infección relativamente poco frecuente en la mujer. Afecta principalmente a mujeres menores de 40 años, y el motivo de consulta más usual es la esterilidad, de ahí la importancia de su diagnóstico precoz. CASO CLÍNICO clínico: Se presenta el caso de una paciente con dolor pélvico crónico que acude a nuestras consultas para valoración. Durante el estudio se toma biopsia dirigida de la cavidad endometrial diagnosticándose la presencia de granulomas no necrotizantes. Posteriormente se realiza un cultivo microbiológico que resulta positivo para micobacterias y se determina el DNA, mediante reacción en cadena de la polimerasa, de mycobacterium tuberculosis, como causante del cuadro. DISCUSIÓN: El diagnóstico definitivo de TBC requiere el aislamiento en cultivo del bacilo de Koch, aunque en los casos de TBC genital, al ser una entidad paucibacilar, puede no resultar positivo. En éste caso, sería suficiente el diagnóstico de presunción basado en la sospecha clínica y el hallazgo histológico de granulomas. CONCLUSIÓN: La tuberculosis genital es una entidad poco frecuente en nuestro medio, aunque es una causa importante de infertilidad femenina y su predominio generalmente se subestima debido a la naturaleza paucisintomática de la misma. El diagnóstico temprano y el tratamiento multidisciplinar son fundamentales.

INTRODUCTION: Genital tuberculosis (TB) is a relatively rare afection in women. It mainly affects women younger than 40 years, and the most frequent reason for consultation is sterility, therefore early diagnosis is important. CLINICAL CASE: We presented the case of a patient with chronic pelvic pain who comes to our consultations. During the study, we take an endometrial biopsy diagnosing the presence of non-necrotizing granulomas. Finally, we determined the mycobacterium tuberculosis DNA through the polymerase chain reaction and positive microbiological culture, as the cause of pathology. DISCUSSION: The definitive diagnosis of TB requires the isolation in culture of the Koch bacillus, although in genital TB cases, as it is a paucibacillary entity, it may not be positive. In this case, the presumptive diagnosis based on clinical suspicion and the histological granulomas would be enough. CONCLUSIONS: Genital tuberculosis is a rare entity in our environment, although it is an important cause of female infertility and its prevalence is generally underestimated due to its paucisymptomatic nature. Early diagnosis and multidisciplinary treatment are essential.

Hypoxanthine Phosphoribosyl Transferase 1 Is Upregulated, Predicts Clinical Outcome and Controls Gene Expression in Breast Cancer.

Hypoxanthine phosphoribosyl transferase 1 (HPRT1) is traditionally believed to be a housekeeping gene; however, recent reports suggest that it is upregulated in several cancers and is associated with clinical outcomes. HPRT1 is located on chromosome X and encodes the HPRT enzyme, which functions in recycling nucleotides to supply for DNA and RNA synthesis in actively dividing cells. Here, we used transcriptomic analyses to interrogate its expression across all known cancer types and elucidated its role in regulating gene expression in breast cancer. We observed elevated HPRT1 RNA levels in malignant tissues when compared to normal controls, indicating its potential as a diagnostic and prognostic marker. Further, in breast cancer, the subtype-specific analysis showed that its expression was highest in basal and triple-negative breast cancer, and HPRT1 knockdown in breast cancer cells suggested that HPRT1 positively regulates genes related to cancer pathways. Collectively, our results essentially highlight the importance of and change the way in which HPRT1's function is studied in biology, warranting careful examination of its role in cancer.

«Secretos culturales¼ y conflictos deportivos en futbolistas del pueblo indígena shipibo-konibo / «Cultural secrets¼ and sports conflicts among soccer players of the Shipibo-Konibo indigenous people

Resumen Objetivo: Este estudio explora el razonamiento moral de un grupo de jugadores de fútbol del pueblo indígena shipibo-konibo sobre el uso de diversas trampas en competencias de dicho deporte. Método : Mediante entrevistas cualitativas, usando cartulinas escritas que presentan situaciones de conflicto comunes a la práctica del fútbol, se identifican primero los recursos secretos propios de su contexto cultural, utilizados para obtener ventajas sobre los rivales. Resultados : Luego de ello, se exploran las creencias y modos de razonar moralmente de estos jugadores sobre el uso de dichos secretos, así como sobre situaciones comunes de trasgresión presentes en la práctica del futbol. Conclusión : Los resultados muestran la compleja articulación entre creencias y cosmovisiones culturales específicas y procesos universales de razonamiento moral, comunes a los miembros de diferentes culturas.

Abstract Objetive : this study explores the moral reasoning of a group of soccer players from the Shipibo-Konibo indigenous people concerning the use of various fouls and misconduct in such sport's competitions. Method : through qualitative interviews, using written cards that show conflict situations in soccer games, the cultural secrets used to gain advantage over rivals are first identified. Results : afterwards, the beliefs and ways of moral reasoning of these players on the use of such secrets, as well as common fouls in soccer games, are examined. Conclusion : the results show the complex relationship that the specific cultural beliefs and worldviews have with the universal processes of moral reasoning common to people from different cultures.

Emerging Roles of Estrogen-Regulated Enhancer and Long Non-Coding RNAs.

Genome-wide RNA sequencing has shown that only a small fraction of the human genome is transcribed into protein-coding mRNAs. While once thought to be "junk" DNA, recent findings indicate that the rest of the genome encodes many types of non-coding RNA molecules with a myriad of functions still being determined. Among the non-coding RNAs, long non-coding RNAs (lncRNA) and enhancer RNAs (eRNA) are found to be most copious. While their exact biological functions and mechanisms of action are currently unknown, technologies such as next-generation RNA sequencing (RNA-seq) and global nuclear run-on sequencing (GRO-seq) have begun deciphering their expression patterns and biological significance. In addition to their identification, it has been shown that the expression of long non-coding RNAs and enhancer RNAs can vary due to spatial, temporal, developmental, or hormonal variations. In this review, we explore newly reported information on estrogen-regulated eRNAs and lncRNAs and their associated biological functions to help outline their markedly prominent roles in estrogen-dependent signaling.

Long noncoding RNAs in cancer: From discovery to therapeutic targets.

Long noncoding RNAs (lncRNAs) have recently gained considerable attention as key players in biological regulation; however, the mechanisms by which lncRNAs govern various disease processes remain mysterious and are just beginning to be understood. The ease of next-generation sequencing technologies has led to an explosion of genomic information, especially for the lncRNA class of noncoding RNAs. LncRNAs exhibit the characteristics of mRNAs, such as polyadenylation, 5' methyl capping, RNA polymerase II-dependent transcription, and splicing. These transcripts comprise more than 200 nucleotides (nt) and are not translated into proteins. Directed interrogation of annotated lncRNAs from RNA-Seq datasets has revealed dramatic differences in their expression, largely driven by alterations in transcription, the cell cycle, and RNA metabolism. The fact that lncRNAs are expressed cell- and tissue-specifically makes them excellent biomarkers for ongoing biological events. Notably, lncRNAs are differentially expressed in several cancers and show a distinct association with clinical outcomes. Novel methods and strategies are being developed to study lncRNA function and will provide researchers with the tools and opportunities to develop lncRNA-based therapeutics for cancer.

Genome-wide analysis and functional prediction of the estrogen-regulated transcriptional response in the mouse uterus†.

The ovarian hormones estrogen and progesterone orchestrate the transcriptional programs required to direct functions of the uterus for initiation and maintenance of pregnancy. Estrogen, acting via estrogen receptor alpha, regulates gene expression by activating and repressing distinct genes involved in signaling pathways that regulate cellular and physiological responses including cell division, water influx, and immune cell recruitment. Historically, these transcriptional responses have been postulated to reflect a biphasic physiological response. In this study, we explored the transcriptional responses of the ovariectomized mouse uterus to 17ß-estradiol (E2) by RNA-seq to obtain global expression profiles of protein-coding transcripts (mRNAs) and long noncoding RNAs (lncRNAs) following 0.5, 1, 2, and 6 hours of treatment. The E2-regulated mRNA and lncRNA expression profiles in the mouse uterus indicate an association between lncRNAs and mRNAs that regulate E2-driven pathways and reproductive phenotypes in the mouse. The transient E2-regulated transcriptome is reflected in the time-dependent shifting of biological processes regulated in the uterus in response to E2. Moreover, high expression of some conserved lncRNAs that are E2 regulated in the mouse uterus are predictive of low overall survival in endometrial carcinoma patients (e.g., H19, KCNQ1OT1, MIR17HG, and FTX). Collectively, this study (1) describes a genomic approach for identifying E2-regulated lncRNAs that may serve critical function in the uterus and (2) provides new insights into our understanding of the regulation of hormone-regulated transcriptional responses with implications in pregnancy and endometrial pathologies.

Evaluación de cicatrización en zonas donantes de injerto de piel parcial con uso de xenoinjerto en comparación con sustituto dérmico sintético de celulosa / Evaluation of healing in partial skin graft donor sites using a xenograft compared to a synthetic cellulose skin substitute

Objetivo: Realizar una evaluación de la cicatrización en la zona donante de injerto de piel parcial con uso de sustituto dérmico comparado con xenoinjerto, en pacientes con lesiones diversas que requirieron injerto de piel parcial. Materiales y métodos: Se presenta el reporte de 20 pacientes entre 19 y 65 años de la Unidad de Cirugía Plástica del Hospital María Auxiliadora de Lima Metropolitana-Perú, entre diciembre 2017 y junio 2018, donde se evaluó la cicatrización en zonas donantes de injerto de piel parcial. El estudio es de tipo intervención, analítico, prospectivo y longitudinal. Emplea el diseño doble ciego para controlar posibles sesgos. Para analizar la significancia estadística se usaron pruebas no paramétricas con un nivel de confianza 95 %. Resultados: Con el uso del sustituto dérmico se aprecia una mejor calidad de cicatrización de zonas donantes de epitelización en comparación con el xenoinjerto. Ambas técnicas se evaluaron con la escala de Vancouver que considera cinco aspectos (cicatrización, vascularidad, pigmentación, flexibilidad y altura), de los cuales, la cicatrización tuvo resultados significativos (p<0,05). Al estimar el riesgo de evolución de cicatrización según el modelo de riesgos proporcionales de Cox, se obtuvo un H=0,60 (IC95% 0,46-0,78), lo cual indica que el menor tiempo de cicatrización se encontró en el grupo en que se empleó el sustituto dérmico. Conclusiones: El sustituto dérmico es una alternativa importante que favorece buena calidad de la cicatrización en las zonas donantes. El sustituto dérmico es más eficiente que el xenoinjerto convencional al ser evaluado y comparado en la escala de cicatrización de Vancouver.

Objective: To evaluate healing in partial skin graft donor sites using a skin substitute compared to a xenograft in patients with different diseases requiring partial skin grafting. Materials and methods: This paper presents a report of 20 patients between 19 and 65 years from the Plastic Surgery Unit of the Hospital María Auxiliadora in Lima Metropolitan Area, Peru, between December 2017 and June 2018, where healing was evaluated in partial skin graft donor sites. An interventional, analytical, prospective and longitudinal study was conducted using a double-blind design to control possible biases. For the statistical significance analysis, nonparametric tests with a 95 % confidence interval were used. Results: Using a skin substitute, a better healing quality of donor sites of epithelialization was seen compared with xenografting. Both techniques were evaluated with the Vancouver scale, which considers five aspects (healing, vascularity, pigmentation, flexibility and height), out of which healing showed significant results (p<0.05). Estimation of the risk in the healing process according to the Cox proportional hazards model showed that H = 0.60 (95 % CI 0.46- 0.78), which indicates that the shortest healing time was found in the skin substitute group. Conclusions: Skin substitutes are an important alternative that favors the good quality of healing in donor sites. skin substitutes proved to be more effective than conventional xenografting when evaluated and compared using the Vancouver healing scale.

[Hyponatremia as a presenting sign of metastatic disease in muscle invasive bladder cancer.] / Hiponatremia como signo de presentación de enfermedad metastásica en el cáncer vesical musculo infiltrante (CVMI).

OBJECTIVE: Bladder cancer is a commonly diagnosed malignancy in Europe, being 30% muscle-invasive at diagnosis. In these patients, metastases can develop both at diagnosis and after progression. Metastatic disease can manifest in a number of different ways, even as hydroelectrolytic alterations. In this work, we go through the causes of hyponatremia in patients suffering from bladder cancer and its relationship with disseminated disease. METHOD: We present two cases of patients with muscleinvasive bladder cancer with a common electrolytic misbalance, hyponatremia. RESULTS: As a result of the study, bone and cerebral metastases were revealed. CONCLUSIONS: The electrolytic alterations in the oncologic patient can have several causes: chemotherapy, urinary diversion, pain, or even to the tumor itself or its metastases. It is necessary to conduct an exhaustive study in order to discard the most important causes of hyponatremia and be able to decide an appropriate treatment.

Técnica ahorradora de tejidos con injertos de piel parcial: sistema Meek versus sistema convencional mallado. Reporte de caso / Tissue sparing technique using partial skin transplantation: Meek technique versus conventional mesh technique. A case report

La técnica Meek es útil en pacientes con sitios donantes limitados, ya que es relativamente eficiente en cuanto a la expansión de la piel; llegando a expandirse hasta 9 veces en comparación al tamaño original, se realizó la evaluación de la cicatrización entre dos técnicas de expansión de tejidos de 1:3 veces entre la técnica Meek y la técnica mallado convencional. Cabe destacar que, con los avances de la bioingeniería, la técnica Meek se integra como un método completo para el tratamiento de autoinjertos. Presentamos un caso de un paciente varón de 34 años con una enfermedad infecciosa poli bacteriana "fascitis necrotizante"; con pérdida de tejidos que comprometen el tórax, abdomen y región inguino perineal, con un 14% de superficie corporal total comprometida. En la valoración cualitativa con la escala de Vancouver y POSAS se observaron mejores resultados de cicatrización con la técnica Meek.

The Meek technique is useful in patients with limited donor sites. It is a relatively efficient technique due to its ability to expand the skin up to nine times its original size. Scarring was assessed using two tissue expansion techniques, i.e. the Meek technique and the conventional mesh technique, which achieved an expansion ratio of 1:3. It should be noted that, with advances in bioengineering, the Meek technique is integrated as a complete method for autografting.1,2 We present the case of a 34-year-old male patient with a polymicrobial infectious disease called "necrotizing fasciitis". He had lost tissues of the thorax, abdomen and inguinal-perineal region, affecting 14% of his total body surface area. A qualitative assessment using the Vancouver scale and the Patient Objective Scar Assessment Scale (POSAS) showed better scarring results with the Meek technique