Identification of circulating microRNA profiles associated with pulmonary function and radiologic features in survivors of SARS-CoV-2-induced ARDS

ABSTRACT There is a limited understanding of the pathophysiology of postacute pulmonary sequelae in severe COVID-19. The aim of current study was to define the circulating microRNA (miRNA) profiles associated with pulmonary function and radiologic features in survivors of SARS-CoV-2-induced ARDS. The study included patients who developed ARDS secondary to SARS-CoV-2 infection (n=167) and a group of infected patients who did not develop ARDS (n=33). Patients were evaluated 3 months after hospital discharge. The follow-up included a complete pulmonary evaluation and chest computed tomography. Plasma miRNA profiling was performed using RT-qPCR. Random forest was used to construct miRNA signatures associated with lung diffusing capacity for carbon monoxide (DLCO) and total severity score (TSS). Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses were conducted. DLCO<80% predicted was observed in 81.8% of the patients. TSS showed a median [P25;P75] of 5 [2;8]. The miRNA model associated with DLCO comprised miR-17-5p, miR-27a-3p, miR-126-3p, miR-146a-5p and miR-495-3p. Concerning radiologic features, a miRNA signature composed by miR-9-5p, miR-21-5p, miR-24-3p and miR-221-3p correlated with TSS values. These associations were not observed in the non-ARDS group. KEGG pathway and GO enrichment analyses provided evidence of molecular mechanisms related not only to profibrotic or anti-inflammatory states but also to cell death, immune response, hypoxia, vascularization, coagulation and viral infection. In conclusion, diffusing capacity and radiological features in survivors from SARS-CoV-2-induced ARDS are associated with specific miRNA profiles. These findings provide novel insights into the possible molecular pathways underlying the pathogenesis of pulmonary sequelae. Trial registration: ClinicalTrials.gov identifier: NCT04457505.. Trial registration: ISRCTN.org identifier: ISRCTN16865246..This work is supported by Instituto de Salud Carlos III (COV20/00110), co-funded by European Regional Development Fund (ERDF)/“A way to make Europe”. CIBERES is an initiative of the Instituto de Salud Carlos III. CIBERES is an initiative of the Instituto de Salud Carlos III. Suported by: Programa de donaciones "estar preparados" UNESPA (Madrid, Spain) and Fundación Francisco Soria Melguizo (Madrid, Spain).. Finançat per La Fundació La Marató de TV3, projecte amb codi 202108-30/-31. COVIDPONENT is funded by Institut Català de la Salut and Gestió de Serveis Sanitaris. MM is the recipient of a predoctoral fellowship (PFIS: FI21/00187) from Instituto de Salud Carlos III. MCGH is the recipient of a predoctoral fellowship from “University of Lleida”. DdGC has received financial support from Instituto de Salud Carlos III (Miguel Servet 2020: CP20/00041), co-funded by the European Social Fund (ESF)/“Investing in your future”. ENL and GL were funded by COVID1005 and ACT210085 from National Agency of Investigation & Development (ANID), Chile."Article signat per 27 autors/es: María C. García-Hidalgo, Jessica González, Iván D. Benítez, Paola Carmona, Sally Santisteve, Manel Pérez-Pons, Anna Moncusí-Moix, Clara Gort-Paniello, Fátima Rodríguez-Jara, Marta Molinero, Thalia Belmonte, Gerard Torres, Gonzalo Labarca, Estefania Nova-Lamperti, Jesús Caballero, Jesús F. Bermejo-Martin, Adrián Ceccato, Laia Fernández-Barat, Ricard Ferrer, Dario Garcia-Gasulla, Rosario Menéndez, Ana Motos ,Oscar Peñuelas, Jordi Riera, Antoni Torres, Ferran Barbé, David de Gonzalo-Calvo & on behalf of the CIBERESUCICOVID Project (COV20/00110 ISCIII)"Postprint (published version

Quantitative comparison of DNA methylation assays for biomarker development and clinical applications

DNA methylation patterns are altered in numerous diseases and often correlate with clinically relevant information such as disease subtypes, prognosis and drug response. With suitable assays and after validation in large cohorts, such associations can be exploited for clinical diagnostics and personalized treatment decisions. Here we describe the results of a community-wide benchmarking study comparing the performance of all widely used methods for DNA methylation analysis that are compatible with routine clinical use. We shipped 32 reference samples to 18 laboratories in seven different countries. Researchers in those laboratories collectively contributed 21 locus-specific assays for an average of 27 predefined genomic regions, as well as six global assays. We evaluated assay sensitivity on low-input samples and assessed the assays' ability to discriminate between cell types. Good agreement was observed across all tested methods, with amplicon bisulfite sequencing and bisulfite pyrosequencing showing the best all-round performance. Our technology comparison can inform the selection, optimization and use of DNA methylation assays in large-scale validation studies, biomarker development and clinical diagnostics

Peroxiredoxin 6 Down-Regulation Induces Metabolic Remodeling and Cell Cycle Arrest in HepG2 Cells

Peroxiredoxin 6 (Prdx6) is the only member of 1-Cys subfamily of peroxiredoxins in human cells. It is the only Prdx acting on phospholipid hydroperoxides possessing two additional sites with phospholipase A2 (PLA2) and lysophosphatidylcholine-acyl transferase (LPCAT) activities. There are contrasting reports on the roles and mechanisms of multifunctional Prdx6 in several pathologies and on its sensitivity to, and influence on, the redox environment. We have down-regulated Prdx6 with specific siRNA in hepatoblastoma HepG2 cells to study its role in cell proliferation, redox homeostasis, and metabolic programming. Cell proliferation and cell number decreased while cell volume increased; import of glucose and nucleotide biosynthesis also diminished while polyamines, phospholipids, and most glycolipids increased. A proteomic quantitative analysis suggested changes in membrane arrangement and vesicle trafficking as well as redox changes in enzymes of carbon and glutathione metabolism, pentose-phosphate pathway, citrate cycle, fatty acid metabolism, biosynthesis of aminoacids, and Glycolysis/Gluconeogenesis. Specific redox changes in Hexokinase-2 (HK2), Prdx6, intracellular chloride ion channel-1 (CLIC1), PEP-carboxykinase-2 (PCK2), and 3-phosphoglycerate dehydrogenase (PHGDH) are compatible with the metabolic remodeling toward a predominant gluconeogenic flow from aminoacids with diversion at 3-phospohglycerate toward serine and other biosynthetic pathways thereon and with cell cycle arrest at G1/S transition

Characterization of the plankton community composition in Málaga Bay (NW Alboran Sea) by means of integrative taxonomy.

The Alboran Sea is highly dynamic from a hydrographical point of view. Depending on the strength of the currents and the direction of the wind the surface coastal water masses can be either of Atlantic or Mediterranean origin. This variability affects both the phytoplankton and zooplankton components of the community inhabiting the Bay of Málaga. In addition, fish larvae distribution varies with the diel cycle, affecting zooplankton distribution in shallow waters. In order to provide a first insight into the variability of the planktonic community composition in the area during a 24 hour cycle, we applied an integrative approach combining morphological and molecular tools

Brain aging and Parkinson's disease: new therapeutic approaches using drugs delivery systems

ABSTRACT The etiology and pathogenesis of Parkinson’s disease (PD) is unknown, aging being the strongest risk factor for brain degeneration. Understanding PD pathogenesis and how aging increases the risk of disease would aid the development of therapies able to slow or prevent the progression of this neurodegenerative disorder. In this review we provide an overview of the most promising therapeutic targets and strategies to delay the loss of dopaminergic neurons observed both in PD and aging. Among them, handling alphasynuclein toxicity, enhancing proteasome and lysosome clearance, ameliorating mitochondrial disruptions and modifying the glial environment are so far the most promising candidates. These new and conventional drugs may present problems related to their labile nature and to the difficulties in reaching the brain. Thus, we highlight the latest types of drug delivery system (DDS)-based strategies for PD treatment, including DDS for local and systemic drug delivery. Finally, the ongoing challenges for the discovery of new targets and the opportunities for DDS-based therapies to improve and efficacious PD therapy will be discussed

Nerve growth factor (NGF) pathway biomarkers in Down syndrome prior to and after the onset of clinical Alzheimer's disease : A paired CSF and plasma study

Altres ajuts: This work was also supported by the National Institutes of Health (R21AG056974 and R01AG061566 to JF); Departament de Salut de la Generalitat de Catalunya, Pla Estratègic de Recerca i Innovació en Salut (SLT002/16/00408 to AL); Fundació La Marató de TV3 (20141210 to JF, 044412 to RB). Fundació Catalana Síndrome de Down and Fundació Víctor Grífols i Lucas partially supported this work. This work was also supported by Generalitat de Catalunya (SLT006/17/00119 to JF) and a grant from the Fundació Bancaria La Caixa to RB.The discovery that nerve growth factor (NGF) metabolism is altered in Down syndrome (DS) and Alzheimer's disease (AD) brains offered a framework for the identification of novel biomarkers signalling NGF deregulation in AD pathology. We examined levels of NGF pathway proteins (proNGF, neuroserpin, tissue plasminogen activator [tPA], and metalloproteases [MMP]) in matched cerebrospinal fluid (CSF)/plasma samples from AD-symptomatic (DSAD) and AD-asymptomatic (aDS) individuals with DS, as well as controls (HC). ProNGF and MMP-3 were elevated while tPA was decreased in plasma from individuals with DS. CSF from individuals with DS showed elevated proNGF, neuroserpin, MMP-3, and MMP-9. ProNGF and MMP-9 in CSF differentiated DSAD from aDS (area under the curve = 0.86, 0.87). NGF pathway markers associated with CSF amyloid beta and tau and differed by sex. Brain NGF metabolism changes can be monitored in plasma and CSF, supporting relevance in AD pathology. These markers could assist staging, subtyping, or precision medicine for AD in DS

Cumplimiento al estándar de historia clínica según la resolución 3100 de 2001 por los médicos especialistas en una clínica oftalmológica de Manizales

El presente artículo evalúa el cumplimiento de los estándares en la historia clínica según resolución 3100 de 2019, por los médicos especialistas de una Clínica Oftalmológica en Manizales Colombia, para el segundo semestre de 2021. La auditoría de historias clínicas es parte de los procesos de calidad de la atención en salud, tiene el propósito de detectar oportunamente fallas en la práctica clínica, prevenir riesgos ético-jurídicos y velar por la seguridad de la información del paciente. Se realizó un estudio descriptivo, observacional, cuantitativo, retrospectivo y de corte transversal; se definió un muestreo probabilístico sistemático obteniendo una muestra de 220 historias clínicas, se caracterizó los médicos especialistas, se aplicó el formato de calificación de historias clínicas de la institución y se definió una meta del 95% de cumplimiento del estándar. Se encontró que el 27.27% de los especialistas se aleja del estándar (calificaciones entre el 82% y el 84%), el 36.36% se acercan al estándar (calificaciones entre 90 a 94%), y el 36.36% cumplen con el estándar (calificaciones iguales o superiores al 95%). Los errores más frecuentes ocurren en el ítem de datos de identificación, motivo de consulta, enfermedad actual, antecedentes personales y antecedentes familiares; la identificación de errores frecuentes como datos de identificación inadecuados, casillas vacías o con caracteres alfanuméricos y no digitar claramente el motivo de consulta, entre otros; permitirá a la institución desarrollar un plan de mejora para que la totalidad de médicos especialistas cumplan el estándar del 95% deseado

Spatio-temporal trends of the bottom trawling activity in a mud volcano field of the north-eastern Gulf of Cádiz (south-western Iberian Peninsula)

Multi-species bottom trawl fisheries are one of the human activities with a great impact on the benthic habitats and their associated biota. This study provides estimates of the bottom trawling activity (effort), catches and landings of the main commercial species as well as an estimation of the total revenue (TR) generated inside a mud volcano field located in the Spanish margin of the Gulf of Cádiz, during a time series from 2007 to 2012. To date, no studies have been carried out to analyse the temporal evolution of bottom trawling activity and TR in a mud volcano fied, or the economic consequences of possible potential bottom trawling regulation of certain sectors harbouring vulnerable and/or threatened habitats. In this study, Vessel Monitoring System data, logbooks and sales slips were used. The spatial distribution of the bottom trawling activity, catches and TR were related to the seafloor morphology and specific bottom types of the mud volcano field. During the time series, a high bottom trawling activity and associated catches was detected in flat sandy and muddy bottoms, including the Anastasya sector and between the Guadalquivir and Cádiz Diapiric Ridges. Low bottom trawling activity and catches were detected in the deepest areas but also in areas with hard and detritic bottoms such as Gazul and Chica sectors as well as in the Diapiric Ridges. A similar spatial pattern was detected for the TR asociated with these bottom trawling fisheries. An increase in bottom trawling activity was detected during the time series, mainly at the end, probably for increasing the TR and mantaining the economic profit due to the instability and increases in fuel prices and offset the increased costs. Based on the obtained information, bottom trawling regulations should be implemented in certain sectors harboring singular and/or threatened habitats and species. In some of these sectors, a low TR from bottom trawling was detected and, bottom trawling regulation may potentially have a low socioeconomic impact. This specific bottom trawling regulation could provide a sustainable balance between bottom trawling activities and habitat conservation in this mud volcano field according to the aims of the Habitats Directive (92/43/EEC) and the European Marine Strategy Framework Directive (2008/56/EEC).En prens

Pk/pd of morphine for postoperative analgesia after coronary artery bypass grafting : Intrathecal morphine significantly reduces drug consumption

The aim of the present study was to evaluate intrathecal morphine outcome on postoperative pain and apply pharmacokinetic/pharmacodynamic model to justify morphine consumption, plasma concentration and pain intensity during coronary artery bypass grafting surgery. Thirty six patients were prospectively randomized for general anesthesia and allocated in the control or morphine (400 μg intrathecal) group. At postoperative period, all patients received a loading dose of morphine (1 mg bolus), and then patient-controlled analgesia device was installed and delivered until 36 h. Blood samples was collected from venous catheter, morphine plasma concentrations were determined by liquid chromatography and pain intensity evaluated by visual analogue scale. Drug dose requirements and pain intensity at rest were different between groups. No kinetic parameters difference was obtained. Maximum effect model and hysteresis curve were proposed to correlate drug plasma concentration versus time, drug consumption and pain intensity. Intrathecal morphine reduces at rest morphine consumption and pain intensity postoperatively; the best fit pharmacokinetic/pharmacodynamic models were maximum effect and hysteresis curveColegio de Farmacéuticos de la Provincia de Buenos Aire

Challenges associated with biomarker-based classification systems for Alzheimer's disease

Altres ajuts: This work was also supported by research grants from the Carlos III Institute of Health, Spain and the CIBERNED program (Program 1, Alzheimer Disease to Alberto Lleó and SIGNAL study, www.signalstudy.es), partly funded by Fondo Europeo de Desarrollo Regional (FEDER), Unión Europea, "Una manera de hacer Europa". This work has also been supported by a "Marató TV3" grant (20141210 to Juan Fortea and 044412 to Rafael Blesa) and by Generalitat de Catalunya and a grant from the Fundació Bancaria La Caixa to Rafael Blesa. I. Illán-Gala is supported by the i-PFIS grant from the FIS, Instituto de Salud Carlos III and the Rio Hortega grant (CM17/00074) from "Acción estratégica en Salud 2013-2016" and the European Social Fund. USPHS NIH grants awarded to M.J.d.L. include: AG13616, AG022374, AG12101, and AG057570.We aimed to evaluate the consistency of the A/T/N classification system. We included healthy controls, mild cognitive impairment, and dementia patients from Alzheimer's disease Neuroimaging Initiative. We assessed subject classification consistency with different biomarker combinations and the agreement and correlation between biomarkers. Subject classification discordance ranged from 12.2% to 44.5% in the whole sample; 17.3%-46.4% in healthy controls; 11.9%-46.5% in mild cognitive impairment, and 1%-35.7% in dementia patients. Amyloid, but not neurodegeneration biomarkers, showed good agreement both in the whole sample and in the clinical subgroups. Amyloid biomarkers were correlated in the whole sample, but not along the Alzheimer's disease continuum (as defined by a positive amyloid positron emission tomography). Neurodegeneration biomarkers were poorly correlated both in the whole sample and along the Alzheimer's disease continuum. The relationship between biomarkers was stage-dependent. Our findings suggest that the current A/T/N classification system does not achieve the required consistency to be used in the clinical setting