Impacto del estado emocional materno, el consumo de tóxicos durante el embarazo y la intervención farmacológica periparto sobre el resultado perinatal, el grado de satisfacción materna y la programación de la salud infantil. Propuesta de un programa educacional para gestantes.

La epigenética y la programación perinatal son campos recientes y en expansión, aunque poco explorados en la obstetricia moderna. Factores ambientales, influyendo en el periodo perinatal, pueden producir modificaciones epigenéticas en el recién nacido con alteraciones fenotípicas y mayor predisposición a enfermedades en su vida adulta. Objetivos: Determinar los factores estresores materno-fetales sobre los que actuar reduciendo su impacto negativo en la programación perinatal y el vínculo materno-filial para desarrollar intervenciones (médico-educativas) en esta línea. Estudiar la satisfacción materna y efectos perinatales de nuestras actuaciones intraparto analizando la relación de analgesia con satisfacción materna y efecto neonatal y de oxitocina con vínculo materno-filial, lactancia y neurodesarrollo pediátrico. Valorar los factores psicosomáticos del embarazo y parto, concretamente identificar la ansiedad y depresión prenatales para reconocerlas, tratarlas, buscar factores de riesgo y descubrir su repercusión sobre neonato, embarazo, parto y vínculo materno-filial. Y estudiar los factores psicosomáticos indirectos tales como los hábitos tóxicos en gestantes, para valorar la exposición prenatal de recién nacidos a sustancias de abuso. Finalmente, a partir de todos los datos obtenidos plantear un programa educacional con estrategias de mejora de calidad de la educación perinatal actual, para mejorar su impacto en el consumo en gestantes de tóxicos y sustancias de abuso, proponiendo una campaña de educación sanitaria sobre el consumo alcohólico prenatal para reducir su ingesta y mejorar resultados perinatales. Material y métodos 1. Realizamos un estudio prospectivo sobre la satisfacción materna y los efectos perinatales del uso de analgesia epidural o intravenosa en el parto siguiendo a madre y recién nacido en pre-parto, parto, post-parto inmediato y los dos o tres días posteriores. 2. Estudiamos los factores psicosomáticos y su relación con el desarrollo del vínculo materno-filial, valorando los efectos del estres, ansiedad o depresión de las gestantes sobre los resultados gestacionales, lactancia y adaptación entre madre y recién nacido. 3. Estudiamos el efecto de la oxitocina en el parto sobre la lactancia y desarrollo psicoevolutivo de los niños a los 5 años, mediante un estudio de cohortes retrospectivo. 4. Realizamos un estudio observacional, descriptivo, de corte transversal de prevalencia sobre consumo de tóxicos y sustancias de abuso en el embarazo. 5. Nuesta propuesta educacional está elaborada pero pendiente de evaluar mediante la puesta en marcha de un ensayo clínico aleatorizado y controlado sobre la eficacia de un programa extensivo de educación sanitaria en la reducción / abstinencia del consumo de alcohol en el embarazo, cuyo impacto se evaluará mediante entrevistas postparto y determinación en el pelo de trazas de alcohol procedentes de consumo reciente. Resultados y discusión 1. Las gestantes consideran la analgesia intraparto epidural como la mejor opción para aliviar el dolor y que permite un mayor grado de satisfacción materna. En ausencia de diferencias en la forma determinar el parto, eutócico vs. no eutócico, y condiciones equiparables de normalidad del estado neonatal postparto, las gestantes valoraron más positivamente, la menor intensidad de dolor y la menor duración del tiempo en trabajo de parto, que coincidían con el menor grado de ansiedad de las pacientes y su mayor cooperación en el trabajo de parto. 2. Respecto a la influencia de factores psicosomáticos observamos: Más alteraciones psicológicas en multíparas y con abortos previos, amas de casa y trabajadoras de hostelería. Los problemas psicopatológicos y de pareja, influyen en la vulnerabilidad psíquica de las gestantes. Los principales cuadros fueron hiperémesis y ansiedad, seguidos de depresión. El tratamiento en la ansiedad fue opiaceo, y en depresión, ISRS. Hubo un 16% de parto prematuro (mayor que en población normal) y casi 1/10 casos de dificultad de adaptación al recién nacido y peor vínculo materno-filial. 3. La oxitocina intraparto, tuvo impacto negativo en el inicio y duración de la lactancia, sobretodo en ciertos grupos pero, aunque no afectó al riesgo total de tener puntuaciones bajas en el Inventario de Desarrollo Battelle, sí tuvo efecto según edad y tipo de parto. 4. Sobre la exposición prenatal a sustancias de abuso, en cada trimemtre hubo una prevalencia de consumo del 21.2%, 18.5% y 13.3% para tabaco; 40.7%, 23.1% y 17.1% para alcohol y del 4.8%, 1.9% y 1.2% para cannabis. Además un mayor nivel de estudios se asoció a menor consumo de tabaco y mayor exposición a alcohol. Conclusiones principales Gracias a nuestro trabajo sobre anestesia intraparto, sabemos que ciertas conductas médicas pueden influir en la forma de percibir la paciente el nacimiento de su hijo. Dicha vivencia puede desencadenar sentimientos de satisfacción o frustación que se asocien a nivel físico o psicológico con situaciones estresoras que al ocurrir en un momento tan delicado, tendrían un potencial efecto a nivel epigenético en el vínculo materno-filial y posiblemente sobre la futura salud de la descendencia. Nuestros resultados sobre el estudio de los problemas psicosomáticos en la gestación permite acercarnos a un perfil de embarazada con mayor vulnerabilidad psíquica, que alertaría de los casos que necesitan ayuda, incitándonos a investigar más a fondo su salud emocional. Nuestra detección ampliada de la patología psicosomática puede ayudar a mejorar la calidad de nuestra atención, disminuyendo sus efectos nocivos sobre la paciente y el desarrollo de su descendencia, contribuyendo a mejorar situaciones como la prematuridad o la dificultad de adaptacion materno-filial. La oxitocina exógena intraparto puede interferir en la lactancia, alterando su inicio y duración y afectar al desarrollo neuropsicológico infantil, efecto que se modifica según el tipo de parto y edad materna. Los resultados sobre la prevalencia de hábitos tóxicos en gestantes, son suficientemente llamativos como para alertar a los proveedores de atención obstétrica sobre la necesidad de poner en marcha medidas preventivas que reduzcan la exposición prenatal a sustancias que podrían relacionarse con daños epigenéticos en la descendencia. Nuestra investigación demuestra que es necesaria la puesta en marcha de medidas eficaces que como una campaña específica de educación sanitaria en gestantes, para reducir el consumo de sustancias de abuso, concretamente del alcohol

Measuring Resilience in Women with Endometriosis

Endometriosis is a multifactorial disease with pathophysiological factors not yet well known; it also presents a wide symptomatic range that makes us think about the need for multidisciplinary management. It is a chronic disease in which there is no definitive treatment, and is associated in a large majority of cases with psychological pathology. Connecting comorbidities and multimorbidities on a neurobiological, neuropsychological, and pathophysiological level could significantly contribute to their more successful prevention and treatment. In our study, resilience is analyzed as an adjunctive measure in the management of endometriosis. Methods: A multi-centre, cross-sectional study was performed to analyse resilience levels in a sample of Spanish women suffering from endometriosis. CDRIS-25, CDRIS-10, BDI, the STAI, and the SF-36 Health Questionnaire were used for assessments. A representative group of 202 women with endometriosis was recruited by consecutive sampling. Exploratory and confirmatory factor analyses were performed for both resilience scales. Results: Mean CDRIS-25 and CDRIS-10 scores were 69.58 (SD 15.1) and 29.37 (SD 7.2), respectively. Women with adenomyosis and without signs of deep endometriosis showed the lowest scores. The best predictive model included women's age, years of endometriosis evolution, number of pregnancies, and history of fertility problems as the best predictive factors. Conclusions: Women build resilience as the number of years of evolution of the disease increases. Symptoms such as dyspareunia and continued abdominal pain were more prevalent among less resilient women

Obstetric and Perinatal Outcomes after Very Early Preterm Premature Rupture of Membranes (PPROM)-A Retrospective Analysis over the Period 2000-2020

Background and Objectives: Pre-term premature rupture of membranes (PPROM) responds for one third of preterm births, and it is associated with other complications that increase the risk of maternal or fetal poor outcome. To reduce uncertainty and provide accurate information to patients, the analysis of the large series is of great importance. In order to learn about the evolution over the time of the obstetric and perinatal outcomes in cases of PPROM at, or before, 28 weeks (very early PPROM) managed with an expectant/conservative protocol, we have designed the present study. Materials and Methods: We retrospectively studied all cases of very early PPROM attended in Malaga University Regional Hospital from 2000 to 2020. Results: Among 119,888 deliveries assisted, 592 cases of PPROM occurred in pregnancies at or before 28 weeks (0.49% of all deliveries, 3.9% of all preterm births and 12.9% of all cases of PPROM). The mean duration of the latency period between PPROM and delivery was 13.5 days (range 0 to 88 days), enlarging over the years. The mean gestational age at delivery was 27 weeks (SD 2.9; range 17-34). The proportion of cesarean deliveries was 52.5%. The overall perinatal mortality rate was 26.5%, decreasing over the period with a significant correlation Pearson's coefficient -0.128 (p < 0.05). Conclusions: In the period 2000-2020, there was an improvement in the outcomes of very early PPROM cases and perinatal mortality showed a clear trend to decrease.This publication was financed with funds from the University of Malaga

Influence of induction therapy, immunosuppressive regimen and anti-viral prophylaxis on development of lymphomas after heart transplantation: data from the spanish post–heart transplant tumour registry

[Abstract] Background. Lymphoma after heart transplantation (HT) has been associated with induction therapy and herpesvirus infection. It is not known whether anti-viral agents administered immediately after HT can reduce the incidence of lymphoma. Methods. This study was a retrospective review of 3,393 patients who underwent HT in Spain between 1984 and December 2003. Variables examined included development of lymphoma and, as possible risk factors, recipient gender and age, induction therapies (anti-thymocyte globulin, OKT3 and anti–interleukin-2 receptor antibodies) and anti-viral prophylaxis (acyclovir or ganciclovir). To study the effect of evolving treatment strategy, three HT eras were considered: 1984 to 1995; 1996 to 2000; and 2001 to 2003. Results. Induction therapy was employed in >60% of HTs, and anti-viral prophylaxis in >50%. There were 62 cases of lymphoma (3.1 per 1,000 person-years, 95% confidence interval: 2.4 to 4.0). Univariate analyses showed no influence of gender, age at transplant, HT era, pre-HT smoking or the immunosuppressive maintenance drugs used in the first 3 months post-HT. The induction agent anti-thymocyte globulin (ATG) was associated with increased risk of lymphoma, and prophylaxis with acyclovir with decreased risk of lymphoma. Multivariate analyses (controlling for age group, gender, pre-HT smoking and immunosuppression in the first 3 months with mycophenolate mofetil and/or tacrolimus) showed that induction increased the risk of lymphoma if anti-viral prophylaxis was not used (regardless of induction agent and anti-viral agent), but did not increase the risk if anti-viral prophylaxis was used. Conclusions. Induction therapies with ATG or OKT3 do or do not increase the risk of lymphoma depending on whether anti-viral prophylaxis with acyclovir or ganciclovir is or is not employed, respectively

Aberrant upregulation of the glycolytic enzyme PFKFB3 in CLN7 neuronal ceroid lipofuscinosis

CLN7 neuronal ceroid lipofuscinosis is an inherited lysosomal storage neurodegenerative disease highly prevalent in children. CLN7/MFSD8 gene encodes a lysosomal membrane glycoprotein, but the biochemical processes affected by CLN7-loss of function are unexplored thus preventing development of potential treatments. Here, we found, in the Cln7∆ex2 mouse model of CLN7 disease, that failure in autophagy causes accumulation of structurally and bioenergetically impaired neuronal mitochondria. In vivo genetic approach reveals elevated mitochondrial reactive oxygen species (mROS) in Cln7∆ex2 neurons that mediates glycolytic enzyme PFKFB3 activation and contributes to CLN7 pathogenesis. Mechanistically, mROS sustains a signaling cascade leading to protein stabilization of PFKFB3, normally unstable in healthy neurons. Administration of the highly selective PFKFB3 inhibitor AZ67 in Cln7∆ex2 mouse brain in vivo and in CLN7 patients-derived cells rectifies key disease hallmarks. Thus, aberrant upregulation of the glycolytic enzyme PFKFB3 in neurons may contribute to CLN7 pathogenesis and targeting PFKFB3 could alleviate this and other lysosomal storage diseases

Aberrant upregulation of the glycolytic enzyme PFKFB3 in CLN7 neuronal ceroid lipofuscinosis

CLN7 neuronal ceroid lipofuscinosis is an inherited lysosomal storage neurodegenerative disease highly prevalent in children. CLN7/MFSD8 gene encodes a lysosomal membrane glycoprotein, but the biochemical processes affected by CLN7-loss of function are unexplored thus preventing development of potential treatments. Here, we found, in the Cln7∆ex2 mouse model of CLN7 disease, that failure in autophagy causes accumulation of structurally and bioenergetically impaired neuronal mitochondria. In vivo genetic approach reveals elevated mitochondrial reactive oxygen species (mROS) in Cln7∆ex2 neurons that mediates glycolytic enzyme PFKFB3 activation and contributes to CLN7 pathogenesis. Mechanistically, mROS sustains a signaling cascade leading to protein stabilization of PFKFB3, normally unstable in healthy neurons. Administration of the highly selective PFKFB3 inhibitor AZ67 in Cln7∆ex2 mouse brain in vivo and in CLN7 patients-derived cells rectifies key disease hallmarks. Thus, aberrant upregulation of the glycolytic enzyme PFKFB3 in neurons may contribute to CLN7 pathogenesis and targeting PFKFB3 could alleviate this and other lysosomal storage diseases.This work was funded by the European Regional Development Fund, European Union’s Horizon 2020 Research and Innovation Programme (BATCure grant No. 666918 to J.P.B., S.E.M., D.L.M., S.S., and T.R.M.; PANA grant No. 686009 to A.A.), Agencia Estatal de Investigación (PID2019-105699RB-I00/AEI/10.13039/501100011033 and RED2018‐102576‐T to J.P.B.; SAF2017-90794-REDT to A.A.), Instituto de Salud Carlos III (CB16/10/00282 to J.P.B.; PI18/00285; RD16/0019/0018 to A.A.), Junta de Castilla y León (CS/151P20 and Escalera de Excelencia CLU-2017-03 to J.P.B. and A.A.), Ayudas Equipos Investigación Biomedicina 2017 Fundación BBVA (to J.P.B.), and Fundación Ramón Areces (to J.P.B. and A.A.). SM benefits from MRC funding to the MRC Laboratory for Molecular Cell Biology University Unit at UCL (award code MC_U12266B) towards lab and office space. Part of this work was funded by Gero Discovery L.L.C. M.G.M. is an ISCIII-Sara Borrel contract recipient (CD18/00203)

Transmitted Fetal Immune Response in Cases of SARS-CoV-2 Infections during Pregnancy

(1) Background: Little is known about the effects of SARS-CoV-2 on the placenta, and whether the maternal inflammatory response is transmitted vertically. This research aims to provide information about the effects of SARS-CoV-2 infection on maternal and fetal immunity. (2) Methods: We have studied placental changes and humoral and cellular immunity in maternal and umbilical cord blood (UCB) samples from a group of pregnant women delivering after the diagnosis of SARS-CoV-2 infection during pregnancy. IgG and IgM SARS-CoV-2 antibodies, Interleukin 1b (IL1b), Interleukin 6 (IL6), and gamma-Interferon (IFN-γ), have been studied in the UCB samples. Lymphocyte subsets were studied according to CD3, CD8, CD4, CD34, and invariant natural Killer T cells (iNKT) markers. We used in situ hybridization techniques for the detection of viral RNA in placentas. (3) Results: During the study period, 79 pregnant women and their corresponding newborns were recruited. The main gestational age at the time of delivery was 39.1 weeks (SD 1.3). We did not find traces of the SARS-CoV-2 virus RNA in any of the analyzed placental samples. Detectable concentrations of IgG anti-SARS-CoV-2 antibodies, IL1b, IL6, and IFN-γ, in UCB were found in all cases, but IgM antibodies anti-ARS-CoV-2 were systematically undetectable. We found significant correlations between fetal CD3+ mononuclear cells and UCB IgG concentrations. We also found significant correlations between UCB IgG concentrations and fetal CD3+/CD4+, as well as CD3+/CD8+ T cells subsets. We also discovered that fetal CD3+/CD8+ cell counts were significantly higher in those cases with placental infarctions. (4) Conclusion: we have not verified the placental transfer of SARS-CoV-2. However, we have discovered that a significant immune response is being transmitted to the fetus in cases of SARS-CoV-2 maternal infection.Partial funding for open access charge: Universidad de Málaga. This research was funded by Ferring COVID-19 Investigational Grant Placental injury and immune reaction transmitted to the neonates in cases of SARS-CoV-2 infections during pregnancy. Study on placental and blood cord samples. The APC was funded by University of Málaga. Funding institutions did not participate in the design, recruitment, analysis, or interpretation of the results

Dual latent tuberculosis screening with tuberculin skin tests and QuantiFERON-TB assays before TNF-α inhibitor initiation in children in Spain

Tumor-necrosis-factor-α inhibitors (anti-TNF-α) are associated with an increased risk of tuberculosis (TB) disease, primarily due to reactivation of latent TB infection (LTBI). We assessed the performance of parallel LTBI screening with tuberculin skin test (TST) and QuantiFERON-TB Gold In-Tube assays (QFT-GIT) before anti-TNF-α treatment in children with immune-mediated inflammatory disorders in a low TB-burden setting. We conducted a multicenter cohort study involving 17 pediatric tertiary centers in Spain. LTBI was defined as the presence of a positive TST and/or QFT-GIT result without clinical or radiological signs of TB disease. A total of 270 patients (median age:11.0 years) were included, mainly with rheumatological (55.9%) or inflammatory bowel disease (34.8%). Twelve patients (4.4%) were diagnosed with TB infection at screening (LTBI, n = 11; TB disease, n = 1). Concordance between TST and QFT-GIT results was moderate (TST+/QFT-GIT+, n = 4; TST-/QFT-GIT+, n = 3; TST+/QFT-GIT-, n = 5; kappa coefficient: 0.48, 95% CI: 0.36-0.60). Indeterminate QFT-GIT results occurred in 10 patients (3.7%) and were associated with young age and elevated C-reactive protein concentrations. Eleven of 12 patients with TB infection uneventfully completed standard LTBI or TB treatment. During a median follow-up period of 6.4 years, only 2 patients developed TB disease (incidence density: 130 (95% CI: 20-440) per 100,000 person-years), both probable de novo infections. Conclusion: A substantial number of patients were diagnosed with LTBI during screening. The dual strategy identified more cases than either of the tests alone, and test agreement was only moderate. Our data show that in children in a low TB prevalence setting, a dual screening strategy with TST and IGRA before anti-TNF-α treatment is effective

Impact of the first wave of the SARS-CoV-2 pandemic on the outcome of neurosurgical patients: A nationwide study in Spain

Objective To assess the effect of the first wave of the SARS-CoV-2 pandemic on the outcome of neurosurgical patients in Spain. Settings The initial flood of COVID-19 patients overwhelmed an unprepared healthcare system. Different measures were taken to deal with this overburden. The effect of these measures on neurosurgical patients, as well as the effect of COVID-19 itself, has not been thoroughly studied. Participants This was a multicentre, nationwide, observational retrospective study of patients who underwent any neurosurgical operation from March to July 2020. Interventions An exploratory factorial analysis was performed to select the most relevant variables of the sample. Primary and secondary outcome measures Univariate and multivariate analyses were performed to identify independent predictors of mortality and postoperative SARS-CoV-2 infection. Results Sixteen hospitals registered 1677 operated patients. The overall mortality was 6.4%, and 2.9% (44 patients) suffered a perioperative SARS-CoV-2 infection. Of those infections, 24 were diagnosed postoperatively. Age (OR 1.05), perioperative SARS-CoV-2 infection (OR 4.7), community COVID-19 incidence (cases/10 5 people/week) (OR 1.006), postoperative neurological worsening (OR 5.9), postoperative need for airway support (OR 5.38), ASA grade =3 (OR 2.5) and preoperative GCS 3-8 (OR 2.82) were independently associated with mortality. For SARS-CoV-2 postoperative infection, screening swab test <72 hours preoperatively (OR 0.76), community COVID-19 incidence (cases/10 5 people/week) (OR 1.011), preoperative cognitive impairment (OR 2.784), postoperative sepsis (OR 3.807) and an absence of postoperative complications (OR 0.188) were independently associated. Conclusions Perioperative SARS-CoV-2 infection in neurosurgical patients was associated with an increase in mortality by almost fivefold. Community COVID-19 incidence (cases/10 5 people/week) was a statistically independent predictor of mortality. Trial registration number CEIM 20/217

Report: Labour and social security law in Spain in 2013

El informe ha sido elaborado por la Sección Juvenil de la Asociación Española de Derecho del Trabajo y Seguridad SocialEste documento intenta reflejar algunos de los principales cambios y novedades del ordenamiento laboral español en 2013, levantando acta de cómo la mutabilidad de nuestro Derecho del Trabajo es imparable. Este informe, consciente de ello, ofrece una selección de elementos esenciales, a juicio de sus autores, especialistas en cada una de las materias, encuadrados en la Sección Juvenil de la Asociación Española de Derecho del Trabajo y de la Seguridad Social. En él, conforme a la organización de dicha Sección en grupos de trabajo, se abordan las novedades más relevantes en materia de derechos fundamentales inespecíficos, contratación laboral, vicisitudes del contrato de trabajo, Derecho colectivo, conciliación y corresponsabilidad, protección social y prevención de riesgos laborales.This paper tries to show some of the many changes and novelties in Spanish Labour Law during 2013, drawing up a record of the unstoppable character of our Labour legal system. This report offers a selection of essential elements, according to its authors, all of them specialists in each one of the subjects, being part of the Young Scholars’ Section of the Spanish Association for Labour and Social Security Law. According to the organization of the said Section in working groups, we can find novelties concerning unspecific fundamental rights, work contracts, the life of the work contract and collective Labour Law, reconciliation and co responsibility, social protection and occupational risk preventio