MGRN1 depletion promotes intercellular adhesion in melanoma by upregulation of E-cadherin and inhibition of CDC42.

Mahogunin Ring Finger 1 is an E3-ubiquitin ligase encoded by the color gene MGRN1. Our previous in vitro and in vivo studies demonstrated that Mgrn1 deletion in mouse melanoma cells induced cell differentiation and adhesion, and decreased cell motility and invasion on collagen I, and lung colonization in an in vivo model. Here, we investigated the role of MGRN1 on human melanoma cell morphology, adhesion and expression of genes/proteins involved in an EMT-like transition. We demonstrated that wild-type BRAF human melanoma cells adopted a clustering-like morphology on collagen I, with permanent MGRN1 abrogation resulting in bigger cell clusters. Enhanced intercellular adhesion was mostly mediated by induction of E-cadherin and higher co-localization with ß-catenin. Transcriptional upregulation of E-cadherin likely occurred through downregulation of the ZEB1 repressor. Finally, pulldown assays showed reduced activation of CDC42 in the absence of MGRN1, which was reverted after E-cadherin silencing. Overall, these findings highlight a new MGRN1-dependent pathway regulating melanoma cell shape, motility, and invasion potential.

Perfil de uso de tigeciclina en un hospital universitario en Chile / Profile of tigecycline use in a university hospital in Chile

INTRODUCCIÓN: El uso de tigeciclina ha ido en aumento en los últimos años, debido al incremento de la resistencia bacteriana y la escasez de alternativas terapéuticas. OBJETIVO: Caracterizar y evaluar las prescripciones de tigeciclina en pacientes internados en un hospital universitario, durante los años 2017 y 2018. METODOLOGÍA: Estudio observacional retrospectivo, donde se caracterizaron los pacientes, las terapias, la microbiología asociada, los desenlaces clínicos y las reacciones adversas asociadas a los tratamientos con tigeciclina. Se determinó la proporción de prescripciones apropiadas por un comité de expertos y el consumo de tigeciclina medido en DDD/100 camas-día. RESULTADOS: Se caracterizaron 89 pacientes, de los cuales 67 (75,3%) cumplieron los criterios de selección. El 53,7% de los pacientes eran hombres, con una edad promedio de 60 ± 15 años. El principal motivo de hospitalización fue quirúrgico (65,7%). El 67,1% de los tratamientos con tigeciclina se inició en una Unidad de Paciente Critico y el foco de infección predominante fue abdominal (64,3%). El 50% de las terapias con tigeciclina fueron dirigidas según la microbiología identificada. En 65,7% de los casos se usó tigeciclina como monoterapia en la dosis habitual (62,9%). Náuseas (8,6%), diarrea (7,1%) y vómitos (4,3%) fueron los efectos adversos más reportados. El 84,3% de los tratamientos se consideraron apropiados. El año 2017 se consumió 0,4 DDD/100 camas-día y 0,6 DDD/100 camas/día el 2018, siendo la UCI el servicio que presentó el mayor uso en ambos años. DISCUSIÓN: Tigeciclina fue utilizada principalmente en monoterapia para el tratamiento de infecciones intraabdominales en pacientes hospitalizados, por motivos quirúrgicos, en una unidad de paciente crítico, en las dosis habituales recomendadas de 100 mg como dosis de carga seguida de 50 mg cada 12 hs IV. En 50% de los casos, la terapia fue dirigida según microbiología. Los eventos adversos más habituales fueron los gastrointestinales. CONCLUSIÓN: La mayoría de las terapias prescritas fueron consideradas apropiadas por el comité de expertos.

BACKGROUND: The use of tigecycline has been increasing in recent years, due to increase in bacterial resistance and the scarcity of therapeutics alternatives. AIM: To characterize and evaluate the tigecycline prescriptions of patients hospitalized in a university hospital, during the years 2017 and 2018. METHODS: A retrospective observational study was carried out, where the patients, the therapies, the associated microbiology, the clinical outcomes and the adverse reactions associated with tigecycline were characterized. The proportion of appropriate prescriptions was determined by committee of experts and the consumption of tigecycline measure in DDD/100 bed-days. RESULTS: 89 patients who used tigecycline were characterized, of which 67 (75.3%) met the selection criteria. 53.7% of the patients were male, with a mean age of 60 +/- 15 years The main reason for hospitalization was surgical (65.7%). 67.1% of the treatments with tigecycline were started in a critical patient unit and the predominant focus of the infection was the abdomen (64.3%). 50% of the therapies with tigecycline were ordered according to the identified microbiology. In 65.7% of the cases, tigecyclin was used as monotherapy at the usual dose (62.9%). Nausea (8.6%), diarrhea (7.1%) and vomiting (4.3%) were the most reported adverse events. 84.3% of the treatments were considered appropriate. In 2017, 0.4 DDD/100 bed/days were consumed and 0.6 DDD/100 bed/days in 2018, with de ICU being the service that presented the highest use in both years. DISCUSSION: Tigecycline was mainly used as monotherapy for the treatment of intra-abdominal infections in patients hospitalized for surgical reasons in a critical patient unit at the usual doses of 100 mg loading followed by 50 mg every 12 hours IV. In 50% of the case the therapy was directed according to microbiology. The most common adverse events were gastrointestinal. CONCLUSION: Most of the prescribed therapies were considered appropriate by the expert committee.

Caracterización de la utilización de colistín en un hospital de alta complejidad / Evaluation of colistin use in a highly complex hospital

RESUMEN: El aumento de la resistencia y la escasez de nuevos antibacterianos ha requerido la reintroducción de antiguos antimicrobianos entre ellos colistín. OBJETIVO: Caracterizar la utilización de colistín durante el año 2017 en un hospital universitario, mediante la descripción de los pacientes, los tratamientos, la microbiología asociada y efectos adversos. PACIENTES Y MÉTODOS: Trabajo observacional retrospectivo. Se revisaron los datos de todos los pacientes que recibieron colistín intravenoso (IV) por al menos 48 horas, durante el año 2017. RESULTADOS: Se incluyeron 53 pacientes, equivalentes a 91 tratamientos. El foco respiratorio fue el principal (46,2%). El 68,1% de los tratamientos fue iniciado en la UCI. La mayoría de los pacientes tenía una hospitalización reciente (83,5%), y presentaban uso previo de antibacterianos (89%). Los dos patógenos mayoritariamente identificados fueron Pseudomonas aeruginosa y Klebsiella spp. El consumo promedio de colistín fue de 2,4 DDD/100 camas/día. El servicio que más consumió colistín fue la UCI, con 45,5 DDD/100 camas/día, usando generalmente la dosis de 3 MUI cada 8 horas IV y con una baja utilización de dosis de carga. CONCLUSIÓN: Colistín corresponde a un antimicrobiano de uso restringido a infecciones sospechadas o confirmadas por agentes bacterianos multi resistentes. En esta serie, su uso inicial fue principalmente empírico, en pacientes con factores de riesgo para resistencia antibacteriana; se usó en forma asociada a otros antimicrobianos, siendo el foco principal el respiratorio.

BACKGROUND: The increase in resistance and the shortage of new antibiotics has led to the reintroduction of old antimicrobials such as colistin. AIM: To evaluate the use of colistin during 2017 in a university hospital, through the characterization of patients and treatment, associated microbiology, response to treatment and adverse effects. METHODS: Retrospective observational design. The data of all patients who received colistin for at least 48 hours during the year 2017 were reviewed. RESULTS: 55 patients were included, equivalent to 144 treatments. The respiratory focus was the main one (57.9%). 64% of the treatments began in the ICU, while 7% in the ward. Most of the patients has a recent hospitalization (86.8%) and has previous use of antibiotics (90.4%). The two main pathogens identified were Pseudomonas aeruginosa and Klebsiella spp. In 87.1% of the cases with microbiological justifications for the use of colistin, a favorable response was obtained. The average consumption of colistin was 2.4 DDD/100 beds/day. The department that consumed the most colistin was the ICU, with 45,5 DDD/100 beds/day, generally using a dose of 3 MIU every 8 hours IV and with low use of loading doses. CONCLUSION: Colistin corresponds to an antibiotic whose use is restricted to infections suspected or confirmed by multi-resistant bacterial agents. Its initial use in this serie was mainly empirical, in patients with risk factors for antibiotics resistance, it was used in association with other antimicrobials, being the respiratory the main infectious focus.

[Obstacles and enablers for the use of barrier methods to avoid HIV/AIDS transmission]. / Obstáculos y facilitadores para el uso de métodos de barrera para la transmisión de VIH/SIDA.

BACKGROUND: There is an increase in HIV/AIDS transmission rates world-wide Aim: To explore obstacles and facilitators in the use of barrier methods for the prevention of HIV/AIDS among Chilean young people between 20 and 29 years of age. MATERIAL AND METHODS: During the second semester of the year 2020, 134 young Chileans answered an online questionnaire with open-ended questions about barrier methods. A qualitative methodology that considered the main techniques of grounded theory for data analysis was used. RESULTS: There are individual, interpersonal, sociocultural, and structural factors that operate as obstacles and facilitators for the use of barrier methods to prevent the transmission of HIV/AIDS. CONCLUSIONS: There are culturally embedded beliefs among young people, such as, a perception of invulnerability caused by not being part of risk groups, among others, that affect self-care.

Obstáculos y facilitadores para el uso de métodos de barrera para la transmisión de VIH/SIDA / Obstacles and enablers for the use of barrier methods to avoid HIV/AIDS transmission

BACKGROUND: There is an increase in HIV/AIDS transmission rates world-wide Aim: To explore obstacles and facilitators in the use of barrier methods for the prevention of HIV/AIDS among Chilean young people between 20 and 29 years of age. MATERIAL AND METHODS: During the second semester of the year 2020, 134 young Chileans answered an online questionnaire with open-ended questions about barrier methods. A qualitative methodology that considered the main techniques of grounded theory for data analysis was used. Results: There are individual, interpersonal, sociocultural, and structural factors that operate as obstacles and facilitators for the use of barrier methods to prevent the transmission of HIV/AIDS. CONCLUSIONS: There are culturally embedded beliefs among young people, such as, a perception of invulnerability caused by not being part of risk groups, among others, that affect self-care.

Procuramiento y uso de aloinjertos cutáneos de piel total criopreservados obtenidos de pacientes sometidas a abdominoplastía / Procurement and use of cryopreserved whole skin cutaneous allografts obtained from patients undergoing abdominoplasty

Resumen Introducción: Los aloinjerto cutáneos (AC) son excelentes sustitutos cutáneos temporales, sin embargo, la donación y procura de piel cadavérica, fuente habitual de AC, es baja. Objetivo: Evaluar la factibilidad de utilizar la piel proveniente de abdominoplastías como fuente de AC y su eficacia clínica. Materiales y Método: Entre el 17 de agosto de 2020 al 28 de febrero de 2021 se analizó una cohorte prospectiva de 14 pacientes femeninas sometidas a abdominoplastía por motivos estéticos, que aceptaron donar la piel del colgajo cutáneo abdominal redundante, la cual fue criopreservada. Se utilizaron los AC de piel total criopreservados (ACPTC) en 10 pacientes con diagnósticos de: pie diabético (4), laparostomía contenida (2) herida compleja extremidad inferior (2), sarcoma de cuero cabelludo recidivado (1) y melanoma (1). Resultados: Se obtuvieron 14 colgajos de piel total, los cuales fueron procesados obteniendo una superficie promedio de 302 cm2 y 8,3 láminas de distintos tamaños de utilidad clínica por paciente. En todos los pacientes en que se utilizó ACPTC hubo un prendimiento inicial del AC para posteriormente, en promedio 21 días, presentar una escara necrótica que al ser retirada presentaba un tejido vital adherido al receptor rico en fibroblastos, siendo algunos pacientes auto injertados y otros manejados con cicatrización por segunda intención como tratamiento definitivo. Discusión: Los ACPTC proporcionan una cobertura intermedia, pues una parte se integra en forma definitiva, actuando como un andamiaje biológico para la formación de una interfase sobre la cual se puede autoinjertar o dejar evolucionar con cicatrización por segunda intención y una parte es rechazada. Conclusión: La procura de piel de donante vivo, en pacientes sometidos a cirugías de contorno corporal es un proceso factible, fuente de ACPTC, los cuales permiten una nueva cobertura intermedia con múltiples aplicaciones clínicas.

Introduction: Skin allografts (SA) are outstanding temporary skin substitutes; however, cadaveric skin donation and procurement, a common source of SA, remains low. Aim: To evaluate the feasibility and clinical efficacy of using skin from abdominoplasties as a source of SA. Materials and Method: A prospective cohort was analyzed from August 17th, 2020 and February 28th, 2021, with 14 female patients submitted to abdominoplasty surgeries for aesthetic motives, who authorized skin donation from the redundant abdominal flap which was posteriorly cryopreserved. Cryopreserved total skin allografts (CTSA) was used in 10 patients with the following diagnoses: diabetic foot (4), contained laparostomy (2) complex wound of the lower limb (2), relapsing sarcoma of the scalp (1), and melanoma (1). Results: 14 CTSA were obtained, which were processed, obtaining an average area of 302 cm2 and 8.3 sheets of different sizes and clinical applications from each patient. In all patients who received CTSA, an initial attachment was observed, followed by the appearance of a necrotic scar in an average of21 days. The peeling of the latter revealed a vital tissue tightly adhered to the receptor and rich in fibroblasts. Some of the patients received autografts, and others were managed with secondary intention scarring as a definite treatment. Discussion: CTSA provide an intermediate coverage since one part is definitely adhered to, acting as a biologic scaffolding for the formation of an interface that can be autografted or left for a secondary intention scarring, and the host rejects the other portion. Conclusión: skin procurement from a living donor in patients submitted to body contour surgeries is a feasible process and significant source of CTSA, which permits a new intermediate coverage with multiple clinical uses.

Densidad de APE en pacientes PI-RADS 3: un parámetro clínico útil para su manejo / PSA density as a new approach for PIRADS 3 patient's management

Resumen: Objetivo: Analizar las biopsias realizadas en paciente categorizados PIRADS 3 en nuestra institución desde el segundo semestre del año 2016 al primer semestre del año 2018 y describir la correlación de la densidad de PSA con la incidencia de cáncer de próstata. Evaluar el rol de la densidad de PSA en la indicación de estudio histológico en pacientes PIRADS 3. Método: Trabajo autorizado por el comité de ética de nuestra institución. Se realizó búsqueda en el PACs, de todos los informes de RM multiparamétricas de próstata que incluyeran la categoría ¨PIRADS 3¨ en el periodo señalado. De ellos se calculó la densidad de PSA, con el último valor de PSA registrado en la ficha clínica previo a RM y volumen prostático en RM. Se procedió a buscar los pacientes con estudio histológico. Se correlacionó los resultados de biopsias con el valor de densidad de PSA. Realizamos análisis uni y multivariados, análisis estadísticos con sensibilidad, especificidad y uso de curva ROC. Resultados: De las 2416 RMmp de próstata realizadas en nuestra institución en las fechas ya descritas, se encontraron 424 informes catalogados con score PIRADS 3, y 267 de esos pacientes tenían estudio y seguimiento institucional, de los cuales 134 contaban con biopsia. La muestra tenía un promedio de edad de 60 años, y una mediana de densidad de PSA de 0,10 (RIC 0,07-0,14). Se encontraron 36 biopsias con cáncer clínicamente significativo (Gleason > 6), lo que corresponde a 26,8% de la muestra, valor similar al encontrado en la literuatua. En estos pacientes se obtuvo un punto de corte óptimo de densidad de PSA de 0,11, con una sensibilidad y especificidad de 67% y un AUC de 0,68. Una densidad de PSA de 0,11 presenta un OR de 4,1, con una probabilidad de 4 veces más de encontrar un cáncer de próstata por sobre este valor (IC 95% 1,3-9,8), lo cuál es estadísticamente significativo con un p igual a 0,01. Conclusión: La DAPE sobre 0,11 ng/ml/cc puede considerarse como una herramienta adicional para indicar biopsia en pacientes con RMmp PI-RADS 3, aumentando la precisión para la detección de cáncer de próstata clínicamente significativos ayudando a disminuir estudios histológicos innecesarios.

Abstract: Objective: To analyze the biopsies performed in patients categorized PIRADS 3 in our institution from the second half of 2016 to the first half of 2018 and describe the correlation of PSA density with the incidence of prostate cancer. To evaluate the role of PSA density in the indication of histological study in PIRADS 3 patients. Method: Work authorized by the ethics committee of our institution. The PACs were searched for all multiparameter prostate MRI reports that included the category "PIRADS 3" in the period indicated. The PSA density was calculated, with the last PSA value recorded in the clinical record before MRI and prostate volume in MRI. We proceeded to look for patients with the histological study. The biopsy results were correlated with the PSA density value. We perform uni and multivariate analyzes, statistical analyzes with sensitivity, specificity and use of the ROC curve. Results: Of the 2416 RMmp of the prostate performed in our institution on the dates already described, 424 reports catalogued with PIRADS 3 score were found, and 267 of those patients had study and institutional follow-up, of which 134 had a biopsy. The sample had an average age of 60 years and a median PSA density of 0.10 (RIC 0.075-0.146). We found 36 biopsies with clinically significant cancer (Gleason> 6), which corresponds to 26.8% of the sample, a value similar to that found in the literature. In these patients, an optimal cut-off point of PSA density of 0.11 was obtained, with a sensitivity and specificity of 67% and an AUC of 0.68. A PSA density of 0.11 has an OR of 4.1, with a 4-fold probability of finding prostate cancer above this value (95% CI 1.3-9.8), which It is statistically significant with a p equal to 0.01. Conclusion: DAPE over 0.11 ng/ml/cc can be considered as an additional tool to indicate biopsy in patients with RMmp PI-RADS 3, increasing the accuracy for the detection of clinically significant prostate cancer helping to reduce unnecessary histological studies.

Características clínicas de los pacientes con apneas obstructivas del sueño: diferencias según género / Clinical features in patients with obstructive sleep apnea syndrome: differences by gender

INTRODUCCIÓN: El síndrome de apnea obstructiva del sueño (SAHOS) es más prevalente en hombres, los estudios poblacionales muestran una relación de 2:1, sin embargo, en los estudios clínicos la frecuencia llega a ser de hasta de 6:1. Estas diferencias en el ambiente clínico puede ser consecuencia de variaciones en el reporte de síntomas en hombres comparados con mujeres. OBJETIVO: Evaluar las diferencias de género en la presentación clínica de apnea obstructiva de sueño. Pacientes: Estudio transversal de pacientes sometidos a una poligrafía respiratoria (PR) con sospecha clínica de SAHOS. Se recolectaron datos demográficos, antropométricos, comorbilidades y las variables de la PR. Se realizó estudio t de student, Mann-Whitney y chi-cuadrado según correspondiera. RESULTADOS: Se incluyeron 1.044 pacientes: edad promedio 53,2 ± 14 años, 76% hombres. Las mujeres con SAHOS poseen mayor IMC (32,2 ± 6,1 vs 30,8 ± 5,0; p=0,002) y edad (61,4 ± 12,2 vs 52,6 ± 13,9; p < 0,001), pero menor circunferencia de cuello (CC) (38,1 ± 3,6 vs 43,2 ± 3,3; p < 0,001), además, presentan menor IA/H y menor duración de las apneas. No hubo diferencias en los síntomas clásicos de apneas presenciada y somnolencia diurna, sin embargo, describen más frecuentemente insomnio, cefalea matinal, depresión y uso de fármacos hipnóticos. CONCLUSIONES: Las mujeres al momento del diagnóstico son de mayor edad y más obesas, aunque presentan una CC menor, presentan una enfermedad más leve, pero refieren más fatiga, cansancio, cefalea e insomnio. Debemos estar alerta en la presentación clínica diferente de las mujeres para mejorar la sospecha diagnóstica.

INTRODUCTION: Obstructive sleep apnea (OSA) is more prevalent in men, population studies show a ratio of 2:1, however in clinical studies the frequency is as high as 6:1. These differences in the clinical setting may be a consequence of variations in the reporting of symptoms in men compared to women. OBJECTIVE: To evaluate gender differences between women and men with recent diagnosis of OSA. Patients: A cross-sectional, study of patients undergoing home sleep apnea testing (HSAT) with clinical suspicion of OSA. Demographic, anthropometric, comorbidities and HSAT variables were collected. We performed t student analysis, Mann-Whitney test or chi square test as appropriate. RESULTS: 1,044 patients were included: mean age 53.2 ± 14 years, 76% men. Women with OSA have a higher BMI (32.2 ± 6.1 vs 30.8 ± 5.0, p = 0.002), were older (61.4 ± 12.2 vs 52.6 ± 13.9, p <0.001), but have a lower neck circumference (NC) (38.1 ± 3.6 vs. 43.2 ± 3.3, p <0.001). The women presented lower AHI and shorter duration of apneas. Although the classic symptoms of apnea and daytime sleepiness showed no differences, women reported more frequently insomnia, morning headache, depression and use of hypnotic drugs. CONCLUSIONS:: Clinical differences between gender are present at time of diagnosis. Woman are older and more obese, although they have a lower NC. They have a milder disease, but they refer to be more tired, headache, insomnia and depression. We must be alert in the different clinical presentation of women to improve the diagnostic suspicion.

Mini-percoll gradient may be used for frozen-thawed sperm selection in sheep / Gradiente de mini-Percoll pode ser utilizado na seleção espermática de sêmen congelado de ovinos

This study evaluated the effect of increasing centrifugal force and reducing centrifugation time and volume in Percoll protocols on ram sperm parameters. Commercial semen of Santa Inês rams were used and five treatments were performed: traditional Percoll and mini-Percoll (MP) techniques (I- 5000 x g, 5min; II- 2500 x g, 5min; III- 1250 x g, 5min; IV- 700 x g, 10min). At post-thawing (PT) and post-selection protocols (0h), samples were assessed for spermatozoa recovery rate, motility, plasma membrane (PM) integrity, sperm capacitation and morphology and incubated at 37 C for 1, 2 and 3h. The sperm recovery rate averaged 9.1±1.4%, and most motility parameters were similar (P> 0.05) among protocols. VCL (µm/s) was higher (P< 0.05) after MP-II, III and IV (66.1±4.5) than traditional Percoll (46.3±4.9). Capacitation status and PM integrity were similar (P> 0.05) among treatments. For the first time, we have demonstrated the reduction of the gradient volume and centrifugation time associated with an increase on centrifugation force at Percoll can be successfully used for frozen-thawed ram sperm selection. MP may be used instead of traditional Percoll, decreasing costs and semen handling time.(AU)

O presente estudo avaliou o efeito do aumento da força de centrifugação, bem como da redução do tempo de centrifugação e do volume do gradiente de Percoll em diferentes protocolos nos parâmetros espermáticos de ovinos. Foi utilizado sêmen comercial de carneiros da raça Santa Inês, e cinco tratamentos foram realizados: Percoll tradicional e quatro técnicas de mini-Percoll (I- 5000 x g, 5min; II- 2500 x g, 5min; III- 1250 x g, 5min; IV- 700 x g, 10min). Após o descongelamento e a seleção espermática em cada técnica utilizada (0h), amostras foram avaliadas quanto à taxa de recuperação espermática, motilidade, integridade de membrana plasmática, capacitação e morfologia. Ao final, foram incubadas a 37 ºC por uma, duas e três horas. A taxa de recuperação média (9,1±1,4%) e a maioria dos parâmetros de motilidade foram similares (P>0,05) entre os tratamentos. VCL foi maior (P<0,05) após MP-II, III e IV (66,1±4,5) quando comparados ao Percoll tradicional (46,3±4,9). O status da capacitação e a integridade de membrana foram similares (P>0,05) entre os tratamentos. Pela primeira vez, foi demonstrado que a redução do volume do gradiente utilizado e do tempo de centrifugação, associada com o aumento da força de centrifugação nos protocolos de Percoll, pode ser usada com sucesso na seleção espermática de sêmen congelado de ovinos. O mini-Percoll pode ser utilizado em alternativa à técnica de Percoll tradicional, diminuindo custos e tempo de manipulação do sêmen durante a técnica.(AU)

Chikungunya: educación y prevención como pilares fundamentales para enfermedad sin cura / Chikungunya: education and prevention as fundamental support for disease without cure

Chikungunya virus is an alphavirus, member of the Togaviridae family, first discovered in Africa in 1952. Since then it caused sporadic outbreaks in Africa and Asia, but since 2000, outbreaks had been more frequent, being identified in Europe, America and the Caribbean. Chikungunya virus can cause chronic and incapacitating arthralgia, with an important morbidity, being considered as a relevant re-emerging public health problem. This review intends to update our knowledge in epidemiology, transmission, pathogenesis, treatment and vaccination strategies of Chikungunya virus. (AU)

RSV infection in a macrophage-cell line activates the non-canonical NF-κB pathway and induces pro-inflammatory cytokine expression.

Respiratory syncytial virus (RSV) is a highly prevalent infectious agent that causes severe respiratory tract illnesses in infants and children worldwide. Children who have suffered severe RSV infections during infancy are prone to develop recurrent episodes of wheezing and asthma that may be associated with viral persistence. RSV infections in humans and animal models are characterized by extensive inflammatory responses. Epithelial cell lines acutely infected by RSV have shown activation of the NF-κB signaling through two independent pathways: the canonical pathway, mediated by RelA and p50 subunits, and the non-canonical pathway, mediated by the subunits RelB and p52. Herein, we investigated the state of activation of the canonical and non-canonical NF-κB signaling pathways in macrophages either acutely or persistently infected by RSV and examined the expression of pro-inflammatory mediators. Activation of NF-κB subunits was analyzed through Western blot assays using acutely RSV-infected epithelial cells as a control. The expression levels of two pro-inflammatory cytokines and a chemokine were determined by quantitative RT-PCR and through immunobead assays. The results showed that p52 was abundant during acute and persistent RSV infection, indicating that macrophages predominantly activate the non-canonical pathway. We also observed activation of IL-1ß, TNF-α and CCL5/RANTES transcription, though at higher levels in persistently infected macrophages than in acutely infected macrophages. In contrast, the protein levels of these cytokines/chemokine did not correlate with their mRNA transcription, as quantitation displayed higher levels during acute infection than in persistent infection, suggesting post-transcriptional regulation by RSV persistence.

Percepción de escolares chilenos de distinto nivel socioeconómico sobre la regulación de la publicidad de alimentos / Perception of Chilean schoolchildren from different socioeconomic status on food advertising regulation

El objetivo del estudio fue analizar la percepción de escolares de 8 a 12 años, de ambos sexos, distinto nivel socioeconómico (NSE) y estado nutricional, sobre la regulación de la publicidad de alimentos y bebidas azucaradas. En un estudio de corte transversal, se aplicó una encuesta previamente validada a 812 escolares (399 niños y 413 niñas) de NSE alto y bajo en 3 ciudades del país. Los datos se analizaron según NSE y estado nutricional. La obesidad fue más prevalente en los niños de NSE bajo, quienes veían más comerciales de alimentos y bebidas en televisión y los de NSE alto en Internet y celulares. Sobre el 65% de los escolares en ambos NSE llevaba dinero para comprar alimentos en el horario escolar. En los primeros meses de entrada en vigencia de la Ley 20.606, el 80% de los niños indicaron que les gustaba ser informados de lo que contenían los alimentos y los sellos Alto en Calorías, Alto en Grasas Saturadas y Alto en Sodio fueron significativamente más importantes para los de NSE alto. El sello Alto en Azúcares fue igualmente importante en ambos NSE. Estos resultados permitirán apoyar intervenciones de educación en nutrición y marketing social que motiven la alimentación saludable en niños, padres y profesores(AU)

The objective of this study was to analyze the perception of schoolchildren, 8 to 12 years, both sex, of different socioeconomic status (SES) and nutritional status, on food and sugary beverages advertising regulation. A cross-sectional study that used a previously validated survey to 812 schoolchildren (399 boys and 413 girls) of high and low SES in 3 Chilean cities was performed. The data was analyzed according to NSE and nutritional status. Obesity was more prevalent in low-SES children. These children watched significantly more food and beverages TV ads while high SES children do it more through Internet and cell phones. Over 65% of children of both SES brought money to school to buy food. In the first months after the 20.606 Law was implemented, 80% of the children indicated that they like to be informed on food content. On the other hand, the symbols "High in Calories", "High in Saturated Fats", and "High in Sodium", were significantly more relevant for children of high SES. The symbol "High in Sugars" was equally important for children of both SES. These results will support the design of nutrition education and social marketing interventions that promote healthy eating in children, parents and teachers(AU)

Utilidad del score PI-RADS 2 en la práctica clínica ¿Se justifica el estudio histológico? / PI-RADS 2 Score utility in clinical practice ¿Is histologic asses justified?

Resumen: Objetivo: Evaluar los resultados de estudios histológicos y si estos se justifican en pacientes categorizados como PI-RADS 2. Materiales y métodos: Se realizó una búsqueda en el PACS de nuestra institución de todos los informes de RM de próstata que incluyeran categoría "PI-RADS 2" entre enero del 2015 y junio del 2017, identificando 1287 informes. Resultados: De los 1287 informes PI-RADS 2, 646 pacientes fueron controlados posterior a la RM en nuestra institución. De ellos, 91 (14,08%) tuvieron un estudio histológico. Se encontraron 10 casos (10,98%) de cáncer prostático (6 con score de Gleason 6, y 4 score de Gleason 7). Conclusión: En nuestro estudio la RM score PI-RADS 2 descartó correctamente neoplasia clínicamente significativa en el 95,6% de los casos. Dar a conocer esta información podría tener un impacto en la conducta del tratante, disminuyendo el número de biopsias prostáticas.

Abstract: Objective: To evaluate the results of histological studies and if these are justified in patients categorized as PI-RADS 2. Materials and methods: A search was made in the PACS of our institution of all prostate MRI reports that included category "PI-RADS 2" between January 2015 and June 2017, identifying 1287 reports. Results: Of the 1287 PI-RADS 2 reports, 646 patients were monitored after the MRI in our institution. Of these, 91 (14.08%) had an histological study. We found 10 cases (10.98%) of prostate cancer (6 with Gleason score 6, and 4 Gleason score 7). Conclusion: In our study, the MR PI-RADS 2 score correctly ruled out clinically significant neoplasia in 95.6% of cases. Making this information known could have an impact on the doctor's course of action, decreasing the number of prostate biopsies.

Occurrence and environmental impact of pharmaceutical residues from conventional and natural wastewater treatment plants in Gran Canaria (Spain).

The presence and fate of pharmaceutical residues in environmental samples are of great interest. There is a vast number of studies published regarding their input, presence, effects and risks in ecosystems. Moreover, it has been demonstrated that the primary source of input of these contaminants in the environment is from Wastewater Treatment Plants (WWTPs). It is therefore essential to evaluate the efficiency of commonly used treatments and the necessity of applying novel purification processes in order to eliminate or reduce the concentration of pharmaceuticals from wastewater or from the effluent of WWTPs. The aim of this work was to quantify twenty-three pharmaceutical compounds in the aqueous phase at different stages of a conventional and a natural WWTP situated in Gran Canaria (Spain). The results indicate concentration levels in the range of 0.004±0.001 to 59.2±11.7µgL-1 and 0.018±0.001 to 148±14.7µgL-1 from conventional and natural WWTPs, respectively. Better efficiency was, however, offered by the conventional WWTP with a removal median of 99.7%. In addition, the impact on different aquatic organisms (algae, daphnids and fish) was assessed in terms of risk quotients. The results reveal a possible highly harmful effect towards organisms by gemfibrozil, ibuprofen and ofloxacin.

Simplified solid-phase extraction procedure combined with liquid chromatography tandem-mass spectrometry for multiresidue assessment of pharmaceutical compounds in environmental liquid samples.

To follow the twelve "green analytical chemistry" (GAC) principles, it is necessary to continuously develop analytical extraction and determination methodologies to assess the presence of micropollutants, such as pharmaceuticals, in environmental samples. A reduction in the analysis time and solvent quantity, which is one of the GAC principles, has been achieved through a simplified solid-phase extraction (SPE) procedure combined with high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the determination of twenty-three pharmaceuticals in liquid environmental samples using N-vinylpyrrolidone-divinylbenzene copolymer (OASIS HLB) cartridges. The optimal SPE conditions were studied. In these optimized conditions, 82.6% of the data have a median recovery above 70% for all compounds in each sample. The relative standard deviations (RSDs) were below 14.4% and 22.0% for intra- and inter-day repeatability, respectively. Method detection limits (MDLs) and method quantification limits (MQLs) ranged from 0.011 to 188ngL-1 and from 0.033 to 628ngL-1, respectively. The applicability of the method was evaluated in real samples from natural and conventional wastewater treatment plants (WWTPs), and results were obtained in concentration ranges from 0.013 to 91.5µgL-1 and from 0.004 to 49.1µgL-1, respectively.

Virus Zika: epidemiología, manifestaciones clínicas y prevención / Zika virus: epidemiology, clinical manifestations and prevention

Zika virus is an arbovirus that was first discovered in Africa in 1947. Until some time ago, it was an unnoticed emergent virus, due to its low epidemiological impact and its mild flu-like symptoms. However, from 2007 on, Zika virus started to propagate throughout the world and was first locally transmitted in America in 2015. Since then, autochthonous cases of Zika infection have been reported on 33 countries of the Americas. The most relevant impact of the Zika virus outspread is its supposed link to the increase in birth defects and microcephaly in newborns in regions with high Zika virus infection incidence during the past two years. Therefore, the World Health Organization declared Zika virus a public health emergency of international concern. This review describes Zika virus epidemiology, transmission mechanisms and pathogeny, such as its clinical presentation, adverse fetal outcomes, diagnosis, treatment and current recommendations for transmission prevention.

Donor characteristics that are associated with survival in liver transplant recipients older than 70 years with grafts.

INTRODUCTION: The use of grafts from donors older than 70 years of age is increasing due to the decrease in the number of donors and the increase in waiting list patients. MATERIAL AND METHODS: We undertook a univariate and multivariate analysis of 980 adult recipients of whole liver grafts, 129 of them from donors aged 70 years or older. RESULTS: No differences were found in patient survival compared with recipients of younger grafts. There were no higher rates of rejection, vascular or biliary complications, postoperative bleeding, or infections, but older grafts were associated with graft dysfunction (P = .01) and a higher frequency of postoperative refractory ascites (P = .007), but without a greater need for retransplantation. As graft-associated factors, the joint presence in the donor of diabetes (P = .00; confidence interval [CI] = 0.04-0.117), hypertension (P = .00; CI = 0.22-0.39), and weight of more than 90 kg (P = .031; CI = 0.05-0.104) were suggestive of poor prognostic factors in recipient survival. Survival in hepatitis C virus (HCV) recipients or recipients aged older than 60 years was worse with donors aged older than 70 years, although not significantly so. With grafts from donors aged older than 80 years (n = 15), although patient survival rate was good (70% at 10 years), there was a higher rate of retransplantation (20%) and the early mortality rate was 13.3%. CONCLUSIONS: Use of grafts from donors aged older than 70 years is safe, with similar survival to patients with younger grafts. The appearance of initial dysfunction with prolonged ascites may be due to a delay in reaching a correct functionality, but was not associated with increased mortality, complications, or need for retransplantation. It should also be avoided in recipients older than 60 years or with HCV. Grafts older than 80 years were associated with a good long-term patient survival but at the expense of a higher rate of retransplantation. However, it helps to reduce the time on the waiting list and, thus, mortality. We noted decreased survival associated with donor hypertension, diabetes, and obesity, so these donors should be selected more rigorously.

Intervención en alimentación y nutrición para mineros con factores de riesgo cardiovascular, basada en la investigación formativa / Food and nutrition intervention for miners with cardiovascular risk factors, based on formative research

We designed and implemented an intervention to improve the diet of 94 miners with cardiovascular risk of a mining company. The diagnosis included a qualitative study of the desires, motivations and barriers that workers have to lead a healthy life, a survey of food consumption and checking the institutional food service. Anthropometric and biochemical data were provided by the company. Based on the results, the intervention included improving the supply of healthy foods and conducting the communication campaign "Minero 100% Filete", workshops and nutritional counseling for them and their families. After 8 months of intervention we found a significant increase in the consumption of fruits and vegetables and a decreased consumption of fried, cured and red meats. There was no significant change in BMI. However, there were significant decreases in systolic blood pressure, blood glucose levels, triglycerides and an increase in HDL cholesterol. Although the program was well received by the workers, it is acknowledged that there are significant adverse factors which merit improvement.

Se diseñó e implementó una intervención de 8 meses para mejorar la alimentación de 94 mineros con factores de riesgo cardiovascular. El diagnóstico incluyó un estudio cualitativo de los deseos, motivaciones y barreras de los trabajadores, una encuesta de consumo de alimentos y la revisión del aporte de la alimentación institucional. Los datos antropométricos y bioquímicos fueron proporcionados por la compañía minera. Con esta base, se solicitó mejorar la oferta de alimentos saludables y se realizó la campaña comunicacional "Minero 100% Filete", consejería nutricional, y talleres con las familias. Al finalizar la intervención se observó un aumento significativo del consumo de frutas y verduras y una disminución del consumo de frituras, cecinas y carnes rojas. No hubo cambios significativos en el IMC. Se registraron disminuciones significativas en la presión arterial sistólica, glicemia, triglicéridos y un aumento del colesterol HDL. El programa fue bien aceptado por los trabajadores, pero se reconocen factores ambientales adversos importantes de mejorar.

Proceso de formulación y validación de las guías alimentarias para la población chilena / Development and validation process of food-based dietary guidelines for the chilean population

The Food Based Dietary Guidelines (FBDG) are educational tools that help people to select appropriate foods for good nutrition and health. Most countries have FBDG's, but its dissemination and implementation have shown weaknesses. This paper presents the development process and validation of the 2012 FBDG for the Chilean population. The latest scientific evidence was reviewed and new messages were validated with METAPLAN, a qualitative-quantitative method for problem analysis applied to information gathered with 48 focus groups from Arica, Santiago and Chillán-Concepción. The messages promote consumption of healthy foods, focusing on critical nutrients (sugar, saturated fats, sodium) and energy intake reduction. Final version of the messages considered comments and suggestions from participants and from two expert panels. Its implementation should include promotion strategies that involve the Ministry of Health, Education, Agriculture, universities, industry and mass media, in order to achieve changes in feeding behavior in the most vulnerable segments of the Chilean population.

Las Guías Alimentarias Basadas en Alimentos (GABA), son instrumentos educativos que ayudan a la población a seleccionar alimentos apropiados para una buena nutrición y salud. La mayoría de los países tienen GABA, pero su difusión e implementación presentan grandes debilidades. Se presenta el proceso para la formulación y validación de las GABA 2012 para la población chilena. Se revisó la evidencia científica reciente y se validaron los mensajes con el Metaplán, método para el análisis de problemas, con 48 grupos focales en Arica, Santiago y Chillán-Concepción. Los mensajes promueven el consumo de alimentos saludables, un menor consumo de energía y de nutrientes críticos. En los mensajes definitivos se incorporó los comentarios y sugerencias de los participantes y de 2 paneles de expertos. Su implementación debería incorporar estrategias de promoción de los Ministerios de Salud, Educación, Agricultura, universidades, la industria y los medios masivos, para lograr cambios en el comportamiento alimentario de los segmentos más vulnerables de la población chilena.

Natural therapies assessment for the treatment of endometriosis.

STUDY QUESTION: Can resveratrol and epigallocatechin-3-gallate (EGCG) inhibit the growth and survival of endometriotic-like lesions in vivo in a BALB/c model of endometriosis, and in vitro in primary cultures of human endometrial epithelial cells (EECs)? SUMMARY ANSWER: Resveratrol and EGCG exerted a potent inhibitory effect on the development of endometriosis in a BALB/c murine model and on the survival of EECs. WHAT IS KNOWN ALREADY: Endometriosis is a common condition associated with infertility and pelvic pain in women of reproductive age. Resveratrol and EGCG are two polyphenols with anticarcinogenic and antioxidant properties that have been proposed as natural therapies to treat endometriosis. STUDY DESIGN, SIZE, DURATION: Fifty-six 2-month-old female BALB/c mice underwent surgical induction of endometriosis. Treatments with resveratrol or EGCG started 15 days post-surgery and continued for 4 weeks. Human biopsies were taken with a metal Novak curette from the posterior uterine wall from 16 patients with untreated endometriosis and 15 controls who underwent diagnostic laparoscopy for infertility. MATERIALS, SETTING, METHODS: After the treatments, animals were sacrificed and lesions were counted, measured, excised and fixed. Immunohistochemistry for proliferating cell nuclear antigen and CD34 was performed for cell proliferation and vascularization assessment in the lesions. The terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) technique was performed for apoptosis evaluation. Peritoneal fluid was collected to analyze vascular endothelial growth factor levels. Human EECs were purified from proliferative-phase endometrial biopsies and cultured. The effect of both polyphenols on cell proliferation was determined by a colorimetric assay using the CellTiter 96®AQueous One Solution Cell Proliferation Assay kit and on apoptosis by the TUNEL technique, using an In Situ Cell Death Detection Kit with Fluorescein. MAIN RESULTS: In the mouse model, both treatments significantly reduced the mean number (P < 0.05 versus control) and the volume of established lesions (P < 0.05 versus control). Treatments consistently statistically significantly diminished cell proliferation (resveratrol P < 0.01 and EGCG P < 0.05, versus control), reduced vascular density (resveratrol P < 0.01 and EGCG P < 0.001, versus control) and increased apoptosis within the lesions (resveratrol P < 0.01 and EGCG P < 0.05, versus control). Both compounds induced reduction in human EEC proliferation (P < 0.05 versus basal) and increased apoptosis (P < 0.05 versus basal) in primary cultures. LIMITATIONS: In vitro studies were only carried out in epithelial cells from human eutopic endometrium. WIDER IMPLICATIONS OF THE FINDINGS: The present findings are promising and will assist the development of novel natural treatments for endometriosis. STUDY FUNDING: This study was supported by ANPCYT (PICT 6384 BID 1201 OC-AR) and CONICET (PIP 5471), Argentina. None of the authors has any conflict of interest to declare.