Structural vulnerability in EPCR suggests functional modulation.

The endothelial protein C receptor (EPCR) is a fundamental component of the vascular system in mammals due to its contribution in maintaining blood in a non-prothrombotic state, which is crucial for overall life development. It accomplishes this by enhancing the conversion of protein C (PC) into the anticoagulant activated protein C (APC), with this property being dependent on a known EPCR conformation that enables direct interaction with PC/APC. In this study, we report a previously unidentified conformation of EPCR whereby Tyr154, critical for PC/APC binding, shows a striking non-canonical configuration. This unconventional form is incompatible with PC/APC binding, and reveals, for the first time, a region of structural vulnerability and potential modulation in EPCR. The identification of this malleability enhances our understanding of this receptor, prompting inquiries into the interplay between its plasticity and function, as well as its significance within the broader framework of EPCR's biology, which extends to immune conditions.

Frecuencia de los defectos del tubo neural en Asturias: impacto del diagnóstico prenatal / Prevalence of neural tube defects in Asturias (Spain): impact of prenatal diagnosis

ObjetivoDescribir la frecuencia de defectos del tubo neural (DTN) –anencefalia, espina bífida y encefalocele—en Asturias, su evolución temporal y el impacto del diagnóstico prenatal.MétodosSe estudiaron los casos de DTN en nacidos y abortos inducidos durante el período 1990–2004, utilizando la base de datos del Registro de Defectos Congénitos de Asturias, de base poblacional. Se calcularon las tasas de prevalencia total y al nacimiento.ResultadosLa prevalencia total de DTN fue de 12,2 casos por 10.000 nacidos (5,9 anencefalias, 5,0 espinas bífidas y 1,3 encefaloceles) y mostró una tendencia ligeramente descendente, con un descenso significativo de la espina bífida, mientras que las cifras de anencefalia y encefalocele se mantuvieron estables. Finalizaron en aborto inducido tras el diagnóstico prenatal el 88% de los casos (anencefalia 96,7%; espina bífida 80%; encefalocele 84,6%), lo que determinó una prevalencia al nacimiento muy baja (1,4 DTN por 10.000 nacidos).ConclusionesEn Asturias, en los últimos 15 años se ha producido un descenso selectivo en la prevalencia total de espina bífida de causa no aclarada. La prevención secundaria, mediante los programas de diagnóstico prenatal y la consiguiente interrupción del embarazo, fue el motivo del marcado descenso de la frecuencia en los nacidos; la simple recomendación de suplementación periconcepcional con ácido fólico no parece haber logrado el efecto buscado(AU)

ObjectiveTo describe the frequency and prevalence trend for neural tube defects (NTD) (anencephaly, spina bifida and encephalocele) in Asturias (Spain), as well as the impact of prenatal diagnosis programs.MethodsAll cases of NTD in births and induced abortions were studied, using data from the Registry of Congenital Defects of Asturias for 1990-2004. Total and birth prevalence rates were calculated.ResultsThe prevalence of NTD for 1990–2004 was 12.2 per 10,000 births (5.9 anencephaly, 5.0 spina bifida and 1.3 encephalocele) and showed a slightly decreasing trend due to a significant decline in spina bifida prevalence. The prevalence of anencephaly and encephalocele remained stable. The percentage of induced abortions after prenatal diagnosis among all NTD was 88% (anencephaly 96.7%, spina bifida 80% and encephalocele 84.6%), leading to a very low birth prevalence (1.4 per 10,000) for the entire period.ConclusionsThe total prevalence of spina bifida has decreased in the last 15 years in Asturias. Secondary prevention through prenatal diagnosis and interruption of affected pregnancies have resulted in a marked decrease in NTD at birth. The recommendation of periconceptional use of folic acid seems not to have achieved the desired effect (AU)

Frecuencia y tendencia temporal de los defectos congénitos en Asturias. La necesidad de la vigilancia clinicoepidemiológica / Prevalence and secular trend of congenital defects in Asturias, Spain. The need for clinical-epidemiological surveillance

ObjetivoLos defectos congénitos son la segunda causa de muerte perinatal e infantil, y la tercera entre los 2 y 5 años de edad en Asturias. Además, generan una importante morbilidad. El objetivo de nuestro estudio fue conocer la frecuencia global de los defectos congénitos en Asturias y su forma de presentación.MétodosSe analizaron los datos del Registro de Defectos Congénitos de Asturias (RDCA), de base poblacional, durante el período 1990–2004. Los datos se refieren a nacidos y abortos inducidos después del diagnóstico prenatal, y se presentan como prevalencias al nacimiento y total (incluye los abortos inducidos).ResultadosSe registraron 3.035 casos de defectos congénitos entre 103.452 nacidos, con una prevalencia total de 2,9 casos por 100 nacidos y una prevalencia al nacimiento del 2,5%. Estas frecuencias presentaron una tendencia al aumento. Fueron 2.516 (82,9%) neonatos, 46 (1,5%) mortinatos y 473 (15,6%) abortos inducidos. El diagnóstico prenatal fue aumentando durante el citado período. Un 63% presentó un defecto aislado o una secuencia, un 17% un síndrome y el 20% restante defectos múltiples sin un patrón sindrómico conocido. Los defectos más frecuentes y graves fueron los del tubo neural (12,2 casos por 10.000 nacidos), las anomalías del corazón (75,2 por 10.000) y las cromosómicas (34,4 por 10.000).ConclusionesLa experiencia de 15 años del RDCA pone de manifiesto la necesidad de estos sistemas de información para evaluar los programas de diagnóstico prenatal, planificar adecuadamente los recursos de atención a las mujeres embarazadas que pudieran estar afectadas, así como a los recién nacidos, y asegurar la vigilancia epidemiológica de los defectos congénitos en relación con las exposiciones medioambientales y medicamentosas, y con las técnicas de reproducción asistida(AU)

ObjectiveCongenital defects remain the second cause of perinatal and infant death and the third cause between the second and fifth years of life in Asturias. These anomalies generate substantial morbidity. The aim of the present study was to describe the population-based frequency of congenital defects in Asturias and their forms of presentation.MethodsData from the population-based Registry of Congenital Defects of Asturias for 1990–2004 were analyzed. The data related to live births, stillbirths and induced abortions after prenatal diagnosis and are presented as birth prevalence and total prevalence (including induced abortions).ResultsThe total number of births was 103,452 and there were 3,035 cases of congenital defects, representing a total prevalence of 2.9 cases per 100 births and a birth prevalence of 2.5%. These figures showed a tendency to increase throughout the study period. A total of 2,516 (82.9%) cases were live births, 46 (1.5%) were stillbirths and 473 (15.6%) were induced abortions. Prenatal diagnosis increased throughout the period. Sixtythree percent of total cases showed an isolated defect, 17% a recognized syndrome and the remaining 20% had multiple malformations without a syndromic pattern. The most frequent and severe defects registered were neural tube defects (12.2 per 10,000 births), chromosomal abnormalities (34.4 per 10,000), and cardiac defects (75.2 per 10,000).ConclusionsThe 15-year experience of the Registry of Congenital Defects of Asturias reveals the utility of this type of database to evaluate prenatal screening programs, plan the resources needed in affected pregnant women and infants, and perform epidemiological surveillance of congenital defects in relation to environmental risks, drug exposure and assisted reproduction techniques(AU)

[Prevalence of neural tube defects in Asturias (Spain): impact of prenatal diagnosis]. / Frecuencia de los defectos del tubo neural en Asturias: impacto del diagnóstico prenatal.

OBJECTIVE: To describe the frequency and prevalence trend for neural tube defects (NTD) (anencephaly, spina bifida and encephalocele) in Asturias (Spain), as well as the impact of prenatal diagnosis programs. METHODS: All cases of NTD in births and induced abortions were studied, using data from the Registry of Congenital Defects of Asturias for 1990-2004. Total and birth prevalence rates were calculated. RESULTS: The prevalence of NTD for 1990-2004 was 12.2 per 10,000 births (5.9 anencephaly, 5.0 spina bifida and 1.3 encephalocele) and showed a slightly decreasing trend due to a significant decline in spina bifida prevalence. The prevalence of anencephaly and encephalocele remained stable. The percentage of induced abortions after prenatal diagnosis among all NTD was 88% (anencephaly 96.7%, spina bifida 80% and encephalocele 84.6%), leading to a very low birth prevalence (1.4 per 10,000) for the entire period. CONCLUSIONS: The total prevalence of spina bifida has decreased in the last 15 years in Asturias. Secondary prevention through prenatal diagnosis and interruption of affected pregnancies have resulted in a marked decrease in NTD at birth. The recommendation of periconceptional use of folic acid seems not to have achieved the desired effect.

[Prevalence and secular trend of congenital defects in Asturias, Spain. The need for clinical-epidemiological surveillance]. / Frecuencia y tendencia temporal de los defectos congénitos en Asturias. La necesidad de la vigilancia clinicoepidemiológica.

OBJECTIVE: Congenital defects remain the second cause of perinatal and infant death and the third cause between the second and fifth years of life in Asturias. These anomalies generate substantial morbidity. The aim of the present study was to describe the population-based frequency of congenital defects in Asturias and their forms of presentation. METHODS: Data from the population-based Registry of Congenital Defects of Asturias for 1990-2004 were analyzed. The data related to live births, stillbirths and induced abortions after prenatal diagnosis and are presented as birth prevalence and total prevalence (including induced abortions). RESULTS: The total number of births was 103,452 and there were 3,035 cases of congenital defects, representing a total prevalence of 2.9 cases per 100 births and a birth prevalence of 2.5%. These figures showed a tendency to increase throughout the study period. A total of 2,516 (82.9%) cases were live births, 46 (1.5%) were stillbirths and 473 (15.6%) were induced abortions. Prenatal diagnosis increased throughout the period. Sixtythree percent of total cases showed an isolated defect, 17% a recognized syndrome and the remaining 20% had multiple malformations without a syndromic pattern. The most frequent and severe defects registered were neural tube defects (12.2 per 10,000 births), chromosomal abnormalities (34.4 per 10,000), and cardiac defects (75.2 per 10,000). CONCLUSIONS: The 15-year experience of the Registry of Congenital Defects of Asturias reveals the utility of this type of database to evaluate prenatal screening programs, plan the resources needed in affected pregnant women and infants, and perform epidemiological surveillance of congenital defects in relation to environmental risks, drug exposure and assisted reproduction techniques.

[Varicella and parvovirus B19 immunity among pregnant women in Gijón, Spain]. / Prevalencia de inmunidad frente al virus de la varicela y al parvovirus B19 en gestantes de Gijón.

BACKGROUND: We aimed at determining the inmunological status regarding varicella and parvovirus B19 in pregnant women in Gijón, Spain, and its correlation with several clinical and epidemiological parameters. PATIENTS AND METHOD: Blood samples taken during the first trimester of pregnancy in the area of Gijón were analysed to determine the immunological status with respect to varicella and parvovirus B19. The study included 2 groups: 99 non-European (all tested for both varicella and parvovirus) and 2,188 Europeans (406 were randomly selected for varicella test and 287 for parvovirus test). All patients underwent a clinical-epidemiological survey. RESULTS: With regard to varicella, while 89% of pregnant women aged 14 to 35 years displayed immunity, this percentage reached 100% in those older than 35 years. Sensitivity was 73.8%, specificity 74.4%, positive predictive value 96.6% and negative predictive value was 22.6%. As for parvovirus B19, immunity was observed in 59.9% of Europeans and 67.7% of non-Europeans, without significant differences in the analysed parameters. CONCLUSIONS: Susceptibility to infection by varicella among pregnant women younger than 36 years reaches 10% in Gijón. Clinical surveys are useful to avoid a pre-vaccination serological study in an already immune population. Just over one third of these pregnant women are susceptible to infection by parvovirus B19.

Prevalencia de inmunidad frente al virus de la varicela y al parvovirus B19 en gestantes de Gijón / Varicella and parvovirus B19 immunity among pregnant women in Gijón, Spain

FUNDAMENTO: Conocer el estado inmunitario frente al virus de la varicela y parvovirus B19 entre gestantes del Área Sanitaria de Gijón y su correlación con los antecedentes clínico-epidemiológicos. PACIENTES Y MÉTODO: Estudio de muestras serológicas del primer trimestre gestacional (99 gestantes no europeas y muestra aleatoria entre 2.188 europeas, 406 para varicela y 287 para parvovirus B19), obtenidas entre diciembre 1998 y agosto 1997 en gestantes del área sanitaria de Gijón, realizándose una encuesta clínico-epidemiológica durante la hospitalización. RESULTADOS: Por lo que se refiere a la varicela, un 89 por ciento de las pacientes de entre 14 y 35 años eran inmunes; en mayores de 35 años, un 100 por ciento eran inmunes. La encuesta clínica presentó una sensibilidad del 73,8 por ciento; una especificidad del 74,4 por ciento; un valor predictivo positivo del 96,6 por ciento, y un valor predictivo negativo del 22,6 por ciento. En cuanto al parvovirus B19, eran inmunes el 59,9 por ciento de las pacientes europeas y un 67,7 por ciento de las no europeas. CONCLUSIONES: La susceptibilidad a la infección por la varicela detectada entre gestantes de menos de 36 años alcanza el 10 por ciento; la encuesta clínica es útil para evitar un estudio serológico prevacunal entre la población realmente inmune. Algo más de la tercera parte de nuestras gestantes son susceptibles a la infección por el parvovirus B19 (AU)