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BACKGROUND: In a previous phase 3 trial, treatment with trifluridine-tipiracil (FTD-TPI) prolonged overall survival among patients with metastatic colorectal cancer. Preliminary data from single-group and randomized phase 2 trials suggest that treatment with FTD-TPI in addition to bevacizumab has the potential to extend survival. METHODS: We randomly assigned, in a 1:1 ratio, adult patients who had received no more than two previous chemotherapy regimens for the treatment of advanced colorectal cancer to receive FTD-TPI plus bevacizumab (combination group) or FTD-TPI alone (FTD-TPI group). The primary end point was overall survival. Secondary end points were progression-free survival and safety, including the time to worsening of the Eastern Cooperative Oncology Group (ECOG) performance-status score from 0 or 1 to 2 or more (on a scale from 0 to 5, with higher scores indicating greater disability). RESULTS: A total of 246 patients were assigned to each group. The median overall survival was 10.8 months in the combination group and 7.5 months in the FTD-TPI group (hazard ratio for death, 0.61; 95% confidence interval [CI], 0.49 to 0.77; P<0.001). The median progression-free survival was 5.6 months in the combination group and 2.4 months in the FTD-TPI group (hazard ratio for disease progression or death, 0.44; 95% CI, 0.36 to 0.54; P<0.001). The most common adverse events in both groups were neutropenia, nausea, and anemia. No treatment-related deaths were reported. The median time to worsening of the ECOG performance-status score from 0 or 1 to 2 or more was 9.3 months in the combination group and 6.3 months in the FTD-TPI group (hazard ratio, 0.54; 95% CI, 0.43 to 0.67). CONCLUSIONS: Among patients with refractory metastatic colorectal cancer, treatment with FTD-TPI plus bevacizumab resulted in longer overall survival than FTD-TPI alone. (Funded by Servier and Taiho Oncology; SUNLIGHT ClinicalTrials.gov number, NCT04737187; EudraCT number, 2020-001976-14.).
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Neoplasias del Colon , Neoplasias Colorrectales , Neoplasias del Recto , Adulto , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bevacizumab/efectos adversos , Bevacizumab/uso terapéutico , Neoplasias del Colon/tratamiento farmacológico , Neoplasias Colorrectales/tratamiento farmacológico , Combinación de Medicamentos , Pirrolidinas/efectos adversos , Pirrolidinas/uso terapéutico , Neoplasias del Recto/tratamiento farmacológico , Trifluridina/efectos adversos , Trifluridina/uso terapéutico , UraciloRESUMEN
The Alvinellidae are a family of worms that are endemic to deep-sea hydrothermal vents in the Pacific and Indian Oceans. These annelid worms, a sister group to the Ampharetidae, occupy a wide range of thermal habitats. The family includes the most thermotolerant marine animals described to date such as the Pompeii worm Alvinella pompejana, and other species living at much lower temperatures such as Paralvinella grasslei or Paralvinella pandorae. The phylogeny of this family has not been studied extensively. It is, however, a complex case where molecular phylogenies have given conflicting results, especially concerning the monophyletic or polyphyletic nature of the genus Paralvinella. We carried out a comprehensive study of the phylogeny of this family using the best molecular data currently available from RNAseq datasets, leading to several hundred orthologous transcripts for 11 of the 14 species currently described or in description. The results obtained by the two most popular phylogenetic inference models (using either gene concatenation with maximum likelihood, or a coalescent-based model from gene trees) were compared using a series of ampharetid and terebellid outgroups. Our study shows that the global phylogenetic signal favors the hypothesis of paraphyly for the Paralvinella genus, with P. pandorae being sister species of the other Alvinellidae. However, a high number of gene trees also supports the hypothesis of alternative trees in which the monophyly of the Paralvinella genus, as initially proposed by Desbruyères and Laubier, is valid with the species P. pandorae and Paralvinella unidentata being sister species. According to molecular dating, the radiation of the Alvinellidae was rapid and took place in a short period of time between 80 and 110 million years ago. This is reflected at the genomic scale by gene trees equally separated between different phylogenetic hypothesis, showing high rates of incomplete lineage sorting between the first lineages of the Alvinellidae and probable gene transfers. Although different genomic regions seem to have different phylogenetic stories in the early step of the alvinellid radiation, our study supports the view that the two P. pandorae species can be grouped into a separate genus (possibly Nautalvinella) and that the Miralvinella subgenus, defined by Desbruyères and Laubier, is not valid anymore.
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There is a great scientific curiosity to discover all environments sheltering microalgae, especially those with exceptional characteristics from coldest to hottest ones, the purpose remains to explore the potential of the native microalgae flora and the research for new bioactive compounds. This study aimed to isolate a polysaccharide-producing microalga from an extreme ecosystem and to evaluate its capacity to inhibit the α-D-glucosidase enzyme. Chlorella strain is isolated from hypersaline Lake in the Algerian desert. The exopolysaccharide extraction was performed by the concentration of free-cell supernatant in a rotary evaporator. The infrared analysis showed a characteristic footprint of carbohydrates with particular functional groups, such as sulfate. Gas chromatography-mass spectrometry has revealed a hetero-exopolysaccharide composed of galactose 35.75%, glucose 21.13%, xylose 16.81%, fructose 6.96%, arabinose 5.10%, and glucuronic acid 2.68%. The evaluation of the anti-hyperglycemic activity demonstrated a significant α-D-glucosidase inhibition of 80.94 ± 0.01% at 10 mg mL-1 with IC50 equal to 4.31 ± 0.20 mg mL-1. This study opens a vast prospect to use exopolysaccharides as natural nutraceutical or food additive.
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Chlorella , Sulfatos , Ecosistema , Arabinosa , GlucosidasasRESUMEN
Alginates extracted from two Moroccan brown seaweeds and their derivatives were investigated for their ability to induce phenolic metabolism in the roots and leaves of tomato seedlings. Sodium alginates (ALSM and ALCM) were extracted from the brown seaweeds Sargassum muticum and Cystoseira myriophylloides, respectively. Low-molecular-weight alginates (OASM and OACM) were obtained after radical hydrolysis of the native alginates. Elicitation was carried out by foliar spraying 20 mL of aqueous solutions (1 g/L) on 45-day-old tomato seedlings. Elicitor capacities were evaluated by monitoring phenylalanine ammonia-lyase (PAL) activity, polyphenols, and lignin production in the roots and leaves after 0, 12, 24, 48, and 72 h of treatment. The molecular weights (Mw) of the different fractions were 202 kDa for ALSM, 76 kDa for ALCM, 19 kDa for OACM, and 3 kDa for OASM. FTIR analysis revealed that the structures of OACM and OASM did not change after oxidative degradation of the native alginates. These molecules showed their differential capacity to induce natural defenses in tomato seedlings by increasing PAL activity and through the accumulation of polyphenol and lignin content in the leaves and roots. The oxidative alginates (OASM and OACM) exhibited an effective induction of the key enzyme of phenolic metabolism (PAL) compared to the alginate polymers (ALSM and ALCM). These results suggest that low-molecular-weight alginates may be good candidates for stimulating the natural defenses of plants.
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Phaeophyceae , Sargassum , Algas Marinas , Sargassum/química , Alginatos/química , Lignina/farmacología , Peso Molecular , Phaeophyceae/química , Algas Marinas/química , Estrés OxidativoRESUMEN
Methods based on 64-beam LiDAR can provide very precise 3D object detection. However, highly accurate LiDAR sensors are extremely costly: a 64-beam model can cost approximately USD 75,000. We previously proposed SLS-Fusion (sparse LiDAR and stereo fusion) to fuse low-cost four-beam LiDAR with stereo cameras that outperform most advanced stereo-LiDAR fusion methods. In this paper, and according to the number of LiDAR beams used, we analyzed how the stereo and LiDAR sensors contributed to the performance of the SLS-Fusion model for 3D object detection. Data coming from the stereo camera play a significant role in the fusion model. However, it is necessary to quantify this contribution and identify the variations in such a contribution with respect to the number of LiDAR beams used inside the model. Thus, to evaluate the roles of the parts of the SLS-Fusion network that represent LiDAR and stereo camera architectures, we propose dividing the model into two independent decoder networks. The results of this study show that-starting from four beams-increasing the number of LiDAR beams has no significant impact on the SLS-Fusion performance. The presented results can guide the design decisions by practitioners.
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INTRODUCTION: Psychotherapy has proved its efficacy for treating a wide range of psychological disorders. Most types of psychotherapy have been developed to treat specific disorders and validated through controlled-randomized trials. In recent years, researchers have developed a new way to conceptualize patients' difficulties, focusing on processes instead of diagnoses. However, there is no simple scale that evaluates transdiagnostic processes, and the development of such a tool is thus the aim of this study. METHOD: We identified 12 processes that can be targeted in cognitive behavior therapy and created the Transdiagnostic Skills Scale (T2S) to evaluate them. We measured its internal consistency, factor structure and convergent validity in clinical and non-clinical samples. RESULTS: We found a 6-factor structure composed of emotion regulation, behavioral activation/planning, emotional identification, assertiveness, problem solving and emotional confrontation. The T2S has high internal consistency (Cronbach's alpha = 0.95). We found negative associations between skills and symptoms of anxiety, depression and eating disorders. We found no association between these processes and symptoms of either alcohol or cannabis use disorder. CONCLUSIONS: The T2S is a useful and valid tool to identify the skills that clinicians should work on with their patients. It offers a complementary way to understand patients' difficulties when categorical assessment is complicated.
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Terapia Cognitivo-Conductual , Emociones , Humanos , Resultado del Tratamiento , Ansiedad/terapia , Trastornos de Ansiedad/psicologíaRESUMEN
Aspergillus fumigatus is an opportunistic mold that infects patients who are immunocompromised or have chronic lung disease, causing significant morbidity and mortality in these populations. While the factors governing the host response to A. fumigatus remain poorly defined, neutrophil recruitment to the site of infection is critical to clear the fungus. Galectin-3 is a mammalian ß-galactose-binding lectin with both antimicrobial and immunomodulatory activities, however the role of galectin-3 in the defense against molds has not been studied. Here we show that galectin-3 expression is markedly up-regulated in mice and humans with pulmonary aspergillosis. Galectin-3 deficient mice displayed increased fungal burden and higher mortality during pulmonary infection. In contrast to previous reports with pathogenic yeast, galectin-3 exhibited no antifungal activity against A. fumigatus in vitro. Galectin-3 deficient mice exhibited fewer neutrophils in their airways during infection, despite normal numbers of total lung neutrophils. Intravital imaging studies confirmed that galectin-3 was required for normal neutrophil migration to the airspaces during fungal infection. Adoptive transfer experiments demonstrated that stromal rather than neutrophil-intrinsic galectin-3 was necessary for normal neutrophil entry into the airspaces. Live cell imaging studies revealed that extracellular galectin-3 directly increases neutrophil motility. Taken together, these data demonstrate that extracellular galectin-3 facilitates recruitment of neutrophils to the site of A. fumigatus infection, and reveals a novel role for galectin-3 in host defense against fungal infections.
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Aspergilosis/inmunología , Aspergillus fumigatus/fisiología , Galectina 3/inmunología , Pulmón/microbiología , Neutrófilos/citología , Animales , Aspergilosis/genética , Aspergilosis/microbiología , Aspergilosis/fisiopatología , Aspergillus fumigatus/genética , Movimiento Celular , Femenino , Galectina 3/genética , Humanos , Pulmón/inmunología , Masculino , Ratones , Ratones Endogámicos C57BL , Neutrófilos/inmunologíaRESUMEN
Rescue transcatheter aortic valve replacement (TAVR) in patients with cardiogenic shock is challenging, and there is limited literature on these critical patients. The aim of this study was to determine the characteristics and outcomes of patients undergoing TAVR, feasibility and safety of the procedure, and 1-year mortality factors. Thirty-eight patients with severe aortic disease and cardiogenic shock admitted to two French hospitals from 2015 to 2019 were included. The patients were critical, 78.9% of them had a left ventricular ejection fraction of <30%, and all of them received inotropic support. "Valve-in-valve" procedures were performed in 15.8% and 13.2% underwent balloon aortic valvuloplasty before TAVR. Edwards Sapien3® and Medtronic CoreValve EvolutR® were used. The survival probability remained reasonable for patients with cardiogenic shock who underwent rescue TAVR. The 30-day mortality rate was 7.9% and 21.1% at 1 year. No patient died during the intervention. The procedure was safe, with few complications except for acute kidney failure, the development of a left bundle branch block, and the need for pacemaker implantation. Both functional and echocardiographic results were good at 1 year, although 29% of the patients underwent rehospitalization within 1 year. The development of a left bundle branch block was found to be a mortality risk factor. This procedure is a safe and effective therapy with acceptable survivorship in critically ill patients. The benefits to their quality of life should be evaluated in future studies, and the need for providing early cardiac resynchronization therapy must be emphasized.
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Estenosis de la Válvula Aórtica , Prótesis Valvulares Cardíacas , Reemplazo de la Válvula Aórtica Transcatéter , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/complicaciones , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Estenosis de la Válvula Aórtica/cirugía , Arritmias Cardíacas , Bloqueo de Rama/etiología , Prótesis Valvulares Cardíacas/efectos adversos , Humanos , Calidad de Vida , Estudios Retrospectivos , Factores de Riesgo , Choque Cardiogénico/diagnóstico , Choque Cardiogénico/etiología , Choque Cardiogénico/terapia , Volumen Sistólico , Resultado del Tratamiento , Función Ventricular IzquierdaRESUMEN
OBJECTIVES: Report contemporary outcomes in patients included in the Mitragister registry and treated with transcatheter mitral valve implantation for failed surgical annuloplasty rings or deteriorated bioprosthesis. BACKGROUND: Midterm survival rates have been reported, but little is known about contemporary morbimortality endpoints. METHODS: The primary safety outcome was the technical success rate. The primary efficacy composite endpoint was a composite of cardiovascular mortality and heart failure hospitalizations. RESULTS: From 2016 to 2021, 102 patients (median age: 81 [74;84] years, 61% female, Euroscore II 11.0% [7.8;16.0]) undergoing valve-in-valve (ViV; n = 89) or valve-in-ring (ViR; n = 13) procedures were consecutively included. At baseline, ViR group patients had worse left ventricular ejection fraction (50% vs. 60%; p = 0.004) and more frequently severe regurgitation (46% vs. 15%; p = 0.014). The primary safety outcome was 95%: 77% and 98% in the ViR and ViV populations, respectively, (p = 0.014). At intermediate follow-up (6-12 months) clinical improvement was notable, 88% of the patients were in NYHA class ≤ II (vs. 25% at baseline; p < 0.001). At a mean follow-up of 17.1 ± 11.0 months, the primary efficacy composite reached 27%. By multivariate analysis, paravalvular leak (PVL) was the only independent predictor (hazard ratio: 2.39, 95% confidence interval: 1.08-5.29; p = 0.031) while ViR was not found statistically associated (p = 0.456). CONCLUSIONS: This study confirms the safety and efficacy of the mitral ViV procedure. ViR patients appear at higher risk of procedural complications. The presence of PVL could be associated with markedly worse midterm prognosis. Whatever the intervention, procedural strategies to reduce PVL incidence remain to be assessed to prevent latter adverse outcomes.
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Bioprótesis , Implantación de Prótesis de Válvulas Cardíacas , Prótesis Valvulares Cardíacas , Insuficiencia de la Válvula Mitral , Anciano de 80 o más Años , Bioprótesis/efectos adversos , Cateterismo Cardíaco/métodos , Femenino , Implantación de Prótesis de Válvulas Cardíacas/métodos , Humanos , Masculino , Válvula Mitral/diagnóstico por imagen , Válvula Mitral/cirugía , Insuficiencia de la Válvula Mitral/diagnóstico por imagen , Insuficiencia de la Válvula Mitral/cirugía , Falla de Prótesis , Sistema de Registros , Volumen Sistólico , Resultado del Tratamiento , Función Ventricular IzquierdaRESUMEN
In many African countries, the Bayoud is a common disease spread involving the fungus Fusarium oxusporum f. sp. albedinis (Foa). The induction of plant natural defenses through the use of seaweed polysaccharides to help plants against pathogens is currently a biological and ecological approach that is gaining more and more importance. In the present study, we used alginate, a natural polysaccharide extracted from a brown algae Bifurcaria bifurcata, to activate date palm defenses, which involve phenylalanine ammonia-lyase (PAL), a key enzyme of phenylpropanoid metabolism. The results obtained showed that at low concentration (1 g·L-1), alginate stimulated PAL activity in date palm roots 5 times more compared to the negative control (water-treated) after 24 h following treatment and 2.5 times more compared to the laminarin used as a positive stimulator of plant natural defenses (positive control of induction). Using qRT-PCR, the expression of a selection of genes involved in three different levels of defense mechanisms known to be involved in response to biotic stresses were investigated. The results showed that, generally, the PAL gene tested and the genes encoding enzymes involved in early oxidative events (SOD and LOX) were overexpressed in the alginate-treated plants compared to their levels in the positive and negative controls. POD and PR protein genes selected encoding ß-(1,3)-glucanases and chitinases in this study did not show any significant difference between treatments; suggesting that other genes encoding POD and PR proteins that were not selected may be involved. After 17 weeks following the inoculation of the plants with the pathogen Foa, treatment with alginate reduced the mortality rate by up to 80% compared to the rate in control plants (non-elicited) and plants pretreated with laminarin, which agrees with the induction of defense gene expression and the stimulation of natural defenses in date palm with alginate after 24 h. These results open promising prospects for the use of alginate in agriculture as an inducer that triggers immunity of plants against telluric pathogens in general and of date palm against Fusarium oxysporum f. sp. albedinis in particular.
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Alginatos/farmacología , Phaeophyceae/química , Phoeniceae/microbiología , Enfermedades de las Plantas/prevención & control , Alginatos/aislamiento & purificación , Fusariosis/prevención & control , Fusarium/aislamiento & purificación , Regulación de la Expresión Génica de las Plantas/genética , Glucanos/farmacología , Lipooxigenasa/metabolismo , Phoeniceae/genética , Enfermedades de las Plantas/microbiología , Metabolismo Secundario , Superóxido Dismutasa/metabolismoRESUMEN
A novel sulfated xylogalactan (JASX) was extracted and purified from the rhodophyceae Jania adhaerens. JASX was characterized by chromatography (GC/MS-EI and SEC/MALLS) and spectroscopy (ATR-FTIR and 1H/13C NMR) techniques. Results showed that JASX was constituted by repeating units of (â3)-ß-d-Galp-(1,4)-3,6-α-l-AnGalp-(1â)n and (â3)-ß-d-Galp-(1,4)-α-l-Galp-(1â)n substituted on O-2 and O-3 of the α-(1,4)-l-Galp units by methoxy and/or sulfate groups but also on O-6 of the ß-(1,3)-d-Galp mainly by ß-xylosyl side chains and less by methoxy and/or sulfate groups. The Mw, Mn, D, [η] and C* of JASX were respectively 600 and 160 kDa, 3.7, 102 mL.g-1 and 7.0 g.L-1. JASX exhibited pseudoplastic behavior influenced by temperature and monovalent salts and highly correlated to the power-law model and the Arrhenius relationship. JASX presented thixotropic characteristics, a gel-like viscoelastic behavior and a great viscoelasticity character. JASX showed important antioxidant activities, outlining its potential as a natural additive to produce functional foods.
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Rhodophyta , Algas Marinas , Antioxidantes/química , Antioxidantes/farmacología , Polisacáridos/química , Polisacáridos/farmacología , Rhodophyta/química , Sales (Química) , Algas Marinas/química , SulfatosRESUMEN
BACKGROUND AND AIM: The mortality rate of patients with post-myocardial infarction (MI) ventricular septal defects (VSDs) is high, and the benefit of surgery is unclear. We aimed to investigate the management and outcomes of post-MI VSD over a 10-year period in a large cohort. METHODS: Data of patients with post-MI VSD admitted in three French university hospitals from 2008 to 2019 were examined. The characteristics of those who underwent surgery were compared with those who received medical treatment. Mortality risk factors, survival curves, and outcomes at 30 days and 1 year after treatment were determined. RESULTS: Of the 92 patients whose data were examined, 50 underwent surgery and 42 received exclusive medical treatment. All patients were critically ill. Overall, 76.1% of patients received inotropic support, and 63% received mechanical ventilation. Circulatory assistance, mainly via intra-aortic balloon pump and extra-corporeal membrane oxygenation, was provided to 46.7% patients, with 14.1% requiring a second assistance. The median time to surgery was 4 days. At 1 year, mortality was 46% in those who underwent surgery and 83.3% in those treated medically (p < .001). Survival curves at 1 and 3 months showed major differences, and the survival rate showed little change 30 days after treatment. Cardiogenic shock and cardiac arrest emerged as risk factors for mortality. CONCLUSIONS: In our retrospective, multicenter study, the mortality resulting from post-MI VSD did not seem to improve over the last decade. Although surgery carried considerable risks, it improved survival.
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Defectos del Tabique Interventricular , Infarto del Miocardio , Humanos , Estudios Retrospectivos , Infarto del Miocardio/complicaciones , Infarto del Miocardio/cirugía , Choque Cardiogénico/etiología , Choque Cardiogénico/terapia , Defectos del Tabique Interventricular/etiología , Factores de Riesgo , Resultado del TratamientoRESUMEN
BACKGROUND: Bifurcation lesions in coronary arteries are complex to treat with coronary stents, which are not designed for that purpose and can be unproperly deployed. Moreover, devices are constantly evolving, and so are angioplasty techniques. OBJECTIVES: The aim of this study was to determine the performances of different stents in the treatment of bifurcation lesions using the re-proximal optimization technique (rePOT). METHODS: Eleven stent platforms were evaluated: Xience Sierra (Abbott), Xience Alpine (Abbott), Synergy (Boston), Coroflex Isar (Bbraun), Cobra PzF (Celonova), Ultimaster (Terumo), Resolute Integrity (Medtronic), Resolute Onyx (Medtronic), Optimax (Hexacath), Orsiro (Biotronik), and Absorb (Abbott). Stents were deployed in a silicone fractal bifurcation model using the rePOT. Micro-computed tomography was performed to assess side branch ostium coverage and strut malapposition, as well as the effect of rePOT on stent cell area. RESULTS: Our study showed significant differences between stent platforms regarding side branch ostium coverage (p = .002). The Synergy and Cobra PzF stents were the most performant devices to avoid ostium coverage. Strut malapposition varied significantly between devices (p = .008) but the percentage of malapposed struts was relatively low. Significant differences were observed between stents regarding the cell area before (p = .002) and also after rePOT (p = .003), and the increase in cell area caused by rePOT varied considerably between devices (p = .08). CONCLUSION: This study highlighted significant differences in the performances of stent platforms deployed in a fractal bifurcation model using rePOT, with a variable impact of the procedure on stent cell area.
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Enfermedad de la Arteria Coronaria , Stents , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/cirugía , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/cirugía , Fractales , Humanos , Diseño de Prótesis , Tomografía de Coherencia Óptica , Resultado del Tratamiento , Microtomografía por Rayos XRESUMEN
OBJECTIVE: Low skeletal muscle mass has emerged as a risk factor for mortality after liver transplantation. We evaluated the prognostic value of muscle mass on length of hospitalization and adverse outcomes after kidney transplantation in aging end-stage renal disease patients. METHODS: One hundred twenty-two patients aged 60 years or older at the time of transplantation were retrospectively analyzed. Skeletal muscle index (SMI), evaluated by computed tomography scan, was calculated from total muscle surface area at L3 vertebral level divided by body height squared. Outcomes were compared according to SMI (namely, length of hospitalization, wound complications, combined endpoint comprising all-cause mortality, and graft failure within 1 year). RESULTS: In male patients, by multivariate analysis, a low SMI (<42 cm2/m2) was associated with longer immediate post-transplantation hospitalization (ß = 17.03 ± 4.3; P = .0002), longer total hospitalization during the first year (ß = 34.3 ± 10.7; P = .002), higher rate of wound complications (odds ratio = 12.1 [1.9-77.0]; P = .008), and higher rate of the combined endpoint of graft loss or death (odds ratio = 3.4 [3.0-399.5]; P = .004). In female patients, low SMI was not associated with length of hospitalization or adverse outcomes after transplantation. CONCLUSION: SMI is an independent marker of morbidity and mortality after kidney transplantation in older men and could help thereby nephrologists better select aging candidates for kidney transplantation with a view to improving post-transplant outcomes.
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Trasplante de Riñón , Sarcopenia , Anciano , Femenino , Humanos , Masculino , Músculo Esquelético , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Sarcopenia/diagnósticoRESUMEN
Syncytin (Syn)-2 is an important fusogenic protein that contributes to the formation of the placental syncytiotrophoblast. Galectin (Gal)-1, a soluble lectin, is also involved in trophoblast cell fusion and modulates the interaction of certain retroviral envelopes with their cellular receptor. This study aimed to investigate the association between Syn-2 and Gal-1 during human trophoblast cell fusion. This association was evaluated in vitro on primary villous cytotrophoblasts (vCTBs) and cell lines using recombinant Gal-1 and Syn-2-pseudotyped viruses. Using lactose, a Gal antagonist, and Gal-1-specific small interfering RNA (siRNA) transfections, we confirmed the implication of Gal-1 in vCTBs and BeWo cell fusion, although RT-PCR and ELISA analyses suggested that Gal-1 alone did not induce syncytialization. Infection assays showed a specific and significant effect of Gal-1 on the infectivity of Syn-2-pseudotyped viruses that depended on the expression of major facilitator superfamily domain-containing 2A (MFSD2a). Moreover, Gal-3, another placental Gal, did not modulate the infectivity of Syn-2-positive viruses, strengthening the specific association between Gal-1 and Syn-2. Interestingly, Gal-1 significantly reduced the infectivity of Syn-1-pseudotyped viruses, suggesting the opposite effects of Gal-1 on Syn-1 and -2. Finally, coimmunoprecipitation experiments showed a glycan-dependent interaction between Syn-2-bearing virions and Gal-1. We conclude that Gal-1 specifically interacts with Syn-2 and possibly regulates Syn-2/MFSD2a interaction during syncytialization of trophoblastic cells.-Toudic, C., Vargas, A., Xiao, Y., St-Pierre, G., Bannert, N., Lafond, J., Rassart, É., Sato, S., Barbeau, B. Galectin-1 interacts with the human endogenous retroviral envelope protein syncytin-2 and potentiates trophoblast fusion in humans.
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Fusión Celular , Galectina 1/metabolismo , Proteínas Gestacionales/metabolismo , Trofoblastos/citología , Retrovirus Endógenos , Femenino , Células HEK293 , Células HeLa , Humanos , Embarazo , Unión ProteicaRESUMEN
BACKGROUND: To report the first case of belatacept-associated multidrug-resistant Cytomegalovirus retinitis in a kidney transplant recipient. CASE PRESENTATION: A 76-year-old African male renal allograft recipient was admitted for acute visual loss of the right eye. Ophthalmological examination of the right eye showed anterior uveitis and vitritis associated with large paravascular haemorrhages and yellow necrotic borders, involving the posterior pole but not the fovea. Both Cytomegalovirus DNA in plasma and aqueous humor were positive. The patient had had several episodes of Cytomegalovirus reactivation subsequent to the introduction of belatacept. His cytomegalovirus was multi-drug resistant, and was treated with maribarir, intravitreal and systemic injections of foscarnet, and anti-Cytomegalovirus human immunoglobulin. In parallel, belatacept was stopped and switched to tacrolimus. Cytomegalovirus DNA became undetectable and there was partial improvement of visual acuity at the last ophthalmologic examination, 18 months after the initial diagnosis of Cytomegalovirus retinitis. CONCLUSION: Cytomegalovirus retinitis is an uncommon opportunistic infection in kidney transplant recipients. Cytomegalovirus retinitis is a serious infection because of the risk of blindness and the occurrence of associated life-threatening opportunistic infections. In view of the recent literature, kidney transplant recipients treated by belatacept immunosuppression may be at increased risk for Cytomegalovirus disease, notably Cytomegalovirus retinitis. The occurrence of Cytomegalovirus retinitis may help improve the selection of patients converted to belatacept.
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Retinitis por Citomegalovirus , Trasplante de Riñón , Abatacept/uso terapéutico , Anciano , Antivirales/uso terapéutico , Retinitis por Citomegalovirus/diagnóstico , Retinitis por Citomegalovirus/tratamiento farmacológico , Ganciclovir/uso terapéutico , Humanos , Trasplante de Riñón/efectos adversos , MasculinoRESUMEN
Fucoidans from Moroccan brown seaweed Bifurcaria bifurcata and Fucus spiralis were tested for their elicitor activity after their purification and complete characterization. The fucoidans of B. bifurcata (BBF) and of F. spiralis (FSF) were extracted and purified then characterized by infrared spectroscopy, proton nuclear magnetic resonance spectroscopy and size exclusion chromatography. The results show that BBF and FSF are mainly sulfated with 45.49 and 49.53% (w/w) sulfate, respectively. Analysis of neutral sugars determined by gas chromatography-mass spectrometry showed that FSF and BBF were mainly composed of 64% and 91% fucose and 20% and 6% galactose, respectively, with a few other sugars such as glucose (8% in FSF), rhamnose (1% in BBF) and mannose (8% in FSF and, 2% in BBF). The eliciting activity of these sulfated polysaccharides in stimulating the natural defenses of the date palm was evaluated through the activity of phenylalanine ammonia-lyase (PAL), and the increase in phenols and lignin content in the roots. The results obtained clearly show that the two fucoidans early and intensely stimulate the natural defenses of the date palm after 24 h of treatments. This remarkable elicitor effect seems to be linked to the sulfated groups compared to non-sulfate alginates extracted from the same algae. These results open promising perspectives for a biological control approach against date palm diseases.
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Agentes de Control Biológico/farmacología , Fucus/metabolismo , Phoeniceae/efectos de los fármacos , Enfermedades de las Plantas/prevención & control , Raíces de Plantas/efectos de los fármacos , Polisacáridos/farmacología , Algas Marinas/metabolismo , Agentes de Control Biológico/aislamiento & purificación , Lignina/metabolismo , Estructura Molecular , Fenoles/metabolismo , Fenilanina Amoníaco-Liasa/metabolismo , Phoeniceae/metabolismo , Raíces de Plantas/metabolismo , Polisacáridos/aislamiento & purificación , Relación Estructura-ActividadRESUMEN
Polysaccharides extracted from marine algae have attracted much attention due to their biotechnological applications, including therapeutics, cosmetics, and mainly in agriculture and horticulture as biostimulants, biofertilizers, and stimulators of the natural defenses of plants. This study aimed to evaluate the ability of alginate isolated from Bifurcaria bifurcata from the Moroccan coast and oligoalginates derivatives to stimulate the natural defenses of tomato seedlings. Elicitation was carried out by the internodal injection of bioelicitor solutions. The elicitor capacities were evaluated by monitoring the activity of phenylalanine ammonia-lyase (PAL) as well as polyphenols content in the leaves located above the elicitation site for 5 days. Alginate and oligoalginates treatments triggered plant defense responses, which showed their capacity to significantly induce the PAL activity and phenolic compounds accumulation in the leaves of tomato seedlings. Elicitation by alginates and oligoalginates showed an intensive induction of PAL activity, increasing from 12 h of treatment and remaining at high levels throughout the period of treatment. The amount of polyphenols in the leaves was increased rapidly and strongly from 12 h of elicitation by both saccharide solutions, representing peaks value after 24 h of application. Oligoalginates exhibited an effective elicitor capacity in polyphenols accumulation compared to alginate polymers. The alginate and oligosaccharides derivatives revealed a similar elicitor capacity in PAL activity whereas the accumulation of phenolic compounds showed a differential effect. Polysaccharides extracted from the brown seaweed Bifurcaria bifurcate and oligosaccharides derivatives induced significantly the phenylpropanoid metabolism in tomato seedlings. These results contribute to the valorization of marine biomass as a potential bioresource for plant protection against phytopathogens in the context of eco-sustainable green technology.
Asunto(s)
Alginatos/farmacología , Oligosacáridos/farmacología , Phaeophyceae/química , Sustancias Protectoras/farmacología , Plantones/metabolismo , Solanum lycopersicum/química , Solanum lycopersicum/metabolismo , Alginatos/química , Alginatos/aislamiento & purificación , Marruecos , Oligosacáridos/química , Oligosacáridos/aislamiento & purificación , Fenilanina Amoníaco-Liasa/análisis , Fenilanina Amoníaco-Liasa/efectos de los fármacos , Fenilanina Amoníaco-Liasa/aislamiento & purificación , Hojas de la Planta/química , Polifenoles/análisis , Polifenoles/aislamiento & purificación , Polifenoles/metabolismo , Sustancias Protectoras/química , Sustancias Protectoras/aislamiento & purificación , Metabolismo Secundario , Plantones/químicaAsunto(s)
Estenosis de la Válvula Aórtica , Prótesis Valvulares Cardíacas , Reemplazo de la Válvula Aórtica Transcatéter , Humanos , Choque Cardiogénico/etiología , Choque Cardiogénico/cirugía , Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/complicaciones , Estenosis de la Válvula Aórtica/cirugía , Resultado del TratamientoRESUMEN
Our study aimed to search for seaweed polysaccharides able to stimulate date palm defense mechanisms. Extraction, purification, characterization, and elicitor activity of sodium alginate (FSSA and BBSA) from Moroccan brown seaweeds Fucus spiralis and Bifurcaria bifurcata were investigated. FSSA and BBSA were characterized by proton nuclear magnetic resonance spectroscopy (1H-NMR) and size exclusion chromatography (HPLC-SEC). The mannuronic acid/guluronic acid (M/G) ratio of FSSA was M/G= 0.92 indicating that FSSA contained 48% and 52% of mannuronic and guluronic acids respectively, and the M/G ratio of BBSA was 0.47 indicating that BBSA contained 32% and 68% of mannuronic and guluronic acids respectively. Elicitor activity of FSSA and BBSA was carried out by developing an innovative study model on the date palm. The elicitor capacities were evaluated by investigating phenolic metabolism including phenylalanine ammonia-lyase (PAL) activity and total polyphenol content in seedling roots of date palm maintained in alginates solution (FSSA and BBSA) at different concentrations. The results obtained show that the PAL activity and the phenolic compound content were significantly stimulated with 1 mg.mL-1 of FSSA and BBSA; after 1 day of treatment with FSSA, and after 12 hours of treatment with BBSA. These results show clearly those alginates extracted from Moroccan brown algae induced in date palm roots the stimulation of natural defense mechanisms.