Articles publicats (Medicina i Cirurgia)
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- ItemOpen AccessAMPK is a mechano-metabolic sensor linking cell adhesion and mitochondrial dynamics to Myosin-dependent cell migration(Nature Research, 2023) Crosas-Molist, Eva; Graziani, Vittoria; Maiques Carlos, Oscar; Pandya, Pahini; Monger, Joanne; Samain, Remi; George, Samantha L.; Malik, Saba; Salise, Jerrine; Morales, Valle; Le Guennec, Adrien; Atkinson, R. Andrew; Martí Laborda, Rosa Ma.; Matias-Guiu, Xavier; Charras, Guillaume; Conte, Maria R.; Elosegui-Artola, Alberto; Holt, Mark; Sanz Moreno, VictoriaCell migration is crucial for cancer dissemination. We find that AMP-activated protein kinase (AMPK) controls cell migration by acting as an adhesion sensing molecular hub. In 3-dimensional matrices, fast-migrating amoeboid cancer cells exert low adhesion/low traction linked to low ATP/AMP, leading to AMPK activation. In turn, AMPK plays a dual role controlling mitochondrial dynamics and cytoskeletal remodelling. High AMPK activity in low adhering migratory cells, induces mitochondrial fission, resulting in lower oxidative phosphorylation and lower mitochondrial ATP. Concurrently, AMPK inactivates Myosin Phosphatase, increasing Myosin II-dependent amoeboid migration. Reducing adhesion or mitochondrial fusion or activating AMPK induces efficient rounded-amoeboid migration. AMPK inhibition suppresses metastatic potential of amoeboid cancer cells in vivo, while a mitochondrial/AMPK-driven switch is observed in regions of human tumours where amoeboid cells are disseminating. We unveil how mitochondrial dynamics control cell migration and suggest that AMPK is a mechano-metabolic sensor linking energetics and the cytoskeleton.
- ItemOpen AccessPlatelet levels and age are determinants of survival after mild-moderate TBI: A prospective study in Spain(Frontiers Media, 2023) Yuguero Torres, Oriol; Vena Martínez, Ana Belén; Bernal, Maria; Martínez Alonso, Montserrat; Farré, Joan; Purroy Garcia, FranciscoIntroduction: Traumatic brain injury (TBI) is a very important reason for consultation in emergency departments. Methods: A hospital cohort study with patients who attended a hospital emergency department between June 1, 2018 and December 31, 2020 due to TBI was studied. Clinical and sociodemographic variables were recorded. The levels of biomarkers and management variables were used. Qualitative variables were analyzed using Pearson's chi-square test, and quantitative variables using the Mann–Whitney U-test. Survival analyses were performed by fitting a multivariable Cox regression model for patient survival during the follow-up of the study in relation to the patient's characteristics upon admission to the emergency department. Results: A total of 540 patients were included. The mean age was 83 years, and 53.9% of the patients were men. Overall, 112 patients (20.7%) died during the study follow-up. The mortality rate per 100 person-years was 14.33 (11.8–17.24), the most frequent mechanism being falls in the home, with none caused on public roads. The multivariable Cox proportional hazards model showed that survival after TBI was significantly associated with age, S100 levels, Charlson index, patient's institutionalized status, the place where the TBI occurred, and hemoglobin and platelet levels. Discussion: The most common profile for a patient with a TBI was male and aged between 80 and 90 years. The combination of the variables age, Charlson index, place of TBI occurrence, and hemoglobin and platelet levels could offer early prediction of survival in our population independently of TBI severity. With the data obtained, a therapeutic algorithm could be established for patients suffering from mild TBI, allowing the patient to be supervised at home, avoiding futile referrals to emergency services.
- ItemOpen AccessCaffeine and the Risk of Diabetic Retinopathy in Type 2 Diabetes Mellitus: Findings from Clinical and Experimental Studies(MDPI, 2023) Alcubierre Calvo, Núria; Granado Casas, Minerva; Bogdanov, Patricia; Hernández, Cristina; Ramos, Hugo; Castelblanco Echavarría, Esmeralda; Real, Jordi; Rubinat, Esther; Traveset Maeso, Alicia; Hernández García, Marta; Jurjo Campo, Carmen; Vioque, Jesús; Navarrete Muñoz, Eva María; Simó, Rafael; Mauricio Puente, DídacThe aim of this study was to assess the potential benefits of caffeine intake in protecting against the development of diabetic retinopathy (DR) in subjects with type 2 diabetes (T2D). Furthermore, we tested the effect of topical administration of caffeine on the early stages of DR in an experimental model of DR. In the cross-sectional study, a total of 144 subjects with DR and 147 individuals without DR were assessed. DR was assessed by an experienced ophthalmologist. A validated food frequency questionnaire (FFQ) was administered. In the experimental model, a total of 20 mice were included. One drop (5 μL) of caffeine (5 mg/mL) (n = 10) or vehicle (5 μL PBS, pH 7.4) (n = 10) was randomly administered directly onto the superior corneal surface twice daily for two weeks in each eye. Glial activation and retinal vascular permeability were assessed using standard methods. In the cross-sectional study in humans, the adjusted-multivariable model showed that a moderate and high (Q2 and Q4) caffeine intake had a protective effect of DR (odds ratio (95% confidence interval) = 0.35 (0.16–0.78); p = 0.011 and 0.35 (0.16–0.77); p = 0.010, respectively). In the experimental model, the administration of caffeine did not improve either reactive gliosis or retinal vascular permeability. Our results suggest a dose-dependent protective effect of caffeine in the development of DR, while the potential benefits of antioxidants in coffee and tea should also be considered. Further research is needed to establish the benefits and mechanisms of caffeinated beverages in the development of DR.
- ItemOpen AccessAntibiotic Susceptibility and Clarithromycin Resistance Determinants in Helicobacter pylori in the Northeast of Spain: A One-Year Prospective Study(MDPI, 2023) Mormeneo Bayo, Saray; Bellés Bellés, Alba; Vázquez Gómez, Diego; Planella de Rubinat, Montse; Bayas Pastor, Diana Carolina; Morales Portillo, Arturo; Jover, Alfredo; López González, Éric; Prim, Núria; Garcia Gonzalez, MercedesHelicobacter pylori is one of the most widespread infections, and it is reaching alarming resistance levels worldwide. The recommended first-line empirical treatment differs according to the local rate of clarithromycin resistance. Macrolide resistance is mainly associated with three point mutations in the 23S rRNA gene. The aim of this study was to describe the antibiotic susceptibility of H. pylori in our healthcare area and the main mechanisms involved in clarithromycin resistance. Gastric biopsies (n = 641) were collected and cultured in a one-year prospective study. Antibiotic susceptibility testing was performed by gradient diffusion. A multiplex real-time PCR test (AllplexTM H.pylori & ClariR Assay, Seegene) was used to detect the most frequent mutations associated with clarithromycin resistance. Overall, 141 isolates were available for antibiotic susceptibility testing. The highest resistance rates were detected in metronidazole and levofloxacin. The rate of clarithromycin resistance was 12.1%, and the associated mutations were A2143G and A2142G. More than half of the clarithromycin-resistant isolates presented high MIC values (>256 mg/L). Tetracycline resistance was not detected, suggesting that therapies that contain tetracycline could be a suitable option. The low clarithromycin resistance rate coupled with the high rates of metronidazole resistance may support the recovery of the classical triple therapy in our healthcare area.
- ItemOpen AccessInter-Rater Variability in the Evaluation of Lung Ultrasound in Videos Acquired from COVID-19 Patients(MDPI, 2023) Herraiz, Joaquin L.; Freijo, Clara; Camacho, Jorge; Muñoz, Mario; González, Ricardo; Alonso Roca, Rafael; Álvarez Troncoso, Jorge; Beltrán Romero, Luis Matías; Bernabeu Wittel, Máximo; Blancas, Rafael; Calvo Cebrián, Antonio; Campo Linares, Ricardo; Chehayeb Morán, Jaldún; Chordá Ribelles, José; García Rubio, Samuel; García de Casasola, Gonzalo; Gil Rodrigo, Adriana; Henríquez Camacho, César; Hernández Píriz, Alba; Hernández Quiles, Carlos; Llamas, Rafael; Luordo, Davide; Marín Baselga, Raquel; Martínez Díaz, María Cristina; Mateos González, María; Méndez Bailon, Manuel; Miralles Aguiar, Francisco; Nogue Bou, Ramon Maria; Nogué, Marta; Ortiz de Urbina Antia, Borja; Oviedo García, Alberto Ángel; Porcel Pérez, José Manuel; Rodríguez, Santiago; Rodríguez Serrano, Diego Aníbal; Sainz, Talía; Sánchez Barrancos, Ignacio Manuel; Torres, Marta; Torres Macho, Juan; Trueba Vicente, Ángela; Villen, Tomas; Zafra-Sánchez, Juan José; Tung Chen, YaleLung ultrasound (LUS) allows for the detection of a series of manifestations of COVID-19, such as B-lines and consolidations. The objective of this work was to study the inter-rater reliability (IRR) when detecting signs associated with COVID-19 in the LUS, as well as the performance of the test in a longitudinal or transverse orientation. Thirty-three physicians with advanced experience in LUS independently evaluated ultrasound videos previously acquired using the ULTRACOV system on 20 patients with confirmed COVID-19. For each patient, 24 videos of 3 s were acquired (using 12 positions with the probe in longitudinal and transverse orientations). The physicians had no information about the patients or other previous evaluations. The score assigned to each acquisition followed the convention applied in previous studies. A substantial IRR was found in the cases of normal LUS (κ = 0.74), with only a fair IRR for the presence of individual B-lines (κ = 0.36) and for confluent B-lines occupying < 50% (κ = 0.26) and a moderate IRR in consolidations and B-lines > 50% (κ = 0.50). No statistically significant differences between the longitudinal and transverse scans were found. The IRR for LUS of COVID-19 patients may benefit from more standardized clinical protocols.