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Climate change is forcing the redistribution of life on Earth at an unprecedented velocity1,2. Migratory birds are thought to help plants to track climate change through long-distance seed dispersal3,4. However, seeds may be consistently dispersed towards cooler or warmer latitudes depending on whether the fruiting period of a plant species coincides with northward or southward migrations. Here we assess the potential of plant communities to keep pace with climate change through long-distance seed dispersal by migratory birds. To do so, we combine phenological and migration information with data on 949 seed-dispersal interactions between 46 bird and 81 plant species from 13 woodland communities across Europe. Most of the plant species (86%) in these communities are dispersed by birds migrating south, whereas only 35% are dispersed by birds migrating north; the latter subset is phylogenetically clustered in lineages that have fruiting periods that overlap with the spring migration. Moreover, the majority of this critical dispersal service northwards is provided by only a few Palaearctic migrant species. The potential of migratory birds to assist a small, non-random sample of plants to track climate change latitudinally is expected to strongly influence the formation of novel plant communities, and thus affect their ecosystem functions and community assembly at higher trophic levels.
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Aclimatación , Migración Animal , Aves/fisiología , Frío , Calentamiento Global , Plantas , Dispersión de Semillas , Animales , Ecosistema , Europa (Continente) , Vuelo Animal , Mar MediterráneoRESUMEN
Seed dispersal by frugivores is a fundamental function for plant community dynamics in fragmented landscapes, where forest remnants are typically embedded in a matrix of anthropogenic habitats. Frugivores can mediate both connectivity among forest remnants and plant colonization of the matrix. However, it remains poorly understood how frugivore communities change from forest to matrix due to the loss or replacement of species with traits that are less advantageous in open habitats and whether such changes ultimately influence the composition and traits of dispersed plants via species interactions. Here, we close this gap by using a unique dataset of seed-dispersal networks that were sampled in forest patches and adjacent matrix habitats of seven fragmented landscapes across Europe. We found a similar diversity of frugivores, plants, and interactions contributing to seed dispersal in forest and matrix, but a high turnover (replacement) in all these components. The turnover of dispersed seeds was smaller than that of frugivore communities because different frugivore species provided complementary seed dispersal in forest and matrix. Importantly, the turnover involved functional changes toward larger and more mobile frugivores in the matrix, which dispersed taller, larger-seeded plants with later fruiting periods. Our study provides a trait-based understanding of frugivore-mediated seed dispersal through fragmented landscapes, uncovering nonrandom shifts that can have cascading consequences for the composition of regenerating plant communities. Our findings also highlight the importance of forest remnants and frugivore faunas for ecosystem resilience, demonstrating a high potential for passive forest restoration of unmanaged lands in the matrix.
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Ecosistema , Dispersión de Semillas , Bosques , Semillas , Frutas , ÁrbolesRESUMEN
AMPK is a highly conserved master regulator of metabolism, which restores energy balance during metabolic stress both at the cellular and physiological levels. The identification of numerous AMPK targets has helped explain how AMPK restores energy homeostasis. Recent advancements illustrate novel mechanisms of AMPK regulation, including changes in subcellular localization and phosphorylation by non-canonical upstream kinases. Notably, the therapeutic potential of AMPK is widely recognized and heavily pursued for treatment of metabolic diseases such as diabetes, but also obesity, inflammation, and cancer. Moreover, the recently solved crystal structure of AMPK has shed light both into how nucleotides activate AMPK and, importantly, also into the sites bound by small molecule activators, thus providing a path for improved drugs.
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Proteínas Quinasas Activadas por AMP/metabolismo , Metabolismo Energético , Transducción de Señal , Proteínas Quinasas Activadas por AMP/química , Animales , Autofagia , Metabolismo Energético/efectos de los fármacos , Activación Enzimática , Activadores de Enzimas/uso terapéutico , Humanos , Enfermedades Metabólicas/tratamiento farmacológico , Enfermedades Metabólicas/enzimología , Enfermedades Metabólicas/patología , Mitocondrias/enzimología , Mitocondrias/patología , Mitofagia , Modelos Moleculares , Fosforilación , Conformación Proteica , Proteolisis , Transducción de Señal/efectos de los fármacos , Relación Estructura-Actividad , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
BACKGROUND: Classical pulmonary thromboembolism (TE) and local pulmonary thrombosis (PT) have been suggested as mechanisms of thrombosis in COVID-19. However, robust evidence is still lacking because this was mainly based on retrospective studies, in which patients were included when TE was suspected. METHODS: All patients with COVID-19 pneumonia underwent computed tomography and pulmonary angiography in a prospective study. The main objective was to determine the number and percentage of thrombi surrounded by lung opacification (TSO) in each patient, as well as their relationship with percentage of lung involvement (TLI), to distinguish classical TE (with a random location of thrombi that should correspond to a percentage of TSO equivalent to the TLI) from PT. We determined TLI by artificial intelligence. Analyses at patient level (TLI and percentage of TSO) and at thrombi level (TLI and TSO) were performed. RESULTS: We diagnosed TE in 70 out of 184 patients. Three (2-8) thrombi/patient were detected. The percentage of TSO was 100% (75-100) per patient, and TLI was 19.9% (4.6-35.2). Sixty-five patients (92.9%) were above the random scenario with higher percentage of TSO than TLI. Most thrombi were TSO (n = 299, 75.1%). When evaluating by TLI (<10%, 10%-20%, 20%-30% and >30%), percentage of TSO was higher in most groups. Thrombi were mainly in subsegmental/segmental arteries, and percentage of TSO was higher in all locations. CONCLUSIONS: Thrombi in COVID-19 were found within lung opacities in a higher percentage than lung involvement, regardless of TLI and clot location, supporting the hypothesis of local PT rather than "classic TE".
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COVID-19 , Embolia Pulmonar , Tomografía Computarizada por Rayos X , Humanos , COVID-19/complicaciones , COVID-19/diagnóstico por imagen , Embolia Pulmonar/diagnóstico por imagen , Masculino , Femenino , Persona de Mediana Edad , Anciano , Estudios Prospectivos , Pulmón/diagnóstico por imagen , SARS-CoV-2 , Angiografía por Tomografía Computarizada , Anciano de 80 o más Años , Adulto , Trombosis/diagnóstico por imagenRESUMEN
We surveyed the presence of perchlorate-reducing microorganisms in available metagenomic data of halite environments from the Atacama Desert, an extreme environment characterized by high perchlorate concentrations, intense ultraviolet radiation, saline and oxidizing soils, and severe desiccation. While the presence of perchlorate might suggest a broad community of perchlorate reducers or a high abundance of a dominant taxa, our search reveals a scarce presence. In fact, we identified only one halophilic species, Salinibacter sp003022435, carrying the pcrA and pcrC genes, represented in low abundance. Moreover, we also discovered some napA genes and organisms carrying the nitrate reductase nasB gene, which hints at the possibility of cryptic perchlorate reduction occurring in these ecosystems. Our findings contribute with the knowledge of perchlorate reduction metabolism potentially occurring in halites from Atacama Desert and point towards promising future research into the perchlorate-reducing mechanism in Salinibacter, a common halophilic bacterium found in hypersaline ecosystems, whose metabolic potential remains largely unknown.
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Clima Desértico , Ambientes Extremos , Oxidación-Reducción , Percloratos , Percloratos/metabolismo , Metagenoma , MicrobiotaRESUMEN
BACKGROUND AND PURPOSE: Peripheral inflammation is probably involved in the pathogenesis of progressive supranuclear palsy (PSP) and it may be a common feature with Parkinson's disease (PD). The peripheral immune profile in PSP remains unclear, as well as whether the inflammatory pathways differ from those in PD. The neutrophil-to-lymphocyte ratio (NLR) has been proven to be a well-established biomarker of systemic inflammation. This study aimed to evaluate the peripheral immune profile in PSP compared with PD. METHODS: A cross-sectional study was conducted including patients with PSP and PD and healthy controls (HCs). Leukocyte subpopulations and the NLR were measured in peripheral blood. Multivariate linear regression and post hoc tests were applied. Electronic databases were searched in November 2023 to perform meta-analyses to clarify the peripheral immune profile in PSP. RESULTS: Our cohort included 121 patients with PSP, 127 patients with PD and 266 HCs. The NLR was higher in PSP and PD compared with HCs. PSP had a higher neutrophil count compared with HCs. Whilst a lower lymphocyte count was found in PD compared with HCs, the lymphocyte count did not differ between PSP and HCs. The meta-analyses supported this immune profile. CONCLUSIONS: PSP and PD show an increased peripheral inflammation and a higher NLR compared with HCs. Different pathogenic inflammatory mechanisms are probably involved in PSP and PD, since in PSP this altered peripheral immune profile is mainly driven by neutrophils. Understanding the neutrophils' role in PSP may allow for the development of targeted therapies.
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Globally accelerating trends in societal development and human environmental impacts since the mid-twentieth century 1-7 are known as the Great Acceleration and have been discussed as a key indicator of the onset of the Anthropocene epoch 6 . While reports on ecological responses (for example, changes in species range or local extinctions) to the Great Acceleration are multiplying 8, 9 , it is unknown whether such biotic responses are undergoing a similar acceleration over time. This knowledge gap stems from the limited availability of time series data on biodiversity changes across large temporal and geographical extents. Here we use a dataset of repeated plant surveys from 302 mountain summits across Europe, spanning 145 years of observation, to assess the temporal trajectory of mountain biodiversity changes as a globally coherent imprint of the Anthropocene. We find a continent-wide acceleration in the rate of increase in plant species richness, with five times as much species enrichment between 2007 and 2016 as fifty years ago, between 1957 and 1966. This acceleration is strikingly synchronized with accelerated global warming and is not linked to alternative global change drivers. The accelerating increases in species richness on mountain summits across this broad spatial extent demonstrate that acceleration in climate-induced biotic change is occurring even in remote places on Earth, with potentially far-ranging consequences not only for biodiversity, but also for ecosystem functioning and services.
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Altitud , Biodiversidad , Mapeo Geográfico , Calentamiento Global/estadística & datos numéricos , Plantas/clasificación , Europa (Continente) , Historia del Siglo XX , Historia del Siglo XXI , TemperaturaRESUMEN
The present study evaluated the acaricidal activity of three Serratia strains isolated from Mimosa pudica nodules in the Lancandon zone Chiapas, Mexico. The analysis of the genomes based on the Average Nucleotide Identity, the phylogenetic relationships allows the isolates to be placed in the Serria ureilytica clade. The size of the genomes of the three strains is 5.4 Mb, with a GC content of 59%. The Serratia UTS2 strain presented the highest mortality with 61.41% against Tyrophagus putrescentiae followed by the Serratia UTS4 strain with 52.66% and Serratia UTS3 with 47.69% at 72 h at a concentration of 1X109 cell/mL. In the bioinformatic analysis of the genomes, genes related to the synthesis of chitinases, proteases and cellulases were identified, which have been reported for the biocontrol of mites. It is the first report of S. ureilytica with acaricidal activity, which may be an alternative for the biocontrol of stored products with high fat and protein content.
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Acaricidas , Filogenia , Serratia , Animales , Serratia/genética , Acaricidas/farmacología , Genoma Bacteriano , Control Biológico de Vectores , Quitinasas/genética , Quitinasas/metabolismo , MéxicoRESUMEN
BACKGROUND: The physical activity (PA) prescription workshop for physicians, through the global health initiative "Exercise is Medicine" (EIM), has trained more than 4000 health care professionals (HCPs) in Latin America. It has shown to be effective in increasing PA prescription knowledge and awareness among HCPs. The purpose of this paper is to evaluate the curricular and pedagogical approach used by EIM Colombia at the PA prescription workshops implemented between 2014 and 2015. METHODS: A mixed methods study, with a sequential explanatory design was implemented among a convenience sample of HCPs attending twenty-six PA prescription workshops. HCPs health status, PA personal habits, and medical practices were collected using a questionnaire at baseline among 795 participants (pre-test measurement), and subsequently quantitatively analyzed. A workshop satisfaction survey was administered after the completion of the workshop among 602 HCPs. The curricular and pedagogical approach of the workshop, the designers' and students' contextual factors, and perceptions about the workshop were measured using qualitative methods (analysis of the procedures manual, two workshop observations, three semi-structured interviews, and one focus group including 8 HCPs). RESULTS: The workshop is student-centered and guided by an expert with an academic and clinical background. Learning was achieved with theoretical and practical components using authentic performance and collaborative learning. An active teaching and learning approach was used with strategies such as interactive lectures, hands-on elements, and role-playing (patient-counselor). The workshop emphasized an individual approach when prescribing PA integrating in clinical practice not only health benefits but also patient´s beliefs, motivations, needs, and barriers. CONCLUSIONS: Evidence-based practices and authentic performance were the most salient pedagogical elements used by EIM Colombia at the PA prescription workshop. A knowledge assessment that includes the practical aspect is suggested for future workshops. The curricular and pedagogical approach of the PA prescription workshop implemented in Colombia is well received by the medical community and a useful continuing medical education intervention with a potential contribution to current, and future health promotion needs.
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Medicina , Humanos , Colombia , Aprendizaje , Estudiantes , Ejercicio FísicoRESUMEN
Obstructive sleep apnea (OSA) is quite prevalent during pregnancy and is associated with adverse perinatal outcomes, but its potential influence on fetal development remains unclear. This study investigated maternal OSA impact on the fetus by analyzing gene expression profiles in whole cord blood (WCB). Ten women in the third trimester of pregnancy were included, five OSA and five non-OSA cases. WCB RNA expression was analyzed by microarray technology to identify differentially expressed genes (DEGs) under OSA conditions. After data normalization, 3238 genes showed significant differential expression under OSA conditions, with 2690 upregulated genes and 548 downregulated genes. Functional enrichment was conducted using gene set enrichment analysis (GSEA) applied to Gene Ontology annotations. Key biological processes involved in OSA were identified, including response to oxidative stress and hypoxia, apoptosis, insulin response and secretion, and placental development. Moreover, DEGs were confirmed through qPCR analyses in additional WCB samples (7 with OSA and 13 without OSA). This highlighted differential expression of several genes in OSA (EGR1, PFN1 and PRKAR1A), with distinct gene expression profiles observed during rapid eye movement (REM)-OSA in pregnancy (PFN1, UBA52, EGR1, STX4, MYC, JUNB, and MAPKAP). These findings suggest that OSA, particularly during REM sleep, may negatively impact various biological processes during fetal development.
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Sangre Fetal , Desarrollo Fetal , Apnea Obstructiva del Sueño , Humanos , Femenino , Embarazo , Sangre Fetal/metabolismo , Adulto , Apnea Obstructiva del Sueño/genética , Desarrollo Fetal/genética , Transcriptoma , Perfilación de la Expresión Génica , Complicaciones del Embarazo/genéticaRESUMEN
Although pulmonary embolism (PE) is a frequent complication in COVID-19, its consequences remain unknown. We performed pulmonary function tests, echocardiography and computed tomography pulmonary angiography and identified blood biomarkers in a cohort of consecutive hospitalized COVID-19 patients with pneumonia to describe and compare medium-term outcomes according to the presence of PE, as well as to explore their potential predictors. A total of 141 patients (56 with PE) were followed up during a median of 6 months. Post-COVID-19 radiological lung abnormalities (PCRLA) and impaired diffusing capacity for carbon monoxide (DLCOc) were found in 55.2% and 67.6% cases, respectively. A total of 7.3% had PE, and 6.7% presented an intermediate-high probability of pulmonary hypertension. No significant difference was found between PE and non-PE patients. Univariate analysis showed that age > 65, some clinical severity factors, surfactant protein-D, baseline C-reactive protein, and both peak red cell distribution width and Interleukin (IL)-10 were associated with DLCOc < 80%. A score for PCRLA prediction including age > 65, minimum lymphocyte count, and IL-1ß concentration on admission was constructed with excellent overall performance. In conclusion, reduced DLCOc and PCRLA were common in COVID-19 patients after hospital discharge, but PE did not increase the risk. A PCRLA predictive score was developed, which needs further validation.
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COVID-19 , Embolia Pulmonar , Humanos , COVID-19/complicaciones , COVID-19/sangre , Embolia Pulmonar/etiología , Embolia Pulmonar/sangre , Masculino , Femenino , Anciano , Persona de Mediana Edad , SARS-CoV-2/aislamiento & purificación , Pruebas de Función Respiratoria , Pulmón/diagnóstico por imagen , Biomarcadores/sangre , Ecocardiografía , Hipertensión Pulmonar/etiologíaRESUMEN
BACKGROUND: Bioethical dilemmas at the end of life have led to regularization processes for the provision of medical assistance in dying patients in different countries. Since the regulation of euthanasia in Spain in 2021, the euthanasia act has been included as one of the benefits of the health system, which has undergone uneven development and implementation in different autonomous communities. The aim of this study was to review the Spanish version of the Euthanasia Attitude Scale following the partial modification of four items. METHODS: A cross-sectional study was conducted with a non-probabilistic sample of Spanish health workers from Islas Baleares. A self-reported sociodemographic questionnaire and the Euthanasia Attitude Scale were used for data collection. The psychometric properties of the scale were assessed, including reliability and validity, using a confirmatory factor analysis and a parallel analysis. RESULTS: The Cronbach's alpha of the EAS was α = 0.892, which implies good internal consistency. According to the confirmatory factor analysis, a Kaiser-Meyer-Olkin-value of 0.938 was obtained, and the result of Bartlett's test of sphericity was < 0.001. The questionnaire included four loading factors, which explained up to 56.99% of the variance. The parallel analysis revealed three significant factors and a fourth, less interpretative factor. CONCLUSIONS: The EAS-ES-R is a valid instrument for assessing the attitudes toward euthanasia of both trainees and practicing health professionals. It may also be of vital importance in detecting training, support and implementation needs for laws regulating euthanasia in Spain.
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OBJECTIVE: To analyze the prescription of drugs to aid smoking cessation and to detect whether there are differences by age or sex. DESIGN: Retrospective cohort study. SITE: Zamora Health Area. PARTICIPANTS: Persons with smoking cessation attempts employing drugs funded in the period from 2020 to 2023. INTERVENTIONS: Request of pharmaceutical consumption of varenicline, bupropion and cytisine to the Pharmacy Information System of the Regional Health Management of Castilla y León. MAIN MEASUREMENTS: Number of quit attempts per person, treatment drug, number of medication containers per attempt, year, age and sex. Descriptive and statistical analysis using SPSS© v. 20. RESULTS: 2581 people tried to quit smoking with drugs, 2206 made one attempt and 375 made several attempts. Mean age was 50.7 years (95% CI: 50.2-51.1). No significant differences were found for age (P=.71) or sex (P=.74). There was a preference for prescribing varenicline over bupropion and low drug compliance, with only one container of medication being collected in about 50% of cases. A total of 1680 attempts were made to quit using cytisine in 2023, equivalent to 55.4% of the total number of treatment drugs used in the four years. The estimated cumulative incidence rate of drug withdrawal attempts in smokers between 18 and 65 years of age was 11.9%. CONCLUSIONS: The drug intervention had a low reach and poor compliance with the recommended treatment. It is essential to emphasize patient follow-up and drug adherence.
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Hematological malignancies are a highly heterogeneous group of diseases with varied molecular and phenotypical characteristics. SWI/SNF (SWItch/Sucrose Non-Fermentable) chromatin remodeling complexes play significant roles in the regulation of gene expression, being essential for processes such as cell maintenance and differentiation in hematopoietic stem cells. Furthermore, alterations in SWI/SNF complex subunits, especially in ARID1A/1B/2, SMARCA2/4, and BCL7A, are highly recurrent across a wide variety of lymphoid and myeloid malignancies. Most genetic alterations cause a loss of function of the subunit, suggesting a tumor suppressor role. However, SWI/SNF subunits can also be required for tumor maintenance or even play an oncogenic role in certain disease contexts. The recurrent alterations of SWI/SNF subunits highlight not only the biological relevance of SWI/SNF complexes in hematological malignancies but also their clinical potential. In particular, increasing evidence has shown that mutations in SWI/SNF complex subunits confer resistance to several antineoplastic agents routinely used for the treatment of hematological malignancies. Furthermore, mutations in SWI/SNF subunits often create synthetic lethality relationships with other SWI/SNF or non-SWI/SNF proteins that could be exploited therapeutically. In conclusion, SWI/SNF complexes are recurrently altered in hematological malignancies and some SWI/SNF subunits may be essential for tumor maintenance. These alterations, as well as their synthetic lethal relationships with SWI/SNF and non-SWI/SNF proteins, may be pharmacologically exploited for the treatment of diverse hematological cancers.
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Antineoplásicos , Neoplasias Hematológicas , Neoplasias , Humanos , Neoplasias/metabolismo , Genes Supresores de Tumor , Mutación , Neoplasias Hematológicas/genéticaRESUMEN
INTRODUCTION: Liver biopsy (LB) remains essential for the diagnosis and staging of parenchymal liver diseases. Endoscopic ultrasound-guided LB (EUS-LB) has emerged as an attractive alternative to percutaneous and transjugular routes. We aimed at comparing the adequacy of samples obtained by EUS-LB with percutaneous LB. METHODS: A single-center, randomized, controlled clinical trial was designed. Patients undergoing LB were randomly assigned to EUS-LB or percutaneous LB groups. EUS-LB was performed with a 19-gauge Franseen core needle through a transduodenal and transgastric route. Percutaneous LB was performed with a 16-gauge Tru-Cut needle. The main outcome was the percentage of adequate samples obtained. Secondary outcomes were the percentage of accurate histologic diagnosis, number of complete portal tracts (CPT), total and longest specimen length (TSL and LSL), sample fragmentation, adverse events, and patients' satisfaction. An adequate specimen was defined as TSL ≥20 mm and including ≥11 CPT. RESULTS: Ninety patients were randomized (44 to EUS-LB and 46 to percutaneous LB) and included in the analysis. The percentage of adequate tissue samples was 32.6% and 70.4% for percutaneous LB and EUS-LB, respectively ( P < 0.001). A final histologic diagnosis was provided in all cases but one. TSL was longer after EUS-LB (23.5 vs 17.5 mm, P = 0.01), whereas the number of CPT was similar in both groups. Sample fragmentation occurred more often after EUS-LB ( P < 0.001). No differences in adverse events were found. Satisfaction reported with both procedures was high. DISCUSSION: EUS-LB is safe and accurate and may be considered an alternative to percutaneous LB for the evaluation of parenchymal liver diseases.
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Hepatopatías , Humanos , Hepatopatías/diagnóstico , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico/métodos , Estudios Prospectivos , Biopsia Guiada por ImagenRESUMEN
BACKGROUND: Peripheral inflammatory immune responses are suggested to play a major role in dopaminergic degeneration in Parkinson's disease (PD). The neutrophil-to-lymphocyte ratio (NLR) is a well-established biomarker of systemic inflammation in PD. Degeneration of the nigrostriatal dopaminergic system can be assessed in vivo using [123 I]FP-CIT single photon emission computed tomography imaging of striatal dopamine transporter (DAT) density. OBJECTIVES: To assess the relationship between the peripheral immune profile (NLR, lymphocytes, and neutrophils) and striatal DAT density in patients with PD. METHODS: We assessed clinical features, the peripheral immune profile, and striatal [123 I]FP-CIT DAT binding levels of 211 patients with PD (primary-cohort). Covariate-controlled associations between the immune response and striatal DAT levels were assessed using linear regression analyses. For replication purposes, we also studied a separate cohort of 344 de novo patients with PD enrolled in the Parkinson's Progression Markers Initiative (PPMI-cohort). RESULTS: A higher NLR was significantly associated with lower DAT levels in the caudate (primary-cohort: ß = -0.01, p < 0.001; PPMI-cohort: ß = -0.05, p = 0.05) and the putamen (primary-cohort: ß = -0.05, p = 0.02; PPMI-cohort: ß = -0.06, p = 0.02). Intriguingly, a lower lymphocyte count was significantly associated with lower DAT levels in both the caudate (primary-cohort: ß = +0.09, p < 0.05; PPMI-cohort: ß = +0.11, p = 0.02) and the putamen (primary-cohort: ß = +0.09, p < 0.05, PPMI-cohort: ß = +0.14, p = 0.01), but an association with the neutrophil count was not consistently observed (caudate; primary-cohort: ß = -0.05, p = 0.02; PPMI-cohort: ß = 0, p = 0.94; putamen; primary-cohort: ß = -0.04, p = 0.08; PPMI-cohort: ß = -0.01, p = 0.73). CONCLUSIONS: Our findings across two independent cohorts suggest a relationship between systemic inflammation and dopaminergic degeneration in patients with PD. This relationship was mainly driven by the lymphocyte count. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/diagnóstico por imagen , Enfermedad de Parkinson/metabolismo , Tropanos , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/metabolismo , Cuerpo Estriado/metabolismo , Tomografía Computarizada de Emisión de Fotón Único/métodos , Inflamación/diagnóstico por imagenRESUMEN
BACKGROUND: Mild hypoxic-ischemic encephalopathy (HIE) is a condition that predisposes to negative outcomes such as neuroanatomical injury, mood disorders, and motor or cognitive disabilities. The neuroinflammation plays an important role in the neurological damage; therefore, reducing it could provide neuroprotection. The leuprolide acetate (LA) has shown to have neuroregenerative and immunomodulator properties in other nervous system injuries. OBJECTIVE: The aim of this study was to evaluate the immunomodulatory effect of LA in the acute phase of mild HIE and its effects in motor activity and behavior in a subacute phase. METHOD: Forty-five Wistar rats on postnatal day 7 were divided into Sham, HIE treated with saline solution (HIE-SS), and HIE-LA. The HIE was performed cutting of the right carotid artery followed by 60 min of hypoxia. The expression of the inflammatory cytokines interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and the chemokine CXCL-1 were evaluated 72 h after HIE by RT-qPCR and the motor activity and behavior were evaluated by open field test at postnatal day 33. RESULTS: HIE-SS animals showed increased expression of IL-1ß, TNF-α, IFN-γ, and CXCL-1 genes in injured tissue. However, the HIE-LA group exhibited similar expression levels of IL-1ß and TNF-α to the Sham group, while IFN-γ and CXCL-1 mRNA expression were attenuated with LA treatment. LA treatment also prevented anxiety-like behavior in the open field test. CONCLUSION: Treatment with LA partially reverses HIE-induced neuroinflammation and prevents anxiety-like behavior in neonatal rats.
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Hipoxia-Isquemia Encefálica , Animales , Ratas , Hipoxia-Isquemia Encefálica/tratamiento farmacológico , Hipoxia-Isquemia Encefálica/metabolismo , Hipoxia-Isquemia Encefálica/patología , Animales Recién Nacidos , Leuprolida/farmacología , Leuprolida/uso terapéutico , Factor de Necrosis Tumoral alfa , Enfermedades Neuroinflamatorias , Ratas Wistar , Factores Inmunológicos , Ansiedad/tratamiento farmacológico , Ansiedad/etiologíaRESUMEN
BACKGROUND AND AIM: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver disease. Increasing evidence indicates that the gut microbiota can play an important role in the pathophysiology of NAFLD. Recently, several studies have tested the predictive value of gut microbiome profiles in NAFLD progression; however, comparisons of microbial signatures in NAFLD or non-alcoholic steatohepatitis (NASH) have produced discrepant results, possibly due to ethnic and environmental factors. Thus, we aimed to characterize the gut metagenome composition of patients with fatty liver disease. METHODS: Gut microbiome of 45 well-characterized patients with obesity and biopsy-proven NAFLD was evaluated using shot-gun sequencing: 11 non-alcoholic fatty liver controls (non-NAFL), 11 with fatty liver, and 23 with NASH. RESULTS: Our study showed that Parabacteroides distasonis and Alistipes putredenis were enriched in fatty liver but not in NASH patients. Notably, in a hierarchical clustering analysis, microbial profiles were differentially distributed among groups, and membership to a Prevotella copri dominant cluster was associated with a greater risk of developing NASH. Functional analyses showed that although no differences in LPS biosynthesis pathways were observed, Prevotella-dominant subjects had higher circulating levels of LPS and a lower abundance of pathways encoding butyrate production. CONCLUSIONS: Our findings suggest that a Prevotella copri dominant bacterial community is associated with a greater risk for NAFLD disease progression, probably linked to higher intestinal permeability and lower capacity for butyrate production.
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Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Metagenoma , Lipopolisacáridos , Prevotella/genética , Obesidad/complicaciones , ButiratosRESUMEN
Children and adolescents worldwide, especially girls, do not meet moderate to vigorous physical activity (MVPA) guidelines, a situation which is related to obesity and other comorbidities. Sex/gender differences in the practice of MVPA and motivations to engage in physical activity have not been previously examined among Spanish students considering different educational levels. Therefore, the purpose of this study was to explore these differences and analyse if motivations mediate the relationship between educational levels and MVPA in a large sample of students. From different schools in the Madrid region (primary: 11,122; lower secondary: 12,379; upper secondary: 3228) 26,729 students (13,491 boys and 13,238 girls; 9-19 years old) were recruited to participate in this study. The short form of the International Physical Activity Questionnaire and the third version of the Behavioural Regulation in Exercise Questionnaire were used to evaluate, MVPA and motivations to exercise, respectively. Two-way ANCOVA and a mediation analysis were performed. Female students were found to be less active than males (43.4±38.7 and 58.6±45.9 min of MVPA; p < 0.001; ηp2 = 0.023) and showed lower intrinsic (ηp2 = 0.003), and integrated (ηp2 = 0.007) motivations than their male counterparts (p < 0.001). Primary school students were more active than lower and upper secondary students (53.3±44.2, 49.9±42.3 and 48.0±42.8 min of MVPA; p < 0.001; ηp2 = 0.002) and also presented higher intrinsic (ηp2 = 0.011) and integrated (ηp2 = 0.010) motivation than secondary school students (p < 0.001). Conclusion: Among Spanish children and adolescents, females showed lower levels of MVPA and intrinsic and integrated motivation across all the educational levels, and among primary school students in comparison to secondary school. This suggests that inner motivation is more determinant of increased engagement in MVPA and thus, there is need to reinforce it before the transition to secondary school and with special focus on females' preferences. What is Known: â¢Many children and adolescents worldwide, do not meet physical activity (PA) recommendations. ⢠Within the self-determination theory, autonomous motivation seems to be the main responsible of greater PA levels. What is New: â¢This study shows for the first time sex and educational level differences in PA levels in a representative sample of Spanish students (9-19 yrs). â¢Autonomous motivation decreased from primary school onwards and was lower in female students than in their male counterparts.
Asunto(s)
Ejercicio Físico , Motivación , Humanos , Masculino , Niño , Femenino , Adolescente , Adulto Joven , Adulto , Instituciones Académicas , Obesidad , EscolaridadRESUMEN
Technical challenges remain in the sequencing of RNA viruses due to their high intra-host diversity. This bottleneck is particularly pronounced when interrogating long-range co-evolved genetic interactions given the read-length limitations of next-generation sequencing platforms. This has hampered the direct observation of these genetic interactions that code for protein-protein interfaces with relevance in both drug and vaccine development. Here we overcome these technical limitations by developing a nanopore-based long-range viral sequencing pipeline that yields accurate single molecule sequences of circulating virions from clinical samples. We demonstrate its utility in observing the evolution of individual HIV Gag-Pol genomes in response to antiviral pressure. Our pipeline, called Multi-read Hairpin Mediated Error-correction Reaction (MrHAMER), yields >1000s of viral genomes per sample at 99.9% accuracy, maintains the original proportion of sequenced virions present in a complex mixture, and allows the detection of rare viral genomes with their associated mutations present at <1% frequency. This method facilitates scalable investigation of genetic correlates of resistance to both antiviral therapy and immune pressure and enables the identification of novel host-viral and viral-viral interfaces that can be modulated for therapeutic benefit.