Non-invasive fetal diagnosis testing from maternal blood

RESUMEN : Objetivo: conocer las intervenciones llevadas a cabo actualmente sobre la detección prenatal de anomalías genéticas en sangre materna en el Sistema Público de Salud en España, así como sus limitaciones y perspectivas futuras. Metodología: revisión narrativa mediante una búsqueda bibliográfica en las bases de datos Pubmed, Cuiden, Crochane y Scielo de estudios publicados entre 2012 y 2020. Se establecieron criterios de inclusión, exclusión y limitadores. Resultados: en este análisis han sido incluidos diferentes artículos y ensayos clínicos en los que se obtuvieron temas comunes que inciden en las intervenciones de estudio: 1) diagnóstico prenatal no invasivo en sangre materna; 2) Secuenciación de segunda generación y otras técnicas moleculares; 3) protocolos de análisis de sangre materna y de edad materna de las gestantes; 4) Fecundación y cribado de gestantes de alto riesgo. Conclusiones: el test de diagnostico prenatal no invasivo en sangre materna es actualmente un método válido para la búsqueda de numerosas anomalías cromosómicas. Aun así, sigue siendo un método de cribado, y para la confirmación de las pruebas que resulten positivas se requieren métodos invasivos, como la amniocentesis. El incremento de la edad materna es una realidad actual que implica un aumento de riesgo relacionado con la presentación de anomalías cromosómicas en el feto. Actualmente este método está ya implantado en muchos de los servicios públicos de salud en aquellas gestantes en las que se detecte alto riesgo mediante las pruebas que forman parte del triple screening. También se puede acceder a este test a través de laboratorios privados, aunque su elevado coste continúa siendo un problema. Los laboratorios tienen en común la realización de las pruebas para la detección de las trisomías 21, 13 y 18, así como la determinación del sexo fetal y del factor Rh, pudiendo después contar con pruebas más ampliadas para la determinación de otras anomalías. El creciente avance de las técnicas moleculares, como es el desarrollo de la secuenciación de segunda generación, nos permite hoy en día el diagnóstico de numerosos síndromes asociados a aneuploidías, además de deleciones, duplicaciones y mutaciones más complejas asociadas a una herencia monogénica de origen paterno. A pesar del gran avance en la capacidad diagnóstica de estas pruebas, aún tiene importantes limitaciones, como el diagnostico de inversiones, traslocaciones y otras reorganizaciones cromosómicas, ante las cuales sería necesario el uso de pruebas invasivas.ABSTRACT : Objective: to learn about the assistance offered by the Spanish Public Health System on prenatal diagnosis of genetic diseases; in particular on non-invasive fetal DNA testing from maternal blood Methodology: a review was conducted using PubMed, Cuiden, Cochrane and Scielo databases of studies published between 2012 and 2020. Inclusive exclusive criteria and limiters were established. Results: In this analysis, different articles and clinical trials have been included in which common themes that affect study interventions were obtained: 1) non-invasive fetal diagnosis testing from maternal blood; 2) Next generation sequencing and other molecular techniques; 3) protocols for analysis of maternal blood and maternal age of pregnant women; 4) Fertilization and screening of high-risk pregnant women. Conclusions: The non-invasive fetal diagnosis testing from maternal blood is currently a valid diagnostic method in the search for chromosomal abnormalities. Even so, it continues to be a screening method, and invasive methods, such as amniocentesis, are required to confirm positive tests. The increase in the maternal age is a real problem since it implies a high risk for chromosomal abnormalities in the fetus. Currently, testing from maternal blood is already implanted in many of the public health services and it is offered to pregnant women with a high risk detected by means of triple screening tests. Testing from maternal blood is also available at some private laboratories, although with a high cost. Laboratories offering this test are able to detect 21, 13 and 18 trisomies, as well as determine the fetal sex and Rh factor, together with other abnormalities. The increasing advance in molecular techniques, such as the development of next generation sequencing, allows us today the diagnosis of aneuploidies, deletions, duplications, as well as more complex mutations with a paternal monogenic inheritance. Despite the significant progress in the diagnostic capability of these tests, they still have important limitations, such as the diagnosis of inversions and chromosomal translocations, which require the use of invasive tests.Grado en Medicin

Modulation of plant root growth by nitrogen source-defined regulation of polar auxin transport

Availability of the essential macronutrient nitrogen in soil plays a critical role in plant growth, development, and impacts agricultural productivity. Plants have evolved different strategies for sensing and responding to heterogeneous nitrogen distribution. Modulation of root system architecture, including primary root growth and branching, is among the most essential plant adaptions to ensure adequate nitrogen acquisition. However, the immediate molecular pathways coordinating the adjustment of root growth in response to distinct nitrogen sources, such as nitrate or ammonium, are poorly understood. Here, we show that growth as manifested by cell division and elongation is synchronized by coordinated auxin flux between two adjacent outer tissue layers of the root. This coordination is achieved by nitrate‐dependent dephosphorylation of the PIN2 auxin efflux carrier at a previously uncharacterized phosphorylation site, leading to subsequent PIN2 lateralization and thereby regulating auxin flow between adjacent tissues. A dynamic computer model based on our experimental data successfully recapitulates experimental observations. Our study provides mechanistic insights broadening our understanding of root growth mechanisms in dynamic environments

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Modulation of root growth by nutrient-defined fine-tuning of polar auxin transport

Nitrogen is an essential macronutrient and its availability in soil plays a critical role in plant growth, development and impacts agricultural productivity. Plants have evolved different strategies to sense and respond to heterogeneous nitrogen distribution. Modulating root system architecture, including primary root growth and branching, is among the most essential plant adaptions to ensure adequate nitrogen acquisition. However, the immediate molecular pathways coordinating the adjustment of root growth in response to varying nitrogen sources are poorly understood. Here, using a combination of physiological, live in vivo high- and super resolution imaging, we describe a novel adaptation strategy of root growth on available nitrogen source. We show that growth, i.e. tissue-specific cell division and elongation rates are fine-tuned by modulating auxin flux within and between tissues. Changes in auxin redistribution are achieved by nitrogen source dependent post-translational modification of PIN2, a major auxin efflux carrier, at an uncharacterized, evolutionary conserved phosphosite. Further, we generate a computer model based on our results which successfully recapitulate our experimental observations and creates new predictions that could broaden our understanding of root growth mechanisms in the dynamic environment

Trends in Outcomes for Neonates Born Very Preterm and Very Low Birth Weight in 11 High-Income Countries

OBJECTIVE: To evaluate outcome trends of neonates born very preterm in 11 high-income countries participating in the International Network for Evaluating Outcomes of neonates. STUDY DESIGN: In a retrospective cohort study, we included 154 233 neonates admitted to 529 neonatal units between January 1, 2007, and December 31, 2015, at 24(0/7) to 31(6/7) weeks of gestational age and birth weight <1500 g. Composite outcomes were in-hospital mortality or any of severe neurologic injury, treated retinopathy of prematurity, and bronchopulmonary dysplasia (BPD); and same composite outcome excluding BPD. Secondary outcomes were mortality and individual morbidities. For each country, annual outcome trends and adjusted relative risks comparing epoch 2 (2012-2015) to epoch 1 (2007-2011) were analyzed. RESULTS: For composite outcome including BPD, the trend decreased in Canada and Israel but increased in Australia and New Zealand, Japan, Spain, Sweden, and the United Kingdom. For composite outcome excluding BPD, the trend decreased in all countries except Spain, Sweden, Tuscany, and the United Kingdom. The risk of composite outcome was lower in epoch 2 than epoch 1 in Canada (adjusted relative risks 0.78; 95% CI 0.74-0.82) only. The risk of composite outcome excluding BPD was significantly lower in epoch 2 compared with epoch 1 in Australia and New Zealand, Canada, Finland, Japan, and Switzerland. Mortality rates reduced in most countries in epoch 2. BPD rates increased significantly in all countries except Canada, Israel, Finland, and Tuscany. CONCLUSIONS: In most countries, mortality decreased whereas BPD increased for neonates born very preterm

Diminishing benefits of urban living for children and adolescents’ growth and development

Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified