Generación de un modelo celular de síndrome PAPA utilizando la técnica CRISPR/Cas9.

Con los datos proporcionados previamente, podemos definir como objetivo del trabajo la obtención de un modelo celular del síndrome PAPA, analizando los efectos a pequeña escala de las mutaciones que provocan la enfermedad, usando una línea celular de estirpe monocítica. Para ello se seleccionan las dos mutaciones más recurrentes encontradas en pacientes con el síndrome PAPA (A230T y E250Q), y se introducen en una línea celular humana a través del sistema de endonucleasas CRISPR/Cas9. Para este fin, se plantean los siguientes objetivos: - Construcción de vectores que contengan el gen de la nucleasa Cas9 nickasa y las secuencias guía específicas, con el fin de obtener cortes de cadena simple en lugares específicos del genoma en el gen CD2BP1 en las células diana. - Construcción de dos plásmidos donantes que contengan parte del gen CD2BP1 con sendas mutaciones que causan el síndrome PAPA. - Introducción de los plásmidos CRISPR junto con los plásmidos donantes en células THP-1 mediante nucleofección. - Selección de los clones celulares modificados que incorporan la mutación mediante PCR y dilución límite.Instituto de Biología y Genética Molecular (IBGM)Máster en Investigación Biomédic

Efecto de una intervención educativa en la hemoglobina capilar en una comunidad indígena de la Huasteca Potosina. Estudio piloto

Introduction: The aim of this study was to assess an educational intervention emphasizing the use of foods available in an indigenous community in the Huasteca Potosina on capillary hemoglobin.Material and methods: A quasi-experimental one-group pretest-posttest study was carried out December 2014 to December 2015 in children aged 0 to 5 years in the community of Tocoy, San Antonio, San Luis Potosí, Mexico. A 6 months intervention consisted in nutritional education workshops which included informational talks, cooking workshops and feedback of the main topics was carried out. An evaluation was performed in which nutritional status (anthropometric measurements and capillary hemoglobin concentration) and macro and micronutrient intake (24-hour recall) were assessed before and 4 months after the intervention. Results: We found that our intervention had significant effects on hemoglobin values increased from 11.3±1.3 to 12.0±1.4 mg/dl (p=0.025), and the anemia prevalence decrease from 37% to 25,9%. Conclusions: An educational intervention emphasizing the use of foods available in the community could contribute to improve capillary hemoglobin concentration in children from an indigenous community in the Huasteca Potosina.Introducción: El objetivo de esta investigación fue evaluar el efecto de una intervención educativa contextualizada a los alimentos disponibles en una comunidad indígena de la Huasteca Potosina, sobre la hemoglobina capilar.Material y métodos: Se llevó a cabo un estudio cuasiexperimental pretest-postest de un solo grupo, de diciembre de 2014 a diciembre de 2015 en niños indígenas de 0 a 5 años, de la comunidad de Tocoy, San Antonio, San Luis Potosí, México. Se realizó una intervención de 6 meses y constó de talleres de educación nutricional los cuales incluían pláticas informativas, talleres de cocina y retroalimentación de los conocimientos impartidos. Se realizó una evaluación previa a la intervención y 4 meses posteriores a esta, en la que se valoró el estado nutricio (medidas antropométricas y concentración de hemoglobina capilar) y la ingesta de macro y micronutrimentos (recordatorios de 24 horas). Resultados: Se encontró un aumento en la concentración de hemoglobina capilar de 11,3±1,3 a 12,0±1,4 mg/dl (p=0,025) y la prevalencia de anemia disminuyó de 37 a 25.9%.Conclusiones: Una intervención educativa contextualizada a los alimentos disponibles en una comunidad puede contribuir a mejorar las concentraciones de hemoglobina capilar en niños menores de 5 años en una comunidad indígena de la Huasteca potosina

Early Stepdown From Echinocandin to Fluconazole Treatment in Candidemia: A Post Hoc Analysis of Three Cohort Studies

[Background] There are no clear criteria for antifungal de-escalation after initial empirical treatments. We hypothesized that early de-escalation (ED) (within 5 days) to fluconazole is safe in fluconazole-susceptible candidemia with controlled source of infection.[Methods] This is a multicenter post hoc study that included consecutive patients from 3 prospective candidemia cohorts (2007–2016). The impact of ED and factors associated with mortality were assessed.[Results] Of 1023 candidemia episodes, 235 met inclusion criteria. Of these, 54 (23%) were classified as the ED group and 181 (77%) were classified as the non-ED group. ED was more common in catheter-related candidemia (51.9% vs 31.5%; P = .006) and episodes caused by Candida parapsilosis, yet it was less frequent in patients in the intensive care unit (24.1% vs 39.2%; P = .043), infections caused by Nakaseomyces glabrata (0% vs 9.9%; P = .016), and candidemia from an unknown source (24.1% vs 47%; P = .003). In the ED and non-ED groups, 30-day mortality was 11.1% and 29.8% (P = .006), respectively. Chronic obstructive pulmonary disease (odds ratio [OR], 3.97; 95% confidence interval [CI], 1.48–10.61), Pitt score > 2 (OR, 4.39; 95% CI, 1.94–9.20), unknown source of candidemia (OR, 2.59; 95% CI, 1.14–5.86), candidemia caused by Candida albicans (OR, 3.92; 95% CI, 1.48–10.61), and prior surgery (OR, 0.29; 95% CI, 0.08–0.97) were independent predictors of mortality. Similar results were found when a propensity score for receiving ED was incorporated into the model. ED had no significant impact on mortality (OR, 0.50; 95% CI, 0.16–1.53).[Conclusions] Early de-escalation is a safe strategy in patients with candidemia caused by fluconazole-susceptible strains with controlled source of bloodstream infection and hemodynamic stability. These results are important to apply antifungal stewardship strategies.This research forms part of an activity that has received funding from EIT Health. EIT Health is supported by the European Institute of Innovation and Technology (EIT), a body of the European Union that receives support from the European Union´s Horizon 2020 Research and Innovation Program. This study has been cofunded by the European Regional Development Fund. E. M.-G. (PI18/01061), P. P.-A. (“Rio Hortega” contract CM18/00132), M. F.-R. (“Miguel Servet” contract CP18/00073), and C. G.-V. (FIS PI18/01061) have received research grants from the Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III.Peer reviewe

BRAF V600E mutational load as a prognosis biomarker in malignant melanoma

Analyzing the mutational load of driver mutations in melanoma could provide valuable information regarding its progression. We aimed at analyzing the heterogeneity of mutational load of BRAF V600E in biopsies of melanoma patients of different stages, and investigating its potential as a prognosis factor. Mutational load of BRAF V600E was analyzed by digital PCR in 78 biopsies of melanoma patients of different stages and 10 nevi. The BRAF V600E load was compared among biopsies of different stages. Results showed a great variability in the load of V600E (0%-81%). Interestingly, we observed a significant difference in the load of V600E between the early and late melanoma stages, in the sense of an inverse correlation between BRAF V600E mutational load and melanoma progression. In addition, a machine learning approach showed that the mutational load of BRAF V600E could be a good predictor of metastasis in stage II patients. Our results suggest that BRAF V600E is a promising biomarker of prognosis in stage II patients.This research was supported by the Basque Government (grants ELKARTEK-KK2016-036 and KK2017-041 to MDB, grant IT1138-16 to SA and predoctoral fellowship PRE_2014_1_419 to AS), and by the University of the Basque Country (UPV/EHU) (grant GIU17/066). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Factors associated with the development of septic shock in patients with candidemia: a post hoc analysis from two prospective cohorts

[Background] Almost one third of the patients with candidemia develop septic shock. The understanding why some patients do and others do not develop septic shock is very limited. The objective of this study was to identify variables associated with septic shock development in a large population of patients with candidemia.[Methods] A post hoc analysis was performed on two prospective, multicenter cohort of patients with candidemia from 12 hospitals in Spain and Italy. All episodes occurring from September 2016 to February 2018 were analyzed to assess variables associated with septic shock development defined according to The Third International Consensus Definition for Sepsis and Septic Shock (Sepsis-3).[Results] Of 317 candidemic patients, 99 (31.2%) presented septic shock attributable to candidemia. Multivariate logistic regression analysis identifies the following factors associated with septic shock development: age > 50 years (OR 2.57, 95% CI 1.03–6.41, p = 0.04), abdominal source of the infection (OR 2.18, 95% CI 1.04–4.55, p = 0.04), and admission to a general ward at the time of candidemia onset (OR 0.21, 95% CI, 0.12–0.44, p = 0.001). Septic shock development was independently associated with a greater risk of 30-day mortality (OR 2.14, 95% CI 1.08–4.24, p = 0.02).[Conclusions] Age and abdominal source of the infection are the most important factors significantly associated with the development of septic shock in patients with candidemia. Our findings suggest that host factors and source of the infection may be more important for development of septic shock than intrinsic virulence factors of organisms.This study was funded by a research grant from the Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III [FIS PI15/00744], European Regional Development Fund (ERDF); CGV is a recipient of an INTENSIFICACIÓ Grant from the “Strategic plan for research and innovation in health-PERIS 2016-2020” and forms part of the Fungi CLINIC Research group (AGAUR-Project 2017SGR1432 of the Catalan Health Agency)

El papel de las mujeres en el Turismo y la Gastronomía: Historia, Restos y Perspectivas.

El presente trabajo es el primero de una serie que conformarán la colección Estudios de Género de la Facultad de Turismo y Gastronomía de la Universidad Autónoma del Estado de México. Este libro es un primer esfuerzo por generar conocimiento en un tema tan relevante como es el papel de la mujer en el turismo y la gastronomía. Tradicionalmente, la mujer ha desempeñado un rol preponderante en ambas especialidades, sin embargo, éste no ha sido reconocido principalmente por el predominio masculino en todas las esferas públicas, privadas y sociales. De ahí el interés por iniciar la formación de un acervo propio que distinga aquellos aspectos históricos, rurales y sociales vinculantes entre la mujer y estas disciplinas. A lo largo de estos cincos capítulos, el lector podrá descubrir una visión un tanto de corte feminista, pero a la vez reivindicativa que busca concientizar a través de la investigación la importancia del género femenino en el turismo y la gastronomía

Genomics improves risk stratifi cation of adults with T-cell acute lymphoblastic leukemia enrolled in measurable residual disease-oriented trials

Genetic information has been crucial to understand the pathogenesis of T-cell acute lymphoblastic leukemia (T-ALL) at diagnosis and at relapse, but still nowadays has a limited value in a clinical context. Few genetic markers are associated with the outcome of T-ALL patients, independently of measurable residual disease (MRD) status after therapy. In addition, the prognostic relevance of genetic features may be modulated by the specific treatment used. We analyzed the genetic profile of 145 T-ALL patients by targeted deep sequencing. Genomic information was integrated with the clinical -biological and survival data of a subset of 116 adult patients enrolled in two consecutive MRD-oriented trials of the Spanish PETHEMA (Programa Espanol de Tratamientos en Hematologia) group. Genetic analysis revealed a mutational profile defined by DNMT3A/ N/KRAS/ MSH2/ U2AF1 gene mutations that identified refractory/resistant patients. Mutations in the DMNT3A gene were also found in the non-leukemic cell fraction of patients with T-ALL, revealing a possible mutational-driven clonal hematopoiesis event to prime T-ALL in elderly. The prognostic impact of this adverse genetic profile was independent of MRD status on day +35 of induction therapy. The combined worse-outcome genetic signature and MRD on day +35 allowed risk stratification of T-ALL into standard or high-risk groups with significantly different 5 -year overall survival (OS) of 52% (95% confidence interval: 37-67) and 17% (95% confidence interval: 1-33), respectively. These results confirm the relevance of the tumor genetic profile in predicting patient outcome in adult T-ALL and highlight the need for novel gene-targeted chemotherapeutic schedules to improve the OS of poor-prognosis T-ALL patients

Personas adultas mayores frente a la inclusión digital en América Latina: un estudio en red - Volumen 1

El presente libro es la culminación de un proyecto denominado Personas adultas mayores frente a la inclusión digital en América Latina – un estudio en red, desarrollado mediante una red de investigadores latinoamericanos. La idea de dicho proyecto surgió cuando la profesora Maria Consuelo Oliveira Santos finalizó su posdoctorado en la Facultad de Ciencias de la Comunicación de la Universidad Autónoma deNuevo León (UANL), en la ciudad de Monterrey, estado de Nuevo León, México. En cierto modo, es la continuación de la investigación sobre las nuevas tecnologías y los adultos mayores en Monterrey, iniciada en dicha institución. Se constató que era una temática que suscitaba estudios más verticalizados y que sería oportuno poder establecer una red de investigadores y así obtener una visión más amplia sobre la inclusión digital, en la realidad latinoamericana. El propósito del estudio fue conocer, contrastar y comprender las relaciones de las personas adultas mayores con las nuevas tecnologías y la repercusión de dichas relaciones en sus vidas. Igualmente observar la importancia de las condiciones sociales, políticas y culturales que repercuten en el acceso o no a las nuevas tecnologías. La implicación de investigadores integrantes de diferentes instituciones académicas, pertenecientes a diversas áreas del conocimiento fue consecuencia de invitaciones formuladas directamente por diferentes medios de comunicación, explicándoles la idea del proyecto en red para estudiar dicha temática a partir de sus realidades.El presente libro es la culminación de un proyecto denominado Personas adultas mayores frente a la inclusión digital en América Latina – un estudio en red, desarrollado mediante una red de investigadores latinoamericanos. La idea de dicho proyecto surgió cuando la profesora Maria Consuelo Oliveira Santos finalizó su posdoctorado en la Facultad de Ciencias de la Comunicación de la Universidad Autónoma deNuevo León (UANL), en la ciudad de Monterrey, estado de Nuevo León, México. En cierto modo, es la continuación de la investigación sobre las nuevas tecnologías y los adultos mayores en Monterrey, iniciada en dicha institución. Se constató que era una temática que suscitaba estudios más verticalizados y que sería oportuno poder establecer una red de investigadores y así obtener una visión más amplia sobre la inclusión digital, en la realidad latinoamericana. El propósito del estudio fue conocer, contrastar y comprender las relaciones de las personas adultas mayores con las nuevas tecnologías y la repercusión de dichas relaciones en sus vidas. Igualmente observar la importancia de las condiciones sociales, políticas y culturales que repercuten en el acceso o no a las nuevas tecnologías. La implicación de investigadores integrantes de diferentes instituciones académicas, pertenecientes a diversas áreas del conocimiento fue consecuencia de invitaciones formuladas directamente por diferentes medios de comunicación, explicándoles la idea del proyecto en red para estudiar dicha temática a partir de sus realidades

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality