@article {814, title = {Aripiprazole as protector against COVID-19 mortality.}, journal = {Sci Rep}, volume = {14}, year = {2024}, month = {2024 May 29}, pages = {12362}, abstract = {

The relation of antipsychotics with severe Coronavirus Disease 19 (COVID-19) outcomes is a matter of debate since the beginning of the pandemic. To date, controversial results have been published on this issue. We aimed to prove whether antipsychotics might exert adverse or protective effects against fatal outcomes derived from COVID-19. A population-based retrospective cohort study (January 2020 to November 2020) comprising inpatients (15,968 patients) who were at least 18~years old and had a laboratory-confirmed COVID-19 infection. Two sub-cohorts were delineated, comprising a total of 2536 inpatients: individuals who either had no prescription medication or were prescribed an antipsychotic within the 15~days preceding hospitalization. We conducted survival and odds ratio analyses to assess the association between antipsychotic use and mortality, reporting both unadjusted and covariate-adjusted results. We computed the average treatment effects, using the untreated group as the reference, and the average treatment effect on the treated, focusing solely on the antipsychotic-treated population. Among the eight antipsychotics found to be in use, only aripiprazole showed a significant decrease in the risk of death from COVID-19 [adjusted odds ratio (OR) = 0.86; 95\% CI, 0.79-0.93, multiple-testing adjusted p-value < 0.05]. Importantly, these findings were consistent for both covariate-adjusted and unadjusted analyses. Aripiprazole has been shown to have a differentiated beneficial effect in protecting against fatal clinical outcome in COVID-19 infected individuals. We speculate that the differential effect of aripiprazole on controlling immunological pathways and inducible inflammatory enzymes, that are critical in COVID19 illness, may be associated with our findings herein.

}, keywords = {Adult, Aged, Aged, 80 and over, Antipsychotic Agents, Aripiprazole, COVID-19, COVID-19 Drug Treatment, Female, Humans, Male, Middle Aged, Retrospective Studies, SARS-CoV-2}, issn = {2045-2322}, doi = {10.1038/s41598-024-60297-y}, author = {Loucera-Mu{\~n}ecas, C and Canal-Rivero, M and Ruiz-Veguilla, M and Carmona, R and Bostelmann, G and Garrido-Torres, N and Dopazo, J and Crespo-Facorro, B} } @article {811, title = {Genotypic characterization and antimicrobial susceptibility of human isolates in Southern Spain.}, journal = {Microbiol Spectr}, volume = {12}, year = {2024}, month = {2024 Oct 03}, pages = {e0102824}, abstract = {

is the main cause of bacterial gastroenteritis and a public health problem worldwide. Little information is available on the genotypic characteristics of human in Spain. This study is based on an analysis of the resistome, virulome, and phylogenetic relationship, antibiogram prediction, and antimicrobial susceptibility of 114 human isolates of from a tertiary hospital in southern Spain from October 2020 to June 2023. The isolates were sequenced using Illumina technology, and a bioinformatic analysis was subsequently performed. The susceptibility of isolates to ciprofloxacin, tetracycline, and erythromycin was also tested. The resistance rates for each antibiotic were 90.3\% for ciprofloxacin, 66.7\% for tetracycline, and 0.88\% for erythromycin. The fluoroquinolone resistance rate obtained is well above the European average (69.1\%). CC-21 ( = 23), ST-572 ( = 13), and ST-6532 ( = 13) were the most prevalent clonal complexes (CCs) and sequence types (STs). In the virulome, the , and genes were detected in all the isolates. A prevalence of 20.1\% was obtained for the genes and , which are related to the pathogenesis of Guillain-Barr{\'e} syndrome (GBS). The prevalence of the main antimicrobial resistance markers detected were CmeABC (92.1\%), RE-cmeABC (7.9\%), the T86I substitution in (88.9\%), (72.6\%) (65.8\%), and (17.1\%). High antibiogram prediction rates (>97\%) were obtained, except for in the case of the erythromycin-resistant phenotype. This study contributes significantly to the knowledge of genomics for the prevention, treatment, and control of infections caused by this pathogen.IMPORTANCEDespite being the pathogen with the greatest number of gastroenteritis cases worldwide, remains a poorly studied microorganism. A sustained increase in fluoroquinolone resistance in human isolates is a problem when treating infections. The development of whole genome sequencing (WGS) techniques has allowed us to better understand the genotypic characteristics of this pathogen and relate them to antibiotic resistance phenotypes. These techniques complement the data obtained from the phenotypic analysis of isolates. The zoonotic transmission of through the consumption of contaminated poultry supports approaching the study of this pathogen through "One Health" approach. In addition, due to the limited information on the genomic characteristics of in Spain, this study provides important data and allows us to compare the results with those obtained in other countries.

}, keywords = {Adolescent, Adult, Aged, Aged, 80 and over, Anti-Bacterial Agents, Campylobacter Infections, Campylobacter jejuni, Child, Child, Preschool, Ciprofloxacin, Drug Resistance, Bacterial, Erythromycin, Female, Genotype, Humans, Infant, Male, Microbial Sensitivity Tests, Middle Aged, Phylogeny, Spain, Tetracycline, Young Adult}, issn = {2165-0497}, doi = {10.1128/spectrum.01028-24}, author = {Fern{\'a}ndez-Palacios, Pablo and Gal{\'a}n-S{\'a}nchez, F{\'a}tima and Casimiro-Soriguer, Carlos S and Jurado-Tarifa, Estefan{\'\i}a and Arroyo, Federico and Lara, Mar{\'\i}a and Chaves, J Alberto and Dopazo, Joaquin and Rodriguez-Iglesias, Manuel A} } @article {561, title = {Human DNA methylomes of neurodegenerative diseases show common epigenomic patterns.}, journal = {Transl Psychiatry}, volume = {6}, year = {2016}, month = {2016 Jan 19}, pages = {e718}, abstract = {

Different neurodegenerative disorders often show similar lesions, such as the presence of amyloid plaques, TAU-neurotangles and synuclein inclusions. The genetically inherited forms are rare, so we wondered whether shared epigenetic aberrations, such as those affecting DNA methylation, might also exist. The studied samples were gray matter samples from the prefrontal cortex of control and neurodegenerative disease-associated cases. We performed the DNA methylation analyses of Alzheimer{\textquoteright}s disease, dementia with Lewy bodies, Parkinson{\textquoteright}s disease and Alzheimer-like neurodegenerative profile associated with Down{\textquoteright}s syndrome samples. The DNA methylation landscapes obtained show that neurodegenerative diseases share similar aberrant CpG methylation shifts targeting a defined gene set. Our findings suggest that neurodegenerative disorders might have similar pathogenetic mechanisms that subsequently evolve into different clinical entities. The identified aberrant DNA methylation changes can be used as biomarkers of the disorders and as potential new targets for the development of new therapies.

}, keywords = {Adult, Aged, Aged, 80 and over, DNA Methylation, Epigenomics, Female, Humans, Male, Middle Aged, neurodegenerative diseases, Prefrontal Cortex, Tissue Array Analysis}, issn = {2158-3188}, doi = {10.1038/tp.2015.214}, author = {Sanchez-Mut, J V and Heyn, H and Vidal, E and Moran, S and Sayols, S and Delgado-Morales, R and Schultz, M D and Ansoleaga, B and Garcia-Esparcia, P and Pons-Espinal, M and de Lagran, M M and Dopazo, J and Rabano, A and Avila, J and Dierssen, M and Lott, I and Ferrer, I and Ecker, J R and Esteller, M} } @article {456, title = {The EGR2 gene is involved in axonal Charcot-Marie-Tooth disease.}, journal = {Eur J Neurol}, volume = {22}, year = {2015}, month = {2015 Dec}, pages = {1548-55}, abstract = {

BACKGROUND AND PURPOSE: A three-generation family affected by axonal Charcot-Marie-Tooth disease (CMT) was investigated with the aim of discovering genetic defects and to further characterize the phenotype.

METHODS: The clinical, nerve conduction studies and muscle magnetic resonance images of the patients were reviewed. A whole exome sequencing was performed and the changes were investigated by genetic studies, in silico analysis and luciferase reporter assays.

RESULTS: A novel c.1226G>A change (p.R409Q) in the EGR2 gene was identified. Patients presented with a typical, late-onset axonal CMT phenotype with variable severity that was confirmed in the ancillary tests. The in silico studies showed that the residue R409 is an evolutionary conserved amino acid. The p.R409Q mutation, which is predicted as probably damaging, would alter the conformation of the protein slightly and would cause a decrease of gene expression.

CONCLUSIONS: This is the first report of an EGR2 mutation presenting as an axonal CMT phenotype with variable severity. This study broadens the phenotype of the EGR2-related neuropathies and suggests that the genetic testing of patients suffering from axonal CMT should include the EGR2 gene.

}, keywords = {Adult, Aged, Aged, 80 and over, Axons, Charcot-Marie-Tooth Disease, Early Growth Response Protein 2, Exome, Female, Humans, Male, Middle Aged, mutation, Pedigree, Phenotype, Severity of Illness Index, Young Adult}, issn = {1468-1331}, doi = {10.1111/ene.12782}, author = {Sevilla, T and Sivera, R and Mart{\'\i}nez-Rubio, D and Lupo, V and Chumillas, M J and Calpena, E and Dopazo, J and V{\'\i}lchez, J J and Palau, F and Espin{\'o}s, C} } @article {501, title = {Role of CPI-17 in restoring skin homoeostasis in cutaneous field of cancerization: effects of topical application of a film-forming medical device containing photolyase and UV filters.}, journal = {Exp Dermatol}, volume = {22}, year = {2013}, month = {2013 Jul}, pages = {494-6}, abstract = {

Cutaneous field of cancerization (CFC) is caused in part by the carcinogenic effect of the cyclobutane pyrimidine dimers CPD and 6-4 photoproducts (6-4PPs). Photoreactivation is carried out by photolyases which specifically recognize and repair both photoproducts. The study evaluates the molecular effects of topical application of a film-forming medical device containing photolyase and UV filters on the precancerous field in AK from seven patients. Skin improvement after treatment was confirmed in all patients by histopathological and molecular assessment. A gene set analysis showed that skin recovery was associated with biological processes involved in tissue homoeostasis and cell maintenance. The CFC response was associated with over-expression of the CPI-17 gene, and a dependence on the initial expression level was observed (P~=~0.001). Low CPI-17 levels were directly associated with pro-inflammatory genes such as TNF (P~=~0.012) and IL-1B (P~=~0.07). Our results suggest a role for CPI-17 in restoring skin homoeostasis in CFC lesions.

}, keywords = {Administration, Topical, Adult, Aged, Aged, 80 and over, Biopsy, Deoxyribodipyrimidine Photo-Lyase, Female, Gene Expression Profiling, Gene Expression Regulation, Enzymologic, Gene Expression Regulation, Neoplastic, Homeostasis, Humans, Inflammation, Intracellular Signaling Peptides and Proteins, Liposomes, Male, Middle Aged, Muscle Proteins, Phenotype, Phosphoprotein Phosphatases, Reactive Oxygen Species, Skin, Skin Neoplasms, Ultraviolet Rays}, issn = {1600-0625}, doi = {10.1111/exd.12177}, author = {Puig-Butille, Joan Anton and Malvehy, Josep and Potrony, Miriam and Trullas, Carles and Garcia-Garcia, Francisco and Dopazo, Joaquin and Puig, Susana} }