Articles publicats (Medicina Experimental)
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- ItemOpen AccessSleep spindles and slow oscillations predict cognition and biomarkers of neurodegeneration in mild to moderate Alzheimer's disease(Wiley, 2025) Páez, Arsenio; Gillman, Sam O.; Dogaheh, Shahla Bakian; Carnes Vendrell, Anna; Dakterzada, Farida; Barbé Illa, Ferran; Dang-Vu, Thien Thanh; Piñol Ripoll, GerardIntroduction: Changes in sleep physiology can predate cognitive symptoms by decades in persons with Alzheimer's disease (AD), but it remains unclear which sleep characteristics predict cognitive and neurodegenerative changes after AD onset. Methods: Using data from a prospective cohort of mild to moderate AD (n = 60), we analyzed non-rapid eye movement sleep spindles and slow oscillations (SOs) at baseline and their associations with baseline amyloid beta (Aβ) and tau and with cognition from baseline to 3-year follow-up. Results: Higher spindle and SO activity predicted significant changes in Aβ and tau at baseline, lower Alzheimer's Disease Assessment Scale Cognitive Subscale (better cognitive performance) score, and higher Mini-Mental State Examination score from baseline to 36 months. Spindles and SOs mediated the effect of phosphorylated tau 181 (pTau181)/Aβ42 on cognition, while pTau181/aβ42 moderated the effect of spindles and SOs on cognition. Discussion: Our findings demonstrate that spindle and SO activity during sleep constitute predictive and non-invasive biomarkers of neurodegeneration and cognition in AD patients. Highlights: Sleep spindles predict long-term cognitive performance in AD. Sleep spindle and SOs can be predictive, non-invasive biomarkers for AD. Sleep may be one of the most important modifiable risk factors for AD progression. Sleep microarchitecture is a novel therapeutic target for preserving brain heath. Sleep physiology can provide novel therapeutic targets to slow AD progression.
- ItemOpen AccessClinical and ultrasound characteristics in patients with sars-cov-2 pneumonia, associated with hospitalization prognosis. e-covid Project(BioMed Central, 2024) Fàbrega Ramon, Noemí; Ortega Bravo, Marta; Torres Cortada, Gerard; Sol, Joaquim; Solanes Cabús, Mònica; Palacín Peruga, Jose MaríaBackground: During the COVID-19 pandemia, the imaging test of choice to diagnose COVID-19 pneumonia as chest computed tomography (CT). However, access was limited in the hospital setting and patients treated in Primary Care (PC) could only access the chest x-ray as an imaging test. Several scientific articles that demonstrated the sensitivity of lung ultrasound, being superior to chest x-ray [Cleverley J et al., BMJ 370, 202013] and comparable to CT scan [Tung-Chen Y et al., Ultrasound Med Biol 46:2918-2926, 2020], promoted the incorporation of this technique in the assessment of COVID-19 patients in PC. [Pérez J et al., Arch. Bronconeumol 56:27-30, 2020; Gargani L et al., Eur Heart J Cardiovasc Imaging 21:941-8, 2020, Soldati G et al., J Ultrasound Med 39:1459, 2020] A prior study in our territory (Lleida, Spain) was designed to predict complications (hospital admission) of COVID-19 pneumonia in PC patients, being different patterns of Lung ultrasounds (LUS) risk factors for hospital admission. [Martínez Redondo J et al., Int J Environ Res Public Health 18:3481, 2021] The rationale for conducting this study lies in the urgent need to understand the determinants of severity and prognosis in COVID-19 patients with interstitial pneumonia, according to its lung ultrasound patterns. This research is crucial to provide a deeper understanding of how these pre-existing ultrasound patterns related to disease progression influence the medical treatment. Methods: The objective of the study is to generate predictive models of lung ultrasound patterns for the prediction of lung areas characteristics associated with hospitalizations and admissions to the Intensive Care Unit (ICU) associated with COVID-19 disease, using ultrasound, sociodemographic and medical data obtained through the computerized medical history. Results: A single relevant variable has been found for the prediction of hospitalization (number of total regions with potentially pathological presence of B lines) and one for the prediction of ICU admission (number of regions of the right lung with potentially pathological presence of B lines). In both cases it has been determined that the optimal point for classification was 2 or more lung affected areas. Those areas under the curve have been obtained with good predictive capacity and consistency in both cohorts. Conclusions: The results of this study will contribute to the determination of the ultrasound prognostic value based on the number of lung areas affected, the presence of pulmonary condensation or the irregularity of pleural effusion patterns in COVID-19 patients, being able to be extended to other lung viral infections with similar patterns.
- ItemOpen AccessMediterranean Diet Is a Predictor of Progression of Subclinical Atherosclerosis in a Mediterranean Population: The ILERVAS Prospective Cohort Study(MDPI, 2024) Rojo López, Marina Idalia; Bermúdez López, Marcelino; Castro, Eva; Farràs, Cristina; Torres, Gerard; Pamplona Gras, Reinald; Lecube Torelló, Albert; Valdivieso, José Manuel; Fernández, Elvira; Julve, Josep; Castelblanco Echavarría, Esmeralda; Alonso, Núria; Antentas, Maria; Barranco Altirriba, María; Perera-Lluna, Alexandre; Franch-Nadal, Josep; Granado Casas, Minerva; Mauricio Puente, Dídac; ILERVAS Project CollaboratorsAtherosclerotic cardiovascular disease remains a major health issue, often developing silently as subclinical atherosclerotic disease (SAD). The Mediterranean diet (MDiet) is known for its cardiovascular benefits, but the combined influence of both MDiet adherence and physical activity (PA) on SAD progression has not been previously documented. Objective: We aimed to investigate how adherence to a healthy lifestyle, defined as MDiet adherence and PA level, influences SAD progression in subjects from the ILERVAS cohort follow-up. Methods: A study on 3097 participants from the ILERVAS prospective cohort was conducted. MDiet adherence was assessed using the MEDAS score, and PA categories were established using the IPAQ, both categorized into low, moderate, and high levels. Two different lifestyle scores integrating the MDiet and PA categories were built. The presence of atherosclerotic plaques was assessed by carotid and femoral ultrasound examination. Demographic, clinical, and biochemical data were also obtained. Multivariable linear, logistic, and Poisson regression models adjusted for potential confounders were used to analyze the association between the lifestyle scores and SAD progression, as well as the MDiet and PA as separate variables and number of territories with plaque. Results: A healthier lifestyle score did not show an effect on SAD progression. However, a higher MEDAS score was associated with a 3% decrease in the number of territories with plaque (IRR 0.97, 95% CI 0.96–0.99, p < 0.001), suggesting a protective effect of the adherence to the MDiet. PA did not show a significant association (IRR 1.00, 95% CI 1.00–1.00, p = 0.269). Older age, hypertension, dyslipidemia, smoking, and lower eGFR were associated with SAD progression, while the female sex was protective (IRR 0.67, 95% CI 0.63–0.72, p < 0.001). Conclusions: The findings of this study show that higher adherence to the MDiet is associated with reduced incidence of SAD, indicating its potential role in cardiovascular prevention strategies. Although a higher lifestyle score or physical activity levels did not show any significant effect, promoting the MDiet, alongside managing traditional cardiovascular risk factors, could be an effective public health intervention to prevent atherosclerosis and reduce the burden of cardiovascular disease.
- ItemOpen AccessExposure of a cryptic Hsp70 binding site determines the cytotoxicity of the ALS-associated SOD1-mutant A4V(Oxford University Press, 2019) Claes, Filip; Rudyak, Stanislav; Laird, Angela S.; Louros, Nikolaos; Beerten, Jacinte; Debulpaep, Maja; Michiels, Emiel; van der Kant, Rob; Van Durme, Joost; De Baets, Greet; Houben, Bert; Ramakers, Meine; Yuan, Kristy; Gwee, Serene S. L.; Hernández i Estanyol, Sara; Broersen, Kerensa; Oliveberg, Mikael; Moahamed, Barbara; Kirstein, Janine; Robberecht, Wim; Rousseau, Frederic; Schymkowitz, JoostThe accumulation of toxic protein aggregates is thought to play a key role in a range of degenerative pathologies, but it remains unclear why aggregation of polypeptides into non-native assemblies is toxic and why cellular clearance pathways offer ineffective protection. We here study the A4V mutant of SOD1, which forms toxic aggregates in motor neurons of patients with familial amyotrophic lateral sclerosis (ALS). A comparison of the location of aggregation prone regions (APRs) and Hsp70 binding sites in the denatured state of SOD1 reveals that ALS-associated mutations promote exposure of the APRs more than the strongest Hsc/Hsp70 binding site that we could detect. Mutations designed to increase the exposure of this Hsp70 interaction site in the denatured state promote aggregation but also display an increased interaction with Hsp70 chaperones. Depending on the cell type, in vitro this resulted in cellular inclusion body formation or increased clearance, accompanied with a suppression of cytotoxicity. The latter was also observed in a zebrafish model in vivo. Our results suggest that the uncontrolled accumulation of toxic SOD1A4V aggregates results from insufficient detection by the cellular surveillance network.
- ItemOpen AccessPhenotypic upregulation of hexocylceramides and ether-linked phosphocholines as markers of human extreme longevity(Anatomical Society, 2024) Fernández Bernal, Anna; Sol, Joaquim; Galo-Licona, José Daniel; Mota Martorell, Natàlia; Mas-Bargues, Cristina; Belenguer-Varea, Ángel; Obis Monné, Èlia; Viña Ribes, José; Borrás, Consuelo; Jové Font, Mariona; Pamplona Gras, ReinaldCentenarians and their relatives possess a notable survival advantage, with higher longevity and reduced susceptibility to major age-related diseases. To date, characteristic omics profiles of centenarians have been described, demonstrating that these individuals with exceptional longevity regulate their metabolism to adapt and incorporate more resilient biomolecules into their cells. Among these adaptations, the lipidomic profile stands out. However, it has not yet been determined whether this lipidomic profile is specific to centenarians or is the consequence of extreme longevity genetics and is also present in centenarians' offspring. This distinction is crucial for defining potential therapeutic targets that could help delay the aging process and associated pathologies. We applied mass-spectrometry-based techniques to quantify 569 lipid species in plasma samples from 39 centenarians, 63 centenarians' offspring, and 69 noncentenarians' offspring without familial connections. Based on this profile, we calculated different indexes to characterize the functional and structural properties of plasma lipidome. Our findings demonstrate that extreme longevity genetics (centenarians and centenarians' offspring) determines a specific lipidomic signature characterized by (i) an enrichment of hexosylceramides, (ii) a decrease of specific species of ceramides and sulfatides, (iii) a global increase of ether-PC and ether-LPC, and (iv) changes in the fluidity and diversity of specific lipid classes. We point out the conversion of ceramides to hexosylceramides and the maintenance of the levels of the ether-linked PC as a phenotypic trait to guarantee extreme longevity. We propose that this molecular signature is the result of an intrinsic adaptive program that preserves protective mechanisms and cellular identity.