mRNA Decapping Activator Pat1 Is Required for Efficient Yeast Adaptive Transcriptional Responses via the Cell Wall Integrity MAPK Pathway.

Cellular mRNA levels, particularly under stress conditions, can be finely regulated by the coordinated action of transcription and degradation processes. Elements of the 5'-3' mRNA degradation pathway, functionally associated with the exonuclease Xrn1, can bind to nuclear chromatin and modulate gene transcription. Within this group are the so-called decapping activators, including Pat1, Dhh1, and Lsm1. In this work, we have investigated the role of Pat1 in the yeast adaptive transcriptional response to cell wall stress. Thus, we demonstrated that in the absence of Pat1, the transcriptional induction of genes regulated by the Cell Wall Integrity MAPK pathway was significantly affected, with no effect on the stability of these transcripts. Furthermore, under cell wall stress conditions, Pat1 is recruited to Cell Wall Integrity-responsive genes in parallel with the RNA Pol II complex, participating both in pre-initiation complex assembly and transcriptional elongation. Indeed, strains lacking Pat1 showed lower recruitment of the transcription factor Rlm1, less histone H3 displacement at Cell Wall Integrity gene promoters, and impaired recruitment and progression of RNA Pol II. Moreover, Pat1 and the MAPK Slt2 occupied the coding regions interdependently. Our results support the idea that Pat1 and presumably other decay factors behave as transcriptional regulators of Cell Wall Integrity-responsive genes under cell wall stress conditions.

Intelligent digital tools for screening of brain connectivity and dementia risk estimation in people affected by mild cognitive impairment: the AI-Mind clinical study protocol.

More than 10 million Europeans show signs of mild cognitive impairment (MCI), a transitional stage between normal brain aging and dementia stage memory disorder. The path MCI takes can be divergent; while some maintain stability or even revert to cognitive norms, alarmingly, up to half of the cases progress to dementia within 5 years. Current diagnostic practice lacks the necessary screening tools to identify those at risk of progression. The European patient experience often involves a long journey from the initial signs of MCI to the eventual diagnosis of dementia. The trajectory is far from ideal. Here, we introduce the AI-Mind project, a pioneering initiative with an innovative approach to early risk assessment through the implementation of advanced artificial intelligence (AI) on multimodal data. The cutting-edge AI-based tools developed in the project aim not only to accelerate the diagnostic process but also to deliver highly accurate predictions regarding an individual's risk of developing dementia when prevention and intervention may still be possible. AI-Mind is a European Research and Innovation Action (RIA H2020-SC1-BHC-06-2020, No. 964220) financed between 2021 and 2026. First, the AI-Mind Connector identifies dysfunctional brain networks based on high-density magneto- and electroencephalography (M/EEG) recordings. Second, the AI-Mind Predictor predicts dementia risk using data from the Connector, enriched with computerized cognitive tests, genetic and protein biomarkers, as well as sociodemographic and clinical variables. AI-Mind is integrated within a network of major European initiatives, including The Virtual Brain, The Virtual Epileptic Patient, and EBRAINS AISBL service for sensitive data, HealthDataCloud, where big patient data are generated for advancing digital and virtual twin technology development. AI-Mind's innovation lies not only in its early prediction of dementia risk, but it also enables a virtual laboratory scenario for hypothesis-driven personalized intervention research. This article introduces the background of the AI-Mind project and its clinical study protocol, setting the stage for future scientific contributions.

Cambios en la transmisión vertical del virus de la inmunodeficiencia humana: comparación de los años 1994 y 2004 / Changes in vertical HIV transmission: comparison between 1994 and 2004

Fundamento y objetivo: Desde la publicación del estudio PACTG 076 en 1994 se han desarrollado medidas profilácticas frente a la transmisión vertical (TV) del virus de la inmunodeficiencia humana (VIH), principal vía de infección infantil por el VIH. Se comparan las características de las embarazadas infectadas por el VIH y las tasas de TV del VIH de 1994 y las de 2004. Pacientes y método: Se estudian las variables maternas, obstétricas y pediátricas de mujeres infectadas por el VIH y sus hijos, nacidos en 1994 y 2004 y seguidos en el Hospital La Paz. Resultados: Se incluye a 40 parejas madre-hijo de 1994 y 35 de 2004. La tasa de TV del VIH fue del 35% en 1994 y del 0% en 2004. No se observaron cambios en la TV del virus de la hepatitis (VHC). En 1994 las madres infectadas por el VIH estaban más sintomáticas y la vía de infección era el uso de drogas intravenosas, el parto vaginal era el más frecuente, y el tiempo de bolsa rota, más prolongado. En 2004 la vía de infección materna por el VIH fue principalmente sexual, se ha generalizado el tratamiento antirretroviral combinado en la mujer seropositiva, en la gestación, la cesárea programada era más frecuente y todos los neonatos recibieron zidovudina. Conclusiones: En una década se han producido importantes cambios epidemiológicos en las gestantes infectadas por el VIH en nuestro medio. La administración de antirretrovirales en el embarazo y al neonato y las medidas obstétricas preventivas pueden evitar la TV del VIH. No obstante, no se ha observado modificación en el riesgo de TV del VHC

Background and objective: Vertical transmission (VT) is the main route of human immunodeficiency virus (HIV) infection in children. Since the publication of PACTG 076 study in 1994, several preventive methods against the vertical transmission of the HIV have been developed. In this study, we compare the clinical and epidemiological profile of HIV-infected pregnant women and the VT rate in the years 1994 and 2004. Patients and method: We looked at maternal, obstetric and pediatric variables of HIV-infected women and their children, born in 1994 and 2004, who were followed in Hospital La Paz. Results: We included 40 mother-infant couples in 1994 and 35 couples in 2004. The HIV vertical transmission rate was 35% in 1994 and 0% in 2004. We did not find changes in Hepatitis C virus (HCV) vertical transmission. In 1994, HIV-infected mothers had a more advanced HIV-disease and the major route of HIV-transmission was the intravenous drug use. Vaginal delivery was more frequent and rupture of membranes was longer than in 2004. The main route of maternal HIV infection in 2004 was sexual contact. In this same year, the use of combination antiretroviral therapy, even during pregnancy, was generalized, the elective cesarean section was the most frequent form of delivery, and every newborn received zidovudine. Conclusions: In the last decade, there have been important epidemiological changes in HIV-infected mothers in our society. The administration of antiretroviral therapy during pregnancy and to the newborn, as well as other obstetric strategies, can prevent HIV vertical transmission. Nevertheless, we did not find any change in the risk of HCV vertical transmission

Revaluación del método estándar (criterios de Light) para identificar exudados pleurales / Reappraisal of the standard method (Light's criteria) for identifying pleural exudates

Fundamento y objetivos: Los criterios de Light se consideran el mejor método para diferenciar los exudados de los trasudados pleurales. Nos proponemos evaluar sus características operativas, así como las que resultan de eliminar el cociente de lactatodeshidrogenasa (LDH) entre líquido pleural y suero de los criterios originales (criterios de Light abreviados), en una serie amplia de pacientes. Asimismo buscamos la mejor combinación de parámetros bioquímicos del líquido pleural (entre ellas proteínas, LDH y colesterol), capaz de identificar exudados. Pacientes y método: Se analizó retrospectivamente a 1.490 pacientes consecutivos con derrame pleural a quienes se había realizado una toracentesis. El diagnóstico final fue de exudado en 1.192 y de trasudado en 298. Se calcularon la sensibilidad, especificidad, área bajo la curva de eficacia diagnóstica y odds ratio tanto de parámetros individuales como combinados del líquido pleural. Resultados: La sensibilidad y especificidad de los criterios de Light fueron del 97,5 y el 80%, respectivamente. Tanto los criterios de Light abreviados (sensibilidad del 95,4% y especificidad del 83,3%) como la combinación, con una regla en «o», de las proteínas y LDH del líquido pleural (sensibilidad del 95,4% y especificidad del 80,2%) tuvieron la misma capacidad discriminatoria que los criterios estándar. Conclusiones: La identificación de los exudados pleurales se puede realizar con los criterios de Light abreviados cuando no se dispone del valor de la LDH sérica. Por otro lado, si la extracción sanguínea no es posible (circunstancia infrecuente), la combinación de proteínas y LDH pleurales serviría también como criterio diagnóstico alternativo a los criterios clásicos de Light

Background and objectives: Light's criteria remain the best method for separating pleural exudates from transudates. We assessed their operating characteristics, as well as those resulting from omitting the pleural fluid to serum lactate dehydrogenase (LDH) ratio from the original criteria (abbreviated Light criteria), in a large series of patients. We also searched for the best combination of pleural fluid parameters, including protein, LDH and cholesterol that identify exudates. Patients and method: We conducted a retrospective study of 1,490 consecutive patients with pleural effusion who underwent a diagnostic thoracentesis. There were 1,192 exudates and 298 transudates. Sensitivity, specificity, area under ROC curve, and odds ratio for both individual and combined pleural fluid parameters were calculated. Results: Light's criteria yielded 97.5% sensitivity and 80% specificity. Both abbreviated Light criteria (sensitivity: 95.4%; specificity: 83.3%) and the combined use in an «or» rule of pleural fluid protein and LDH (sensitivity: 95.4%; specificity: 80,2%) had similar discriminative properties than standard criteria. Conclusions: Diagnostic separation of pleural effusions into exudates or transudates can be done effectively thorough the abbreviated Light criteria when the serum LDH value is not available. On the other hand, if venipuncture wants to be avoided (an unusual circumstance) the combination of pleural fluid protein and LDH represents an alternative to Light's criteria

Presentación clínica de meningiomas intracraneales durante los tratamientos prolongados con progesterona ULO / Clinical onset of intracranial meningiomas during prolonged progesterone therapy

En este artículo describimos 3 casos clínicos de pacientes que, por diferentes causas ginecológicas, recibieron progesterona durante largos períodos. Los 3 casos se presentaron con clínica neurológica, y en las pruebas de imagen se descubrieron meningiomas intracraneales. Las pacientes fueron intervenidas y la anatomía patológica de todas ellas reveló la presencia de meningiomas intracraneales con receptores positivos para progesterona. Los tratamientos prolongados con progesterona podrían promover el crecimiento de meningiomas intracraneales en algunas pacientes

In this article we describe three cases reports about patients who were treated with progestins long time by different gynaecologic causes. Three patients started with neurological clinic and their imaging studies discovered intracraneal meningiomas of various sizes. All of them required treatment with combination of excision and stereotactic surgery. All of excised tumors showed positive staining for progesterone receptors of inmunohistochemical examination. Prolonged therapy with progesterone could promote the growth of benign intracranial meningiomas in some patients, indepently of doses and administration ways