Profile of retinal pigment epithelium response to ethanol: Role of CYP2E1

El epitelio pigmentario de la retina (RPE) es esencial para la visión. Como parte de la barrera hematorretiniana (BRB) su papel principal es el mantenimiento de la homeostasis de la retina y coroides. El alcohol se ha convertido en la droga adictiva más aceptada por la sociedad causando problemas de salud, sociales y económicos. El estrés oxidativo (OS) inducido por etanol (EtOH) genera toxicidad celular aumentando la aparición de especies reactivas del oxígeno (ROS) que activan respuestas en el organismo como pueden ser inflamación y muerte celular. El enzima citocromo p450 2E1 (CYP2E1) tiene una alta afinidad por el EtOH. Su actividad es la principal fuente de ROS durante la oxidación del EtOH por las células. A pesar de que el CYP2E1 ha sido identificado en el RPE humano y que podría jugar un papel fundamental en la función del ciclo visual del RPE, no se conoce nada sobre su regulación y la respuesta celular que desencadena. Nuestro objetivo fue estudiar el rol del CYP2E1 en el RPE, en respuesta al tratamiento con EtOH. Fueron empleadas células ARPE-19, hRPE y hiPSC-RPE como modelos de RPE. Simultáneamente al EtOH, se realizaron tratamientos con DAS (inhibidor específico del CYP2E1) y con NAC (como antioxidante) para bloquear el efecto del EtOH en las células. Se realizaron estudios de viabilidad y citotoxicidad con EthD-1, calcein y XTT. El ROS intracelular y los aniones superóxido fueron cuantificados usando sondas fluorescentes (DCF y DHE respectivamente). Los marcadores de estrés celular, angiogénesis e inflamación fueron determinados con kits de expresión proteica. La integridad de la función de la barrera formada por el RPE se determinó midiendo la resistencia eléctrica transepitelial (TER) y el estado de las uniones intercelulares por inmunofluorescencia (IF). Se utilizaron western blot (WB), qPCR, IF y ELISA para cuantificar la expresión del CYP2E1 y los principales factores y moléculas liberadas por el RPE. La actividad del CYP2E se midió mediante HPLC. El EtOH aumentó los niveles ROS en las células del RPE, dando lugar a la muerte celular por apoptosis. Provocó una disfunción del RPE disminuyendo la integridad de las uniones intercelulares y modificando el perfil de expresión y liberación de factores de crecimiento, inflamación y angiogénesis. El EtOH aumentó la expresión del CYP2E1. El uso de DAS y NAC revirtió el daño causado en la células del RPE revelando que el CYP2E1 en el RPE estaría regulado por el OS. Finalmente, la presencia del CYP2E1 refuerza el papel protector del RPE y sugiere otros roles diferentes del CYP2E1 relacionados con la degeneración del RPE.Generalitat ValencianaUniversidad Católica de Valencia San Vicente MártirMedicinaCiencias de la Salu

Exploring the Human-Nipah Virus Protein-Protein Interactome

Nipah virus is an emerging, highly pathogenic, zoonotic virus of the Paramyxoviridae family. Human transmission occurs by close contact with infected animals, the consumption of contaminated food, or, occasionally, via other infected individuals. Currently, we lack therapeutic or prophylactic treatments for Nipah virus. To develop these agents we must now improve our understanding of the host-virus interactions that underpin a productive infection. This aim led us to perform the present work, in which we identified 101 human-Nipah virus protein-protein interactions (PPIs), most of which (88) are novel. This data set provides a comprehensive view of the host complexes that are manipulated by viral proteins. Host targets include the PRP19 complex and the microRNA (miRNA) processing machinery. Furthermore, we explored the biologic consequences of the interaction with the PRP19 complex and found that the Nipah virus W protein is capable of altering p53 control and gene expression. We anticipate that these data will help in guiding the development of novel interventional strategies to counter this emerging viral threat

Tratamientos innovadores utilizados en el manejo de las heridas crónicas

RESUMENIntroducción: Del tipo de tratamiento y la eficacia del mismo depende la evolución y la mejora en la calidad de vida del paciente con heridas crónicas; existen diversos tratamientos para las heridas crónicas de acuerdo con el tipo de lesión, la duración del tratamiento y los factores individuales del paciente. Los diversos tratamientos innovadores demuestran resultados favorables en cuanto a la reducción del tiempo y el tamaño de las heridas crónicas. Este artículo tiene como objetivo describir los tratamientos innovadores utilizados en el manejo de las heridas crónicas, de uso poco frecuente en las clínicas de heridas. Metodología: revisión de la literatura estructurada en tres fases: recolección de artículos en bases de datos como Scopus, Pubmed, Dialnet, Ebscohots, y Elsevier; uso de palabras clave como pie diabético, herida crónica y úlcera por presión; revisión y clasificación de 50 artículos en idioma español, inglés y portugués. Resultados: se registraron 12 tratamientos innovadores para el manejo de las heridas cónicas, cada uno con evidencia científica de su utilidad en los distintos tipos de heridas crónicas. Conclusión: conocer nuevos tratamientos ayuda al enfermero a ampliar las opciones de intervención, presentar alternativas de tratamiento de menor costo, o más rápida dependiendo del tipo de herida y la condición del paciente.PALABRAS CLAVE: Úlcera de la Pierna, pie diabético, úlcera por presión.INNOVATIVE TREATMENTS USED IN THE HANDLING OF CHRONIC WOUNDSABSTRACTIntroduction: The type of treatment and its efficacy depends on the evolution and the improvement of the quality of life of the patient with chronic wounds; diverse treatments exist for chronic wounds according to the type of injury, duration of the treatment, and the individual factors of the patient. The diverse innovative treatments demonstrate favorable results in terms of reduction of time and size of chronic wounds. This article has as its objective to describe the innovative treatments used in the handling of chronic wounds, of infrequent use in wound care centers. Methodology: review of the structured literature in three phases: recollection of articles in databases such as Scopus, Pubmed, Dialnet, Ebscohots, and Elsevier; use of keywords such as diabetic foot, chronic wound, and pressure ulcer; review and classification of 50 articles in Spanish, English, and Portuguese. Results: 12 innovative treatments were registered for the handling of chronic wounds, each one with scientific evidence of their utility in the different types of chronic wounds. Conclusion: determine new treatments helps the nurse to extent the intervention options, and present treatment alternatives of lower cost or faster treatment depending on the type of wound and the condition of the patient.KEYWORDS: Leg ulcer, diabetic foot, pressure ulcerTRATAMENTOS INOVADORES UTILIZADOS NO MANEJO DAS FERIDAS CRÓNICASRESUMO Introdução: Do tipo de tratamento e da eficácia do mesmo depende a evolução e a melhora na qualidade de vida do paciente com feridas crónicas; existem   diversos tratamentos para as feridas crónicas de acordo ao tipo de lesão, à duração do tratamento, e aos fatores individuais do paciente. Os diversos tratamentos inovadores demostram resultados favoráveis em quanto à redução do tempo e o tamanho das feridas crónicas. Este artigo tem como objetivo descrever os tratamentos inovadores utilizados no manejo das feridas crónicas, de uso pouco frequente nas clínicas de feridas. Metodologia: revisão da literatura estruturada em três fases: recolecção de artigos em bases de dados como Scopus, Pubmed, Dialnet, Ebscohots e Elsevier; uso de palavras chave como pé diabético, ferida crónica e úlcera por pressão; revisão e classificação de 50 artigos em idioma Espanhol, Inglês e Português. Resultados: registraram-se 12 tratamentos inovadores para o manejo das feridas cónicas, cada um com evidencia científica de sua utilidade nos diferentes tipos de feridas crónicas. Conclusão: o conhecimento de novos tratamentos ajuda ao enfermeiro a ampliar as opções de intervenção, apresentando alternativas de tratamento mais rápidas ou de menor custo, dependendo do tipo de ferida e da condição do paciente.Palavras-chave: Pé diabético, Úlcera da Perna, Úlcera por pressão

Gradual Increase in Environmental Light Intensity Induces Oxidative Stress and Inflammation and Accelerates Retinal Neurodegeneration

Purpose: Retinitis pigmentosa (RP) is a blinding neurodegenerative disease of the retina that can be affected by many factors. The present study aimed to analyze the effect of different environmental light intensities in rd10 mice retina. Methods: C57BL/6J and rd10 mice were bred and housed under three different environmental light intensities: scotopic (5 lux), mesopic (50 lux), and photopic (300 lux). Visual function was studied using electroretinography and optomotor testing. The structural and morphological integrity of the retinas was evaluated by optical coherence tomography imaging and immunohistochemistry. Additionally, inflammatory processes and oxidative stress markers were analyzed by flow cytometry and western blotting. Results: When the environmental light intensity was higher, retinal function decreased in rd10 mice and was accompanied by light-dependent photoreceptor loss, followed by morphological alterations, and synaptic connectivity loss. Moreover, light-dependent retinal degeneration was accompanied by an increased number of inflammatory cells, which became more activated and phagocytic, and by an exacerbated reactive gliosis. Furthermore, light-dependent increment in oxidative stress markers in rd10 mice retina pointed to a possible mechanism for light-induced photoreceptor degeneration. Conclusions: An increase in rd10 mice housing light intensity accelerates retinal degeneration, activating cell death, oxidative stress pathways, and inflammatory cells. Lighting intensity is a key factor in the progression of retinal degeneration, and standardized lighting conditions are advisable for proper analysis and interpretation of experimental results from RP animal models, and specifically from rd10 mice. Also, it can be hypothesized that light protection could be an option to slow down retinal degeneration in some cases of RP.Supported by grants from the Spanish Ministry of Economy and Competitiveness (MINECO-FEDER BFU2015-67139-R); Spanish Ministry of Education (FPU16/04114); Instituto de Salud Carlos III co-financed by European Regional Development funds (RETICS-FEDER RD16/0008/0016); and Asociación Retina Asturias, FARPE-FUNDALUCE, Generalitat Valenciana (PROMETEO/2016/158, ACIF/2016/055 and FEDER IDIFEDER/2017/064)

Ischemia-Reperfusion Increases TRPM7 Expression in Mouse Retinas

Ischemia is the main cause of cell death in retinal diseases such as vascular occlusions, diabetic retinopathy, glaucoma, or retinopathy of prematurity. Although excitotoxicity is considered the primary mechanism of cell death during an ischemic event, antagonists of glutamatergic receptors have been unsuccessful in clinical trials with patients suffering ischemia or stroke. Our main purpose was to analyze if the transient receptor potential channel 7 (TRPM7) could contribute to retinal dysfunction in retinal pathologies associated with ischemia. By using an experimental model of acute retinal ischemia, we analyzed the changes in retinal function by electroretinography and the changes in retinal morphology by optical coherence tomography (OCT) and OCT-angiography (OCTA). Immunohistochemistry was performed to assess the pattern of TRPM7 and its expression level in the retina. Our results show that ischemia elicited a decrease in retinal responsiveness to light stimuli along with reactive gliosis and a significant increase in the expression of TRPM7 in Müller cells. TRPM7 could emerge as a new drug target to be explored in retinal pathologies associated with ischemia.We acknowledge financial support from the Ministerio de Ciencia e Innovación (FEDER-PID 2019-106230RB-I00), Ministerio de Universidades (FPU16/04114, FPU-18/02964). Generalitat Valenciana-FEDER (IDIFEDER/2017/064, PROMETEO/2021/024), Es Retina Asturias (2019/00286/001). MARSALAS21-35, financiado por la Unión Europea-Next Generation EU

Phenotypic Differences in a PRPH2 Mutation in Members of the Same Family Assessed with OCT and OCTA

Choroidal dystrophies comprise a group of chorioretinal degenerations. However, the different findings observed among these patients make it difficult to establish a correct clinical diagnosis. The objective of this study was to characterize new clinical findings by optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) in these patients. Four family members with a PRPH2 gene mutation (p.Arg195Leu) were included. OCT was performed at the macula, and the thickness of the outer and inner retina, total retina, and choroid was measured. The features of the vascular network were analyzed by OCTA. Patients showed a decreased outer nuclear layer in the avascular area compared with the controls. Two patients presented greater foveal and parafoveal degeneration of the outer retina, whereas the most degenerated area in the rest was the perifovea. Disruption of the third outer band at the foveola is one of the first-altered outer bands. Slow blood flow areas or capillary dropout were main signs in the deep capillary plexus. Microaneurysms were frequently observed in less degenerated retinas. Vascular loops and intraretinal microvascular abnormalities (IRMAs) were present in the superficial plexus. Extensive degeneration of the choriocapillaris was detected. Phenotypic differences were found between patients: two showed central areolar choroidal dystrophy and the rest had extensive chorioretinal atrophy. These signs observed in OCT and OCTA can help to more appropriately define the clinical disease in patients with choroidal dystrophies.This research was funded by grants from the Spanish Ministry of Science and Innovation (FEDER- PID2019-106230RB-I00, RD16/0008/0001), Spanish Ministry of Universities (FPU16/04114 and FPU18/02964), Instituto de Salud Carlos III (RETICS-FEDER RD16/0008/0016), Asociación Retina Asturias/Cantabria, FARPE-FUNDALUCE, and Generalitat Valenciana (IDIFEDER/2017/064)

Perfil de las alteraciones neuroconductuales sobre el desempeño de las actividades de la vida diaria en pacientes con demencia tipo Alzheimer. Estudio de caso

El aumento en la esperanza de vida en la población de los países desarrollados incide en el crecimiento de las cifras de pacientes diagnosticados de demencia tipo Alzheimer (DTA). El objetivo del presente estudio se centra en determinar la influencia de las alteraciones neuroconductuales en las actividades de la vida diaria (AVD) en pacientes con DTA. La muestra estuvo compuesta por 34 personas diagnosticadas de demencia tipo Alzheimer probable (DTAP) que fueron evaluadas de manera ambulatoria por la Unidad de Neuropsicología del Complejo Asistencial de Zamora. Los resultados demuestran que las alteraciones neuroconductuales se relacionan con la capacidad de los pacientes con DTAP para llevar a cabo las AVD, especialmente las relacionadas con el baño, vestido, uso del retrete, movilidad, continencia esfinteriana y alimentación, así como en el uso del teléfono, preparación de las comidas, cuidado de la casa, lavado de la ropa y manejo de asuntos económicos

Risk factors and fetal outcomes for preeclampsia in a Colombian cohort

Q1In Latin America and the Caribbean, hypertensive pregnancy disorders are responsible for almost 26% of allmaternal deaths [1] and, in Colombia, they account for 59% of all severe maternal morbidity (SMM) cases, and59.7% of all SMM cases in adolescents [2]. One of the most important hypertensive pregnancy disorders ispreeclampsia (PE). Lives can be saved, if PE is prevented, or detected early and properly managed. Prevention anddetection depend on identifying the risk factors associated with PE, and, as these have been shown vary bypopulation, they should be determined on a population-by-population basis. The following study utilized thenested case-control model to evaluate 45 potential PE risk factors of a cohort in Bogot a, Colombia, making itperhaps the most comprehensive study of its kind in Colombia. It found PE to have a statistically significantassociation with 7 of the 45 factors evaluated: 1) pre-gestational BMI>30 kg/m2, 2) pregnancy weight gain>12kg, 3) previous history preeclampsia/eclampsia, 4) previous history of IUGR-SGA (Intrauterine GrowthRestriction-Small for Gestational Age), 5) maternal age<20 or 35 years (20–34 was not associated), and 6)family history of diabetes. Finally, prenatal consumption of folic acid was found to lower the risk of PE. Werecommend that, in Colombia, factors 1–6 be used to identify at risk mothers during pregnancy check-ups; thatmothers be encouraged to take folic acid during pregnancy; and, that Colombia's health system and public policyaddress the problem of pregestational obesity.Revista Internacional - Indexad

Accuracy and Survival Outcomes after National Implementation of Sentinel Lymph Node Biopsy in Early Stage Endometrial Cancer

Altres ajuts: acords transformatius de la UABSentinel lymph node (SLN) biopsy has recently been accepted to evaluate nodal status in endometrial cancer at early stage, which is key to tailoring adjuvant treatments. Our aim was to evaluate the national implementation of SLN biopsy in terms of accuracy to detect nodal disease in a clinical setting and oncologic outcomes according to the volume of nodal disease. A total of 29 Spanish centers participated in this retrospective, multicenter registry including patients with endometrial adenocarcinoma at preoperative early stage who had undergone SLN biopsy between 2015 and 2021. Each center collected data regarding demographic, clinical, histologic, therapeutic, and survival characteristics. A total of 892 patients were enrolled. After the surgery, 12.9% were suprastaged to FIGO 2009 stages III-IV and 108 patients (12.1%) had nodal involvement: 54.6% macrometastasis, 22.2% micrometastases, and 23.1% isolated tumor cells (ITC). Sensitivity of SLN biopsy was 93.7% and false negative rate was 6.2%. After a median follow up of 1.81 years, overall surivial and disease-free survival were significantly lower in patients who had macrometastases when compared with patients with negative nodes, micrometastases or ITC. In our nationwide cohort we obtained high sensitivity of SLN biopsy to detect nodal disease. The oncologic outcomes of patients with negative nodes and low-volume disease were similar after tailoring adjuvant treatments. In total, 22% of patients with macrometastasis and 50% of patients with micrometastasis were at low risk of nodal metastasis according to their preoperative risk factors, revealing the importance of SLN biopsy in the surgical management of patients with early stage EC

Inherited Retinal Dystrophies: Role of Oxidative Stress and Inflammation in Their Physiopathology and Therapeutic Implications

Inherited retinal dystrophies (IRDs) are a large group of genetically and clinically heterogeneous diseases characterized by the progressive degeneration of the retina, ultimately leading to loss of visual function. Oxidative stress and inflammation play fundamental roles in the physiopathology of these diseases. Photoreceptor cell death induces an inflammatory state in the retina. The activation of several molecular pathways triggers different cellular responses to injury, including the activation of microglia to eliminate debris and recruit inflammatory cells from circulation. Therapeutical options for IRDs are currently limited, although a small number of patients have been successfully treated by gene therapy. Many other therapeutic strategies are being pursued to mitigate the deleterious effects of IRDs associated with oxidative metabolism and/or inflammation, including inhibiting reactive oxygen species’ accumulation and inflammatory responses, and blocking autophagy. Several compounds are being tested in clinical trials, generating great expectations for their implementation. The present review discusses the main death mechanisms that occur in IRDs and the latest therapies that are under investigation.This research was funded by DGA group B08_17R: Investigación en Retina y Sistema Visual and Fondo Europeo de Desarrollo Regional (FEDER) funds: “Una manera de hacer Europa”, Ministerio de Ciencia e Innovación (FEDER-PID 2019-106230RB-I00), Instituto de Salud Carlos III (PI20/00740-FEDER, RETICS-FEDER RD16/0008/0016), Generalitat Valenciana-FEDER (IDIFEDER/2017/064, PROMETEO/2021/024), Ministerio de Universidades (FPU16/04114), Es Retina Asturias (2019/00286/001). The APC was funded by DGA group B08_17R: Investigación en Retina y Sistema Visual (FEDER)