Nanofibrous gelatin-based biomaterial with improved biomimicry using D-periodic self-assembled atelocollagen

Design of bioinspired materials that mimic the extracellular matrix (ECM) at the nanoscale is a challenge in tissue engineering. While nanofibrillar gelatin materials mimic chemical composition and nano-architecture of natural ECM collagen components, it lacks the characteristic D-staggered array (D-periodicity) of 67 nm, which is an important cue in terms of cell recognition and adhesion properties. In this study, a nanofibrous gelatin matrix with improved biomimicry is achieved using a formulation including a minimal content of D-periodic self-assembled atelocollagen. We suggest a processing route approach consisting of the thermally induced phase separation of the gelatin based biopolymeric mixture precursor followed by chemical-free material cross-linking. The matrix nanostructure is characterized using field emission gun scanning electron microscopy (FEG-SEM), transmission electron microscopy (TEM), wide angle X-ray diffraction (XRD) and Fourier-transform infrared spectroscopy (FT-IR). The cell culture assays indicate that incorporation of 2.6 wt.% content of D-periodic atelocollagen to the gelatin material, produces a significant increase of MC3T3-E1 mouse preosteoblast cells attachment and human mesenchymal stem cells (hMSCs) proliferation, in comparison with related bare gelatin matrices. The presented results demonstrate the achievement of an efficient route to produce a cost-effective, compositionally defined and low immunogenic “collagen-like” instructive biomaterial, based on gelatin

Short-term prognosis of polypharmacy in elderly patients treated in emergency departments: results from the EDEN project

Background: Polypharmacy is a growing phenomenon among elderly individuals. However, there is little information about the frequency of polypharmacy among the elderly population treated in emergency departments (EDs) and its prognostic effect. This study aims to determine the prevalence and short-term prognostic effect of polypharmacy in elderly patients treated in EDs. Methods: A retrospective analysis of the Emergency Department Elderly in Needs (EDEN) project's cohort was performed. This registry included all elderly patients who attended 52 Spanish EDs for any condition. Mild and severe polypharmacy was defined as the use of 5-9 drugs and >10 drugs, respectively. The assessed outcomes were ED revisits, hospital readmissions, and mortality 30 days after discharge. Crude and adjusted logistic regression analyses, including the patient's comorbidities, were performed. Results: A total of 25,557 patients were evaluated [mean age: 78 (IQR: 71-84) years]; 10,534 (41.2%) and 5678 (22.2%) patients presented with mild and severe polypharmacy, respectively. In the adjusted analysis, mild polypharmacy and severe polypharmacy were associated with an increase in ED revisits [odds ratio (OR) 1.13 (95% confidence interval (CI): 1.04-1.23) and 1.38 (95% CI: 1.24-1.51)] and hospital readmissions [OR 1.18 (95% CI: 1.04-1.35) and 1.36 (95% CI: 1.16-1.60)], respectively, compared to non-polypharmacy. Mild and severe polypharmacy were not associated with increased 30-day mortality [OR 1.05 (95% CI: 0.89-2.26) and OR 0.89 (95% CI: 0.72-1.12)], respectively. Conclusion: Polypharmacy was common among the elderly treated in EDs and associated with increased risks of ED revisits and hospital readmissions 10 drugs. In these patients comorbidities were associated with an increase in the number of drugs. In the patients with severe polypharmacy (>10 drugs), diuretics were the most frequently drugs prescribed, followed by antihypertensives and statins. The results obtained indicate that polypharmacy is a frequent phenomenon among the elderly population treated in Emergency departments, being antihypertensives the most frequently used drugs in this population. Those patients who takes >10 drugs have a higher risk of new visits to the emergency room and hospital readmissions in short term period

Aprendizaje basado en proyectos para el diseño de fármacos aplicado

Memoria ID-088 Ayudas de la Universidad de Salamanca para la innovación docente, curso 2020-2021

Adaptación de las clases prácticas de asignaturas de química a un modelo de semipresencialidad y optimización del tiempo de trabajo en laboratorio

Memoria ID-145 Ayudas de la Universidad de Salamanca para la innovación docente, curso 2020-2021

Validation of UVEDAI: An Index for Evaluating the Level of Inflammatory Activity in Uveitis

Introduction Uveitis is the inflammation of the middle layer of the eye, the uvea, and is a major cause of blindness. None of the instruments used in clinical practice are, in themselves, sufficient to evaluate the course of uveitis. Therefore, it is necessary to develop instruments enabling standardized measurement of inflammatory activity. We developed a composite disease activity index for patients with uveitis known as UVEDAI, which considers the overall activity of the eye. The objective of this study was to validate the composite index of ocular inflammation, UVEDAI. Methods A multicenter cross-sectional study involving eight Spanish tertiary hospitals. Sixty-two patients aged ≥ 18 years with acute uveitis were recruited. Participants gave informed consent before participating in the study. A full ophthalmological examination was performed by two ophthalmologists to determine inflammatory activity: one used the UVEDAI score and the other used clinical judgment. The ophthalmologists did not share their findings with each other to avoid introducing bias into the analysis. Construct validity was established by means of factor analysis. The criterion validity of the index was determined using an ordinal multivariate regression model, in which the dependent variable was the degree of uveal inflammation (mild, moderate, or high/severe). Cut-off points were determined for the UVEDAI and for the receiver operating characteristic (ROC) curves. Results Sixty-two patients were included. Total variance with the three components accounted for 80.32% of the construct validity. Each of the three components identified one type of eye involvement. The discriminatory capacity of UVEDAI was 0.867 (95% CI 0.778; 0.955 p < 0.001) for mild versus moderate–high and 0.946 (95% CI 0.879; 1.000 p < 0.001) for high versus mild–moderate. Conclusions The variables included in UVEDAI enable ocular inflammatory activity to be described with a high degree of accuracy. The index may be used to evaluate and classify this activity with considerable discriminatory power.We would like to acknowledge the support of Abbvie: this study was conducted with an unrestricted grant from Abbvie. The Spanish Society of Rheumatology is the sponser and funder of this study and the journal's Rapid Service Fee, and has participated in the study design; in the analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. The corresponding author had full access to all study data and had final responsibility for the decision to submit the manuscript for publication

CSVS, a crowdsourcing database of the Spanish population genetic variability

The knowledge of the genetic variability of the local population is of utmost importance in personalized medicine and has been revealed as a critical factor for the discovery of new disease variants. Here, we present the Collaborative Spanish Variability Server (CSVS), which currently contains more than 2000 genomes and exomes of unrelated Spanish individuals. This database has been generated in a collaborative crowdsourcing effort collecting sequencing data produced by local genomic projects and for other purposes. Sequences have been grouped by ICD10 upper categories. A web interface allows querying the database removing one or more ICD10 categories. In this way, aggregated counts of allele frequencies of the pseudo-control Spanish population can be obtained for diseases belonging to the category removed. Interestingly, in addition to pseudo-control studies, some population studies can be made, as, for example, prevalence of pharmacogenomic variants, etc. In addition, this genomic data has been used to define the first Spanish Genome Reference Panel (SGRP1.0) for imputation. This is the first local repository of variability entirely produced by a crowdsourcing effort and constitutes an example for future initiatives to characterize local variabilityworldwide. CSVS is also part of the GA4GH Beacon network.Spanish Ministry of Economy and Competitiveness SAF2017-88908-R PT17/0009/0006 PI19/00321 CIBERER ACCI-06/07/0036 PI14-948 PI171659Regional Government of Madrid, RAREGenomicsCM B2017/BMD3721 B2017/BMD-3721European Union (EU)European Union (EU) 676559University Chair UAM-IIS-FJD of Genomic MedicineRamon Areces Foundatio

Cumulative Genetic Score and C9orf72 Repeat Status Independently Contribute to Amyotrophic Lateral Sclerosis Risk in 2 Case-Control Studies

[Background and Objectives] Most patients with amyotrophic lateral sclerosis (ALS) lack a monogenic mutation. This study evaluates ALS cumulative genetic risk in an independent Michigan and Spanish replication cohort using polygenic scores.[Methods] Participant samples from University of Michigan were genotyped and assayed for the chromosome 9 open reading frame 72 hexanucleotide expansion. Final cohort size was 219 ALS and 223 healthy controls after genotyping and participant filtering. Polygenic scores excluding the C9 region were generated using an independent ALS genome-wide association study (20,806 cases, 59,804 controls). Adjusted logistic regression and receiver operating characteristic curves evaluated the association and classification between polygenic scores and ALS status, respectively. Population attributable fractions and pathway analyses were conducted. An independent Spanish study sample (548 cases, 2,756 controls) was used for replication.[Results] Polygenic scores constructed from 275 single-nucleotide variation (SNV) had the best model fit in the Michigan cohort. An SD increase in ALS polygenic score associated with 1.28 (95% CI 1.04–1.57) times higher odds of ALS with area under the curve of 0.663 vs a model without the ALS polygenic score (p value = 1 × 10−6). The population attributable fraction of the highest 20th percentile of ALS polygenic scores, relative to the lowest 80th percentile, was 4.1% of ALS cases. Genes annotated to this polygenic score enriched for important ALS pathomechanisms. Meta-analysis with the Spanish study, using a harmonized 132 single nucleotide variation polygenic score, yielded similar logistic regression findings (odds ratio: 1.13, 95% CI 1.04–1.23).[Discussion] ALS polygenic scores can account for cumulative genetic risk in populations and reflect disease-relevant pathways. If further validated, this polygenic score will inform future ALS risk models.National ALS Registry/CDC/ATSDR (1R01TS000289); National ALS Registry/CDC/ATSDR CDCP-DHHS-US (CDC/ATSDR 200-2013-56856); NIEHS K23ES027221; NIEHS R01ES030049; NINDS R01NS127188, ALS Association (20-IIA-532), the Dr. Randall W. Whitcomb Fund for ALS Genetics, the Peter R. Clark Fund for ALS Research, the Scott L. Pranger ALS Clinic Fund, and the NeuroNetwork for Emerging Therapies at the University of Michigan. This work was supported in part by the Intramural Research Program of the NIH, National Institute on Aging (Z01-AG000949-02). Project “ALS Genetic study in Madrid Autonomous Community” funded by “ESTRATEGIAS FRENTE A ENFERMEDADES NEURODEGENERATIVAS” from Spanish Ministry of Health.Peer reviewe

A crowdsourcing database for the copy-number variation of the Spanish population

Background: Despite being a very common type of genetic variation, the distribution of copy-number variations (CNVs) in the population is still poorly understood. The knowledge of the genetic variability, especially at the level of the local population, is a critical factor for distinguishing pathogenic from non-pathogenic variation in the discovery of new disease variants. Results: Here, we present the SPAnish Copy Number Alterations Collaborative Server (SPACNACS), which currently contains copy number variation profiles obtained from more than 400 genomes and exomes of unrelated Spanish individuals. By means of a collaborative crowdsourcing effort whole genome and whole exome sequencing data, produced by local genomic projects and for other purposes, is continuously collected. Once checked both, the Spanish ancestry and the lack of kinship with other individuals in the SPACNACS, the CNVs are inferred for these sequences and they are used to populate the database. A web interface allows querying the database with different filters that include ICD10 upper categories. This allows discarding samples from the disease under study and obtaining pseudo-control CNV profiles from the local population. We also show here additional studies on the local impact of CNVs in some phenotypes and on pharmacogenomic variants. SPACNACS can be accessed at: http://csvs.clinbioinfosspa.es/spacnacs/. Conclusion: SPACNACS facilitates disease gene discovery by providing detailed information of the local variability of the population and exemplifies how to reuse genomic data produced for other purposes to build a local reference database