Epstein-Barr Virus BARF1 Is Expressed in Lung Cancer and Is Associated with Cancer Progression.

BACKGROUND: Epstein-Barr virus (EBV) is involved in the development of lymphomas, nasopharyngeal carcinomas (NPC), and a subgroup of gastric carcinomas (GC), and has also been detected in lung carcinomas, even though the role of the virus in this malignancy has not yet been established. BamH1-A Rightward Frame 1 (BARF1), a suggested exclusive epithelial EBV oncoprotein, is detected in both EBV-associated GCs (EBVaGC) and NPC. The expression and role of BARF1 in lung cancer is unknown. METHODS: A total of 158 lung carcinomas including 80 adenocarcinomas (AdCs) and 78 squamous cell carcinomas (SQCs) from Chilean patients were analyzed for EBV presence via polymerase chain reaction (PCR), Immunohistochemistry (IHC), or chromogenic in situ hybridization (CISH). The expression of BARF1 was evaluated using Reverse Transcription Real-Time PCR (RT-qPCR). Additionally, A549 and BEAS-2B lung epithelial cells were transfected with a construct for ectopic BARF1 expression. Cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) were evaluated. RESULTS: We found that EBV was present in 37 out of 158 (23%) lung carcinomas using PCR. Considering EBV-positive specimens using PCR, IHC for Epstein-Barr nuclear antigen 1 (EBNA1) detected EBV in 24 out of 30 (80%) cases, while EBERs were detected using CISH in 13 out of 16 (81%) cases. Overall, 13 out of 158 (8%) lung carcinomas were shown to be EBV-positive using PCR/IHC/CISH. BARF1 transcripts were detected in 6 out of 13 (46%) EBV-positive lung carcinomas using RT qPCR. Finally, lung cells ectopically expressing BARF1 showed increased migration, invasion, and EMT. CONCLUSIONS: EBV is frequently found in lung carcinomas from Chile with the expression of BARF1 in a significant subset of cases, suggesting that this viral protein may be involved in EBV-associated lung cancer progression.

Molecular evidence of pathogens and endosymbionts in the black horse fly Osca lata (Diptera: Tabanidae) in Southern Chile.

Little is known about the role of horse flies in potential pathogen transmission in Chile. This study provides evidence of the molecular detection of microorganisms in southern Chile. In the present study, adult Osca lata horse flies were trapped from Punucapa (39°45'06"S/73°16'08"W, Región de Los Ríos) and Puyehue (40°39'10"S/72°10'57"W, Región de Los Lagos), Chile. Among the 95 samples analyzed by PCR using specific primers, microorganisms were detected in 23.2% (n = 22) of the samples. Rickettsia spp. DNA was detected in 15.8% (n = 15) of the samples, Trypanosomatidae DNA in 5.3% (n = 5) of the samples, and filarial DNA in 2.1% (n = 2) of the samples. This study found that horse flies in the region are capable of carrying a variety of both parasites and endosymbionts. Further research is needed to understand the specific impact of horse flies as mechanical or biological vectors and develop effective control measures to prevent the spread of any microorganisms associated with disease.

Early mutational signatures and transmissibility of SARS-CoV-2 Gamma and Lambda variants in Chile.

Genomic surveillance (GS) programmes were crucial in identifying and quantifying the mutating patterns of SARS-CoV-2 during the COVID-19 pandemic. In this work, we develop a Bayesian framework to quantify the relative transmissibility of different variants tailored for regions with limited GS. We use it to study the relative transmissibility of SARS-CoV-2 variants in Chile. Among the 3443 SARS-CoV-2 genomes collected between January and June 2021, where sampling was designed to be representative, the Gamma (P.1), Lambda (C.37), Alpha (B.1.1.7), B.1.1.348, and B.1.1 lineages were predominant. We found that Lambda and Gamma variants' reproduction numbers were 5% (95% CI: [1%, 14%]) and 16% (95% CI: [11%, 21%]) larger than Alpha's, respectively. Besides, we observed a systematic mutation enrichment in the Spike gene for all circulating variants, which strongly correlated with variants' transmissibility during the studied period (r = 0.93, p-value = 0.025). We also characterised the mutational signatures of local samples and their evolution over time and with the progress of vaccination, comparing them with those of samples collected in other regions worldwide. Altogether, our work provides a reliable method for quantifying variant transmissibility under subsampling and emphasises the importance of continuous genomic surveillance.

[Strategies and recommendations to face respiratory syncytial virus disease in 2024]. / Estrategias y recomendaciones para enfrentar la enfermedad por virus respiratorio sincicial el año 2024.

During the winter of 2023, Chile faced a complex situation related to the respiratory syncytial virus (RSV). After experiencing a decline in RSV circulation during the years of the SARS-CoV-2 pandemic, a late outbreak was observed in the spring of 2022 and an early onset of the outbreak in 2023, with a significant increase in the number of serious cases. The ineffectiveness of strategic planning and risk communication contributed to the complexity of the situation. To avoid the above next winter, measures such as active surveillance, unification of definitions for acute respiratory infections, identification of RSV variants, public education about infections and advance preparation regarding hospital beds and health personnel are suggested. The importance of immunization and intersectoral collaboration to acquire new preventive alternatives is highlighted, as well as the need for early communication about the importance of immunization and identification of high-risk groups, improvement in training of medical personnel and strategic planning of the Ministry of Health. seeking a proactive and collaborative approach to address the complex RSV situation in future winters. The Chilean Immunization Advisory Committee has already carried out an analysis and recommendation on a new prevention alternative. This working group will support any decision of the Ministry of Health in public policies that attempt a change in the paradigm of control of this disease for the health of the children of our country.

Pllans-II: Unveiling the Action Mechanism of a Promising Chemotherapeutic Agent Targeting Cervical Cancer Cell Adhesion and Survival Pathways.

Despite advances in chemotherapeutic drugs used against cervical cancer, available chemotherapy treatments adversely affect the patient's quality of life. For this reason, new molecules from natural sources with antitumor potential and few side effects are required. In previous research, Pllans-II, a phospholipase A2 type-Asp49 from Porthidium lansbergii lansbergii snake venom, has shown selective attack against the HeLa and Ca Ski cervical cancer cell lines. This work suggests that the cytotoxic effect generated by Pllans-II on HeLa cells is triggered without affecting the integrity of the cytoplasmic membrane or depolarizing the mitochondrial membranes. The results allow us to establish that cell death in HeLa is related to the junction blockage between α5ß1 integrins and fibronectin of the extracellular matrix. Pllans-II reduces the cells' ability of adhesion and affects survival and proliferation pathways mediated by intracellular communication with the external environment. Our findings confirmed Pllans-II as a potential prototype for developing a selective chemotherapeutic drug against cervical cancer.

CD39+ conventional CD4+ T cells with exhaustion traits and cytotoxic potential infiltrate tumors and expand upon CTLA-4 blockade.

Conventional CD4+ T (Tconv) lymphocytes play important roles in tumor immunity; however, their contribution to tumor elimination remains poorly understood. Here, we describe a subset of tumor-infiltrating Tconv cells characterized by the expression of CD39. In several mouse cancer models, we observed that CD39+ Tconv cells accumulated in tumors but were absent in lymphoid organs. Compared to tumor CD39- counterparts, CD39+ Tconv cells exhibited a cytotoxic and exhausted signature at the transcriptomic level, confirmed by high protein expression of inhibitory receptors and transcription factors related to the exhaustion. Additionally, CD39+ Tconv cells showed increased production of IFNγ, granzyme B, perforin and CD107a expression, but reduced production of TNF. Around 55% of OVA-specific Tconv from B16-OVA tumor-bearing mice, expressed CD39. In vivo CTLA-4 blockade induced the expansion of tumor CD39+ Tconv cells, which maintained their cytotoxic and exhausted features. In breast cancer patients, CD39+ Tconv cells were found in tumors and in metastatic lymph nodes but were less frequent in adjacent non-tumoral mammary tissue and not detected in non-metastatic lymph nodes and blood. Human tumor CD39+ Tconv cells constituted a heterogeneous cell population with features of exhaustion, high expression of inhibitory receptors and CD107a. We found that high CD4 and ENTPD1 (CD39) gene expression in human tumor tissues correlated with a higher overall survival rate in breast cancer patients. Our results identify CD39 as a biomarker of Tconv cells, with characteristics of both exhaustion and cytotoxic potential, and indicate CD39+ Tconv cells as players within the immune response against tumors.

PredictION: a predictive model to establish the performance of Oxford sequencing reads of SARS-CoV-2.

The optimization of resources for research in developing countries forces us to consider strategies in the wet lab that allow the reuse of molecular biology reagents to reduce costs. In this study, we used linear regression as a method for predictive modeling of coverage depth given the number of MinION reads sequenced to define the optimum number of reads necessary to obtain >200X coverage depth with a good lineage-clade assignment of SARS-CoV-2 genomes. The research aimed to create and implement a model based on machine learning algorithms to predict different variables (e.g., coverage depth) given the number of MinION reads produced by Nanopore sequencing to maximize the yield of high-quality SARS-CoV-2 genomes, determine the best sequencing runtime, and to be able to reuse the flow cell with the remaining nanopores available for sequencing in a new run. The best accuracy was -0.98 according to the R squared performance metric of the models. A demo version is available at https://genomicdashboard.herokuapp.com/.

Análisis de causas atribuidas a "BRUE" entre los años 2017 a 2020 / Analysis of etiologies attributed to "BRUE" between the years 2017 to 2020

El término BRUE describe un evento en un lactante menor, repentino, breve, ya resuelto y sólo aplica cuando no existe una explicación para este episodio. Es escasa la literatura nacional e internacional sobre el estudio etiológico en BRUE. Objetivos: Caracterizar lactantes con episodio de BRUE y hacer un análisis etiológico. Métodos: Estudio retrospectivo, descriptivo lactantes hospitalizados por BRUE. Resultados: Se encontraron 50 lactantes con BRUE, la mayoría de ellos presentó un solo evento y ninguno requirió reanimación cardiopulmonar. Las características principales de los eventos fueron apnea, cianosis y tono disminuido. Las etiologías encontradas, más habituales, fueron reflujo gastro-esofágico, infección respiratoria, mala técnica alimentaria y crisis epilépticas. La evaluación clínica fue el principal elemento diagnóstico. Discusión: Nuestro análisis etiológico concuerda con la literatura nacional e internacional. La anamnesis y examen físico son la principal herramienta diagnóstica. Es fundamental contar con guías, adaptadas a la realidad nacional y local, que dirijan el estudio de lactantes con BRUE.

BRUE is an event occurring in an infant when the observer reports a sudden, brief, and now-resolved episode. BRUE is a diagnosis of exclusion and is used only when there is no explanation for the event after conducting an appropriate history and physical examination. There is little literature on the etiological study in BRUE. Objectives: To characterize infants with a BRUE episode and to carry out an etiological analysis. Methods: A retrospective study including infants who have experienced a BRUE between the years 2017 to 2020. Results: 50 infants with BRUE, most of them presented a single event and none required cardiopulmonary resuscitation. The main characteristics of the events were apnea, cyanosis and decreased tone. The most common etiologies found were gastroesophageal reflux, respiratory infection, poor feeding technique, and seizures. History and physical examination are the fundamental diagnostic tools. Discussion: Our etiological analysis agrees with the national and international literature. The clinical evaluation was the main diagnostic tool. It is essential to create local guidelines for the evaluation investigation and management of infants with BRUE.

Preliminary identification of pathogenic variants in an Afro-Colombian Raizal family with risk factors for glaucoma.

Objective: To identify pathogenic variants in an Afro-Colombian Raizal family with risk factors for glaucoma. Methods: In the present study, whole exome sequencing was performed on seven members of a Raizal family from the archipelago of San Andrés, Providencia, and Santa Catalina, in the Caribbean region of Colombia. Four of them had been diagnosed with glaucoma. In addition, two healthy volunteers from the island were included. Results: Of the 198 single nucleotide variants associated with glaucoma, previously reported by the DisGeNET database, four were identified in members of the Raizal family: rs11938093, rs7336216, rs3817672, and rs983034. Furthermore, single nucleotide variant rs983034 was identified in the Wnt ligand secretion mediator gene in all members of the family but not in healthy volunteers. Notably, WLS dysfunctions have been linked to pathology in the trabecular meshwork of the eye. Trabecular meshwork is an important regulator of the outflow of aqueous humor that maintains intraocular pressure (intraocular pressure) at normal levels. Damage to trabecular meshwork is associated with ocular hypertension, which leads to glaucoma progression. In relation to the other single nucleotide variants that were identified, their presence was confirmed in some members of the Raizal family. However, it is still unclear the pathophysiological cause that associates these single nucleotide variants with glaucoma. Conclusions: It was possible to identify four non-synonymous single nucleotide variants that predict significant damage to the structure and function of genes associated with glaucoma pathology in an Afro-Colombian.

Objetivo: Identificar las variantes patogénicas en una familia raizal afrocolombiana con factores de riesgo para el glaucoma. Métodos: En el presente estudio, se realizó una secuenciación de exoma completo en siete miembros de una familia Raizal del archipiélago de San Andrés, Providencia y Santa Catalina del Caribe colombiano. La mitad de ellos habían sido diagnosticados con glaucoma. Además, se incluyeron dos voluntarios sanos de la isla. Resultados: De las 198 variantes de un solo nucleótido (SNV) asociadas con el glaucoma, previamente informadas por la base de datos DisGeNET, se identificaron cuatro en los miembros de la familia Raizal: rs11938093, rs7336216, rs3817672 y rs983034. Ademas, en todos los miembros de la familia, pero no en voluntarios sanos, se identificó SNV rs983034 en el gen mediador de secreción de ligando Wnt (WLS). Notablemente, las disfunciones WLS se han relacionado con patologías en la red trabecular (TM) del ojo. TM es un regulador importante del flujo de salida del humor acuoso que mantiene la presión intraocular (presión intraocular) en niveles normales. El daño a la TM se asocia con hipertensión ocular que conduce a la progresión del glaucoma. En relación con los demás SNV identificados, se constató su presencia en algunos miembros de la familia Raizal. Sin embargo, aún no está clara la causa fisiopatológica que asocia estas SNV con el glaucoma. Conclusiones: Fue posible identificar cuatro SNVs no sinónimos con predicción de daño significativo en la estructura y función de genes asociados a patología de glaucoma en un afrocolombiano.

Pllans-II Induces Cell Death in Cervical Cancer Squamous Epithelial Cells via Unfolded Protein Accumulation and Endoplasmic Reticulum Stress.

Due to the lack of chemotherapeutic drugs that selectively affect cervical cancer cells, natural sources such as snake venom are currently being investigated for molecules with antitumor potential. Pllans-II, a phospholipase A2 type-Asp49 from Porthidium lansbergii lansbergii snake venom, induced cell death in a cervical cancer cell line-Ca Ski-related to dysfunction in the ability to resolve endoplasmic reticulum stress, evidenced by sub-expression of genes such as PERK, ERO1 PDIs, HSP70, and CHOP. Western blot analysis validated the last two genes' sub-expression at the protein level. In addition, Pllans-II presented a dose-dependent cytotoxic effect on cancer cells and an insignificant effect on healthy endothelial cells (HUVEC). Additionally, Pllans-II inhibited cancer cells' adhesion and migration capacity, induced cell cycle arrest in the G2/M phase, and induced apoptosis stimulated possibly by the extrinsic route. These results demonstrate for the first time that Pllans-II has an antitumor effect on a squamous epithelial cervical cancer cell line and represents a possible biotechnological tool for designing a prominent antitumor agent.

Clinical characteristics of patients with Breast and / or Ovarian Cancer with mutations in the BRCA1 and BRCA2 genes in Córdoba, Argentina / [Características clínicas de pacientes con Cáncer de Mama y / o Cáncer de Ovario con mutaciones en los genes BRCA1 y BRCA2 en Córdoba, Argentina.]

Introduction: Hereditary predisposition syndromes to cancer represent 5-10% of cancer cases, the most studied being HBOC produced by mutations in the BRCA1/2 genes. Objectives: To describe clinical, histopathological and PV characteristics in patients with HBOC in Córdoba, Argentina and compare it with those without BRCA1/2 mutations. Methods: Cross-sectional, correlational and observational analysis of patients from Córdoba. The ANOVA, Student's t test contingency tables and Fisher exact test were used the significance level was α = 0.05. Results: 155 women with BC, OC and BC/OC were studied. 40 BRCA1 / 2 mutations were identified. No differences were found in the age of diagnosis between patients with and without BRCA1/2 mutations. A significant association was found between VP in BRCA1/2 and the type of cancer (p = 0.003); all cases with BC/OC presented mutations in BRCA1/2. No significant association was found between mutated/non-mutated and personal history, family background, and ER-PR-HER2. 23.1% and 38.1% of BC cases were TN in individuals with VP in BRCA 1 and 2, respectively. The prevalence of mutations was 25.8% and the prevalence of novel PV was 10.0%. Conclusions: Patients with BC-VP BRCA1/2 are associated with ductal histology, and younger age of presentation with VP BRCA1. We did not find significant differences in the age at diagnosis of BC between patients with BRCA1 and BRCA2 mutations, a higher proportion of BC TN is observed than in the general population. In our sample, the prevalence of BRCA1/2 mutations among patients who meet criteria for HBOC is 25.8%, with 10% new pathogenic variant.

Introducción: Los síndromes de predisposición hereditaria al cáncer representan un 5-10% de los casos de cáncer, el más estudiado es HBOC producido por mutaciones en los genes BRCA1/2. Objetivos: Describir características clínicas, histopatológicas y VP en pacientes con HBOC en Córdoba, Argentina y compararla con aquellas sin mutaciones en BRCA1/2. Métodos: Análisis transversal, correlacional y observacional de pacientes de Córdoba. Se utilizó la prueba ANOVA, t de Student, tablas de contingencia y prueba exacta de Fisher, el nivel de significancia fue α=0,05. Resultados: Se estudiaron 155 mujeres con CM, CO y CM/CO. Se identificaron 40 mutaciones en BRCA1/2. No se encontraron diferencias en edad de diagnóstico entre pacientes con y sin mutaciones en BRCA1/2. Se encontró asociación significativa entre VP en BRCA1/2 y el tipo de cáncer (p=0,003); todos los casos con CM/CO presentaron mutaciones en BRCA1/2. No se encontró asociación significativa entre mutados/no mutados y AP, AF, RE-RP-HER2. El 23.1% y 38.1% de los casos de CM fueron TN en individuos con VP en BRCA 1 y 2 respectivamente. La prevalencia de mutaciones fue 25,8% y la prevalencia de VP noveles del 10,0%. Conclusiones: Las pacientes con CM-VP BRCA1/2 están asociadas con histología ductal, y menor edad de presentación con VP BRCA1. No encontramos diferencias significativas en edad de diagnóstico del CM entre pacientes con mutaciones BRCA1 y BRCA2, se observa una mayor proporción CM TN que en la población en general. En nuestra muestra, la prevalencia de mutaciones en BRCA1/2 entre los pacientes que reúnen criterios para HBOC es del 25,8%, con 10% de VP noveles.

Bioinspired Intelligence II.

Bioinspired intelligence methods are currently common approaches for both engineers and the scientists [...].

Preliminary identification of pathogenic variants in an Afro-Colombian Raizal family with risk factors for glaucoma / Identificación preliminar de variantes patógenas en una familia raizal afrocolombiana con factores de riesgo para glaucoma

Abstract Objective: To identify pathogenic variants in an Afro-Colombian Raizal family with risk factors for glaucoma. Methods: In the present study, whole exome sequencing was performed on seven members of a Raizal family from the archipelago of San Andrés, Providencia, and Santa Catalina, in the Caribbean region of Colombia. Four of them had been diagnosed with glaucoma. In addition, two healthy volunteers from the island were included. Results: Of the 198 single nucleotide variants associated with glaucoma, previously reported by the DisGeNET database, four were identified in members of the Raizal family: rs11938093, rs7336216, rs3817672, and rs983034. Furthermore, single nucleotide variant rs983034 was identified in the Wnt ligand secretion mediator gene in all members of the family but not in healthy volunteers. Notably, WLS dysfunctions have been linked to pathology in the trabecular meshwork of the eye. Trabecular meshwork is an important regulator of the outflow of aqueous humor that maintains intraocular pressure (intraocular pressure) at normal levels. Damage to trabecular meshwork is associated with ocular hypertension, which leads to glaucoma progression. In relation to the other single nucleotide variants that were identified, their presence was confirmed in some members of the Raizal family. However, it is still unclear the pathophysiological cause that associates these single nucleotide variants with glaucoma. Conclusions: It was possible to identify four non-synonymous single nucleotide variants that predict significant damage to the structure and function of genes associated with glaucoma pathology in an Afro-Colombian.

Resumen Objetivo: Identificar las variantes patogénicas en una familia raizal afrocolombiana con factores de riesgo para el glaucoma. Métodos: En el presente estudio, se realizó una secuenciación de exoma completo en siete miembros de una familia Raizal del archipiélago de San Andrés, Providencia y Santa Catalina del Caribe colombiano. La mitad de ellos habían sido diagnosticados con glaucoma. Además, se incluyeron dos voluntarios sanos de la isla. Resultados: De las 198 variantes de un solo nucleótido (SNV) asociadas con el glaucoma, previamente informadas por la base de datos DisGeNET, se identificaron cuatro en los miembros de la familia Raizal: rs11938093, rs7336216, rs3817672 y rs983034. Ademas, en todos los miembros de la familia, pero no en voluntarios sanos, se identificó SNV rs983034 en el gen mediador de secreción de ligando Wnt (WLS). Notablemente, las disfunciones WLS se han relacionado con patologías en la red trabecular (TM) del ojo. TM es un regulador importante del flujo de salida del humor acuoso que mantiene la presión intraocular (presión intraocular) en niveles normales. El daño a la TM se asocia con hipertensión ocular que conduce a la progresión del glaucoma. En relación con los demás SNV identificados, se constató su presencia en algunos miembros de la familia Raizal. Sin embargo, aún no está clara la causa fisiopatológica que asocia estas SNV con el glaucoma. Conclusiones: Fue posible identificar cuatro SNVs no sinónimos con predicción de daño significativo en la estructura y función de genes asociados a patología de glaucoma en un afrocolombiano.

[Social, clinical and psychosocial determinants associated with uncontrolled arterial hypertension in older adults. SABE Survey Colombia 2016]. / Determinantes sociales, clínicos y psicosociales asociados a hipertensión arterial no controlada en adultos mayores. Encuesta SABE Colombia 2016.

OBJECTIVE: To evaluate sociodemographic, clinical and psychosocial characteristics that are associated with uncontrolled arterial hypertension (HANC) in older adults in Colombia. METHODS: Secondary analysis of data from the National Survey of Health, Welfare and Aging (SABE Colombia 2016), in which men and women aged 60 years or older in the country who were not institutionalized were interviewed. The dependent variable was uncontrolled hypertension (HANC) (≥140/90mm Hg). The SABE survey surveyed 23694 older adults; 11264 had a diagnosis of arterial hypertension (HTA) and were taking antihypertensive medication. On the other hand, 5106 older adults, randomly selected, had their blood pressure taken. Participants previously diagnosed with HTA under medical management with antihypertensives and who had had their blood pressure taken at the same time were included, resulting in a sample of 2656 participants. Sociodemographic, clinical and psychosocial characteristics were evaluated. Univariate, bivariate, and multivariate analyzes with logistic regression were performed. RESULTS: One thousand one hundred eighty-eight (44.7%) participants presented HANC. A higher prevalence of HANC was observed in adults older than 74 years (OR 1.31; 95% CI 1.09-1.57) and lower prevalence in residents of urban areas (OR 0.55; 95% CI 0.42-0.71). CONCLUSIONS: Age over 74 years and living in a rural area were identified as variables associated with inadequate blood pressure control in non-institutionalized older adults in Colombia.

Factors associated with the presence of the Epstein-Barr virus in the oral cavity of high school students from the city of Cali (Colombia).

INTRODUCTION: The Epstein-Barr virus (EBV) is classified as a group 1 carcinogen. The main route of EBV transmission is oral, through saliva. The present study aimed to determine the frequency of EBV detection in the oral cavity in high school students in the city of Cali (Colombia). MATERIALS AND METHODS: Analytical cross-sectional study in order to determine the frequency of EBV detection in the oral cavity, the reasons for its prevalence and its association with several factors, in 1565 individuals. The variables analyzed were sociodemographic factors, oral hygiene, oral health, sexual behavior, cigarrete smoking and alcohol intake. The association between the EBV detection and the variables evaluated was done through a generalized linear regression model with logarithmic linkage and Poisson distribution with robust variance. RESULTS: The percentage of exposure to EBV in the oral cavity was 38.40% (CI 95%: 36.02-40.84). The frequency of presenting EBV exposure was 22% higher in men and the risk increased according to sexual behaviour. An inverse association with the school grade was found: the eleventh-grade participants had 27% less frequency of exposure to EBV than the lower grades (sixth to eighth). When analyzing the logistic model to study the association between EBV detection and independent variables, the association was overestimated. The overestimation ranged from 27% to 47% depending on the type of variable. CONCLUSIONS: The frequency of EBV detection in the oral cavity of healthy students was similar to that previously described. Factors associated to sexual behavior increased the risk of opportunity to be exposed to EBV.

MYC dosage compensation is mediated by miRNA-transcription factor interactions in aneuploid cancer.

We hypothesize that dosage compensation of critical genes arises from systems-level properties for cancer cells to withstand the negative effects of aneuploidy. We identified several candidate genes in cancer multiomics data and developed a biocomputational platform to construct a mathematical model of their interaction network with micro-RNAs and transcription factors, where the property of dosage compensation emerged for MYC and was dependent on the kinetic parameters of its feedback interactions with three micro-RNAs. These circuits were experimentally validated using a genetic tug-of-war technique to overexpress an exogenous MYC, leading to overexpression of the three microRNAs involved and downregulation of endogenous MYC. In addition, MYC overexpression or inhibition of its compensating miRNAs led to dosage-dependent cytotoxicity in MYC-amplified colon cancer cells. Finally, we identified negative correlation of MYC dosage compensation with patient survival in TCGA breast cancer patients, highlighting the potential of this mechanism to prevent aneuploid cancer progression.

Factores Predictivos de Compromiso Axilar en ocasión de Ganglio Centinela Positivo en Cáncer de Mama Temprano / Predictive Factors of Axillary Compromise on the Occasion of Positive Sentinel Lymph Node in Early Breast Cancer

Introducción: Se ha demostrado en diversos protocolos que, en gran proporción de casos con cáncer de mama en estadíos tempranos y ganglio centinela positivo, no se observa enfermedad metastásica en ganglios linfáticos no centinelas (GNC). A raíz de esto es que se han descripto diferentes factores predictores de metástasis axilar. Esto nos motivó a realizar el presente trabajo. Objetivo: Analizar diferentes factores anatomopatológicos y su influencia en el compromiso metastásico de los ganglios no centinela. Material y método: Se estudiaron casos de cáncer de mama estadíos tempranos (T1-T2) con ganglio centinela positivo y seguidas de vaciamiento axilar, operadas en IMGO entre febrero del año 2000 y diciembre de 2012. De la muestra total se identificaron dos grupos: GnC negativos y GnC positivos. Analizamos diferentes variables anatomopatológicas vinculadas a cada grupo y calculamos su grado de significancia. Finalmente, analizamos estas variables en una tabla de análisis multivariado. Resultados: De una muestra de 205 casos (20,8% del total de ganglios estudia- dos en ese período de tiempo), el 48.3% (n=99) presentaba metástasis solo en el GC. De todas las características anatomopatológicas de mal pronóstico analizadas encontramos que el tamaño tumoral 2, el subtipo lobulillar y la invasión linfovascular tuvieron correlación significativa con la cantidad de GnC comprometidos. En el análisis multivariado encontramos tres factores predictivos, la invasión linfovascular, el tamaño de la metástasis en el ganglio centinela y el número de ganglios centinelas comprometidos. Conclusiones: Los factores independientes de compromiso de ganglios no centinela (GNC) en nuestra serie fueron: la invasión linfovascular, el tamaño de la metástasis en el ganglio centinela y el número de ganglios centinelas comprometidos

Introduction: It has been shown in various protocols that pathologically negative nonsentinel lymph node (NSN) disease, is observed in the rest of the armpit in a large proportion of cases with early stage breast carcinoma and positive sentinel node. As a result of this, different pathological predictors of axillary metastasis have been described. This motivated us to carry out the present work. Objetive: To analyze different pathological factors and their influence on the metastatic involvement of nonsentinel nodes. Material and method: Early stage breast cancer cases (T1-T2) with positive sentinel node and axillary emptying, operated on in IMGO between February 2000 and December 2012, were studied. Two groups were identified from the total sample: negative GnC and positive GnC, and analyzed diffe- rent pathological variables associated with metastatic nonsentinel nodes, calculating their significance. Finally, we analyze these variables in a multivariate analysis table. Results: From a sample of 205 cases (20.8% of the total lymph nodes studied), 48.3% (n = 99) had metastasis only in the SN. Of all the anatomo-pathological characteristics analyzed, we found that tumor size two, lobular subtype, and lymphovascular invasion had a significant correlation with the amount of compromised non-sentinel node (NSN). In the multivariate analysis, we found three predictive factors: lymphovascular invasion, the size of the metastasis in the sentinel node and the number of positive sentinel nodes. Conclusions: The independent factors of nonsentinel node involvement (NSN) in our series are: lymphovascular invasion, the size of the sentinel node metastasis, and the number of sentinel nodes involved

Polyfunctional KLRG-1+CD57+ Senescent CD4+ T Cells Infiltrate Tumors and Are Expanded in Peripheral Blood From Breast Cancer Patients.

Senescent T cells have been described during aging, chronic infections, and cancer; however, a comprehensive study of the phenotype, function, and transcriptional program of this T cell population in breast cancer (BC) patients is missing. Compared to healthy donors (HDs), BC patients exhibit an accumulation of KLRG-1+CD57+ CD4+ and CD8+ T cells in peripheral blood. These T cells infiltrate tumors and tumor-draining lymph nodes. KLRG-1+CD57+ CD4+ and CD8+ T cells from BC patients and HDs exhibit features of senescence, and despite their inhibitory receptor expression, they produce more effector cytokines and exhibit higher expression of Perforin, Granzyme B, and CD107a than non-senescent subsets. When compared to blood counterparts, tumor-infiltrating senescent CD4+ T cells show similar surface phenotype but reduced cytokine production. Transcriptional profiling of senescent CD4+ T cells from the peripheral blood of BC patients reveals enrichment in genes associated with NK or CD8+-mediated cytotoxicity, TCR-mediated stimulation, and cell exhaustion compared to non-senescent T cells. Comparison of the transcriptional profile of senescent CD4+ T cells from peripheral blood of BC patients with those of HDs highlighted marked similarities but also relevant differences. Senescent CD4+ T cells from BC patients show enrichment in T-cell signaling, processes involved in DNA replication, p53 pathways, oncogene-induced senescence, among others compared to their counterparts in HDs. High gene expression of CD4, KLRG-1, and B3GAT1 (CD57), which correlates with increased overall survival for BC patients, underscores the usefulness of the evaluation of the frequency of senescent CD4+ T cells as a biomarker in the follow-up of patients.

Modelo inorgánico de simulación de gastrostomía laparoscópica con impresión 3D, para adquirir habilidades en sutura intracorpórea. Estudio cuasi-experimental / Inorganic model of laparoscopic gastrostomy simulation with 3D printing, to acquire skills in intracorporal suture. Quasy experimental study

La sutura y el anudado laparoscópico intracorpóreo son las habilidades más difíciles de aprender, las mismas son esenciales para realizar procedimientos laparoscópicos avanzados. Los modelos de entrenamiento laparoscópico permiten facilitar la curva de aprendizaje en un ambiente seguro y sin riesgo para el paciente. La impresión 3D ha revolucionado muchos campos industriales, el presente estudio buscar enlazar la tecnología de impresión 3D con la creación de un modelo anatómico de un estómago inorgánico, para simular una gastrostomía laparoscópica con fines didácticos para los residentes de cirugía general y los cirujanos en formación. Objetivo: Desarrollar un modelo inorgánico de simulación de gastrostomía laparoscópica mediante impresión 3D, como herramienta para la adquisición de habilidades y destrezas en sutura y anudado intracorpóreo. Métodos: Se realizó un estudio de tipo prospectivo, experimental y longitudinal. El autor del presente trabajo, realizó 16 prácticas en caja negra con el modelo de entrenamiento laparoscópico creado y fueron evaluadas mediante la escala GOALS y medición del tiempo de ejecución. Resultados: La puntuación obtenida en la escala GOALS fue de 19 puntos en la primera práctica e incrementó hasta 23 puntos en las últimas prácticas (Tau-C de Kendall=0,89) siendo estadísticamente significativo (p<0,00001). El tiempo disminuyó de la primera practica de 18:30 hasta 6:56 minutos en la última (Tau-C de Kendall=-0,49) siendo estadísticamente significativo (p=0,01). Conclusión: El modelo de entrenamiento creado con impresión 3D permite recrear los pasos para realizar una gastrostomía laparoscópica, y demostró ser una herramienta eficaz en la adquisición de habilidades en sutura y anudado intracorpóreo(AU)

Intracorporeal laparoscopic suturing and knotting are the most difficult skills to learn, and they are essential for performing advanced laparoscopic procedures. Laparoscopic training models facilitate the learning curve in a safe environment without risk for the patient. 3D printing has revolutionized many industrial fields, the present study seeks to link 3D printing technology with the creation of an anatomical model of an inorganic stomach, to simulate a laparoscopic gastrostomy for educational purposes for general surgery residents and surgeons in training. Objetive: develop an inorganic simulation model of laparoscopic gastrostomy using 3D printing, as a tool for the acquisition of skills and abilities in suturing and intracorporeal knotting. Methods: A prospective, experimental and longitudinal study was carried out. The author of this work performed 16 black box practices with the laparoscopic training model created and they were evaluated using the GOALS scale and measurement of execution time. Results: The score obtained on the GOALS scale was 19 points in the first practice and increased to 23 points in the last practices (Kendall's Tau-C = 0.89), being statistically significant (p <0.00001). The time decreased from the first practice from 18:30 to 6:56 minutes in the last one (Kendall's Tau-C = -0.49) being statistically significant (p = 0.01). Conclusion: The training model created with 3D printing allows to recreate the steps to perform a laparoscopic gastrostomy, and proved to be an effective tool in the acquisition of skills in suturing and intracorporeal knotting(AU)