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Introduction/Background Epithelial ovarian cancer (EOC) is one of the deadliest gynaecologic malignancies worldwide. Nerve Growth Factor (NGF) and its high affinity receptor TRKA increase during epithelial ovarian cancer progression, promoting cell proliferation and angiogenesis, by increasing several oncogenic proteins. Many reports have showed that microRNA-145 (miR-145) is down-regulated in EOC, promoting the increase of oncoproteins. Our aims of were to evaluate whether NGF changes the miR-145 levels in EOC cells and the role of this miR in vitro and in vivo experiments. Methodology The human tissues and blood samples were obtained with informed consent and approved by Ethic Committee of our Institution. MicroRNA-145 levels were measured by qPCR in EOC samples, EOC cells lines (A2780 and SKOV3) and in serum samples. NGF action on miR-145 levels in EOC cell lines were evaluated using an inhibitor of TRKA (high affinity receptor of NGF). The over-expression of miR-145 in EOC cells were done by lipofectamine 2000 and by pGPGLenti-CMV-GFP vector. As control we also used the empty vector. After the transfection assay it was evaluated the migration and invasion of A2780 and SKOV3 cells. After stable miR over-expression assays, the GFP-expressing cells were sorted using GFP mark and the in vivo assays were done. Animal studies were conducted in accordance with appropriate guidelines of Ethical Committee of the Institution. Two groups of Immune-compromised NOD/SCID mice were injected with 8 x106 cells (intraperitoneal and subcutaneous) of A2780 or SKOV3 cells. Results NGF decreased the miR-145 levels in A2780 and SKOV3 cell lines. Also, when an inhibitor of TRKA receptor was used, levels of this miR increased. Beside, miR-145 levels decreased with the EOC progression in both tissues and plasma samples. MicroRNA-145 over-expression in EOC cells decreased cell proliferation and invasion. Also, the stable over-expression of miR-145 in EOC cells lines decreased malignant ascites presence in the animals. On the other hand, a delay in the tumour formation was observed in EOC cells which over-express miR 145 in subcutaneous lateral flank compared with the mice injected with control EOC cells. Conclusion These results suggest that overexpression/delivery of miR-145 could be a future adjuvant therapy in epithelial ovarian cancer Disclosures The authors declare that there is no conflict of interest. This work was funded by Fondo Nacional de Desarrollo Cientifico y Tecnologico (FONDECYT) N° 1160139 to CR

The detection of viruses in sewage is a method of environmental surveillance, which allows evaluating the circulation of different viruses in a community. This study presents the first results of sewage surveillance to detect the circulation of SARS-CoV-2 virus in Santiago, Chile. Using ultracentrifugation associated with RT-qPCR, we detected SARS-CoV-2 in untreated and treated wastewater samples obtained two treatment plants, which together process around 85% of the wastewater from the city. This is the first report of detection of SARS-CoV-2 in sewage in Chile and indicates that wastewater surveillance could be a sensitive tool useful as a predictive marker of the circulation of the virus in a population and therefore, be used as an early warning tool.

Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) characterized by mucosa damage associated with an uncontrolled inflammatory response. This immunological impairment leads to altered inflammatory mediators such as IL-33, which is shown to increase in the mucosa of active UC (aUC) patients. MicroRNAs present a distorted feature in inflamed colonic mucosa and are potential IL-33 regulating candidates in UC. Therefore, we studied the microRNA and mRNA profiles in inflamed colonic samples of UC patients, evaluating the effect of a microRNA (selected by in silico analysis and its expression in UC patients), on IL-33 under inflammatory conditions. We found that inflamed mucosa (n = 8) showed increased expression of 40 microRNAs and 2,120 mRNAs, while 49 microRNAs and 1,734 mRNAs were decreased, as determined by microarrays. In particular, IL-33 mRNA showed a 3.8-fold increase and eight members of a microRNA family (miR-378), which targets IL-33 mRNA in the 3′UTR, were decreased (−3.9 to −3.0 times). We selected three members of the miR-378 family (miR-378a-3p, miR-422a, and miR-378c) according to background information and interaction energy analysis, for further correlation analyses with IL-33 expression through qPCR and ELISA, respectively. We determined that aUC (n = 24) showed high IL-33 levels, and decreased expression of miR-378a-3p and miR-422a compared to inactive UC (n = 10) and controls (n = 6). Moreover, both microRNAs were inversely correlated with IL-33 expression, while miR-378c does not show a significant difference. To evaluate the effect of TNFα on the studied microRNAs, aUC patients with anti-TNF therapy were compared to aUC receiving other treatments. The levels of miR-378a-3p and miR-378c were higher in aUC patients with anti-TNF. Based on these findings, we selected miR-378a-3p to exploring the molecular mechanism involved by in vitro assays, showing that over-expression of miR-378a-3p decreased the levels of an IL-33 target sequence β-gal-reporter gene in HEK293 cells. Stable miR-378a-3p over-expression/inhibition inversely modulated IL-33 content and altered viability of HT-29 cells. Additionally, in an inflammatory context, TNFα decreased miR-378a-3p levels in HT-29 cells enhancing IL-33 expression. Together, our results propose a regulatory mechanism of IL-33 expression exerted by miR-378a-3p in an inflammatory environment, contributing to the understanding of UC pathogenesis.

Highlights • Bronchiolitis by respiratory syncytial virus is more severe than by rhinovirus. • NA1 genotype had major hospitalization rate, severe disease and higher viral load. • Co-infection by RSV and HRV does not increase the severity of respiratory illness., Background Respiratory syncytial virus (RSV) and rhinovirus (HRV) are the main cause of acute lower respiratory tract infections (ALRTIs) in infants. Viral and host-related risk factors for severe disease have also not been clearly established. Objective To assess whether certain viral features of RSV and, or HRV are associated with severe ALRTI. Study design RSV and HRV were studied in nasopharyngeal samples of infants by immunofluorescence, Luminex® and/or real-time RT-PCR assays. Quantitation and genotyping of RSV and HRV by PCR were done. Results Of 124 virus positive specimens, 74 (59.7%) had RSV; 22 (17.7%) HRV and 28 (22.6%) RSV-HRV co-infection. Hospitalization was required in 57/74 RSV infants (77.0%); in 10/22 HRV cases (45.5%) (p = 0.006) and in 15/28 co-infected by both viruses (53.6%) (p = 0.003). Severe cases were 33/74 (44.6%) RSV infections, 2/22 HRV cases (9.1%), (p

Introduccion: Polyomavirus BK (BKPyV) y JC (JCPyV) son patogenos persistentes con capacidad de reactivacion en inmunocomprometidos, afectando principalmente el sistema urinario y el sistema nervioso central, respectivamente. No existen estudios chilenos en poblacion infectada por VIH. Objetivo: Detectar la presencia de BKPyV y JCPyV en muestras de sangre de pacientes adultos, chilenos, con infeccion por VIH y correlacionar los resultados con variables clinicas. Materiales y Metodos: Analizamos 96 muestras de extractos leucocitarios de pacientes del area norte de Santiago. El genoma viral se detecto mediante RPC en tiempo real. Para el analisis estadistico se utilizo las pruebas chi-cuadrado de Pearson y Mann-Whitney, considerando significativo un valor de p < 0,05. Resultados: 33% de las muestras resultaron positivas para BKPyV y se encontro una correlacion significativa entre la presencia de genoma de BKPyV y la ausencia de carga viral de VIH. Se evidencio la necesidad de considerar mas de un blanco de amplificacion del genoma de BKPyV. Todas las muestras fueron negativas para JCPyV. Discusion: La prevalencia de BKPyV en pacientes chilenos con infeccion por VIH es superior a la informada en la mayoria de los reportes internacionales. Se requiere estudios que evaluen la interaccion entre ambos virus. Estos pacientes deberian ser sometidos a controles urologicos y nefrologicos periodicos.

Introduction In many type of cancer, including epithelial ovarian cancer (EOC), nerve growth factor (NGF) and its high affinity receptor TRKA are over-expressed and also are involved in proliferation and angiogenesis. On the other hand, many inflammatory molecules such as cyclooxigenase-2 (COX-2) and prostaglandins (PGE2) are over-expressed in cancer and also involved in the progression of cancer. Besides, a deregulation of some miRs expression has been described in EOC including miR-145 among others. The relationship of NGF-mirRs-COX2 in EOC has not been studied. Then, the aim of this work was to evaluate COX-2 and miR-145 levels in EOC progression and the changes of COX-2 and miR-145 levels by NGF action in epithelial ovarian cancer cell line (A2780). Also we evaluated COX-2 levels by Western-Blot after over-expression of miR-145 in A2780 cell line. Material and methods Thirty human ovarian tissues (normal, tumour and cancer) were obtained from Obstetrics and Gynaecology Department, Clinical Hospital, University of Chile and also from National Institute of Cancer with written consent and authorised by Ethic Committee of the Institutions. The COX-2 levels in tissues and cells were measured by RT-PCR, IHQ, and Western-Blot and miR-145 was measured by qPCR. Cells A2780 were stimulated with NGF (100 and 150 ng/ml) to measure COX-2 and miR-145 levels. Besides, over-expression of miR-145 was done by transfection assays with lipofectamine-2000 to evaluate cellular invasion and also transduction assays with lenti-virus in order to evaluate COX-2 levels by Western-Blot in A2780 cell line. Results and discussions It was found a significant decrease of miR-145 levels in EOC tissues compared with tumour tissues and normal ovarian tissues (p Conclusion MicroRNA-145 acts as tumour suppressor microRNA in ovarian cancer and these results suggest that miR-145 could be a good therapy for EOC. This work was supported by Grant: Fondecyt 1160139 to CR and ACCDIS - Conicyt-Fondap 15130011

To identify clinical parameters in association with human papilloma virus (HPV) genotypes and histopathology diagnosis in HIV-positive patients with external condylomata acuminata (ECA), 400 Chilean HIV-positive patients were included in the study. Forty-seven patients presented ECA. Clinical parameters and socio demographic data were recorded. Histopathology study and HPV linear array genotyping assay were performed. Intraepithelial neoplasia (IEN) grade 2 or 3 was found in 8.5% of patients, associated to HPV-16. Patients were mainly single, MSM, with history of sexually transmitted disease (STD), multiple sexual partners, receiving antiretroviral therapy and with recurrent lesions. All ECA were mainly perianal, grey or pink colored, exophytic with less than two years evolution. No clinical parameter could predict the development of high grade IEN in HIV patients with ECA. It seems necessary to perform biopsy and genotype all HIV positive patients with ECA.