NFAT5 Is Activated by Hypoxia: Role in Ischemia and Reperfusion in the Rat Kidney

The current hypothesis postulates that NFAT5 activation in the kidney's inner medulla is due to hypertonicity, resulting in cell protection. Additionally, the renal medulla is hypoxic (10–18 mmHg); however there is no information about the effect of hypoxia on NFAT5. Using in vivo and in vitro models, we evaluated the effect of reducing the partial pressure of oxygen (PO2) on NFAT5 activity. We found that 1) Anoxia increased NFAT5 expression and nuclear translocation in primary cultures of IMCD cells from rat kidney. 2) Anoxia increased transcriptional activity and nuclear translocation of NFAT5 in HEK293 cells. 3) The dose-response curve demonstrated that HIF-1α peaked at 2.5% and NFAT5 at 1% of O2. 4) At 2.5% of O2, the time-course curve of hypoxia demonstrated earlier induction of HIF-1α gene expression than NFAT5. 5) siRNA knockdown of NFAT5 increased the hypoxia-induced cell death. 6) siRNA knockdown of HIF-1α did not affect the NFAT5 induction by hypoxia. Additionally, HIF-1α was still induced by hypoxia even when NFAT5 was knocked down. 7) NFAT5 and HIF-1α expression were increased in kidney (cortex and medulla) from rats subjected to an experimental model of ischemia and reperfusion (I/R). 7) Experimental I/R increased the NFAT5-target gene aldose reductase (AR). 8) NFAT5 activators (ATM and PI3K) were induced in vitro (HEK293 cells) and in vivo (I/R kidneys) with the same timing of NFAT5. 8) Wortmannin, which inhibits ATM and PI3K, reduces hypoxia-induced NFAT5 transcriptional activation in HEK293 cells. These results demonstrate for the first time that NFAT5 is induced by hypoxia and could be a protective factor against ischemic damage

Diagnóstico prenatal no invasivo

El estudio no invasivo del material genético fetal es hoy en día una realidad. Mediante el uso de tecnología de avanzada, se puede actualmente determinar el grupo Rh fetal, el sexo fetal y trastornos genéticos fetales. El NIPD (Non Invasive Prenatal Diagnosis) ha generado revuelo en la comunidad científica debido a las grandes perspectivas que se abren desde el punto vista del manejo de las pacientes. En este artículo se presenta el desarrollo que ha tenido el NIPD y sus aplicaciones clínicas actuales

¿MEJORA EL USO DE ÁCIDO URSODEOXICÓLICO EL PRONÓSTICO PERINATAL EN MUJERES EMBARAZADAS CON COLESTASIA INTRAHEPÁTICA DEL EMBARAZO?

La colestasia intrahepática del embarazo (CIÉ) es un cuadro clínico caracterizado por prurito palmo plantar de predominio nocturno y elevación de ácidos biliares conjugados séricos en el tercer trimestre del embarazo. Esta patología puede asociarse a ictericia y complicaciones como la muerte fetal. Aunque el manejo obstétrico de la CIÉ es eminentemente clínico, el ácido ursodeoxicólico (UDCA) ha sido utilizado efectivamente en el tratamiento sintomático de esta patología y en la corrección de los marcadores bioquímicos de la enfermedad. Además se ha sugerido que su uso estaría asociado a una disminución de las complicaciones fetales. Esta revisión tiene por objeto verificar la validez del uso de UDCA para mejorar el pronóstico fetal. Para esto se realizó una búsqueda detallada de la bibliografía médica en diferentes bases de datos. Aplicando distintos criterios se seleccionaron finalmente 4 artículos que constituyen la base de esta revisión. Fundamentados en la evidencia, se concluye que no existen datos suficientes en la literatura que apoyen el uso de UDCA para mejorar en forma efectiva los resultados perinatales. A pesar de que algunos estudios evaluados proponen un mejor desenlace fetal en pacientes tratados con UDCA, éstos no cuentan con la validez y el poder estadístico necesario para modificar la conducta actual frente a esta patologíaIntrahepatic cholestasis of pregnancy (ICP) is a disease of the third trimester of pregnancy involving pruritus and elevated bile acid levels. Once thought to be benign for both mother and fetus, ICP has been associated with maternal jaundice and increased rates of fetal morbidity and mortality. However ursodeoxycholic acid (UDCA) has proved to be effective and safe in patients with ICP, attenuating pruritus and correcting some biochemical abnormalities in the mothers. The fetal outcome has also been suggested to improve in patients receiving UDCA. This review intends to verify the validity of the UDCA uses to reduce fetal morbidity and mortality. For this a detailed search of the medical bibliography was done in different data bases. Applying different criteria, 4 articles were finally selected and this constitutes the base of our review. Based on the research, one concludes that there is not enough evidence in the literature to support the use of UDCA to improve perinatal outcome. Although some studies propose an improved fetal outcome in patient using UDCA, these do not count with the validity and the statistical power to modify the present management of IC

DETERMINACIÓN DEL SEXO FETAL MEDIANTE ADN LIBRE FETAL EN PLASMA MATERNO

Objetivo: Establecer la validez diagnóstica de la identificación del sexo fetal en plasma de mujeres embarazadas durante la primera mitad del embarazo mediante medición de ADN libre fetal (ffDNA) en sangre materna. Método: Se extrajo 20 mi de sangre periférica a 25 pacientes entre las 5 y 15 semanas de gestación, previo consentimiento informado. Se separó el plasma mediante centrifugación obteniéndose ADN genómi-co total (materno y fetal), y se analizó por triplicado mediante PCR en tiempo real (q-PCR), con partidores específicos para secuencia del cromosoma Y (DYS14). El sexo fetal se confirmó mediante ecografía realizada entre las 20 y 25 semanas. Resultados: 12 pacientes presentaron amplificación para DYS14, siendo diagnosticados como fetos masculinos. La menor edad gestacional de diagnóstico fue 6+4 semanas. En 9 pacientes no se generó señal, estableciéndose el sexo fetal como femenino. Hubo 4 casos en donde no se cumplieron los criterios para definir el sexo fetal, estableciéndose estos como indeterminados (todos ellos antes de las 8+3 semanas). La probabilidad de diagnosticar el sexo a partir del test fue de 84% (21 de 25 pacientes). Considerando solo los 21 casos donde se pudo realizar un diagnóstico, la ecografía confirmó el sexo en todos ellos, obteniéndose una correlación del 100%. Conclusión: Es posible diagnosticar el sexo fetal en sangre materna utilizando ffDNA durante la primera mitad del embarazoObjective: To valídate the use of cell free fetal DNA (ffDNA) in maternal plasma to predict fetal sex in the first half of pregnancy. Method: A prospective observational cohort study of 25 pregnancies between 5 and 15 weeks of gestation was studied (median gestational age of 9+1 weeks). Maternal blood was taken and q-PCR was carried out to detect the multi-copy Y chromosome associated DSY14 gene. The end point was gender as assessed by ultrasound at 20-25 weeks. Results: A Y signal was obtained in 12 patients, so a male fetus was predicted. The earliest signal was at 6+4 weeks. In 9 patients we didn't have any signal, so a female fetus was diagnosed. There were 4 cases where the criterion to define fetal sex was not fulfilled and were classified as equivocal (all of them before 8+3 weeks). The probability to predict fetal sex from the test was 84% (21 of 25 patients). However, when the diagnosis of fetal sex is made, there is a 100% correlation between the ultrasound and Q-PCR. Conclusión: Free fetal DNA in maternal plasma allows prediction of fetal sex in the first half of pregnanc

Antenatal steroids elicit neurodegenerative changes in fetal sheep brains independent of lung maturation

The effects of antenatal steroid exposure on the fetal hippocampal transcriptome in ventilated preterm lambs independent of lung maturation status. </p

Urban systems of accumulation: half a century of Chilean neoliberal urban policies

We analyse a half-century of Chilean urban reforms to explain the introduction of a system of urban accumulation by dispossession of public resources and opportunities. Three stages have been conceptualised in the imposition of a neoliberal creative-destructive process: proto-neoliberalism, roll-back and roll-out periods. Empirical studies have traditionally analysed this process by examining a single urban policy's evolution over time. In this paper, we go beyond these types of studies by performing a systemic analysis of multiple urban policy reforms in Santiago, Chile. We use a genealogical thematic analysis to track changes in laws, government programmes and planning documents from between 1952 and 2014. Our analysis identifies different “urban systems of accumulation” by looking at the interplay of four urban policies: (1) urban planning deregulation; (2) social housing privatisation; (3) devolution of territorial taxes; and (4) decreased public service provision. Moreover, our multidimensional policy analysis in Santiago characterises a more radical, fourth expression in the creative destruction process of “accumulation by dismantling”. Consequently, we advocate for more multidimensional urban policy research that goes beyond a three-period analysis in order to gain a deeper understanding of contemporary neoliberal creative-destructive processes in variegated geographies

Proceedings of the OHBM Brainhack 2021

The global pandemic presented new challenges and op-portunities for organizing conferences, and OHBM 2021was no exception. The OHBM Brainhack is an event thatoccurs just prior to the OHBM meeting, typically in-per-son, where scientists of all levels of expertise and interestgather to work and learn together for a few days in a col-laborative hacking-style environment on projects of com-mon interest (1). Building off the success of the OHBM2020 Hackathon (2), the 2021 Open Science SpecialInterest Group came together online to organize a largecoordinated Brainhack event that would take place overthe course of 4 days. The OHBM 2021 Brainhack eventwas organized along two guiding principles, providinga highly inclusive collaborative environment for inter-action between scientists across disciplines and levelsof expertise to push forward important projects thatneed support, also known as the “Hack-Track” of theBrainhack. The second aim of the OHBM Brainhack is toempower scientists to improve the quality of their sci-entific endeavors by providing high-quality hands-ontraining on best practices in open-science approaches.This is best exemplified by the training events providedby the “Train-Track” at the OHBM 2021 Brainhack. Here,we briefly explain both of these elements of the OHBM2021 Brainhack, before continuing on to the Brainhackproceedings