Alcohol Consumption during Pregnancy : Analysis of Two Direct Metabolites of Ethanol in Meconium

Alcohol consumption in young women is a widespread habit that may continue during pregnancy and induce alterations in the fetus. We aimed to characterize prevalence of alcohol consumption in parturient women and to assess fetal ethanol exposure in their newborns by analyzing two direct metabolites of ethanol in meconium. This is a cross-sectional study performed in September 2011 and March 2012 in a series of women admitted to an obstetric unit following childbirth. During admission, socio-demographic and substance use (alcohol, tobacco, cannabis, cocaine, and opiates) during pregnancy were assessed using a structured questionnaire and clinical charts. We also recorded the characteristics of pregnancy, childbirth, and neonates. The meconium analysis was performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) to detect the presence of ethyl glucuronide (EtG) and ethyl sulfate (EtS). Fifty-one parturient and 52 neonates were included and 48 meconium samples were suitable for EtG and EtS detection. The median age of women was 30 years (interquartile range (IQR): 26-34 years); EtG was present in all meconium samples and median concentration of EtG was 67.9 ng/g (IQR: 36.0-110.6 ng/g). With respect to EtS, it was undetectable (<0.01 ng/g) in the majority of samples (79.1%). Only three (6%) women reported alcohol consumption during pregnancy in face-to-face interviews. However, prevalence of fetal exposure to alcohol through the detection of EtG and EtS was 4.2% and 16.7%, respectively. Prevention of alcohol consumption during pregnancy and the detection of substance use with markers of fetal exposure are essential components of maternal and child health

Mutations in SLC39A14 disrupt manganese homeostasis and cause childhood-onset parkinsonism-dystonia.

Although manganese is an essential trace metal, little is known about its transport and homeostatic regulation. Here we have identified a cohort of patients with a novel autosomal recessive manganese transporter defect caused by mutations in SLC39A14. Excessive accumulation of manganese in these patients results in rapidly progressive childhood-onset parkinsonism-dystonia with distinctive brain magnetic resonance imaging appearances and neurodegenerative features on post-mortem examination. We show that mutations in SLC39A14 impair manganese transport in vitro and lead to manganese dyshomeostasis and altered locomotor activity in zebrafish with CRISPR-induced slc39a14 null mutations. Chelation with disodium calcium edetate lowers blood manganese levels in patients and can lead to striking clinical improvement. Our results demonstrate that SLC39A14 functions as a pivotal manganese transporter in vertebrates.Action Medical ResearchThis is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/ncomms1160

La Locura en la historia de la humanidad: discurso de recepción en la Real Academia de Medicina y Cirugía de Barcelona por el académico electo Dr. Wifredo Coroleu y Borrás: discurso de contestación del Dr. Valentín Carulla Margenat, académico numerario

Excmo. Señor, Señores Académicos, Señores: Hay hombres a los cuales se sucede pero que no se reemplaza y uno de ellos es el digno y llorado doctor Comenge, mi antecesor en esta docta Corporación. Era yo aún estudiante cuando en las aulas de la vieja facultad y después de una conversación en que todos habían elegido ya una especialidad en el porvenir, me dijo un compañero hoy médico distinguido al ver que yo me callaba: «Tú con el tiempo vas a ser lo que Comengel» Sorprendióme de una manera tan honda, a la vez que tan grata aquella profecía, que nada acerté a responder. Y cuando hoy después de tantos anos recuerdo aquella escena no puedo menos de pensar que realmente hay en la vida algo del Fatum antiguo que nos trae por ignotas vias a seguir nuestro destino. Trazar la biografía del Dr. Comenge no es hoy mi tarea y relatar su noble labor es superior a mis fuerzas. Yo sólo puedo evocar aquella figura toda ella vida y espíritu que en un cuerpo tan chico encerraba un alma tan grande. Veo aun aquella mirada penetrante, inquisitiva y un si no es burlona pero con la bondad y la indulgencia del talento. Me parece contemplar aquella cara enjuta y aquel cráneo de pensador, de atleta de la inteligencia. Vivo creo verle aun en los sillones del Ateneo su hogar de erudito hojeando libras o revistas. Nada puede borrar de mi memoria aquella visión tan querida y hoy mismo que mi sola presencia en este recinto y entre vosotros es una triste prueba de su muerte me acomete la ilusión que me escucha y me mira cual si viera realizado su deseo de ver un día de la Acade mia. ¿Por qué mi malhadado destino ha querido que fuese su vacante la que yo llenase? Pero si en ello hemos de verme una mano superior y misteriosa bien pudiera creerme que ella senalaba con mayor solemnidad su testamento literario y médico. No puede caber mayor honra ni estímulo para el hijo del historiador de Cataluna de sus fueros y sus Cortes que suceder en esta Academia al eminente historiador de la Medicina catalano-aragonesa. El tiempo dirá y vosotros señores académicos si esta misión no excedía de mis facultades y si no os ha engañado el buen deseo y la confianza que haré siempre cuanto pueda para continuar mereciendo

Alcohol Consumption during Pregnancy: Analysis of Two Direct Metabolites of Ethanol in Meconium

Alcohol consumption in young women is a widespread habit that may continue during pregnancy and induce alterations in the fetus. We aimed to characterize prevalence of alcohol consumption in parturient women and to assess fetal ethanol exposure in their newborns by analyzing two direct metabolites of ethanol in meconium. This is a cross-sectional study performed in September 2011 and March 2012 in a series of women admitted to an obstetric unit following childbirth. During admission, socio-demographic and substance use (alcohol, tobacco, cannabis, cocaine, and opiates) during pregnancy were assessed using a structured questionnaire and clinical charts. We also recorded the characteristics of pregnancy, childbirth, and neonates. The meconium analysis was performed by liquid chromatography—tandem mass spectrometry (LC-MS/MS) to detect the presence of ethyl glucuronide (EtG) and ethyl sulfate (EtS). Fifty-one parturient and 52 neonates were included and 48 meconium samples were suitable for EtG and EtS detection. The median age of women was 30 years (interquartile range (IQR): 26–34 years); EtG was present in all meconium samples and median concentration of EtG was 67.9 ng/g (IQR: 36.0–110.6 ng/g). With respect to EtS, it was undetectable (&lt;0.01 ng/g) in the majority of samples (79.1%). Only three (6%) women reported alcohol consumption during pregnancy in face-to-face interviews. However, prevalence of fetal exposure to alcohol through the detection of EtG and EtS was 4.2% and 16.7%, respectively. Prevention of alcohol consumption during pregnancy and the detection of substance use with markers of fetal exposure are essential components of maternal and child health

Alcohol Consumption during Pregnancy : Analysis of Two Direct Metabolites of Ethanol in Meconium

Alcohol consumption in young women is a widespread habit that may continue during pregnancy and induce alterations in the fetus. We aimed to characterize prevalence of alcohol consumption in parturient women and to assess fetal ethanol exposure in their newborns by analyzing two direct metabolites of ethanol in meconium. This is a cross-sectional study performed in September 2011 and March 2012 in a series of women admitted to an obstetric unit following childbirth. During admission, socio-demographic and substance use (alcohol, tobacco, cannabis, cocaine, and opiates) during pregnancy were assessed using a structured questionnaire and clinical charts. We also recorded the characteristics of pregnancy, childbirth, and neonates. The meconium analysis was performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) to detect the presence of ethyl glucuronide (EtG) and ethyl sulfate (EtS). Fifty-one parturient and 52 neonates were included and 48 meconium samples were suitable for EtG and EtS detection. The median age of women was 30 years (interquartile range (IQR): 26-34 years); EtG was present in all meconium samples and median concentration of EtG was 67.9 ng/g (IQR: 36.0-110.6 ng/g). With respect to EtS, it was undetectable (<0.01 ng/g) in the majority of samples (79.1%). Only three (6%) women reported alcohol consumption during pregnancy in face-to-face interviews. However, prevalence of fetal exposure to alcohol through the detection of EtG and EtS was 4.2% and 16.7%, respectively. Prevention of alcohol consumption during pregnancy and the detection of substance use with markers of fetal exposure are essential components of maternal and child health

Mutations in SLC39A14 disrupt manganese homeostasis and cause childhood-onset parkinsonism-dystonia

Ajudes: beques d'Action Medical Research, Wellcome Trust, Great Ormond Street Hospital Children's Charity, Medical Research Council, Becas Chile scholarship program, CONICYT, NBIA Disorders Association, Gracious Heart Charity Foundation and Rosetrees Trust, Telethon and Mariani Foundation, TIRCON, European Research Council, NIH, E-Rare project GENOMIT, EMBO, NIHR/BRC at Guy's and St Thomas' NHS Foundation Trust, King's College London, UCLH NIHR/BRC i GOSH NIHR/BRCAlthough manganese is an essential trace metal, little is known about its transport and homeostatic regulation. Here we have identified a cohort of patients with a novel autosomal recessive manganese transporter defect caused by mutations in SLC39A14. Excessive accumulation of manganese in these patients results in rapidly progressive childhood-onset parkinsonism-dystonia with distinctive brain magnetic resonance imaging appearances and neurodegenerative features on post-mortem examination. We show that mutations in SLC39A14 impair manganese transport in vitro and lead to manganese dyshomeostasis and altered locomotor activity in zebrafish with CRISPR-induced slc39a14 null mutations. Chelation with disodium calcium edetate lowers blood manganese levels in patients and can lead to striking clinical improvement. Our results demonstrate that SLC39A14 functions as a pivotal manganese transporter in vertebrates