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1.
Nature ; 617(7962): 785-791, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37165193

RESUMEN

Different plant species within the grasses were parallel targets of domestication, giving rise to crops with distinct evolutionary histories and traits1. Key traits that distinguish these species are mediated by specialized cell types2. Here we compare the transcriptomes of root cells in three grass species-Zea mays, Sorghum bicolor and Setaria viridis. We show that single-cell and single-nucleus RNA sequencing provide complementary readouts of cell identity in dicots and monocots, warranting a combined analysis. Cell types were mapped across species to identify robust, orthologous marker genes. The comparative cellular analysis shows that the transcriptomes of some cell types diverged more rapidly than those of others-driven, in part, by recruitment of gene modules from other cell types. The data also show that a recent whole-genome duplication provides a rich source of new, highly localized gene expression domains that favour fast-evolving cell types. Together, the cell-by-cell comparative analysis shows how fine-scale cellular profiling can extract conserved modules from a pan transcriptome and provide insight on the evolution of cells that mediate key functions in crops.


Asunto(s)
Productos Agrícolas , Setaria (Planta) , Sorghum , Transcriptoma , Zea mays , Secuencia de Bases , Regulación de la Expresión Génica de las Plantas/genética , Sorghum/citología , Sorghum/genética , Transcriptoma/genética , Zea mays/citología , Zea mays/genética , Setaria (Planta)/citología , Setaria (Planta)/genética , Raíces de Plantas/citología , Análisis de Expresión Génica de una Sola Célula , Análisis de Secuencia de ARN , Productos Agrícolas/citología , Productos Agrícolas/genética , Evolución Molecular
2.
Gastroenterology ; 165(3): 696-716, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37263305

RESUMEN

BACKGROUND & AIMS: Genetic ancestry or racial differences in health outcomes exist in diseases associated with systemic inflammation (eg, COVID-19). This study aimed to investigate the association of genetic ancestry and race with acute-on-chronic liver failure (ACLF), which is characterized by acute systemic inflammation, multi-organ failure, and high risk of short-term death. METHODS: This prospective cohort study analyzed a comprehensive set of data, including genetic ancestry and race among several others, in 1274 patients with acutely decompensated cirrhosis who were nonelectively admitted to 44 hospitals from 7 Latin American countries. RESULTS: Three hundred ninety-five patients (31.0%) had ACLF of any grade at enrollment. Patients with ACLF had a higher median percentage of Native American genetic ancestry and lower median percentage of European ancestry than patients without ACLF (22.6% vs 12.9% and 53.4% vs 59.6%, respectively). The median percentage of African genetic ancestry was low among patients with ACLF and among those without ACLF. In terms of race, a higher percentage of patients with ACLF than patients without ACLF were Native American and a lower percentage of patients with ACLF than patients without ACLF were European American or African American. In multivariable analyses that adjusted for differences in sociodemographic and clinical characteristics, the odds ratio for ACLF at enrollment was 1.08 (95% CI, 1.03-1.13) with Native American genetic ancestry and 2.57 (95% CI, 1.84-3.58) for Native American race vs European American race CONCLUSIONS: In a large cohort of Latin American patients with acutely decompensated cirrhosis, increasing percentages of Native American ancestry and Native American race were factors independently associated with ACLF at enrollment.


Asunto(s)
Insuficiencia Hepática Crónica Agudizada , COVID-19 , Humanos , América Latina/epidemiología , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/epidemiología , Cirrosis Hepática/genética , Estudios Prospectivos , COVID-19/complicaciones , Insuficiencia Hepática Crónica Agudizada/diagnóstico , Insuficiencia Hepática Crónica Agudizada/epidemiología , Insuficiencia Hepática Crónica Agudizada/genética , Inflamación/complicaciones , Pronóstico
3.
J Transl Med ; 22(1): 599, 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38937846

RESUMEN

BACKGROUND: Patient heterogeneity poses significant challenges for managing individuals and designing clinical trials, especially in complex diseases. Existing classifications rely on outcome-predicting scores, potentially overlooking crucial elements contributing to heterogeneity without necessarily impacting prognosis. METHODS: To address patient heterogeneity, we developed ClustALL, a computational pipeline that simultaneously faces diverse clinical data challenges like mixed types, missing values, and collinearity. ClustALL enables the unsupervised identification of patient stratifications while filtering for stratifications that are robust against minor variations in the population (population-based) and against limited adjustments in the algorithm's parameters (parameter-based). RESULTS: Applied to a European cohort of patients with acutely decompensated cirrhosis (n = 766), ClustALL identified five robust stratifications, using only data at hospital admission. All stratifications included markers of impaired liver function and number of organ dysfunction or failure, and most included precipitating events. When focusing on one of these stratifications, patients were categorized into three clusters characterized by typical clinical features; notably, the 3-cluster stratification showed a prognostic value. Re-assessment of patient stratification during follow-up delineated patients' outcomes, with further improvement of the prognostic value of the stratification. We validated these findings in an independent prospective multicentre cohort of patients from Latin America (n = 580). CONCLUSIONS: By applying ClustALL to patients with acutely decompensated cirrhosis, we identified three patient clusters. Following these clusters over time offers insights that could guide future clinical trial design. ClustALL is a novel and robust stratification method capable of addressing the multiple challenges of patient stratification in most complex diseases.


Asunto(s)
Cirrosis Hepática , Humanos , Masculino , Femenino , Análisis por Conglomerados , Persona de Mediana Edad , Pronóstico , Enfermedad Aguda , Algoritmos , Anciano , Estudios de Cohortes
4.
J Oral Maxillofac Surg ; 82(5): 595-599, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38387856

RESUMEN

The authors present a case report of a 73-year-old male on dual antiplatelet therapy with a retropharyngeal hematoma after a motor vehicle accident. We highlight the clinical, radiographic manifestations, and surgical management of retropharyngeal hematomas, especially on an initially asymptomatic patient. Additionally, we demonstrate the importance of establishing a secure airway early on, and multidisciplinary collaboration to maximize patient outcomes.


Asunto(s)
Accidentes de Tránsito , Hematoma , Enfermedades Faríngeas , Inhibidores de Agregación Plaquetaria , Humanos , Masculino , Anciano , Hematoma/cirugía , Hematoma/diagnóstico por imagen , Hematoma/etiología , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/efectos adversos , Enfermedades Faríngeas/cirugía , Clopidogrel/uso terapéutico , Aspirina/efectos adversos , Aspirina/uso terapéutico , Terapia Antiplaquetaria Doble
5.
Proc Natl Acad Sci U S A ; 118(47)2021 11 23.
Artículo en Inglés | MEDLINE | ID: mdl-34799449

RESUMEN

It is well established that mantle plumes are the main conduits for upwelling geochemically enriched material from Earth's deep interior. The fashion and extent to which lateral flow processes at shallow depths may disperse enriched mantle material far (>1,000 km) from vertical plume conduits, however, remain poorly constrained. Here, we report He and C isotope data from 65 hydrothermal fluids from the southern Central America Margin (CAM) which reveal strikingly high 3He/4He (up to 8.9RA) in low-temperature (≤50 °C) geothermal springs of central Panama that are not associated with active volcanism. Following radiogenic correction, these data imply a mantle source 3He/4He >10.3RA (and potentially up to 26RA, similar to Galápagos hotspot lavas) markedly greater than the upper mantle range (8 ± 1RA). Lava geochemistry (Pb isotopes, Nb/U, and Ce/Pb) and geophysical constraints show that high 3He/4He values in central Panama are likely derived from the infiltration of a Galápagos plume-like mantle through a slab window that opened ∼8 Mya. Two potential transport mechanisms can explain the connection between the Galápagos plume and the slab window: 1) sublithospheric transport of Galápagos plume material channeled by lithosphere thinning along the Panama Fracture Zone or 2) active upwelling of Galápagos plume material blown by a "mantle wind" toward the CAM. We present a model of global mantle flow that supports the second mechanism, whereby most of the eastward transport of Galápagos plume material occurs in the shallow asthenosphere. These findings underscore the potential for lateral mantle flow to transport mantle geochemical heterogeneities thousands of kilometers away from plume conduits.

6.
Gut ; 72(10): 1971-1984, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37541771

RESUMEN

OBJECTIVE: Exhausted T cells with limited effector function are enriched in chronic hepatitis B and C virus (HBV and HCV) infection. Metabolic regulation contributes to exhaustion, but it remains unclear how metabolism relates to different exhaustion states, is impacted by antiviral therapy, and if metabolic checkpoints regulate dysfunction. DESIGN: Metabolic state, exhaustion and transcriptome of virus-specific CD8+ T cells from chronic HBV-infected (n=31) and HCV-infected patients (n=52) were determined ex vivo and during direct-acting antiviral (DAA) therapy. Metabolic flux and metabolic checkpoints were tested in vitro. Intrahepatic virus-specific CD8+ T cells were analysed by scRNA-Seq in a HBV-replicating murine in vivo model of acute and chronic infection. RESULTS: HBV-specific (core18-27, polymerase455-463) and HCV-specific (NS31073-1081, NS31406-1415, NS5B2594-2602) CD8+ T cell responses exhibit heterogeneous metabolic profiles connected to their exhaustion states. The metabolic state was connected to the exhaustion profile rather than the aetiology of infection. Mitochondrial impairment despite intact glucose uptake was prominent in severely exhausted T cells linked to elevated liver inflammation in chronic HCV infection and in HBV polymerase455-463 -specific CD8+ T cell responses. In contrast, relative metabolic fitness was observed in HBeAg-negative HBV infection in HBV core18-27-specific responses. DAA therapy partially improved mitochondrial programmes in severely exhausted HCV-specific T cells and enriched metabolically fit precursors. We identified enolase as a metabolic checkpoint in exhausted T cells. Metabolic bypassing improved glycolysis and T cell effector function. Similarly, enolase deficiency was observed in intrahepatic HBV-specific CD8+ T cells in a murine model of chronic infection. CONCLUSION: Metabolism of HBV-specific and HCV-specific T cells is strongly connected to their exhaustion severity. Our results highlight enolase as metabolic regulator of severely exhausted T cells. They connect differential bioenergetic fitness with distinct exhaustion subtypes and varying liver disease, with implications for therapeutic strategies.


Asunto(s)
Hepatitis B Crónica , Hepatitis C Crónica , Hepatitis C , Humanos , Animales , Ratones , Linfocitos T CD8-positivos/metabolismo , Antivirales/uso terapéutico , Infección Persistente , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/metabolismo , Hepatitis C/tratamiento farmacológico , Virus de Hepatitis , Virus de la Hepatitis B
7.
Gut ; 72(8): 1581-1591, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36788015

RESUMEN

BACKGROUND AND AIMS: Current prognostic scores of patients with acutely decompensated cirrhosis (AD), particularly those with acute-on-chronic liver failure (ACLF), underestimate the risk of mortality. This is probably because systemic inflammation (SI), the major driver of AD/ACLF, is not reflected in the scores. SI induces metabolic changes, which impair delivery of the necessary energy for the immune reaction. This investigation aimed to identify metabolites associated with short-term (28-day) death and to design metabolomic prognostic models. METHODS: Two prospective multicentre large cohorts from Europe for investigating ACLF and development of ACLF, CANONIC (discovery, n=831) and PREDICT (validation, n=851), were explored by untargeted serum metabolomics to identify and validate metabolites which could allow improved prognostic modelling. RESULTS: Three prognostic metabolites strongly associated with death were selected to build the models. 4-Hydroxy-3-methoxyphenylglycol sulfate is a norepinephrine derivative, which may be derived from the brainstem response to SI. Additionally, galacturonic acid and hexanoylcarnitine are associated with mitochondrial dysfunction. Model 1 included only these three prognostic metabolites and age. Model 2 was built around 4-hydroxy-3-methoxyphenylglycol sulfate, hexanoylcarnitine, bilirubin, international normalised ratio (INR) and age. In the discovery cohort, both models were more accurate in predicting death within 7, 14 and 28 days after admission compared with MELDNa score (C-index: 0.9267, 0.9002 and 0.8424, and 0.9369, 0.9206 and 0.8529, with model 1 and model 2, respectively). Similar results were found in the validation cohort (C-index: 0.940, 0.834 and 0.791, and 0.947, 0.857 and 0.810, with model 1 and model 2, respectively). Also, in ACLF, model 1 and model 2 outperformed MELDNa 7, 14 and 28 days after admission for prediction of mortality. CONCLUSIONS: Models including metabolites (CLIF-C MET) reflecting SI, mitochondrial dysfunction and sympathetic system activation are better predictors of short-term mortality than scores based only on organ dysfunction (eg, MELDNa), especially in patients with ACLF.


Asunto(s)
Insuficiencia Hepática Crónica Agudizada , Metoxihidroxifenilglicol , Humanos , Pronóstico , Estudios Prospectivos , Cirrosis Hepática/complicaciones , Inflamación/complicaciones , Metabolómica , Mitocondrias
8.
Mol Ecol ; 2023 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-37194086

RESUMEN

A main goal of evolutionary biology is to understand the genetic basis of adaptive evolution. Although the genes that underlie some adaptive phenotypes are now known, the molecular pathways and regulatory mechanisms mediating the phenotypic effects of those genes often remain a black box. Unveiling this black box is necessary to fully understand the genetic basis of adaptive phenotypes, and to understand why particular genes might be used during phenotypic evolution. Here, we investigated which genes and regulatory mechanisms are mediating the phenotypic effects of the Eda haplotype, a locus responsible for the loss of lateral plates and changes in the sensory lateral line of freshwater threespine stickleback (Gasterosteus aculeatus) populations. Using a combination of RNAseq and a cross design that isolated the Eda haplotype on a fixed genomic background, we found that the Eda haplotype affects both gene expression and alternative splicing of genes related to bone development, neuronal development and immunity. These include genes in conserved pathways, like the BMP, netrin and bradykinin signalling pathways, known to play a role in these biological processes. Furthermore, we found that differentially expressed and differentially spliced genes had different levels of connectivity and expression, suggesting that these factors might influence which regulatory mechanisms are used during phenotypic evolution. Taken together, these results provide a better understanding of the mechanisms mediating the effects of an important adaptive locus in stickleback and suggest that alternative splicing could be an important regulatory mechanism mediating adaptive phenotypes.

9.
Mol Phylogenet Evol ; 189: 107932, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37751827

RESUMEN

Diplomystidae is an early-diverged family of freshwater catfish endemic to southern South America. We have recently collected five juvenile specimens belonging to this family from the Bueno River Basin, a basin which the only previous record was a single juvenile specimen collected in 1996. This finding confirms the distribution of the family further South in northern Patagonia, but poses new questions about the origin of this population in an area with a strong glacial history. We used phylogenetic analyses to evaluate three different hypotheses that could explain the origin of this population in the basin. First, the population could have originated in Atlantic basins (East of the Andes) and dispersed to the Bueno Basin after the Last Glacial Maximum (LGM) via river reversals, as it has been proposed for other population of Diplomystes as well as for other freshwater species from Patagonia. Second, the population could have originated in the geographically close Valdivia Basin (West of the Andes) and dispersed south to its current location in the Bueno Basin. Third, regardless of its geographic origin (West or East of the Andes), the Bueno Basin population could have a longer history in the basin, surviving in situ through the LGM. In addition, we conducted species delimitation analyses using a recently developed method that uses a protracted model of speciation. Our goal was to test the species status of the Bueno Basin population along with another controversial population in Central Chile (Biobío Basin), which appeared highly divergent in previous studies with mtDNA. The phylogenetic analyses showed that the population from the Bueno Basin is more related to Atlantic than to Pacific lineages, although with a deep divergence that predated the LGM, supporting in situ survival rather than postglacial dispersal. In addition, these analyses also showed that the species D. nahuelbutaensis is polyphyletic, supporting the need for a taxonomic reevaluation. The species delimitation analyses supported two new species which are described using molecular diagnostic characters: Diplomystes arratiae sp. nov. from the Biobío, Carampangue, and Laraquete basins, maintaining D. nahuelbutaensis valid only for the Imperial Basin, and Diplomystes habitae sp. nov. from the Bueno Basin. This study greatly increases the number of species within both the family Diplomystidae and Patagonia, and contributes substantially to the knowledge of the evolution of southern South American freshwater biodiversity during its glacial history. Given the important contribution to the phylogenetic diversity of the family, we recommend a high conservation priority for both new species. Finally, this study highlights an exemplary scenario where species descriptions based only on DNA data are particularly valuable, bringing additional elements to the ongoing debate on DNA-based taxonomy.


Asunto(s)
Bagres , Animales , Filogenia , Bagres/genética , Chile , ADN Mitocondrial/genética , Filogeografía , Variación Genética
10.
Nature ; 549(7670): 91-95, 2017 09 07.
Artículo en Inglés | MEDLINE | ID: mdl-28737761

RESUMEN

Glutamate receptors are well characterized channels that mediate cell-to-cell communication during neurotransmission in animals, but their functional role in organisms without a nervous system remains unclear. In plants, genes of the GLUTAMATE RECEPTOR-LIKE (GLR) family have been implicated in defence against pathogens, reproduction, control of stomata aperture and light signal transduction. However, the large number of GLR genes present in angiosperm genomes (20 to 70) has prevented the observation of strong phenotypes in loss-of-function mutants. Here we show that in the basal land plant Physcomitrella patens, mutation of the GLR genes GLR1 and GLR2 causes failure of sperm cells to target the female reproductive organs. In addition, we show that GLR genes encode non-selective Ca2+-permeable channels that can regulate cytoplasmic Ca2+ and are needed to induce the expression of a BELL1-like transcription factor essential for zygote development. Our work reveals functions for GLR channels in sperm chemotaxis and transcriptional regulation. Sperm chemotaxis is essential for fertilization in both animals and early land plants such as bryophytes and pteridophytes. Therefore, our results suggest that ionotropic glutamate receptors may have been conserved throughout plant evolution to mediate cell-to-cell communication during sexual reproduction.


Asunto(s)
Bryopsida/metabolismo , Quimiotaxis , Receptores Ionotrópicos de Glutamato/metabolismo , Bryopsida/embriología , Bryopsida/genética , Calcio/metabolismo , Comunicación Celular/genética , Quimiotaxis/genética , Regulación de la Expresión Génica , Genes Esenciales , Mutación , Receptores Ionotrópicos de Glutamato/genética , Reproducción/genética , Factores de Transcripción/metabolismo , Transcripción Genética , Cigoto/metabolismo
11.
Environ Res ; 216(Pt 2): 114599, 2023 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-36270536

RESUMEN

BACKGROUND: Some studies have documented that cold or hot ambient temperatures increase the risk of motor vehicle crashes. However, the number of existing studies is still limited, especially for the effects of cold. OBJECTIVES: To estimate the relationship between ambient temperatures and risk of motor vehicle crashes in Spain, and to estimate the same association when restricting to those crashes with driver performance-associated factors (namely distraction, fatigue, sleepiness or disease). METHODS: We used data for the period 1993-2013. We conducted a time series analysis controlling for seasonality and trends and using the distributed lag nonlinear model framework to estimate nonlinear and delayed effects of up to 7 days. Analyses were conducted at the province level and combined using multivariate meta-analysis. RESULTS: The study included 1,908,460 motor vehicle crashes, 37% of them with associated driver performance factors. The overall analysis showed that the risk of crashes increased almost linearly with temperature. The estimates of the cumulative effect of lags 0-7 when comparing the 99th percentile and the first percentile of temperature produced a relative risk (RR) of 1.15 (95% confidence interval (CI): 1.11, 1.20). The estimates were slightly higher when analyses were restricted to crashes with driver performance-associated factors (RR: 1.23, 95% CI: 1.17, 1.30). In some provinces that reached temperatures below 0 °C, an increased risk with cold temperatures was also observed. An added effect of both cold spell and heat wave periods was found only in the analysis of crashes with driver performance-associated factors (cold spells, RR: 1.029, 95% CI: 1.005, 1.053; heat waves, RR: 1.020, 95% CI: 1.002, 1.039). CONCLUSIONS: The increase of temperature increased the risk of motor vehicle crashes in Spain. Measures aimed at reducing the influence of heat on the risk of motor vehicle crashes can have important benefits for public health.


Asunto(s)
Accidentes de Tránsito , Frío , Temperatura , España/epidemiología , Vehículos a Motor , Calor
12.
J Oral Maxillofac Surg ; 81(5): 648-653, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36549654

RESUMEN

PURPOSE: Head and neck cancer (HNCA), as well as the sequelae of its treatment, has a significant negative impact on the quality of life (QOL) for patients. We aim to identify patient and surgical factors negatively influencing QOL of patients with HNCA. MATERIALS AND METHODS: A cross-sectional study was used to identify specific risk factors associated with a poorer QOL. The University of Michigan Head and Neck Quality of Life (HNQOL) instrument was used to assess QOL. Predictor variables included risk factors (smoking, alcohol, past medical history), demographic (sex, age, marital status), anatomical features (tumor location, tumor stage), perioperative adjuncts (utilization of a feeding tube, tracheostomy, neck dissection), and postoperative adjuncts (chemotherapy or radiation therapy utilization). The primary outcome variable was the HNQOL score. Descriptive statistics were completed for all the variables. Association between the predictor variables and HNQOL scores were examined using bivariate statistics, and statistical significance was set at P < .05. RESULTS: The study sample composed of 78 patients with HNCA who underwent surgery at Head and Neck Maxillofacial and Reconstructive Surgery Clinic at Ascension Macomb-Oakland from January 2017 to August 2018. Of the 78 patients meeting inclusion, 31 patients completed the HNQOL survey. The median HNCA QOL score was 18 with a maximum score of 80, representing a worse QOL. Radiation therapy (21 vs 5.5, P = .033), and perioperative feeding tube (31 vs 9, P = .012) had statistically significant negative impacts on QOL scores. Variables associated with poorer QOL scores in descending order: radiation therapy perioperative feeding tube utilization of chemotherapy (12.5 vs 9.0, P = .60), male gender (17 vs 9.5, P = .39), perioperative tracheostomy (26 vs 14.5 P = .26), tobacco use (19.5 vs 11.5, P = .81), single marital status (27 vs 16, P = .48), neck dissection (17.5 vs 15.5, P = .91), and alcohol use (18.5 vs 16.0, P = .65). CONCLUSIONS: Feeding tube and radiotherapy utilization had a statistically significant decrease of QOL scores among patients with HNCA. Additional risk factors associated with poorer QOL include chemotherapy, male sex, tracheostomy utilization, tobacco use, single or divorced marital status, neck dissection, and alcohol abuse.


Asunto(s)
Neoplasias de Cabeza y Cuello , Calidad de Vida , Humanos , Masculino , Estudios Transversales , Neoplasias de Cabeza y Cuello/terapia , Factores de Riesgo , Progresión de la Enfermedad
13.
Trop Anim Health Prod ; 55(5): 346, 2023 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-37792078

RESUMEN

The objective of this study was to evaluate the effect of dehydrated orange by-product on the productive parameters, carcass yield, and meat quality of rabbits in the fattening stage. Four diets with increasing levels of orange by-products (0%, 10%, 20%, and 30%) were evaluated, each with six replicates of two 32-day-old crossbred rabbits that were randomly allocated. The experimental period was from 32 to 70 days of age of the rabbits. A higher weight gain (p < 0.05) was achieved for observed with 20% substitution, along with a better feed conversion, without any effects on carcass yield and meat quality parameters. The treatment with 30% citrus pulp showed no differences (p > 0.05) in the parameters evaluated. Based on our results, dehydrated orange by-product can replace up to 30% of the commercial feed concentrate without affecting performance, yield, and carcass quality in rabbits feeding since 32 to 72 days of age.


Asunto(s)
Citrus , Animales , Conejos , Carne , Aumento de Peso
14.
J Hepatol ; 76(5): 1079-1089, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35074475

RESUMEN

BACKGROUND & AIMS: It remains unclear whether rectal colonization with multidrug-resistant organisms (MDROs) is prevalent and predisposes to infections by the same pathogens in patients with cirrhosis. METHODS: Two series of critically ill patients were evaluated. In the Barcelona cohort, 486 consecutive patients were prospectively evaluated, 129 with and 357 without cirrhosis (2015-2016). Rectal swabs were performed at admission and weekly thereafter (until intensive care unit [ICU] discharge) to detect MDRO colonization. Risk factors for colonization and infection by MDROs were evaluated. A retrospective cohort from Frankfurt (421 patients with cirrhosis; 2010-2018) was investigated to evaluate MDRO rectal colonization in another epidemiological scenario. RESULTS: In the Barcelona cohort, 159 patients were colonized by MDROs (32.7%), 102 (64.2%) at admission and 57 (35.8%) during follow-up. Patients with cirrhosis showed higher rates of rectal colonization at admission than those without cirrhosis (28.7% vs. 18.2%, p = 0.01) but similar colonization rates during ICU stay. Extended-spectrum beta-lactamase-Enterobacterales were the most frequent MDROs isolated in both groups. Colonization by MDROs independently increased the risk of infection by MDROs at admission and during follow-up. Risk of new infection by the colonizing strain was also significantly increased in patients with (hazard ratio [HR] 7.41) and without (HR 5.65) cirrhosis. Rectal colonization by MDROs was also highly prevalent in Frankfurt (n = 198; 47%; 131 at admission [66.2%] and 67 [33.8%] during follow-up), with vancomycin-resistant enterococci being the most frequent colonizing organism. Rectal colonization by MDROs was also associated with an increased risk of infection by MDROs in this cohort. Infections occurring in MDR carriers were mainly caused by the colonizing strain. CONCLUSION: Rectal colonization by MDROs is extremely frequent in critically ill patients with cirrhosis. Colonization increases the risk of infection by the colonizing resistant strain. LAY SUMMARY: Rectal colonization by multidrug-resistant organisms (MDROs) is a prevalent problem in patients with cirrhosis requiring critical care. The pattern of colonizing bacteria is heterogeneous with relevant differences between centers. Colonization by MDROs is associated with increased risk of infection by the colonizing bacteria in the short term. This finding suggests that colonization data could be used to guide empirical antibiotic therapy and de-escalation policies in patients with cirrhosis.


Asunto(s)
Enfermedad Crítica , Staphylococcus aureus Resistente a Meticilina , Antibacterianos/uso terapéutico , Bacterias , Farmacorresistencia Bacteriana Múltiple , Humanos , Cirrosis Hepática/complicaciones , Cirrosis Hepática/tratamiento farmacológico , Estudios Retrospectivos
15.
Mol Syst Biol ; 17(4): e10232, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33904651

RESUMEN

Exacerbated pro-inflammatory immune response contributes to COVID-19 pathology. However, despite the mounting evidence about SARS-CoV-2 infecting the human gut, little is known about the antiviral programs triggered in this organ. To address this gap, we performed single-cell transcriptomics of SARS-CoV-2-infected intestinal organoids. We identified a subpopulation of enterocytes as the prime target of SARS-CoV-2 and, interestingly, found the lack of positive correlation between susceptibility to infection and the expression of ACE2. Infected cells activated strong pro-inflammatory programs and produced interferon, while expression of interferon-stimulated genes was limited to bystander cells due to SARS-CoV-2 suppressing the autocrine action of interferon. These findings reveal that SARS-CoV-2 curtails the immune response and highlights the gut as a pro-inflammatory reservoir that should be considered to fully understand SARS-CoV-2 pathogenesis.


Asunto(s)
Intestinos/inmunología , SARS-CoV-2/fisiología , Análisis de la Célula Individual , COVID-19/virología , Microbioma Gastrointestinal , Humanos , Hibridación Fluorescente in Situ , Organoides/metabolismo , Análisis de Secuencia de ARN
16.
Glob Chang Biol ; 28(1): 8-20, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34658117

RESUMEN

Global warming is causing significant losses of marine ice around the polar regions. In Antarctica, the retreat of tidewater glaciers is opening up novel, low-energy habitats (fjords) that have the potential to provide a negative feedback loop to climate change. These fjords are being colonized by organisms on and within the sediment and act as a sink for particulate matter. So far, blue carbon potential in Antarctic habitats has mainly been estimated using epifaunal megazoobenthos (although some studies have also considered macrozoobenthos). We investigated two further pathways of carbon storage and potential sequestration by measuring the concentration of carbon of infaunal macrozoobenthos and total organic carbon (TOC) deposited in the sediment. We took samples along a temporal gradient since time of last glacier ice cover (1-1000 years) at three fjords along the West Antarctic Peninsula. We tested the hypothesis that seabed carbon standing stock would be mainly driven by time since last glacier covered. However, results showed this to be much more complex. Infauna were highly variable over this temporal gradient and showed similar total mass of carbon standing stock per m2 as literature estimates of Antarctic epifauna. TOC mass in the sediment, however, was an order of magnitude greater than stocks of infaunal and epifaunal carbon and increased with time since last ice cover. Thus, blue carbon stocks and recent gains around Antarctica are likely much higher than previously estimated as is their negative feedback on climate change.


Asunto(s)
Cambio Climático , Cubierta de Hielo , Regiones Antárticas , Carbono , Ecosistema , Estuarios , Retroalimentación
17.
Europace ; 24(3): 390-399, 2022 03 02.
Artículo en Inglés | MEDLINE | ID: mdl-34480548

RESUMEN

AIMS: To determine if adapting the ablation index (AI) to the left atrial wall thickness (LAWT), which is a determinant of lesion transmurality, is feasible, effective, and safe during paroxysmal atrial fibrillation (PAF) ablation. METHODS AND RESULTS: Consecutive patients referred for PAF first ablation. Left atrial wall thickness three-dimensional maps were obtained from multidetector computed tomography and integrated into the CARTO navigation system. Left atrial wall thickness was categorized into 1 mm layers and AI was titrated to the LAWT. The ablation line was personalized to avoid thicker regions. Primary endpoints were acute efficacy and safety, and freedom from atrial fibrillation (AF) recurrences. Follow-up (FU) was scheduled at 1, 3, 6, and every 6 months thereafter. Ninety patients [60 (67%) male, age 58 ± 13 years] were included. Mean LAWT was 1.25 ± 0.62 mm. Mean AI was 366 ± 26 on the right pulmonary veins with a first-pass isolation in 84 (93%) patients and 380 ± 42 on the left pulmonary veins with first-pass in 87 (97%). Procedure time was 59 min (49-66); radiofrequency (RF) time 14 min (12.5-16); and fluoroscopy time 0.7 min (0.5-1.4). No major complication occurred. Eighty-four out of 90 (93.3%) patients were free of recurrence after a mean FU of 16 ± 4 months. CONCLUSION: Personalized AF ablation, adapting the AI to LAWT allowed pulmonary vein isolation with low RF delivery, fluoroscopy, and procedure time while obtaining a high rate of first-pass isolation, in this patient population. Freedom from AF recurrences was as high as in more demanding ablation protocols. A multicentre trial is ongoing to evaluate reproducibility of these results.


Asunto(s)
Fibrilación Atrial , Ablación por Catéter , Venas Pulmonares , Anciano , Fibrilación Atrial/diagnóstico por imagen , Fibrilación Atrial/cirugía , Ablación por Catéter/efectos adversos , Ablación por Catéter/métodos , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Venas Pulmonares/diagnóstico por imagen , Venas Pulmonares/cirugía , Recurrencia , Reproducibilidad de los Resultados , Resultado del Tratamiento
18.
J Oral Maxillofac Surg ; 80(12): 1989-1995, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36174663

RESUMEN

PURPOSE: Eagle syndrome is an uncommon disorder that significantly impacts the quality of life (QoL) of patients. No formal QoL study has been carried out on a population of Eagle syndrome patients treated via transcervical approach. We aim to evaluate and analyze the outcomes of the patients with Eagle syndrome treated with transcervical styloidectomy via our modified QoL survey. METHODS: A retrospective cohort study was utilized for patients with Eagle syndrome who underwent transcervical styloidectomy at our institution from January 2008 until December 2018. Two QoL surveys were sent to subjects. Patients were asked preoperatively and postoperatively about the presence and intensity of pain, alteration of speech, diet or chewing, limitations of daily activity, mobility or recreation, and the presence of anxiety or mood disturbances related to the disease. The styloid length on preoperative computed tomography scans and the length of the surgical specimen were obtained, and correlations with the Numeric Pain Rating Scale (NPRS) were analyzed. Spearman's rank correlation coefficient was used to determine numerical correlation. Data are expressed as mean ± standard deviation, and P value less than .05 was considered statistically significant. RESULTS: The study sample comprised 10 patients with Eagle syndrome who underwent transcervical styloidectomy. Eight patients underwent unilateral styloidectomy, and 2 patients were bilateral. Most patients were female (80%) with a mean age of 46.0. Preoperative NPRS score averaged 5.5 ± 2.7 (range 1 to 10) and postoperative NPRS was 2.1 ± 1.4 (range 0 to 4) (P = .008). No correlation was found between preoperative or postoperative NRPS score and preoperative styloid length and length of styloid resected. QoL survey showed a significant improvement in neck mobility and the anxiety felt by the patients. The survey showed that all patients would recommend surgery to a friend or family member with similar symptoms. Seven patients (70%) would recommend the operation as primary treatment, and the rest would recommend it after conservative options fail. CONCLUSIONS: Transcervical styloidectomy was associated with a statistically significant decrease in NPRS and positive QoL changes for patients operated for Eagle syndrome at our institution.


Asunto(s)
Osificación Heterotópica , Calidad de Vida , Humanos , Femenino , Persona de Mediana Edad , Masculino , Estudios Retrospectivos , Hueso Temporal/diagnóstico por imagen , Hueso Temporal/cirugía , Osificación Heterotópica/cirugía , Dolor
19.
J Sports Sci ; 40(13): 1436-1449, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35694782

RESUMEN

This study aimed to 1) develop a consensus (≥70% agreement between experts) on injury risk factors specific to women playing rugby league, 2) establish the importance of the identified injury risk factors and the feasibility of mitigating these risk factors and 3) establish context specific barriers to injury risk management. Aim 1: A Delphi panel, consisting of 12 experts in rugby league and injury (e.g., physiotherapists, research scientists) were asked to identify injury risk factors specific to women playing rugby league. Aim 2: seven coaches of women's rugby league teams were asked to rate each risk factor that achieved consensus by their importance and feasibility to manage. Aim 3: Coaches reported barriers which restrict injury risk factor mitigation. Of the 53 injury risk factors which achieved consensus, the five injury risk factors with the highest combination of importance and feasibility ratings were: "poor tackle technique", "a lack of pre-season intensity", "training session are too short", "the current medical standards", and "limited access to physiotherapists". Following the identification of injury risk factors, their feasibility to manage and context specific barriers, this study proposes three constraint driven, integrated solutions which may reduce the barriers which limit injury risk factor management.


Asunto(s)
Traumatismos en Atletas , Fútbol Americano , Traumatismos en Atletas/prevención & control , Técnica Delphi , Femenino , Fútbol Americano/lesiones , Humanos , Factores de Riesgo , Rugby
20.
Sensors (Basel) ; 22(7)2022 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-35408360

RESUMEN

(1) Background: As breast cancer studies suggest, a high percentage of breast density (PBD) may be related to breast cancer incidence. Although PBD screening is one of the strongest predictors of breast cancer risk, X-ray-based mammography evaluation is subjective. Therefore, new objective PBD measuring techniques are of interest. A case study analyzing the PBD of thirteen female participants using a bioimpedance-based method, the anomalies tracking circle (ATC), is described in this paper. (2) Methods: In the first stage, the breast bioimpedance of each participant was measured. Then, the participant breast density was determined by applying a mammogram just after the breast bioimpedance measurement stage. In the third stage, the ATC algorithm was applied to the measured bioimpedance data for each participant, and a results analysis was done. (3) Results: An ATC variation according to the breast density was observed from the obtained data, this allowed the use of classification techniques to determine the PBD. (4) Conclusions: The described breast density method is a promising approach that might be applied as an auxiliary tool to the mammography in order to obtain precise and objective results for evaluation of breast density and with that determine potential breast cancer risk.


Asunto(s)
Densidad de la Mama , Neoplasias de la Mama , Algoritmos , Mama/diagnóstico por imagen , Neoplasias de la Mama/diagnóstico por imagen , Femenino , Humanos , Mamografía/métodos
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