Identificación de genes de baja penetrancia implicados en la susceptibilidad a la infección por Schistosoma mansoni

[ES]Las enfermedades con resistencia/sensibilidad poligénicas dependen de la suma de efectos de genes con efecto débil, que interactúan entre ellos y el ambiente, provocando que en las mismas condiciones unos individuos desarrollen enfermedad grave y otros no. Estos genes son difíciles de localizar en el hombre, por la heterogeneidad genética y la compleja interacción con el medio. Sin embargo, el ratón ofrece modelos simplificados de líneas puras y cruzamientos para la disección genética de rasgos complejos. El estudio se concibió para identificar los patofenotipos asociados a la infección por «Schistosoma mansoni» empleando un modelo de cruce retrógrado o «backcross». También se pretendió encontrar regiones cromosómicas (eQTL) implicadas en la susceptibilidad a la infección y ligadas a los patofenotipos definidos. Para generar el «backcross» (F2BX), se cruzaron hembras F1C57CBA con machos CBA/2J, para enriquecer nuestra cohorte en alelos de susceptibilidad. Los 120 ratones generados, se infectaron con 150 cercarias de «S. mansoni» y se necropsiaron a las 9 semanas postinfección. Se midieron magnitudes parasitológicas, patológicas e inmunológicas para obtener grupos o patofenotipos de enfermedad. El «backcross» mostró menor de número de vermes y huevos en hígado que el cruce F1C57CBA y más parecido en número de granulomas a la línea parental más susceptible (CBA/2J). Se observó que en el «backcross» no había diferencias entre ratones machos y hembras salvo en el número de granulomas. Mediante el estudio de K-medias y PCA y correlaciones entre las variables parasito-patológicas, se observaron cuatro niveles de gravedad. En el análisis de variación entre medias de los patofenotipos se observó asociación con el daño hepático, independientemente del número de vermes recuperados. Se realizó el genotipado de los ratones con 958 SNPs significativos y su asociación a los fenotipos. En conclusión, tras generar el «backcross», con gran heterogeneidad, para estudiar la influencia de la infección por «S. mansoni», los cuatro patofenotipos observados en la esquistosomosis mansónica experimental en un cruzamiento retrógrado, parecen relacionados con el daño hepático. Las poblaciones celulares tienen importancia en la progresión de la enfermedad y los niveles de anticuerpos no están asociados con la gravedad de la infección. De las 18 regiones cromosómicas eQTL encontradas, hay una en el cromosoma 18 de ratón relacionada con el daño hepático, homóloga con el cromosoma 18 humano, en la región 18q11.2-12.3

Characteristics and Outcome of Acute Heart Failure in Infective Endocarditis: Focus on Cardiogenic Shock

Spanish Collaboration on Endocarditis—Grupo de Apoyo al Manejo de la Endocarditis Infecciosa en España (GAMES).[Background] Studies investigating the impact of cardiogenic shock (CS) on endocarditis are lacking.[Methods] Prospectively collected cohort from 35 Spanish centers (2008-2018). Logistic regression analyses were performed to identify risk factors for developing CS and predictors of mortality.[Results] Among 4856 endocarditis patients, 1652 (34%) had acute heart failure (AHF) and 244 (5%) CS. Compared with patients without AHF and AHF but no CS, patients with CS presented higher rates of surgery (40.5%, 52.5%, and 68%; P < .001) and in-hospital mortality (16.3%, 39.1%, and 52.5%). Compared with patients with septic shock, CS patients presented higher rates of surgery (42.5% vs 68%; P < .001) and lower rates of in-hospital and 1-year mortality (62.3% vs 52.5%, P = .008, and 65.3% vs 57.4%, P = .030). Severe aortic and mitral regurgitation (OR [95% CI], 2.47 [1.82-3.35] and 3.03 [2.26-4.07]; both P < .001), left-ventricle ejection fraction <60% (1.72; 1.22-2.40; P = .002), heart block (2.22; 1.41-3.47; P = .001), tachyarrhythmias (5.07; 3.13-8.19; P < .001), and acute kidney failure (2.29; 1.73-3.03; P < .001) were associated with higher likelihood of developing CS. Prosthetic endocarditis (2.03; 1.06 -3.88; P = .032), Staphylococcus aureus (3.10; 1.16 -8.30; P = .024), tachyarrhythmias (3.09; 1.50-10.13; P = .005), and not performing cardiac surgery (11.40; 4.83-26.90; P < .001) were associated with a higher risk of mortality.[Conclusions] AHF is common among patients with endocarditis. CS is associated with high mortality and should be promptly identified and assessed for cardiac surgery.This work was supported by the Ministerio de Sanidad y Consumo of Spain (grant number FIS NCT00871104; Instituto de Salud Carlos III). Institut d’Investigacions Biomèdiques Pi i Sunyer (IDIBAPS) provided J. M. M. with a persobal IDIBAPS 80:20 research grant during 2017–2021. M. H. M. held a Rio Hortega Research Grant (CM17/00062) from the Instituto de Salud Carlos III” and the Ministerio de Economia y Competitividad, Madrid (Spain) in 2018–2020.Peer reviewe

The educational challenge in infectious diseases: analysis of Official Master's degrees in Spain

[EN] Introduction: Infectious diseases are one of the main causes of morbidity and mortality worldwide. In this way, the Spanish University has increased and complemented postgraduate training with an offer of its own degrees and official master's degrees that seek the most advanced specialization and updating, whether professional or research, in ​​knowledge of infectious diseases. Aim: To know and evaluate the current offer of master's degrees related to infectious diseases in Spanish universities. Methods: Literature review carried out in the months of February-March 2022 for the collection of information on postgraduate studies, specifically Official Master's Degree studies, offered in Health Sciences in Spanish Universities. Results: From the year 2005, when the "Master's Degree in Tropical Parasitic Diseases" was established, until the year 2022, 11 postgraduate studies related to infectious diseases have been implemented in 10 Spanish universities. Most of them have one-year duration and an average teaching load of 70.91±20.23 ECTS-credits. Average number of students per course: 26.27±5.98. Average price: €3,095.8±2,479.4. There are currently master's degrees in 8 autonomous communities, and non-face-to-face formats are gaining notoriety. Conclusions: The exponential growth in the number of master's degrees in Spain in recent years demonstrates the growing interest and updating needs in this area of ​​knowledge. Although the offer is extensive, it is neither homogeneous nor balanced, presenting potential areas for significant improvement. Health organizations and scientific societies should promote the relationship between the different levels of postgraduate training.[ES] Introducción: Las enfermedades infecciosas son una de las principales causas de morbimortalidad. Por ello, la Universidad Española ha incrementado y complementado la formación postgrado con una oferta de Títulos Propios y Másteres Oficiales que buscan la especialización y actualización más avanzada, ya sea profesional o investigadora, en esta área de conocimiento. Objetivo: Conocer y evaluar la oferta actual de másteres relacionados con las enfermedades infecciosas en las universidades españolas. Métodos: Revisión bibliográfica realizada en los meses de febrero-marzo 2022 para recoger información sobre estudios de Postgrado, específicamente estudios de Máster Oficial, en el área de Ciencias de la Salud en las Universidades españolas. Resultados: Desde 2005 en que se instauró el Máster Universitario en Enfermedades Parasitarias Tropicales , hasta 2022, se han implantado 11 estudios de postgrado relacionados con las enfermedades infecciosas en 10 universidades españolas. La mayoría tienen una duración de un año y una carga docente media de 70,91±20,23 créditos-ECTS. Número medio de alumnos: 26,27±5,98. Precio medio: 3.095,8±2.479,4 . Existen actualmente másteres en 8 comunidades autónomas y los formatos no presenciales van adquiriendo notoriedad. Conclusiones: El crecimiento exponencial del número de másteres en España en los últimos años, demuestra el interés creciente y las necesidades de actualización en esta área de conocimiento. Aunque la oferta es extensa, no es homogénea ni equilibrada, presentando áreas potenciales de mejora significativa. Organismos sanitarios y sociedades científicas deberían fomentar la relación entre los diferentes estamentos de la formación de postgrado.Belhassen García, M.; Hernández-Goenaga, J.; Alonso-Sardón, M.; López-Bernús, A.; Rodríguez-Alonso, B.; Pardo-Lledías, J.; Del Olmo, E.... (2023). El reto formativo en enfermedades infecciosas: análisis de los Másteres Oficiales en España. REDU. Revista de Docencia Universitaria. 21(2):117-131. https://doi.org/10.4995/redu.2023.1879211713121

T cell peptides derived from invasive stages of Schistosoma mansoni as potential schistosomiasis vaccine

Schistosomiasis is a parasitic disease that affects 143 million people in endemic countries. This work analyzed overexpressed sequences from the cercaria phase to the early schistosomulum phase using bioinformatics tools to predict host interaction and selected proteins for predicting T cell epitopes. The final peptides were chemically synthesized, and their toxicity was evaluated in vitro. Peptides were formulated in the Adjuvant Adaptation (ADAD) vaccination system and injected into BALB/c mice that were challenged with S. mansoni cercariae to assess protection and immunogenicity. A total of 39 highly expressed S.mansoni proteins were identified as being of potential interest. Three T cell peptides predicted to bind MHC mouse and human class II were synthesized and formulated for vaccination. SmGSP and SmIKE reduced the number of eggs trapped in the liver by more than 50% in challenged BALB/c mice. The liver of mice vaccinated with either SmGSP or SmTNP had a significantly reduced affected liver surface. Transcriptome-based T cell peptides elicit partial protection and could be candidates for a multiantigen vaccine

Role of age and comorbidities in mortality of patients with infective endocarditis

[Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group

Epidemiological trends of HIV/HCV coinfection in Spain, 2015-2019

Altres ajuts: Spanish AIDS Research Network; European Funding for Regional Development (FEDER).Objectives: We assessed the prevalence of anti-hepatitis C virus (HCV) antibodies and active HCV infection (HCV-RNA-positive) in people living with HIV (PLWH) in Spain in 2019 and compared the results with those of four similar studies performed during 2015-2018. Methods: The study was performed in 41 centres. Sample size was estimated for an accuracy of 1%. Patients were selected by random sampling with proportional allocation. Results: The reference population comprised 41 973 PLWH, and the sample size was 1325. HCV serostatus was known in 1316 PLWH (99.3%), of whom 376 (28.6%) were HCV antibody (Ab)-positive (78.7% were prior injection drug users); 29 were HCV-RNA-positive (2.2%). Of the 29 HCV-RNA-positive PLWH, infection was chronic in 24, it was acute/recent in one, and it was of unknown duration in four. Cirrhosis was present in 71 (5.4%) PLWH overall, three (10.3%) HCV-RNA-positive patients and 68 (23.4%) of those who cleared HCV after anti-HCV therapy (p = 0.04). The prevalence of anti-HCV antibodies decreased steadily from 37.7% in 2015 to 28.6% in 2019 (p < 0.001); the prevalence of active HCV infection decreased from 22.1% in 2015 to 2.2% in 2019 (p < 0.001). Uptake of anti-HCV treatment increased from 53.9% in 2015 to 95.0% in 2019 (p < 0.001). Conclusions: In Spain, the prevalence of active HCV infection among PLWH at the end of 2019 was 2.2%, i.e. 90.0% lower than in 2015. Increased exposure to DAAs was probably the main reason for this sharp reduction. Despite the high coverage of treatment with direct-acting antiviral agents, HCV-related cirrhosis remains significant in this population

Pasados y presente. Estudios para el profesor Ricardo García Cárcel

Ricardo García Cárcel (Requena, 1948) estudió Historia en Valencia bajo el magisterio de Joan Reglà, con quien formó parte del primer profesorado de historia moderna en la Universidad Autónoma de Barcelona. En esta universidad, desde hace prácticamente cincuenta años, ha desarrollado una extraordinaria labor docente y de investigación marcada por un sagaz instinto histórico, que le ha convertido en pionero de casi todo lo que ha estudiado: las Germanías, la historia de la Cataluña moderna, la Inquisición, las culturas del Siglo de Oro, la Leyenda Negra, Felipe II, Felipe V, Austrias y Borbones, la guerra de la Independencia, la historia cultural, los mitos de la historia de España... Muy pocos tienen su capacidad para reflexionar, ordenar, analizar, conceptualizar y proponer una visión amplia y llena de matices sobre el pasado y las interpretaciones historiográficas. A su laboriosidad inimitable se añade una dedicación sin límites en el asesoramiento de alumnos e investigadores e impulsando revistas, dosieres, seminarios o publicaciones colectivas. Una mínima correspondencia a su generosidad lo constituye este volumen a manera de ineludible agradecimiento

Spatiotemporal Characteristics of the Largest HIV-1 CRF02_AG Outbreak in Spain: Evidence for Onward Transmissions

Background and Aim: The circulating recombinant form 02_AG (CRF02_AG) is the predominant clade among the human immunodeficiency virus type-1 (HIV-1) non-Bs with a prevalence of 5.97% (95% Confidence Interval-CI: 5.41–6.57%) across Spain. Our aim was to estimate the levels of regional clustering for CRF02_AG and the spatiotemporal characteristics of the largest CRF02_AG subepidemic in Spain.Methods: We studied 396 CRF02_AG sequences obtained from HIV-1 diagnosed patients during 2000–2014 from 10 autonomous communities of Spain. Phylogenetic analysis was performed on the 391 CRF02_AG sequences along with all globally sampled CRF02_AG sequences (N = 3,302) as references. Phylodynamic and phylogeographic analysis was performed to the largest CRF02_AG monophyletic cluster by a Bayesian method in BEAST v1.8.0 and by reconstructing ancestral states using the criterion of parsimony in Mesquite v3.4, respectively.Results: The HIV-1 CRF02_AG prevalence differed across Spanish autonomous communities we sampled from (p &lt; 0.001). Phylogenetic analysis revealed that 52.7% of the CRF02_AG sequences formed 56 monophyletic clusters, with a range of 2–79 sequences. The CRF02_AG regional dispersal differed across Spain (p = 0.003), as suggested by monophyletic clustering. For the largest monophyletic cluster (subepidemic) (N = 79), 49.4% of the clustered sequences originated from Madrid, while most sequences (51.9%) had been obtained from men having sex with men (MSM). Molecular clock analysis suggested that the origin (tMRCA) of the CRF02_AG subepidemic was in 2002 (median estimate; 95% Highest Posterior Density-HPD interval: 1999–2004). Additionally, we found significant clustering within the CRF02_AG subepidemic according to the ethnic origin.Conclusion: CRF02_AG has been introduced as a result of multiple introductions in Spain, following regional dispersal in several cases. We showed that CRF02_AG transmissions were mostly due to regional dispersal in Spain. The hot-spot for the largest CRF02_AG regional subepidemic in Spain was in Madrid associated with MSM transmission risk group. The existence of subepidemics suggest that several spillovers occurred from Madrid to other areas. CRF02_AG sequences from Hispanics were clustered in a separate subclade suggesting no linkage between the local and Hispanic subepidemics

Biompha-LAMP: A New Rapid Loop-Mediated Isothermal Amplification Assay for Detecting Schistosoma mansoni in Biomphalaria glabrata Snail Host

[EN]Background: Schistosomiasis remains one of the most common endemic parasitic diseases affecting over 230 million people worlwide. Schistosoma mansoni is the main species causing intestinal and hepatic schistosomiasis and the fresh water pulmonate snails of the genus Biomphalaria are best known for their role as intermediate hosts of the parasite. The development of new molecular monitoring assays for large-scale screening of snails from transmission sites to detect the presence of schistosomes is an important point to consider for snail control interventions related to schistosomiasis elimination. Our work was focussed on developing and evaluating a new LAMP assay combined with a simple DNA extraction method to detect S. mansoni in experimentally infected snails as a diagnostic tool for field conditions. Methodology/Principal findings: A LAMP assay using a set of six primers targeting a sequence of S. mansoni ribosomal intergenic spacer 28S-18S rRNA was designed. The detection limit of the LAMP assay was 0.1 fg of S. mansoni DNA at 63°C for 50 minutes. LAMP was evaluated by examining S. mansoni DNA in B. glabrata snails experimentally exposed to miracidia at different times post-exposure: early prepatent period (before cercarial shedding), light infections (snails exposed to a low number of miracidia) and detection of infected snails in pooled samples (within a group of uninfected snails). DNA for LAMP assays was obtained by using a commercial DNA extraction kit or a simple heat NaOH extraction method. We detected S. mansoni DNA in all groups of snails by using no complicated requirement procedure for DNA obtaining. Conclusions/Significance: Our LAMP assay, named Biompha-LAMP, is specific, sensitive, rapid and potentially adaptable as a cost-effective method for screening of intermediate hosts infected with S. mansoni in both individual snails and pooled samples. The assay could be suitable for large-scale field surveys for schistosomes control campaigns in endemic areas

Pacientes en ventilación mecánica con traqueostomía

Introducción: la traqueostomía es una técnica que habitualmente se indica en enfermos críticos ingresados en las unidades de cuidados intensivos que requieren ventilación mecánica por tiempo prolongado. Objetivo: caracterizar algunos aspectos clínico-epidemiológicos de pacientes en ventilación mecánica que necesitaron traqueostomía. Métodos: estudio observacional, descriptivo, longitudinal y retrospectivo de pacientes en ventilación mecánica que necesitaron traqueostomía, en la Unidad de Cuidados Intensivos del Hospital Militar Central "Dr. Carlos J. Finlay" entre enero de 2011 y diciembre de 2012. La muestra fue de 96 pacientes. Se revisó la base de datos de pacientes ingresados en el servicio y las historias clínicas del archivo del hospital. Resultados: la edad media fue de 55,7 ± 16,9 años. Hubo un predominio del sexo masculino (59,4 %) y el grupo etario de 50-64 años (40,6 %). La hipertensión arterial constituyó el antecedente patológico más frecuente (18,8 %). Más de la mitad de los pacientes egresaron fallecidos (62,5 %); la edad media de este grupo fue superior a la de los egresados vivos (60,6 vs. 47,6 años). El motivo principal de ingreso fue no traumático (63,5 %). La media del valor del APACHE II fue de 17,4; en los fallecidos fue mayor que en los vivos (19,8 vs. 13,4). La mayoría de los pacientes estuvieron ventilados por 7 o menos días (51,0 %) y la estadía fue de 8 o más días (86,5 %). Conclusiones: la traqueostomía no influyó sobre el tiempo de ventilación mecánica ni en la mortalidad global