http://hdl.handle.net/20.500.11940/7 2026-04-20T11:11:11Z http://hdl.handle.net/20.500.11940/23261 [EN] Leptin is a hormone that is secreted by adipocytes in proportion to adipose tissue size, and that informs the brain about the energy status of the body. Leptin acts through its receptor LepRb, expressed mainly in the hypothalamus, and induces a negative energy balance by potent inhibition of feeding and activation of energy expenditure. These actions have led to huge expectations for the development of therapeutic targets for metabolic complications based on leptin-derived compounds. However, the majority of patients with obesity presents elevated leptin production, suggesting that in this setting leptin is ineffective in the regulation of energy balance. This resistance to the action of leptin in obesity has led to the development of "leptin sensitizers," which have been tested in preclinical studies. Much research has focused on generating combined treatments that act on multiple levels of the gastrointestinal-brain axis. The gastrointestinal-brain axis secretes a variety of different anorexigenic signals, such as uroguanylin, glucagon-like peptide-1, amylin, or cholecystokinin, which can alleviate the resistance to leptin action. Moreover, alternative mechanism such as pharmacokinetics, proteostasis, the role of specific kinases, chaperones, ER stress and neonatal feeding modifications are also implicated in leptin resistance. This review will cover the current knowledge regarding the interaction of leptin with different endocrine factors from the gastrointestinal-brain axis and other novel mechanisms that improve leptin sensitivity in obesity. 2026-04-10T09:03:29Z http://hdl.handle.net/20.500.11940/23241 [EN] Growth differentiation factor 15 (GDF15) is a stress response cytokine that has been proposed as a relevant metabolic hormone. Descriptive studies have shown that plasma GDF15 levels are regulated by short term changes in nutritional status, such as fasting, or in obesity. However, few data exist regarding how GDF15 levels are regulated in peripheral tissues. The aim of the present work was to study the variations on gastric levels of GDF15 and its precursor under different physiological conditions, such as short-term changes in nutritional status or overfeeding achieved by HFD. Moreover, we also address the sex- and age-dependent alterations in GDF15 physiology. The levels of gastric and plasma GDF15 and its precursor were measured in lean and obese mice, rats and humans by western blot, RT-PCR, ELISA, immunohistochemistry and by an in vitro organ culture system. Our results show a robust regulation of gastric GDF15 production by fasting in rodents. In obesity an increase in GDF15 secretion from the stomach is reflected with an increase in circulating levels of GDF15 in rats and humans. Moreover, gastric GDF15 levels increase with age in both rats and humans. Finally, gastric GDF15 levels display sexual dimorphism, which could explain the difference in circulating GFD15 levels between males and females, observed in both humans and rodents. Our results provide clear evidence that gastric GDF15 is a critical contributor of circulating GDF15 levels and can explain some of the metabolic effects induced by GDF15. 2026-04-10T08:11:06Z http://hdl.handle.net/20.500.11940/23221 Antecedentes/Objetivos: Esta revisión sistemática (RS) tuvo como objetivo analizar la existencia, características y efectividad de programas de prevención escolar, familiar y comunitaria en América Latina dirigidos al Uso Problemático de Internet (UPI), el juego problemático y la adicción a videojuegos. Método: La RS se desarrolló siguiendo las directrices PRISMA y fue registrado en PROSPERO. La búsqueda se llevó a cabo en octubre de 2024 en Medline, Embase, PsycInfo, Scielo, Cochrane Library, Web of Science, Scopus, Dialnet y Redalyc. Se recibieron alertas mensuales hasta septiembre de 2025. Resultados: Los programas identificados son de ámbito escolar con un enfoque de promoción de hábitos de salud, abordando únicamente el tiempo de pantallas. No se han dentificado programas de prevención familiar y/o comunitaria. Programas como ACTIVITAL, Mexa-se y Fortaleça sua Saúde han mostrado ciertos logros en la reducción del tiempo frente a pantallas, aunque su impacto a largo plazo y sostenibilidad son limitados. Conclusiones: La falta de métodos de evaluación estandarizados dificulta la comparación y replicación de intervenciones en contextos sociales y culturales diversos. Se subraya la necesidad de estrategias integrales, culturalmente adaptadas y multicomponentes que incluyan a escuelas, familias y comunidades para reducir la creciente prevalencia de estas adicciones comportamentales en América Latina.; Background/Aim: This systematic review (SR) aimed to analyze the existence, characteristics, and effectiveness of school, family, and community prevention programs in Latin America targeting Problematic Internet Use (PIU), problematic gambling, and video game addiction. Method: The SR was conducted following PRISMA guidelines and was registered in PROSPERO. The search was carried out in October 2024 in Medline, Embase, PsycInfo, Scielo, Cochrane Library, Web of Science, Scopus, Dialnet, and Redalyc. Monthly alerts were received until September 2025. Results: The identified programs are school-based with a focus on promoting healthy habits and addressing screen time exclusively. No family and/or community prevention programs have been identified. Programs such as ACTIVITAL, Mexa-se, and Fortaleça sua Saúde have shown some success in reducing screen time, although their long-term impact and sustainability are limited. Conclusions: The lack of standardized evaluation methods hinders the comparison and replication of interventions in diverse cultural and social contexts. The need for comprehensive, culturally adapted, and multicomponent strategies involving schools, families, and communities is emphasized to reduce the increasing prevalence of these behavioral addictions in Latin America.; Antecedentes/Obxectivos: Esta revisión sistemática (RS) tivo como obxectivo analizar a existencia, características e efectividade de programas de prevención escolar, familiar e comunitaria en América Latina dirixidos ao Uso Problemático da internet, o xogo problemático e a adicción a videoxogos. Método: A RS desenvolveuse seguindo as directrices PRISMA e foi rexistrado en PROSPERO. A procura levou a cabo en outubro de 2024 en Medline, Embase, PsycInfo, Scielo, Cochrane Library, Web of Science, Scopus, Dialnet e Redalyc. Recibíronse alertas mensuais ata setembro de 2025. Resultados: Os programas identificados son de ámbito escolar cun enfoque de promoción de hábitos de saúde, abordando unicamente o tempo de pantallas. Non se han dentificado programas de prevención familiar e/o comunitaria. Programas como ACTIVITAL, Mexa-se e Fortaleça sua Saúde mostraron certos logros na redución do tempo fronte a pantallas, aínda que o seu impacto a longo prazo e sustentabilidade son limitados. Conclusións: A falta de métodos de avaliación estandarizados dificulta a comparación e replicación de intervencións en contextos sociais e culturais diversos. Sublíñase a necesidade de estratexias integrais, culturalmente adaptadas e multicomponentes que inclúan a escolas, familias e comunidades para reducir a crecente prevalencia destas adiccións comportamentales en América Latina. 2026-04-09T06:35:15Z http://hdl.handle.net/20.500.11940/23123 [EN] Postmortem normothermic regional perfusion (NRP) is a rising preservation strategy in controlled donation after circulatory determination of death (cDCD). Herein, we present results for cDCD liver transplants performed in Spain 2012-2019, with outcomes evaluated through December 31, 2020. Results were analyzed retrospectively and according to recovery technique (abdominal NRP [A-NRP] or standard rapid recovery [SRR]). During the study period, 545 cDCD liver transplants were performed with A-NRP and 258 with SRR. Median donor age was 59 years (interquartile range 49-67 years). Adjusted risk estimates were improved with A-NRP for overall biliary complications (OR 0.300, 95% CI 0.197-0.459, p < .001), ischemic type biliary lesions (OR 0.112, 95% CI 0.042-0.299, p < .001), graft loss (HR 0.371, 95% CI 0.267-0.516, p < .001), and patient death (HR 0.540, 95% CI 0.373-0.781, p = .001). Cold ischemia time (HR 1.004, 95% CI 1.001-1.007, p = .021) and re-transplantation indication (HR 9.552, 95% CI 3.519-25.930, p < .001) were significant independent predictors for graft loss among cDCD livers with A-NRP. While use of A-NRP helps overcome traditional limitations in cDCD liver transplantation, opportunity for improvement remains for cases with prolonged cold ischemia and/or technically complex recipients, indicating a potential role for complimentary ex situ perfusion preservation techniques. 2026-03-17T11:41:38Z http://hdl.handle.net/20.500.11940/23122 [EN] The incidence and outcomes of coronavirus disease 2019 (COVID-19) in immunocompromised patients are a matter of debate. We performed a prospective nationwide study including a consecutive cohort of liver transplant patients with COVID-19 recruited during the Spanish outbreak from 28 February to 7 April, 2020. The primary outcome was severe COVID-19, defined as the need for mechanical ventilation, intensive care, and/or death. Age- and gender-standardised incidence and mortality ratios (SIR and SMR) were calculated using data from the Ministry of Health and the Spanish liver transplant registry. Independent predictors of severe COVID-19 among hospitalised patients were analysed using multivariate Cox regression. A total of 111 liver transplant patients were diagnosed with COVID-19 (SIR = 191.2 [95% CI 190.3-192.2]). The epidemiological curve and geographic distribution overlapped widely between the liver transplant and general populations. After a median follow-up of 23 days, 96 patients (86.5%) were admitted to hospital and 22 patients (19.8%) required respiratory support. A total of 12 patients were admitted to the ICU (10.8%). The mortality rate was 18%, which was lower than in the matched general population (SMR = 95.5 [95% CI 94.2-96.8]). Overall, 35 patients (31.5%) met criteria of severe COVID-19. Baseline immunosuppression containing mycophenolate was an independent predictor of severe COVID-19 (relative risk = 3.94; 95% CI 1.59-9.74; p = 0.003), particularly at doses higher than 1,000 mg/day (p = 0.003). This deleterious effect was not observed with calcineurin inhibitors or everolimus and complete immunosuppression withdrawal showed no benefit. Being chronically immunosuppressed, liver transplant patients have an increased risk of acquiring COVID-19 but their mortality rates are lower than the matched general population. Upon hospital admission, mycophenolate dose reduction or withdrawal could help in preventing severe COVID-19. However, complete immunosuppression withdrawal should be discouraged. In liver transplant patients, chronic immunosuppression increases the risk of acquiring COVID-19 but it could reduce disease severity. Complete immunosuppression withdrawal may not be justified. However, mycophenolate withdrawal or temporary conversion to calcineurin inhibitors or everolimus until disease resolution could be beneficial in hospitalised patients. 2026-03-17T11:39:28Z