Correlation between serum content of the main COPs (cholesterol oxidation products) from autoxidation and cardiovascular risk factors

BACKGROUND/AIMS: Risk factors for cardiovascular disease (CVD) have been proven to be associated with an increased oxidative stress. Several studies have considered cholesterol oxidation products (COPs) as specific in vivo markers of oxidative stress. The aim of this study was to investigate the association between the levels of COPs derived from autoxidation processes and established cardiovascular risk factors, comparing the levels of serum COPs in subjects with or without showing values out of the reference ranges. METHODS: It was a cross-sectional study in which 88 subjects were recruited and individual and total COPs from autoxidation origin was analyzed in serum by GC-MS. The simultaneous correlation of COPs with different CVD risk factors have been analyzed. RESULTS AND DISCUSSION: A great variability of total COPs concentrations were found. Subjects presented total COPs values from 0.091 to 2.052 μg/mL. Total COPs were significantly higher (p < 0.05) in patients with hypertriglycerolemia, hypertension, diabetes and overweight/ obesity status compared to those subjects who did not present those CVD risk factors. Moreover, 7α and 7β hydroxycholesterol and 7-ketocholesterol were significantly higher (p < 0.05) in patients with hypertension and diabetes. No significant differences in total COPs were found between patients with and without hypercholesterolemia. CONCLUSIONS: The obtained results showed that the analyzed COPs correlate well with at least 4 out of 6 risk factors of development of CVD

Novel ortho-OPE metallofoldamers: binding-induced folding promoted by nucleating Ag(i)-alkyne interactions

We have developed a new family of ortho-oligophenylene ethynylene (o-OPE) metallofoldamers. The folding of these helicates is induced by nucleating carbon-metal interactions between Ag(i) cations and the alkynes of the inner core of the o-OPEs. These o-OPEs form metal-organic assemblies where at least three alkyne moieties are held in close proximity to form novel Ag(i)-complexes with the metal ion lodged into the helical cavity. NMR titration experiments and photokinetic studies have provided quantitative data about the thermodynamic and kinetic features of such binding/folding phenomena. X-ray diffraction and DFT studies have been performed to extract structural information on how the Ag(i) cation is accommodated into the cavity. The great simplicity and versatility of these new metallofoldamers open up the possibility to develop novel structures with applications in material science and/or in asymmetric catalysisThis research was funded by the Regional Government of Andalucía (project P09-FQM-4571) and the ICIQ Foundation. DM thanks Regional Government of Andalucía for her contract. AML thanks MICINN for her FPU fellowship. The authors thank the Centro de Servicios de Informática y Redes de Comunicaciones (CSIRC), Universidad de Granada, for providing the computing tim

Morphosedimentary characterization of the Capbreton submarine canyon system, Bay of Biscay (Cantabrian Sea)

Various studies have been carried out to the declaration of new marine protected areas for their importance for habitats, according to the Natura 2000 Network. One of these sites is a sector of the Capbreton Submarine Canyon System, located in front of the Basque Country coast, in the Bay of Biscay (North Atlantic). During the Intemares_CapBreton 0619 and 0620 surveys; bathymetric, backscatter, high-resolution parametric data and samples of sediments, rocks and benthic communities from the seabed were acquired. The study was completed by recording video transects with the underwater vehicle ROTV Politolana from the IEO. The processing and analysis of the geophysical information has allowed obtaining a detailed bathymetry grid of 10 × 10 m, from which the first morphosedimentary characterization of the system of tributary canyons to the E-W trending main canyon and its interfluves has been made. One of the main features of this canyon system is the presence of a large pockmark field on adjacent platforms between canyons, located between 500 and 1000 m water depth. Within this field, pockmarks are shown as circular to elliptical depressions, most likely related to gas rich-fluid emissions to the subsurface.Versión del edito

Genotype–phenotype correlation in patients with Usher syndrome and pathogenic variants in MYO7A: implications for future clinical trials

Purpose: We aimed to establish correlations between the clinical features of a cohort of Usher syndrome (USH) patients with pathogenic variants in MYO7A, type of pathogenic variant, and location on the protein domain. Methods: Sixty-two USH patients from 46 families with biallelic variants in MYO7A were examined for visual and audiological features. Participants were evaluated based on self-reported ophthalmological history and ophthalmological investigations (computerized visual field testing, best-corrected visual acuity, and ophthalmoscopic and electrophysiological examination). Optical coherence tomography and fundus autofluorescence imaging were performed when possible. Auditory and vestibular functions were evaluated. Patients were classified according to the type of variant and the protein domain where the variants were located. Results: Most patients displayed a typical USH1 phenotype, that is, prelingual severe-profound sensorineural hearing loss, prepubertal retinitis pigmentosa (RP) and vestibular dysfunction. No statistically significant differences were observed for the variables analysed except for the onset of hearing loss due to the existence of two USH2 cases, defined as postlingual sensorineural hearing loss, postpubertal onset of RP, and absence of vestibular dysfunction, and one atypical case of USH. Conclusion: We were unable to find a correlation between genotype and phenotype for MYO7A. However, our findings could prove useful for the assessment of efficacy in clinical trials, since the type of MYO7A variant does not seem to change the onset, severity or course of visual disease.This project was financially supported by the Center for Biomedical Network Research on Rare Diseases (CIBERER), FIS (PI16/00425, PI16/00539 and IIS‐FJD Biobank PT13/0010/0012). LG‐M and IPR were supported by the Río Hortega and predoctoral Programs (CM16/00126 and FI17/00192, respectively) from Institute of Health Carlos III (ISCIII, Spanish Ministry of the Economy, Industry and Competitiveness), Regional Government of Madrid (CAM, B2017/BMD37), and Regional Government of the Valencian Community (PROMETEU/2018/135), with partial support from the European Regional Development Fund (ERDF). Additional support was received from the Ramon Areces Foundation, the University Chair UAM‐IIS‐FJD of Genomic Medicine, ONCE Foundation and the Spanish National Organization of the Blind (ONCE). Drafting of this manuscript was possible thanks to the UshTher project (Clinical trial of gene therapy with dual AAV vectors for retinitis pigmentosa in patients with Usher syndrome type IB), which has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 754848. The authors are grateful to the families that participated in this study and to the colleagues who referred patients to us. We also thank the Genetics and Ophthalmology Departments of Fundación Jimenez Diaz University Hospital (FJD, Madrid) and Asunción Giménez, Cristina Villaverde, and Ignacio Mahillo for their technical assistance

Characteristics and outcome of Streptococcus pneumoniae endocarditis in the XXI Century: a systematic review of 111 cases (2000-2013)

Streptococcus pneumoniae is an infrequent cause of severe infectious endocarditis (IE). The aim of our study was to describe the epidemiology, clinical and microbiological characteristics, and outcome of a series of cases of S. pneumoniae IE diagnosed in Spain and in a series of cases published since 2000 in the medical literature. We prospectively collected all cases of IE diagnosed in a multicenter cohort of patients from 27 Spanish hospitals (n = 2539). We also performed a systematic review of the literature since 2000 and retrieved all cases with complete clinical data using a pre-established protocol. Predictors of mortality were identified using a logistic regression model. We collected 111 cases of pneumococcal IE: 24 patients from the Spanish cohort and 87 cases from the literature review. Median age was 51 years, and 23 patients (20.7%) were under 15 years. Men accounted for 64% of patients, and infection was community-acquired in 96.4% of cases. The most important underlying conditions were liver disease (27.9%) and immunosuppression (10.8%). A predisposing heart condition was present in only 18 patients (16.2%). Pneumococcal IE affected a native valve in 93.7% of patients. Left-sided endocarditis predominated (aortic valve 53.2% and mitral valve 40.5%). The microbiological diagnosis was obtained from blood cultures in 84.7% of cases. In the Spanish cohort, nonsusceptibility to penicillin was detected in 4.2%. The most common clinical manifestations included fever (71.2%), a new heart murmur (55%), pneumonia (45.9%), meningitis (40.5%), and Austrian syndrome (26.1%). Cardiac surgery was performed in 47.7% of patients. The in-hospital mortality rate was 20.7%. The multivariate analysis revealed the independent risk factors for mortality to be meningitis (OR, 4.3; 95% CI, 1.4-12.9; P < 0.01). Valve surgery was protective (OR, 0.1; 95% CI, 0.04-0.4; P < 0.01). Streptococcus pneumoniae IE is a community-acquired disease that mainly affects native aortic valves. Half of the cases in the present study had concomitant pneumonia, and a considerable number developed meningitis. Mortality was high, mainly in patients with central nervous system (CNS) involvement. Surgery was protective

Informe de distribución espacial de características geomorfológicas y sedimentarias del sector meridional del LIC ESZZ15002 Espacio marino del oriente y sur de Lanzarote-Fuerteventura

En este informe se presenta una caracterización morfosedimentaria y estructural del margen sur de Fuerteventura, nueva y ampliada, que ha supuesto un beneficio para el estudio de las características morfológicas y de los hábitats bentónicos del margen sur de Fuerteventura. Para ello se ha realizado el reprocesado de los datos batimétricos y de reflectividad disponibles en la zona, que ha permitido mejorar su resolución y calidad, y ampliar de manera considerable la zona de estudio en relación a la estudiada en el proyecto anterior LIFE+INDEMARES. Los datos batimétricos se han interpretado junto con los registros de sonda paramétrica de alta resolución y los datos sedimentológicos (granulometría, mineralogía, contenido en materia orgánica y carbonatos) y petrológicos (tipo de roca) de muestras del fondo marino obtenidas durante en el proyecto LIFE+INDEMARES. Entre los tipos morfológicos cartografiados en la zona abundan los rasgos estructurales y erosivos, pero también existen rasgos deposicionales y biogénicos a lo largo de toda el área de estudio. Además se han identificado varios conos volcánicos situados a lo largo del talud. Las muestras de sedimento recuperadas se sitúan preferentemente en el techo del Banco de Amanay y en la zona de El Banquete, corresponden, fundamentalmente, a sedimentos gruesos de tipo arena-arena gravosa y en menor medida arena fangosa, con alto contenido en carbonato. Por su parte, dentro del material rocoso predominan las rocas volcánicas, principalmente los basaltos olivínicos, y las rocas carbonatadas ferruginosas. Entre las principales carencias identificadas, que podrían ser consideradas como una actividad futura para la mejora del conocimiento de la zona, destaca la ausencia de (1) una malla apropiada de registros de sonda paramétrica, ya que los existentes se centran en el techo del Banco de Amanay y en El Banquete, dejando las zonas profundas sin estudiar; y (2) una distribución adecuada de los muestreos de sedimento, ya que como en el punto anterior, las muestras recuperadas se limitan, fundamentalmente al techo del Banco de Amanay y El Banquete, dejando muchas áreas sin explorar. Esta escasez de muestras no permite un calibrado suficientemente correcto de los datos de reflectividad que son clave en la realización de modelos de predicción de hábitat.This report presents a new and expanded morphosedimentary and structural characterization of the southern margin of Fuerteventura. The multibeam data (bathymetry and backscatter) available in the study area have been reprocessed, and high resolution parametric profiles, sedimentological (grain size, mineralogy, organic matter, and carbonate content) and petrological (type of rock) data have been integrated to achieve a more complete approach. The reprocessing of bathymetric data has substantially improved the resolution and quality of the data, and the addition of data from previous projects (ZEE project) has allowed to extend the study area. All this new information provides a benefit to the study of the morphological characteristics and the benthic habitats from the south of Fuerteventura area. Among the morphological types mapped in the study area, structural and erosive features are frequent, but depositional and biogenic features also appear in the whole area. Moreover, several volcanic cones have been mapped along the slope. Sediment samples retrieved at the study area, mostly located at the top of the Amanay Bank and El Banquete, correspond to coarse sediments as sand-gravelly sand and, in a lesser extent, with muddy sand of high carbonate content. The analysis from the rock samples indicates the presence of both volcanic (mainly olivine basalts) and carbonate (ferruginous) rocks. We identify two shortcomings in this study: (1) the absence of a suitable grid of high resolution sub-bottom profiles, since the available records are limited to the top of Amanay Bank and El Banquete area and, (2) the absence of a spatially more homogeneous and intensive grid for surficial sediment samples; this makes impossible to obtain a good calibration between the sediment samples and the backscatter data. For these reasons, we strongly recommend future activities to improve the knowledge of the area with a more detailed geophysical and sedimentological study, which will result in better habitat prediction models.Fondos LIFE, Comisión Europea. Fundación Biodiversidad. LIFE IP-PAF INTEMARE

Estrategia para mejorar la seguridad en la prescripción de dosis altas de ácido acetilsalicílico en atención primaria

Objetivo: Se planteó un estudio cuyo objetivo principal fue cuantificar el cambio en el número de pacientes con edad ≥74 años en tratamiento crónico con dosis altas de ácido acetilsalicílico (AAS) (> 150 mg), después de una estrategia de intervención del farmacéutico de atención primaria (FAP).  Método: estudio transversal de intervención en pacientes ≥74 años con AAS >150 mg, dispensados en un periodo de 6 meses (enero-julio 2021), en 40 centros de salud.  Resultados: 731 pacientes ≥74 años con dosis altas de AAS (3,6%). 56,6% mujeres, edad media=85,0 años (IC 95% 84,6-85,5); media de años con AAS > 150 mg = 6,5 (IC 95% 6,2-6,8). Se consiguió una reducción de la dosis en 394 pacientes (53,9%; IC 95% 50,2 -57,6). El número total de pacientes y porcentaje en el que la aceptación de la intervención fue mayor del 50% según el diagnóstico fue: insuficiencia venosa (n=8; 87,5%), enfermedad trombótica venosa (n=4; 75,0%), diagnóstico incierto (n=56; 69,6%), fibrilación auricular (n=25; 64,0%), prevención primaria de enfermedad cardiovascular (n=102; 62,7%), arteriopatía periférica (n=22; 54,5%) y accidente cerebrovascular (n= 362; 51,7%). Un 17,2% (IC 95% 14,57-20,17) no estaban en tratamiento concomitante con un IBP.  Conclusiones: a pesar de la evidencia científica, se siguen encontrando prescripciones de AAS a dosis altas en mayores, exponiéndoles a un mayor riesgo de hemorragias. Esta estrategia ha sido eficaz ya que ha permitido adecuar la dosis a más de la mitad de los pacientes. Los FAP pueden desempeñar una importante labor en la detección y resolución de potenciales reacciones adversas

PREVALENCIA DE PATOLOGÍA RESPIRATORIA CRÓNICA EN PACIENTES MAYORES DE 75 AÑOS EN TRATAMIENTO CON GABAPENTINOIDES Y OPIOIDES

Introducción: Tras la reciente publicación de la alerta de la Food and Drug Administration (FDA) que advierte sobre la posible aparición de dificultades respiratorias en pacientes con fármacos gabapentinoides y factores de riesgo respiratorio, se plantea un estudio cuyo objetivo principal es conocer la prevalencia de patología respiratoria crónica en mayores de 75 años, en tratamiento concomitante con gabapentinoides y opioides potentes. Material y métodos: Estudio transversal descriptivo realizado en pacientes >75 años con prescripción concomitante de gabapentinoides y opioides potentes, y al menos 3 envases dispensados en un periodo de 6 meses (julio-diciembre 2019), en 40 centros de salud. Resultados: Tras realizar muestreo, se analizaron 57 pacientes. Edad media=84,1 (DE 5,0) años; 82,5%mujeres. Un 25,3% de la población presentaba patología respiratoria crónica asociada. El promedio del Índice de comorbilidad Charlson fue=6,4 (DE 1,88). La indicación para patología lumbar se detectó en el 50,9% de la prescripción con gabapentinoides y 47,3% con opioides. Un 68,4% tenían incluido en su tratamiento otro depresor. Conclusiones: Los resultados muestran una población mayor frágil, con una elevada carga de comorbilidad. Alrededor de un cuarto de la muestra analizada ya presentaba patología respiratoria crónica, con lo que en estos pacientes el riesgo se incrementa notablemente. El uso de gabapentinoides y de opioides fue para la indicación de dolor lumbar en casi la mitad de los pacientes. La evidencia disponible en esta indicación es cuestionable y limitada.  Por otro lado, el abordaje de tratamiento para dolor de tipo lumbar es complejo, y requiere un planteamiento global

PREVALENCIA DE PATOLOGÍA RESPIRATORIA CRÓNICA EN PACIENTES MAYORES DE 75 AÑOS EN TRATAMIENTO CON GABAPENTINOIDES Y OPIOIDES

Introducción: Tras la reciente publicación de la alerta de la Food and Drug Administration (FDA) que advierte sobre la posible aparición de dificultades respiratorias en pacientes con fármacos gabapentinoides y factores de riesgo respiratorio, se plantea un estudio cuyo objetivo principal es conocer la prevalencia de patología respiratoria crónica en mayores de 75 años, en tratamiento concomitante con gabapentinoides y opioides potentes. Material y métodos: Estudio transversal descriptivo realizado en pacientes >75 años con prescripción concomitante de gabapentinoides y opioides potentes, y al menos 3 envases dispensados en un periodo de 6 meses (julio-diciembre 2019), en 40 centros de salud. Resultados: Tras realizar muestreo, se analizaron 57 pacientes. Edad media=84,1 (DE 5,0) años; 82,5%mujeres. Un 25,3% de la población presentaba patología respiratoria crónica asociada. El promedio del Índice de comorbilidad Charlson fue=6,4 (DE 1,88). La indicación para patología lumbar se detectó en el 50,9% de la prescripción con gabapentinoides y 47,3% con opioides. Un 68,4% tenían incluido en su tratamiento otro depresor. Conclusiones: Los resultados muestran una población mayor frágil, con una elevada carga de comorbilidad. Alrededor de un cuarto de la muestra analizada ya presentaba patología respiratoria crónica, con lo que en estos pacientes el riesgo se incrementa notablemente. El uso de gabapentinoides y de opioides fue para la indicación de dolor lumbar en casi la mitad de los pacientes. La evidencia disponible en esta indicación es cuestionable y limitada.  Por otro lado, el abordaje de tratamiento para dolor de tipo lumbar es complejo, y requiere un planteamiento global

Impact of FLT3–ITD Mutation Status and Its Ratio in a Cohort of 2901 Patients Undergoing Upfront Intensive Chemotherapy: A PETHEMA Registry Study

FLT3–ITD results in a poor prognosis in terms of overall survival (OS) and relapse-free survival (RFS) in acute myeloid leukemia (AML). However, the prognostic usefulness of the allelic ratio (AR) to select post-remission therapy remains controversial. Our study focuses on the prognostic impact of FLT3–ITD and its ratio in a series of 2901 adult patients treated intensively in the pre-FLT3 inhibitor era and reported in the PETHEMA registry. A total of 579 of these patients (20%) harbored FLT3–ITD mutations. In multivariate analyses, patients with an FLT3–ITD allele ratio (AR) of >0.5 showed a lower complete remission (CR rate) and OS (HR 1.47, p = 0.009), while AR > 0.8 was associated with poorer RFS (HR 2.1; p 0.5). Using the maximally selected log-rank statistics, we established an optimal cutoff of FLT3–ITD AR of 0.44 for OS, and 0.8 for RFS. We analyzed the OS and RFS according to FLT3–ITD status in all patients, and we found that the group of FLT3–ITD-positive patients with AR 0.44, allo-HSCT was superior to auto-HSCT in terms of OS and RFS. This study provides more evidence for a better characterization of patients with AML harboring FLT3–ITD mutations.This study was fundedby Instituto de Salud Carlos III (ISCIII) through the project PI19/01518 and PI19/00730 and co- funded by the European Union, the CRIS Against Cancer Foundation, grant 2018/001, and by the Instituto de Investigación Hospital 12 de Octubre (IMAS12). APeer reviewe