Genotypic and Phenotypic Characterization of Staphylococcus aureus Isolates from the Respiratory Tract in Mechanically-Ventilated Patients

Staphylococcus aureus is a commensal and frequent colonizer of the upper respiratory tract. When mechanical ventilation disrupts natural defenses, S. aureus is frequently isolated from the lower airways, but distinguishing between colonization and infection is difficult. The objectives of this study were (1) to investigate the bacterial genome sequence in consecutive isolates in order to identify changes related to the pathological adaptation to the lower respiratory tract and (2) to explore the relationship between specific phenotypic and genotypic features with the patient's study group, persistence of the clinical isolate and clinical outcome. A set of 94 clinical isolates were selected and corresponded to 34 patients that were classified as having pneumonia (10), tracheobronchitis (11) and bronchial colonization (13). Clinical strains were phenotypically characterized by conventional identification and susceptibility testing methods. Isolates underwent whole genome sequencing using Illumina HiSeq4000. Genotypic characterization was performed with an in-house pipeline (BacterialTyper). Genomic variation arising within-host was determined by comparing mapped sequences and de novo assemblies. Virulence factors important in staphylococcal colonization and infection were characterized using previously established functional assays. (1) Toxin production was assessed using a THP-1 cytotoxicity assay, which reports on the gross cytotoxicity of individual isolates. In addition, we investigated the expression of the major virulence factor, alpha-toxin (Hla) by Western blot. (2) Adhesion to the important extracellular matrix molecule, fibronectin, was determined using a standardized microtitre plate assay. Finally, invasion experiments using THP-1 and A539 cell lines and selected clinical strains were also performed. Repeated isolation of S. aureus from endotracheal aspirate usually reflects persistence of the same strain. Within-host variation is detectable in this setting, but it shows no evidence of pathological adaptation related to virulence, resistance or niche adaptations. Cytotoxicity was variable among isolates with 14 strains showing no cytotoxicity, with these latter presenting an unaltered Fn binding capacity. No changes on cytotoxicity were reported when comparing study groups. Fn binding capacity was reported for almost all strains, with the exception of two strains that presented the lowest values. Strains isolated from patients with pneumonia presented a lower capacity of adhesion in comparison to those isolated during tracheobronchitis (p = 0.002). Hla was detected in 71 strains (75.5%), with most of the producer strains in pneumonia and bronchial colonization group (p = 0.06). In our cohort, Hla expression (presence or absence) in sequential isolates was usually preserved (70%) although in seven cases the expression varied over time. No relationship was found between low cytotoxicity and intracellular persistence in invasion experiments. In our study population, persistent S. aureus isolation from airways in ventilated patients does not reflect pathological adaptation. There is an important diversity of sequence types. Cytotoxicity is variable among strains, but no association with study groups was found, whereas isolates from patients with pneumonia had lower adhesion capability. Favorable clinical outcome correlated with increased bacterial adhesion in vitro. Most of the strains isolated from the lower airways were Hla producers and no correlation with an adverse outcome was reported. The identification of microbial factors that contribute to virulence is relevant to optimize patient management during lower respiratory tract infections

GCAT|Panel, a comprehensive structural variant haplotype map of the Iberian population from high-coverage whole-genome sequencing

The combined analysis of haplotype panels with phenotype clinical cohorts is a common approach to explore the genetic architecture of human diseases. However, genetic studies are mainly based on single nucleotide variants (SNVs) and small insertions and deletions (indels). Here, we contribute to fill this gap by generating a dense haplotype map focused on the identification, characterization, and phasing of structural variants (SVs). By integrating multiple variant identification methods and Logistic Regression Models (LRMs), we present a catalogue of 35 431 441 variants, including 89 178 SVs (≥50 bp), 30 325 064 SNVs and 5 017 199 indels, across 785 Illumina high coverage (30x) whole-genomes from the Iberian GCAT Cohort, containing a median of 3.52M SNVs, 606 336 indels and 6393 SVs per individual. The haplotype panel is able to impute up to 14 360 728 SNVs/indels and 23 179 SVs, showing a 2.7-fold increase for SVs compared with available genetic variation panels. The value of this panel for SVs analysis is shown through an imputed rare Alu element located in a new locus associated with Mononeuritis of lower limb, a rare neuromuscular disease. This study represents the first deep characterization of genetic variation within the Iberian population and the first operational haplotype panel to systematically include the SVs into genome-wide genetic studies

Gender-Based Differences by Age Range in Patients Hospitalized with COVID-19: A Spanish Observational Cohort Study

There is some evidence that male gender could have a negative impact on the prognosis and severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The aim of the present study was to compare the characteristics of coronavirus disease 2019 (COVID-19) between hospitalized men and women with confirmed SARS-CoV-2 infection. This multicenter, retrospective, observational study is based on the SEMI-COVID-19 Registry. We analyzed the differences between men and women for a wide variety of demographic, clinical, and treatment variables, and the sex distribution of the reported COVID-19 deaths, as well as intensive care unit (ICU) admission by age subgroups. This work analyzed 12,063 patients (56.8% men). The women in our study were older than the men, on average (67.9 vs. 65.7 years; p < 001). Bilateral condensation was more frequent among men than women (31.8% vs. 29.9%; p = 0.007). The men needed non-invasive and invasive mechanical ventilation more frequently (5.6% vs. 3.6%, p < 0.001, and 7.9% vs. 4.8%, p < 0.001, respectively). The most prevalent complication was acute respiratory distress syndrome, with severe cases in 19.9% of men (p < 0.001). In men, intensive care unit admission was more frequent (10% vs. 6.1%; p < 0.001) and the mortality rate was higher (23.1% vs. 18.9%; p < 0.001). Regarding mortality, the differences by gender were statistically significant in the age groups from 55 years to 89 years of age. A multivariate analysis showed that female sex was significantly and independently associated with a lower risk of mortality in our study. Male sex appears to be related to worse progress in COVID-19 patients and is an independent prognostic factor for mortality. In order to fully understand its prognostic impact, other factors associated with sex must be considered

Heterozygous and Homozygous Variants in SORL1 Gene in Alzheimer's Disease Patients: Clinical, Neuroimaging and Neuropathological Findings

In the last few years, the SORL1 gene has been strongly implicated in the development of Alzheimer’s disease (AD). We performed whole-exome sequencing on 37 patients with early-onset dementia or family history suggestive of autosomal dominant dementia. Data analysis was based on a custom panel that included 46 genes related to AD and dementia. SORL1 variants were present in a high proportion of patients with candidate variants (15%, 3/20). We expand the clinical manifestations associated with the SORL1 gene by reporting detailed clinical and neuroimaging findings of six unrelated patients with AD and SORL1 mutations. We also present for the first time a patient with the homozygous truncating variant c.364C>T (p.R122*) in SORL1, who also had severe cerebral amyloid angiopathy. Furthermore, we report neuropathological findings and immunochemistry assays from one patient with the splicing variant c.4519+5G>A in the SORL1 gene, in which AD was confirmed by neuropathological examination. Our results highlight the heterogeneity of clinical presentation and familial dementia background of SORL1-associated AD and suggest that SORL1 might be contributing to AD development as a risk factor gene rather than as a major autosomal dominant gene.This work was supported by the Instituto de Salud Carlos III (PI17/01067) and AGAUR from the Autonomous Catalan Government (2017SGR1134). Dr. Víctor Antonio Blanco-Palmero is supported by the Instituto de Salud Carlos III (ISCIII, Spanish Biomedical Research Institute) through a “Río Hortega” contract (CM18/0095). Dr. Sara Llamas-Velasco is supported by the Instituto de Salud Carlos III (ISCIII; Spanish Biomedical Research Institute) through a “Juan Rodés” contract (JR 18/00046).S

Diseño y primeros resultados de una cámara PET para animales pequeños basada en cristales LYSO continuos y fotomulplicadores sensibles a la posición

[ES] En este artículo presentamos el diseño de un nuevo escáner PET para animales pequeños basado en una tecnología completamente innovadora. Los resultados preliminares son muy prometedores, permitiendo obtener imágenes funcionales de alta resolución con una instrumentación compacta y de bajo coste. Los prototipos desarrollados se encuentran actualmente en pruebas en diversos centros de investigación médica, obteniéndose imá- genes de alta calidad en los campos de oncología, neurología y cardiología. Este diseño puede ser fácilmente extendido a cámaras PET dedicadas a la exploración del cerebro o de la mama. La innovación más notable de la presente tecnología consiste en el uso de un único cristal continuo por módulo, a diferencia de otras cámaras PET comerciales donde se utilizan cientos de cristales pixelados. El uso de un único cristal continuo permite abaratar el coste de fabricación, al tiempo que mejora las características de funcionamiento: resolución intrínseca en posición de 1,2 mm, resolución en energía media del 14%, resolución en la profundidad de interacción de 3 mm, sensibilidad > 4% y campo de visión transaxial de 80 mm de diámetro. En el presente artículo se describen en detalle el diseño de esta nueva cámara PET, los principios de funcionamiento, el método utilizado para su calibración y se anticipan algunas imágenes "in vivo" del miocardio y el cerebro de un ratón, permitiendo apreciar de forma preliminar la resolución y calidad alcanzadas.[EN] In this paper we present the design of a new small animal PET scanner based on a completely innovative technology. The achieved results are very promising, showing the possibility to obtain high resolution functional images with a compact and low cost scanner. Several prototypes have been developed and are currently being used at different research medical institutions. High resolution images are being obtained in application fields like oncology, neurology and cardiology. This technology can be easily applied in PET cameras for brain or breast exploration. The most significant innovation of the design is the fact of using a single crystal per module instead of hundreds of pixellated crystals as in other commercial PETs. It has the advantage of decreasing the manufacturing costs and simultaneously improves its performance: 1.2 mm position intrinsic resolution, mean energy resolution as good as 14%, 3 mm depth of interaction resolution, sensitivity above 4%, and 80 mm diameter of transaxial field of view. In this paper we describe in detail the design of this new PET camera, its principle, the calibration methodology and also some preliminary "in vivo" images of a mouse myocardium and brain, showing the achieved image resolution and qualityBenlloch Baviera, JM.; González Martínez, AJ.; Carrilero, V.; Catret, JV.; Correcher, C.; Lerche, CW.; Morera, C.... (2007). Diseño y primeros resultados de una cámara PET para animales pequeños basada en cristales LYSO continuos y fotomulplicadores sensibles a la posición. Revista de física médica. 8(2):315-321. http://hdl.handle.net/10251/79285S3153218

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Healthcare workers hospitalized due to COVID-19 have no higher risk of death than general population. Data from the Spanish SEMI-COVID-19 Registry

Aim To determine whether healthcare workers (HCW) hospitalized in Spain due to COVID-19 have a worse prognosis than non-healthcare workers (NHCW). Methods Observational cohort study based on the SEMI-COVID-19 Registry, a nationwide registry that collects sociodemographic, clinical, laboratory, and treatment data on patients hospitalised with COVID-19 in Spain. Patients aged 20-65 years were selected. A multivariate logistic regression model was performed to identify factors associated with mortality. Results As of 22 May 2020, 4393 patients were included, of whom 419 (9.5%) were HCW. Median (interquartile range) age of HCW was 52 (15) years and 62.4% were women. Prevalence of comorbidities and severe radiological findings upon admission were less frequent in HCW. There were no difference in need of respiratory support and admission to intensive care unit, but occurrence of sepsis and in-hospital mortality was lower in HCW (1.7% vs. 3.9%; p = 0.024 and 0.7% vs. 4.8%; p<0.001 respectively). Age, male sex and comorbidity, were independently associated with higher in-hospital mortality and healthcare working with lower mortality (OR 0.211, 95%CI 0.067-0.667, p = 0.008). 30-days survival was higher in HCW (0.968 vs. 0.851 p<0.001). Conclusions Hospitalized COVID-19 HCW had fewer comorbidities and a better prognosis than NHCW. Our results suggest that professional exposure to COVID-19 in HCW does not carry more clinical severity nor mortality

Reseñas

[ES] Seguí de la Riva , Javier. Sobre dibujar y proyectar (por Javier Seguí de la Riva) pp. 4.-- Dibujar, proyectar LVI y LVII Arte y muerte I y II ( por Javier Seguí de la Riva) pp. 6.-- dibujar, proyectar LVIII El imaginario del dibujar (por Javier Seguí de la Riva) pp. 6 y 7.-- Dibujar, proyectar LVI y LVII Diagrama, diagramar I y II ( por Javier Seguí de la Riva) pp. 7.-- DIBUJAR, proyectar LVIII El imaginario del dibujar ( por Javier Seguí de la Riva) pp. 6 y 7.-- DIBUJAR, PROYECTAR LVI y LVII Diagrama, diagramar I y II (por Javier Seguí de la Riva) pp.7.-- DIBUJAR, PROYECTAR LIX, LX y LXI Escritos críticos I, II y III ( por Javier Seguí de la Riva) pp. 7 .-- Rehabilitacion del Antiguo Hospital San Juan de Dios para Biblioteca y Archivo Historico de Orihuela (por Ana Torres Barchino) pp. 8.-- Arnau Amo, Joaquín. Arquitectura. Ritos y ritmos (por María Elia Gutiérrez Mozo) pp. 8 y 9.—Cardone, Vito. Viaggiatori d’architettura in Italia. Da Brunelleschi a Charles Garnier (por Cesare Cundari) pp. 9 y 10.-- Casado de Amezúa Vázquez, Joaquín. Las casas reales de la Alhambra. Geometría y espacio. Una aproximación al proceso de formación del espacio ( por Pilar Chías Navarro)pp. 10.-- Jaén i Urban, Gaspar; Baldomá Soto, Montserrat y Carrasco Martí, Maria Antonia. One century of photography and preservation in catalonia: the service for local architectural heritage ( por Pilar Chías Navarro) pp. 10 y 11.-- Jaén i Urban, Gaspar. El paisaje urbano de Nueva York en la obra escrita de Federico García Lorca (por Concepción López González y Jorge García valldecabres) pp. 11.—Trachana, Angelique. Urbe Ludens ( por Gonzalo García-Rosales) pp. 12.-- Fernández-Palacios, Victoria; Yanguas, Ana; Jiménez Fdez-Palacios, Luz. Manuel Aires Mateus. Cuaderno de La Alhambra ( por José Mª Gentil Baldrich) pp. 12 y 13.-- Agustín, Luis; Miret, Elena; Vallespín, Aurelio. Representación del espacio arquitectónico. 2011.12 (por Jesús Aparicio Guisado) pp. 14.—Herschdorfer, Nathalie y Lada Umstätter, Thames. Le Corbusier and the Power of Photography (por víctor A. Lafuente Sánchez) pp. 14 y 15.-- Roma en el bolsillo. Cuadernos de dibujo y aprendizaje artístico en el siglo XVIII ( por Fernando Linares García) pp. 15 y 16.-- Vicens y Hualde, Ignacio. Dicho y hecho ( por Fernando Linares García) pp 16.-- Le Corbusier. El arte decorativo de hoy ( por Carlos Montes Serrano )pp. 16 y 17.—Jenkins Birkhäuser, Eric J. Drawn to Design: Analyzing Architecture Through Freehand Drawing ( por víctor A. Lafuente Sánchez) pp. 17 y 18.—Sobrino, Miguel. Monasterios. Las biografías desconocidas de los cenobios de España ( por Javier García-Gutiérrez Mosteiro) pp. 18 y 19.-- Jiménez Martín, Alfonso. Anatomía de la Catedral de Sevilla ( por Francisco Pinto Puerto) pp. 19.-- Raposo Grau, Javier Fco; Butragueño Díaz-Guerra, Belen y Paredes Maldonado, Miguel. Dibujar, analizar, proyectar (2010) Título I. Colección dibujo, proyecto y arquitectura ( por Mariasun Salgado de la Rosa) pp. 19 y 20.-- Raposo Grau, Fco Javier; Butragueño Díaz-Guerra, Belen y Paredes Maldonado, Miguel. Dibujar, analizar, proyectar (2011) Título III. Colección dibujo, proyecto y arquitectura ( por Carlos L. Marcos Alba) pp. 20-22.-- García Doménech, Sergio. Reflexiones urbanas sobre el espacio público de Alicante. Una interpretación de la ciudad y sus escenarios ( por Juan Calduch Cervera) pp. 22 y 23.—Cundari, Casere. Il rilievo architettonico. Ragioni. Fondamenti. Applicazioni ( por Antonio Álvaro Tordesillas) pp. 23 y 24.—Autores varios. Perspectiva-Prospettiva. La práctica de la perspectiva ( por José Mª Gentil Baldrich) pp. 24 y 25.-- Soler Sanz, Felipe. Trazados Reguladores en la Arquitectura ( por Jorge García Valldecabres) pp. 25.-- Jiménez Alcañiz, Cesar. Análisis de las metodologías para la recuperación patrimonial de entornos urbanos protegidos. Propuesta metodológica: desde los valores históricos a los nuevos modelos energéticos. Russafa desde el siglo XIX( Por Pablo Navarro Esteve) pp. 26.-- de Coca Leicher, José. El recinto ferial de la Casa de Campo de Madrid (1950-75)( por Esteban Herrero Cantalapiedra) pp. 27.-- La arquitectura religiosa renacentista en tierras del Maestre: la iglesia de Nuestra Señora de la Asunción de Vistabella del Maestrazgo ( por José Teodoro Garfella Rubio) pp. 27 y 28.-- Arquitectura de los balnearios en Galicia. Cuenca del Miño. 1816-1936 ( por José Antonio Franco Taboada)pp. 28 y 29.-- Barros da Rocha e Costa. Historia de la representación gráfica del Castillo de Peñíscola. Del grafito al láser ( por Pablo Navarro Esteve) pp. 29.-- Rivas López, Esteban José. El Carmen de la fundación Rodríguez-Acosta. Una indagación gráfica ( por Joaquín Casado de Amezúa) pp.30.-- Verdejo Gimeno, Pedro. Estaciones intermedias de ferrocarril. La sección “Non nata” Teruel-Alcañiz (por Jorge Girbés Pérez) pp. 30 y 31.-- Sender Contell, Marina. El Monasterio de Santa María de la Murta. Análisis arquitectónico de un Monasterio Jerónimo ( por Pablo Navarro Esteve) pp. 32.-- Iñarra Abad, Susana. El Render de Arquitectura. Análisis de la Respuesta Emocional del Observador ( por Pablo Navarro Esteve) pp. 32 y 33.-- Fernández Morales, Angélica. De concreto a conceptual. Relaciones entre arte y arquitectura en el contexto helvético contemporáneo ( por Luis Agustín) pp. 33.—EXPOSICIÓN: Intervenciones cromáticas en los comercios del centro histórico ( por Jorge Llopis verdú) pp. 34 y 35.Seguí De La Riva, J.; Torres Barchino, A.; Gutiérrez Mozo, ME.; Cundari, C.; Chías Navarro, P.; López González, C.; García Valldecabres, J.... (2014). Reseñas. EGA. Revista de Expresión Gráfica Arquitectónica. 19(24):4-35. https://doi.org/10.4995/ega.2014.3268SWORD435192