COVID-19, a Movie Pandemic: Analysis of Ethical Problems

The global panorama resulting from the pandemic experienced by the new SARS-CoV-2 and the disease it produces, COVID-19 has highlighted our fragility not only as individuals but as a society. Management of scarce resources, transparency of information, risks assumed by the health workers, support at the end of life or the search for a safe vaccine are just some of the ethical challenges that have emerged during the health crisis. Previously, cinema and literature had already shown these ethical aspects in extreme situations such as the current one, based on historical pandemics and other science fiction that describe a dystopian world. Collective reflection and prudence must be the epicenter that move us to make solidarity decisions in the social, scientific and political spheres to move away from a discouraging future, in the new world after COVID-19.El panorama mundial resultante de la pandemia vivida por el nuevo SARS-CoV-2 y la enfermedad que produce, la COVID-19 ha puesto de manifiesto nuestra fragilidad no solo como individuos sino como sociedad. La gestión de recursos escasos, la transparencia de la información, los riesgos asumidos por los sanitarios, el acompañamiento al final de la vida o la búsqueda de una vacuna segura son solo algunos de los desafíos éticos que han aflorado durante la crisis sanitaria. Previamente, el cine y la literatura ya habían mostrado estos aspectos éticos en situaciones extremas como la actual, basándose en pandemias históricas y otras de ciencia ficción que describen un mundo distópico. La reflexión colectiva y la prudencia deben ser el epicentro que muevan a tomar decisiones solidarias en el ámbito social, científico y político para alejarnos de un futuro desalentador, en el nuevo mundo tras la COVID-19

Prenatal Exposure to Cigarette Smoke and Anogenital Distance at 4 Years in the INMA-Asturias Cohort

Smoking by women is associated with adverse pregnancy outcomes such as spontaneous abortion, preterm delivery, low birth weight, infertility, and prolonged time to pregnancy. Anogenital distance (AGD) is a sensitive biomarker of prenatal androgen and antiandrogen exposure. We investigated the effect of smoking and passive smoke exposure during pregnancy on anogenital distance in offspring at 4 years in the INMA-Asturias cohort (Spain). Women were interviewed during pregnancy to collect information on tobacco consumption, and anogenital distance was measured in 381 children: Anoscrotal distance in boys and anofourchetal distance in girls. We also measured maternal urinary cotinine levels at 32 weeks of pregnancy. We constructed linear regression models to analyze the association between prenatal smoke exposure and anogenital distance and adjusted the models by relevant covariates. Reported prenatal smoke exposure was associated with statistically significant increased anogenital index (AGI), both at week 12 of pregnancy (β = 0.31, 95% confidence interval: 0.00, 0.63) and at week 32 of pregnancy (β = 0.31, 95% confidence interval: 0.00, 0.63) in male children, suggesting altered androgenic signaling.Funding was provided by CIBERESP (PhD employment contract and fellowship for short stays abroad—2019), FIS-FEDER (grants PI04/2018, PI09/02311, PI13/02429, and PI18/00909), Obra Social Cajastur/Fundación Liberbank, and Universidad de Oviedo

Prenatal exposure to persistent organic pollutants and anogenital distance in children at 18 months

Background: Anogenital distance (AGD) is a measure of in utero exposure to hormonally active agents. The aim of the present study was to evaluate the association between prenatal exposure to persistent organic pollutants (POPs) and AGD. Methods: POP levels were measured in pregnant women, and the AGD was recorded in 43 offspring at 18 months. We used linear regression models to analyze the association between maternal POP exposure and offspring AGD. We defined the anogenital index (AGI) as AGD divided by weight at 18 months (AGI = AGD / weight at 18 months [mm/kg]) and included this variable in the regression models. Results: AGI measure was 2.35 (0.61) and 1.38 (0.45) in males and females, respectively. AGI was inversely associated with lipid-adjusted concentrations of PBDE-99 (β = -0.28, 95% confidence interval [CI]: -0.51, -0.04) and PBDE-153 (β = -0.61, 95% CI: -1.11, -0.11) in males. We did not find any statistically significant relationship between any POPs and AGI in females. Conclusions: Environmental exposure to POPs may affect genital development and result in reproductive tract alterations with potentially relevant health consequences in maturity. © 2018 The Author(s). Published by S. Karger AG, Basel.This study was funded by grants from FIS-FEDER (PI04/2018, PI09/02311, and PI13/02429), Fundación Cajastur-Liberbank, and Universidad de Oviedo.Peer reviewe

Folic Acid Supplementation during Pregnancy and Its Association with Telomere Length in Children at Four Years: Results from the INMA Birth Cohort Study

This study examined the association between folic acid supplements (FAs) during different periods of pregnancy and offspring telomere length (TL) at age four in 666 children from the INMA study. FAs were self-reported using food-structured questionnaires during three periods of pregnancy (the first three months of pregnancy, from month fourth onward, and the whole pregnancy). For each period, the average daily dosage of FAs was categorised into (i) <400 μg/d, (ii) ≥400 to 999 μg/d, (iii) ≥1000 to 4999 μg/d, and (iv) ≥5000 μg/d. Leucocyte TL at age four was measured using quantitative PCR methods. Multiple robust linear log-level regression models were used to report the % difference among FA categories. During the first period, and compared with children whose mothers were classified in the reference group (<400 μg/d), children whose mothers took higher dosages of FAs showed shorter TL at age four (≥5000 μg/d). When the first and the second periods were mutually adjusted, children whose mothers self-reported ≥5000 μg/d during the first period of pregnancy had a statistically significant shorter TL than their counterparts (% difference: −7.28% [95% CI: −14.42 to −0.13]). Similar trends were observed for the whole period of pregnancy. When the analysis was stratified by sex, the association was more evident in boys (% difference: −13.5% [95% CI: −23.0 to −4.04]), whereas no association was observed in girls. This study suggests that high dosages of FAs in the first pregnancy period may be associated with a shorter TL in children at age four, particularly among boys. Further studies should confirm these results.This research was funded by Instituto de Salud Carlos III/Agencia Estatal de Investigación, grant number PI18/00825 Project: “Dieta y actividad física en embarazo y tras el nacimiento y longitud del telómero en niños y adolescentes: Proyecto TeloDiPA” and Unión Europea (FEDER) “Una manera de hacer Europa”; PI07/0314, PI11/01007 incl. FEDER funds; Generalitat Valenciana (GVA/2021/191); Dries Martens holds a postdoctoral grant by the Flemish Scientific Fund (FWO grant 12X9620N). In Sabadell was funded by grants from Instituto de Salud Carlos III (Red INMA G03/176; CB06/02/0041; PI041436; PI081151 incl. FEDER funds; PI12/01890 incl. FEDER funds; CP13/00054 incl. FEDER funds, PI15/00118 incl. FEDER funds, CPII18/00018), CIBERESP, Generalitat de Catalunya-CIRIT 1999SGR 00241, Generalitat de Catalunya-AGAUR (2009 SGR 501, 2014 SGR 822), Fundació La marató de TV3 (090430), Spanish Ministry of Economy and Competitiveness (SAF2012-32991 incl. FEDER funds), Agence Nationale de Securite Sanitaire de l’Alimentation de l’Environnement et du Travail (1262C0010), EU Commission (261357, 308333, 603794 and 634453). We acknowledge support from the Spanish Ministry of Science and Innovation and the State Research Agency through the “Centro de Excelencia Severo Ochoa 2019–2023” Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program. In Asturias was funded by ISCIII: PI04/2018, PI09/02311, PI13/02429, PI18/00909 co-funded by FEDER, “A way to make Europe”/“Investing in your future”, Obra Social Cajastur/Fundación Liberbank, and Universidad de Oviedo. This study was funded by grants from Instituto de Salud Carlos III (FIS-PI06/0867 and FIS-PI09/00090), CIBERESP, Department of Health of the Basque Government (2005111093, 2009111069 and 2013111089), and the Provincial Government of Gipuzkoa (DFG06/002 and DFG08/001) and annual agreements with the municipalities of the study area (Zumarraga, Urretxu, Legazpi, Azkoitia y Azpeitia y Beasain). Jordi Julvez holds the Miguel Servet-II contract (CPII19/00015) awarded by the Instituto de Salud Carlos III (co-funded by the European Social Fund “Investing in your future”)

Susceptible windows of exposure to fine particulate matter and fetal growth trajectories in the Spanish INMA (INfancia y Medio Ambiente) birth cohort

While prior studies report associations between fine particulate matter (PM2.5) exposure and fetal growth, few have explored temporally refined susceptible windows of exposure.We included 2328 women from the Spanish INMA Project from 2003 to 2008. Longitudinal growth curves were constructed for each fetus using ultrasounds from 12, 20, and 34 gestational weeks. Z-scores representing growth trajectories of biparietal diameter, femur length, abdominal circumference (AC), and estimated fetal weight (EFW) during early (0-12 weeks), mid-(12-20 weeks), and late (20-34 weeks) pregnancy were calcu-lated. A spatio-temporal random forest model with back-extrapolation provided weekly PM2.5 exposure estimates for each woman during her pregnancy. Distributed lag non-linear models were implemented within the Bayesian hierarchical framework to identify susceptible windows of exposure for each outcome and cumulative effects [13cum, 95% credible interval (CrI)] were aggregated across adjacent weeks. For comparison, general linear models evaluated associations between PM2.5 averaged across multi-week periods (i.e., weeks 1-11, 12-19, and 20-33) and fetal growth, mutually adjusted for exposure during each period. Results are presented as %change in z-scores per 5 mu g/m3 in PM2.5, adjusted for covariates.Weeks 1-6 [13cum =-0.77%, 95%CrI (-1.07%,-0.47%)] were identified as a susceptible window of exposure for reduced late pregnancy EFW while weeks 29-33 were positively associated with this outcome [13cum = 0.42%, 95%CrI (0.20%, 0.64%)]. A similar pattern was observed for AC in late pregnancy. In linear regression models, PM2.5 exposure averaged across weeks 1-11 was associated with reduced late pregnancy EFW and AC; but, positive associations between PM2.5 and EFW or AC trajectories in late pregnancy were not observed.PM2.5 exposures during specific weeks may affect fetal growth differentially across pregnancy and such as-sociations may be missed by averaging exposure across multi-week periods, highlighting the importance of temporally refined exposure estimates when studying the associations of air pollution with fetal growth

Síndrome de Noonan: actualización genética, clínica y de opciones terapéuticas

El síndrome de Noonan (SN) es una enfermedad de origen genético relativamente frecuente cuyas manifestaciones fundamentales son la talla baja, la cardiopatía congénita y un fenotipo facial característico. La causa del síndrome de Noonan y de otras enfermedades clínicamente solapadas como el síndrome de Noonan con lentiginosis múltiple (anteriormente llamado síndrome LEOPARD), el cardiofaciocutáneo o el síndrome de Costello, son mutaciones en genes que codifican para proteínas de la vía de señalización de las RAS-MAPKinasas. Debido a este sustrato común este grupo de enfermedades son denominadas colectivamente «rasopatías». A pesar de los avances genéticos de las últimas décadas, cerca de 20% de pacientes no tienen causa genética identificada, y el diagnóstico sigue siendo clínico. El síndrome de Noonan se caracteriza por una alta heterogeneidad clínica y genética, con afectación variable, y cambiante con la edad, de múltiples órganos y sistemas. Debido a esta variabilidad es fundamental que los médicos involucrados en su cuidado estén familiarizados con sus manifestaciones y conozcan las recomendaciones de seguimiento, incluido el seguimiento del crecimiento y desarrollo. Hasta la fecha los escasos datos de crecimiento con GH a talla adulta dan resultados de ganancia de talla moderados, semejantes a los obtenidos en el síndrome de Turner. La hiperactivación de la vía RAS-MAPK como base común de esta familia de enfermedades brinda una oportunidad única para el desarrollo de tratamientos dirigidos a la etiología de estos trastornos. Noonan syndrome (NS) is a relatively common genetic condition characterised by short stature, congenital heart defects, and distinctive facial features. NS and other clinically overlapping conditions such as NS with multiple lentigines (formerly called LEOPARD syndrome), cardiofaciocutaneous syndrome, or Costello syndrome, are caused by mutations in genes encoding proteins of the RAS-MAPKinases pathway. Because of this shared mechanism, these conditions have been collectively termed «RASopathies». Despite the recent advances in molecular genetics, nearly 20% of patients still lack a genetic cause, and diagnosis is still made mainly on clinical grounds. NS is a clinically and genetically heterogeneous condition, with variable expressivity and a changing phenotype with age, and affects multiple organs and systems. Therefore, it is essential that physicians involved in the care of these patients are familiarised with their manifestations and the management recommendations, including management of growth and development. Data on growth hormone treatment efficacy are sparse, and show a modest response in height gains, similar to that observed in Turner syndrome. The role of RAS/MAPK hyper-activation in the pathophysiology of this group of disorders offers a unique opportunity for the development of targeted approaches

Expanding the genotypic and phenotypic spectrum of severe serine biosynthesis disorders.

Serine biosynthesis disorders comprise a spectrum of very rare autosomal recessive inborn errors of metabolism with wide phenotypic variability. Neu-Laxova syndrome represents the most severe expression and is characterized by multiple congenital anomalies and pre- or perinatal lethality. Here, we present the mutation spectrum and a detailed phenotypic analysis in 15 unrelated families with severe types of serine biosynthesis disorders. We identified likely disease-causing variants in the PHGDH and PSAT1 genes, several of which have not been reported previously. Phenotype analysis and a comprehensive review of the literature corroborates the evidence that serine biosynthesis disorders represent a continuum with varying degrees of phenotypic expression and suggest that even gradual differences at the severe end of the spectrum may be correlated with particular genotypes. We postulate that the individual residual enzyme activity of mutant proteins is the major determinant of the phenotypic variability, but further functional studies are needed to explore effects at the enzyme protein level.We are indebted to all families for participating in this study. We would like to acknowledge Dr. Natasha Laidlew, who initially suggested the diagnosis in one of the cases and provided important phenotypic information, and Dr. María-Luisa Martínez-Fernández for the critical management of biosamples in ECEMC Program of Spain. Financial assistance was received in support of the study by grants from the German Federal Ministry of Education and Research (BMBF) (GeNeRARe, FKZ: 01GM1519D) to M. Z. and from the Institute of Health Carlos III: Convenio ISCIII-ASEREMAC, and Fundación 1000 sobre Defectos Congénitos, of Spain to E. B.-S. and I. R. G.S

¿Quién decide qué datos deben constar en la historia clínica en relación con el origen biológico?

Cada vez es más frecuente que se produzcan peticiones de pacientes o de sus representantes relativas a que determinada información no quede registrada en la historia clínica o que, si ya lo está, se elimine. Sin duda esto es debido a que saben que a los historiales clínicos acceden numerosos profesionales que en muchas ocasiones no guardan una relación estrictamente asistencial con ellos y que de manera generalizada se copian antecedentes médicos que de forma innecesaria se reproducen en los diversos informes de alta o de asistencia. El problema produce situaciones de conflicto cuando los datos objeto de controversia hacen referencia a aspectos clínicos especialmente sensibles para la intimidad personal y familiar, como ocurre con las técnicas de reproducción asistida. Por ello, la pregunta que cabe formular es: ¿quién decide qué datos deben constar en la historia clínica y en función de qué criterios debe tomarse esa decisión