Articles publicats (IRBLleida)
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L'IRBLleida és un centre de recerca conjunt entre la Universitat i el Departament de Salut de la Generalitat de Catalunya. Té com a funció potenciar les sinergies de recerca biomèdica entre ambdós institucions i està compromès en avançar en la recerca biomèdica com a mitja per millorar la salut de la població i facilitar una activitat assistencial òptima en situacions de malaltia. [Més informació].
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- ItemOpen AccessEfficacy of the Otago‑Exercise‑Programme to reduce falls in community‑dwelling adults aged 65‑80 when delivered as group or individual training: Non‑inferiority‑clinical‑trial(BioMed Central, 2024) Albornos Muñoz, Laura; Blanco Blanco, Joan; Cidoncha-Moreno, María Ángeles; Abad Corpa, Eva; Rivera-Álvarez, Araceli; López-Pisa, Rosa María; Caperos, José Manuel; Moreno-Casbas, Maria TeresaBackground: The Otago Exercise Programme is an effective intervention for falls prevention. However, there is limited evidence in relation to studies that compare efficacy for falls prevention when delivered Otago Exercise Programme in a group or individual format in a primary care context. Objective: To compare the Otago Exercise Programme delivered as a group vs. individual format for community dwelling older adults, over a one year period. The hypothesis was that neither format would be inferior to the other. Methods: DESIGN: A four-year multicentre, randomized, non-inferiority clinical trial, with two arms- Otago Exercise Programme group training and individual Otago exercise training. Setting(s): 21 primary healthcare centers. Participants: A sample size of 728 participants was established. Participants were aged between 65 and 80 years; living in the community; able to walk independently; and agreed to take part in the study and provided signed informed consent. Intervention: The Otago Exercise Programme was delivered mainly by nurses in primary care, with five face to face sessions, and a reinforcement 6 months later. Participants were encouraged to exercise at home between face to face sessions. Data collection: at baseline and after 6 and 12 months from October 2017 to 2020. Primary outcome: people who reported at least one fall. Secondary outcomes: number of falls, cause of falls, consequences and assistance, adherence and satisfaction. Group allocation was blinded to the researchers involved in analysis. Reporting: Consolidated Standards of Reporting Trials recommendations for the Statement for Randomized Trials of Nonpharmacologic Treatments. Results: Eight hundred twenty-seven participants were randomized (226 were allocated in group training and 272 in individual training). The analysis of the proportion of people who reported at least one fall and number of falls showed no differences between individual and group training. Assessment of the equivalence between the interventions at 12 months showed that the confidence interval for the difference of people who reported at least one fall was found to be within the equivalence limit of 10% considered. However, in those participants with a previous history of falls, group format showed potentially greater benefit. The participants in individual training presented higher scores on the Exercise Adherence Rating Scale test. No differences were found in satisfaction between the groups. Conclusions: The group Otago Exercise Programme is equivalent to individually delivered Otago Exercise Programme in terms of prevention of falls over a 12-month follow up. Adherence was higher in individual training. Implications: Healthcare professionals could offer either Otago Exercise Programme format dependent on patient preference and be confident that that standardized intervention provides patient benefit.
- ItemOpen AccessTrioxidized cysteine and aging: a molecular binomial that extends far beyond classical proteinopathic paradigms(Impact Journals, 2024) Sánchez Milán, José Antonio; Mulet, Maria; Serra, Aida; Gallart Palau, Xavier RamonIncreased oxidative stress (OS) and the disruption of the equilibrium between the production of reactive oxygen species and antioxidants are key molecular features of unhealthy aging. OS results in the formation of oxidative posttranslational modifications (PTMs), some of which involve cysteine (Cys) residues in aging proteomes, and specifically, the formation of trioxidized Cys (t-Cys), which leads to permanent protein damage. Recent findings in rodents have uncovered that irregular regulation of t-Cys residues in the aging proteome disrupts homeostatic phosphorylation signaling, resulting in alterations to proteins that are analogous to those caused by phosphorylated serine (p-Ser) residues. This work contextualizes these significant findings and discusses the implications and molecular role(s) of t-Cys in the aging proteome. Furthermore, we present novel data, validating the increase of specific t-Cys sites associated with aging in a blood-related circulating human proteome. The scope and findings included here support the hypothesis that t-Cys residues may serve as important mechanistic and biological markers, warranting further exploration in the context of unhealthy aging and age-related major diseases.
- ItemOpen AccessMolecular Profile of Subungual Melanoma: A MelaNostrum Consortium Study of 68 Cases Reporting BRAF, NRAS, KIT, and TERT Promoter Status(Karger, 2024) Millan Esteban, David; García Casado, Zaida; Macià Armengol, Anna; de la Rosa, Inés; Torrecilla Vall Llossera, Clara; Penin, Rosa Maria; Manrique Silva, Esperanza; Pellegrini, Stefania; Biasin, Maria Raffaella; Rizzolo, Piera; Gavillero, Alicia; Di Stefani, Alessandro; Pellegrini, Cristina; Requena, Celia; Fargnoli, Maria Concetta; Peris, Ketty; Cota, Carlo; Menin, Chiara; Landi, Maria Teresa; Nagore, EduardoBackground: Subungual melanoma (SM) is an unusual type of melanocytic tumor affecting the nail apparatus. The mutational prevalence of the most prominently mutated genes in melanoma has been reported in small cohorts of SM, with unclear conclusions on whether SM is different from the rest of melanomas arising in acral locations or not. Hence, the molecular profile of a large series of SM is yet to be described. Objectives: The aim of this study was to describe the molecular characteristics of a large series of SM and their association with demographic and histopathological features. Methods: Patients diagnosed with SM between 2001 and 2021 were identified from six Spanish and Italian healthcare centers. The mutational status for BRAF, NRAS, KIT, and the promoter region of TERT (TERTp) were determined either by Sanger sequencing or next-generation sequencing. Clinical data were retrieved from the hospital databases to elucidate potential associations. Results: A total of 68 SM cases were included. Mutations were most common in BRAF (10.3%) and KIT (10%), followed by NRAS (7.6%), and TERTp (3.8%). Their prevalence was similar to that of non-subungual acral melanoma but higher in SM located on the hand than on the foot. Conclusions: To date, this study represents the largest cohort of SM patients with data on the known driver gene mutations. The low mutation rate supports a different etiopathogenic mechanism for SM in comparison of non-acral cutaneous melanoma, particularly for SM of the foot.
- ItemOpen AccessMultiple endocrine defects in adult-onset Sprouty1/2/4 triple knockout mice(Nature, 2024) Altés Bargalló, Gisela; Olomí, Anna; Perramon Güell, Aida; Hernández i Estanyol, Sara; Casanovas i Llorens, Anna; Pérez, Aurora; Díaz Tocados, Juan Miguel; Valdivielso Revilla, José Manuel; Megino-Luque, Cristina; Navaridas Fernández de Bobadilla, Raúl; Matias-Guiu, Xavier; Klein, Ophir D.; Egea Navarro, Joaquim; Dolcet Roca, Xavier; Yeramian Hakim, Andree; Encinas Martín, MarioGenes of the Sprouty family (Spry1-4) are feedback inhibitors of receptor tyrosine kinases, especially of Ret and the FGF receptors. As such, they play distinct and overlapping roles in embryo morphogenesis and are considered to be tumor suppressors in adult life. Genetic experiments in mice have defined in great detail the role of these genes during embryonic development, however their function in adult mice is less clearly established. Here we generate adult-onset, whole body Spry1/2/4 triple knockout mice. Tumor incidence in triple mutant mice is comparable to that of wild type littermates of up to one year of age, indicating that Sprouty loss per se is not sufficient to initiate tumorigenesis. On the other hand, triple knockout mice do not gain weight as they age, show less visceral fat, and have lower plasma glucose levels than wild type littermates, despite showing similar food intake and slightly reduced motor function. They also show alopecia, eyelid inflammation, and mild hyperthyroidism. Finally, triple knockout mice present phosphaturia and hypophosphatemia, suggesting exacerbated signaling downstream of FGF23. In conclusion, triple knockout mice develop a series of endocrine abnormalities but do not show increased tumor incidence.
- ItemOpen AccessMetformin-induced changes in the gut microbiome and plasma metabolome are associated with cognition in men(Elsevier, 2024) Rosell Díaz, Marisel; Petit Gay, Anna; Molas Prat, Clàudia; Gallardo Nuell, Laura; Ramió Torrentà, Lluís; Garre Olmo, Josep; Pérez Brocal, Vicente; Moya, Andrés; Jové Font, Mariona; Pamplona Gras, Reinald; Puig, Josep; Ramos, Rafael; Bäckhed, Fredrik; Mayneris Perxachs, Jordi; Fernández Real, José ManuelBackground : An altered gut microbiome characterized by reduced abundance of butyrate producing bacteria and reduced gene richness is associated with type 2 diabetes (T2D). An important complication of T2D is increased risk of cognitive impairment and dementia. The biguanide metformin is a commonly prescribed medication for the control of T2D and metformin treatment has been associated with a significant reduction in the risk of dementia and improved cognition, particularly in people with T2D. Aim : To investigate the associations of metformin use with cognition exploring potential mechanisms by analyzing the gut microbiome and plasma metabolome using shotgun metagenomics and HPLC-ESI-MS/MS, respectively. Methods : We explored two independent cohorts: an observational study (Aging Imageomics) and a phase IV, randomized, double-blind, parallel-group, randomized pilot study (MEIFLO). From the two studies, we analyzed four study groups: (1) individuals with no documented medical history or medical treatment (n = 172); (2) people with long-term T2D on metformin monotherapy (n = 134); (3) people with long-term T2D treated with oral hypoglycemic agents other than metformin (n = 45); (4) a newly diagnosed T2D subjects on metformin monotherapy (n = 22). Analyses were also performed stratifying by sex. Results : Several bacterial species belonging to the Proteobacteria (Escherichia coli) and Verrucomicrobia (Akkermansia muciniphila) phyla were positively associated with metformin treatment, while bacterial species belonging to the Firmicutes phylum (Romboutsia timonensis, Romboutsia ilealis) were negatively associated. Due to the consistent increase in A. muciniphila and decrease in R.ilealis in people with T2D subjects treated with metformin, we investigated the association between this ratio and cognition. In the entire cohort of metformin-treated T2D subjects, the A.muciniphila/R.ilealis ratio was not significantly associated with cognitive test scores. However, after stratifying by sex, the A.muciniphila/R. ilealis ratio was significantly and positively associated with higher memory scores and improved memory in men. Metformin treatment was associated with an enrichment of microbial pathways involved in the TCA cycle, and butanoate, arginine, and proline metabolism in both cohorts. The bacterial genes involved in arginine metabolism, especially in production of glutamate (astA, astB, astC, astD, astE, putA), were enriched following metformin intake. In agreement, in the metabolomics analysis, metformin treatment was strongly associated with the amino acid proline, a metabolite involved in the metabolism of glutamate. Conclusions : The beneficial effects of metformin may be mediated by changes in the composition of the gut microbiota and microbial-host-derived co-metabolites.