Human predecidual stromal cells are mesenchymal stromal/stem cells and have a therapeutic effect in an immune-based mouse model of recurrent spontaneous abortion

Las células estromales deciduales humanas (Decidual Stromal Cells, DSCs) son un tipo celular localizado en la decidua (endometrio gestante) y que están involucradas en el mantenimiento y desarrollo del embarazo al jugar un papel clave en la inducción de la tolerancia materno fetal. Los precursores de DSCs (preDSC) están localizados alrededor de los vasos y han sido relacionados con los pericitos y con las células madre mesenquimales (MSCs). Puesto que las MSCs tienen numerosas propiedades funcionales que les han permitido ser utilizadas como herramienta terapéutica para enfermedades proinflamatorias y/o autoinmunes. En este estudio se pretendió determinar la existencia de un efecto terapéutico de las preDSCs en un modelo murino de aborto de repetición para su posterior uso en enfermedades con un componente inmunitario y/o proinflamatorio. Los resultados mostraron la capacidad de las DSCs en modular el sistema inmunitario al permitir la implantación embrionaria en un cruce abortivo, lo que sugiere la modulación del sistema inmunitario hacia la tolerancia materno-fetal

¿Es Posible el Uso de la Postpartum Depression Screening Scale Short Form en la Depresión Antenatal?

El objetivo fue analizar la validez de la Escala de Depresión Posparto, forma abreviada (PDSS-SF) en la detección de los síntomas de depresión prenatal mediante el uso del cuestionario Patient Health Questionnaire-9 (PHQ-9) como gold standard. La muestra del presente estudio estuvo conformada por 449 gestantes reclutadas en el Hospital Clínico San Carlos de Madrid (España). Se utilizó un análisis de curva ROC. Los resultados indican que el área bajo la curva ROC para la depresión menor, moderada y severa fue .86, p < .001, .95, p < .001, y .99, p < .001, respectivamente. La sensibilidad y especificidad fueron .70 y .81 para la depresión menor con un punto de corte de 11, .85 y .88 para depresión moderada con un punto de corte de 14 y 1 y .99 con un punto de corte de 23 para depresión severa. Los resultados de PDSS-SF proporcionan una buena consistencia interna y muestran combinaciones satisfactorias de sensibilidad y especificidad. La PDSS-SF es una herramienta precisa para evaluar la depresión prenatal

miRNAs as radio-response biomarkers for breast cancer stem cells

In breast cancer (BC), the presence of cancer stem cells (CSCs) has been related to relapse, metastasis, and radioresistance. Radiotherapy (RT) is an extended BC treatment, but is not always effective. CSCs have several mechanisms of radioresistance in place, and some miRNAs are involved in the cellular response to ionizing radiation (IR). Here, we studied how IR affects the expression of miRNAs related to stemness in different molecular BC subtypes. Exposition of BC cells to radiation doses of 2, 4, or 6 Gy affected their phenotype, functional characteristics, pluripotency gene expression, and in vivo tumorigenic capacity. This held true for various molecular subtypes of BC cells (classified by ER, PR and HER-2 status), and for BC cells either plated in monolayer, or being in suspension as mammospheres. However, the effect of IR on the expression of eight stemness- and radioresistance-related miRNAs (miR-210, miR-10b, miR-182, miR-142, miR-221, miR-21, miR-93, miR-15b) varied, depending on cell line subpopulation and clinicopathological features of BC patients. Therefore, clinicopathological features and, potentially also, chemotherapy regimen should be both taken into consideration, for determining a potential miRNA signature by liquid biopsy in BC patients treated with RT. Personalized and precision RT dosage regimes could improve the prognosis, treatment, and survival of BC patients.This work has been partially funded by the Consejería de Economía, Conocimiento, Empresas y Universidad de la Junta de Andalucía and European Regional Development Fund (ERDF), ref. SOMM17/6109/ UGR, and with grants from the Ministry of Economy and Competitiveness (FEDER funds, projects no. PIE16/00045) and from the Chair ‘Doctors Galera- Requena in cancer stem cell research’ (CMC-CTS963)

KAT3-dependent acetylation of cell type-specific genes maintains neuronal identity in the adult mouse brain.

The lysine acetyltransferases type 3 (KAT3) family members CBP and p300 are important transcriptional co-activators, but their specific functions in adult post-mitotic neurons remain unclear. Here, we show that the combined elimination of both proteins in forebrain excitatory neurons of adult mice resulted in a rapidly progressing neurological phenotype associated with severe ataxia, dendritic retraction and reduced electrical activity. At the molecular level, we observed the downregulation of neuronal genes, as well as decreased H3K27 acetylation and pro-neural transcription factor binding at the promoters and enhancers of canonical neuronal genes. The combined deletion of CBP and p300 in hippocampal neurons resulted in the rapid loss of neuronal molecular identity without de- or transdifferentiation. Restoring CBP expression or lysine acetylation rescued neuronal-specific transcription in cultured neurons. Together, these experiments show that KAT3 proteins maintain the excitatory neuron identity through the regulation of histone acetylation at cell type-specific promoter and enhancer regions.The ultrastructure research was sup- ported by the Polish National Science Center Grant UMO-2014/15/N/NZ3/04468 and by the European Regional Development Fund POIG 01.01.02-00-008/08. J.P.L.-A. research is supported by Grants RYC-2015-18056 and RTI2018-102260-B-I00 from MICINN co- financed by ERDF. A.B. research is supported by Grants SAF2017-87928-R, PCIN-2015- 192-C02-01, and SEV-2017-0723 from MICINN co-financed by ERDF, PROMETEO/ 2016/026 from the Generalitat Valenciana, and RGP0039/2017 from the Human Fron- tiers Science Program Organization (HFSPO). The Instituto de Neurociencias is a “Centre of Excellence Severo Ochoa”

Case report: A familial B-acute lymphoblastic leukemia associated with a new germline pathogenic variant in PAX5. The first report in Mexico

B-cell acute lymphoblastic leukemia (B-ALL) is one of the most common childhood cancers worldwide. Although most cases are sporadic, some familial forms, inherited as autosomal dominant traits with incomplete penetrance, have been described over the last few years. Germline pathogenic variants in transcription factors such as PAX5, IKZF1, and ETV6 have been identified as causal in familial forms. The proband was a 7-year-old Mexican girl diagnosed with high-risk B-ALL at five years and 11 months of age. Family history showed that the proband’s mother had high-risk B-ALL at 16 months of age. She received chemotherapy and was discharged at nine years of age without any evidence of recurrence of leukemia. The proband’s father was outside the family nucleus, but no history of leukemia or cancer was present up to the last contact with the mother. We performed exome sequencing on the proband and the proband’s mother and identified the PAX5 variant NM_016734.3:c.963del: p.(Ala322LeufsTer11), located in the transactivation domain of the PAX5 protein. The variant was classified as probably pathogenic according to the ACMG criteria. To the best of our knowledge, this is the first Mexican family with an inherited increased risk of childhood B-ALL caused by a novel germline pathogenic variant of PAX5. Identifying individuals with a hereditary predisposition to cancer is essential for modern oncological practice. Individuals at high risk of leukemia would benefit from hematopoietic stem cell transplantation, but family members carrying the pathogenic variant should be excluded as hematopoietic stem cell donors

FUMEPOC: Early detection of chronic obstructive pulmonary disease in smokers

<p>Abstract</p> <p>Background</p> <p>Currently is not feasible using conventional spirometry as a screening method in Primary Care especially among smoking population to detect chronic obstructive pulmonary disease in early stages. Therefore, the FUMEPOC study protocol intends to analyze the validity and reliability of Vitalograph COPD-6 spirometer as simpler tool to aid screening and diagnosis of this disease in early stages in primary care surgery.</p> <p>Methods / Design</p> <p>Study design: An observational, descriptive study of diagnostic tests, undertaken in Primary Care and Pneumology Outpatient Care Centre at San Juan Hospital and Elda Hospital. All smokers attending the primary care surgery and consent to participate in the study will undergo a test with Vitalograph COPD-6 spirometer. Subsequently, a conventional spirometry will be performed in the hospital and the results will be compared with those of the Vitalograph COPD-6 test.</p> <p>Discussion</p> <p>It is difficult to use the spirometry as screening for early diagnose test in real conditions of primary care clinical practice. The use of a simpler tool, Vitalograph COPD-6 spirometer, can help in the early diagnose and therefore, it could improve the clinical management of the disease.</p

Ultrasound Muscle Evaluation for Predicting the Prognosis of Patients with Head and Neck Cancer: A Large-Scale and Multicenter Prospective Study

© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).Head and neck cancer (HNC) is a prevalent and aggressive form of cancer with high mortality rates and significant implications for nutritional status. Accurate assessment of malnutrition in patients with HNC is crucial for optimizing treatment outcomes and improving survival rates. This study aimed to evaluate the use of ultrasound techniques for predicting nutritional status, malnutrition, and cancer outcomes in patients with HNC. A total of 494 patients with HNC were included in this cross-sectional observational study. Various tools and body composition measurements, including muscle mass and adipose tissue ultrasound evaluations, were implemented. Using regression models, we mainly found that high levels of RF-CSA (rectus femoris cross-sectional area) were associated with a decreased risk of malnutrition (as defined with GLIM criteria (OR = 0.81, 95% CI: 0.68–0.98); as defined with PG-SGA (OR = 0.78, 95% CI: 0.62–0.98)) and sarcopenia (OR = 0.64, 95% CI: 0.49–0.82) after being adjusted for age, sex, and BMI. To predict the importance of muscle mass ultrasound variables on the risk of mortality, a nomogram, a random forest, and decision tree models were conducted. RF-CSA was the most important variable under the random forest model. The obtained C-index for the nomogram was 0.704, and the Brier score was 16.8. With an RF-CSA < 2.7 (AUC of 0.653 (0.59–0.77)) as a split, the decision tree model classified up to 68% of patients as possessing a high probability of survival. According to the cut-off value of 2.7 cm2, patients with a low RF-CSA value lower than 2.7 cm2 had worse survival rates (p < 0.001). The findings of this study highlight the importance of implementing ultrasound tools, for accurate diagnoses and monitoring of malnutrition in patients with HNC. Adipose tissue ultrasound measurements were only weakly associated with malnutrition and not with sarcopenia, indicating that muscle mass is a more important indicator of overall health and nutritional status. These results have the potential to improve survival rates and quality of life by enabling early intervention and personalized nutritional management.H.B. is supported by a predoctoral fellowship (“Plan Propio IBIMA 2020 A.1 Contratos predoctorales”, Ref.: predoc20_002) and by a “Sara Borrell” postdoctoral contract (CD22/00053) from the Instituto de Salud Carlos III—Madrid (Spain), “Financiado por la Unión Europea—NextGenerationEU” y mediante el Plan de Recuperación, Transformación y Resiliencia. This research was funded by FRESENEIUS KABI. The APC was funded by FRESENIUS KABI.Peer reviewe

Immigrant IBD Patients in Spain Are Younger, Have More Extraintestinal Manifestations and Use More Biologics Than Native Patients

BackgroundPrevious studies comparing immigrant ethnic groups and native patients with IBD have yielded clinical and phenotypic differences. To date, no study has focused on the immigrant IBD population in Spain. MethodsProspective, observational, multicenter study comparing cohorts of IBD patients from ENEIDA-registry who were born outside Spain with a cohort of native patients. ResultsWe included 13,524 patients (1,864 immigrant and 11,660 native). The immigrants were younger (45 +/- 12 vs. 54 +/- 16 years, p < 0.001), had been diagnosed younger (31 +/- 12 vs. 36 +/- 15 years, p < 0.001), and had a shorter disease duration (14 +/- 7 vs. 18 +/- 8 years, p < 0.001) than native patients. Family history of IBD (9 vs. 14%, p < 0.001) and smoking (30 vs. 40%, p < 0.001) were more frequent among native patients. The most prevalent ethnic groups among immigrants were Caucasian (41.5%), followed by Latin American (30.8%), Arab (18.3%), and Asian (6.7%). Extraintestinal manifestations, mainly musculoskeletal affections, were more frequent in immigrants (19 vs. 11%, p < 0.001). Use of biologics, mainly anti-TNF, was greater in immigrants (36 vs. 29%, p < 0.001). The risk of having extraintestinal manifestations [OR: 2.23 (1.92-2.58, p < 0.001)] and using biologics [OR: 1.13 (1.0-1.26, p = 0.042)] was independently associated with immigrant status in the multivariate analyses. ConclusionsCompared with native-born patients, first-generation-immigrant IBD patients in Spain were younger at disease onset and showed an increased risk of having extraintestinal manifestations and using biologics. Our study suggests a featured phenotype of immigrant IBD patients in Spain, and constitutes a new landmark in the epidemiological characterization of immigrant IBD populations in Southern Europe

Proyecto Virtus inter pares: el reto de la ética

Contamos la experiencia del primer a&ntilde;o del proyecto de innovaci&oacute;n docente PID 4&ordf;, denominado Virtus inter Pares, durante el curso acad&eacute;mico 2009-2010, en la Universidad de Ja&eacute;n