59 research outputs found

    Variabilidad de vibrios planctónicos y epifíticos en un ambiente costero afectado por proliferaciones de Ostreopsis

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    Vibrios include several pathogenic bacteria that occur in aquatic environments. The presence of Vibrio has been assessed in many ecosystems by culture-based techniques. However, little is known on the contribution of Vibrios in the sea, especially in areas subject to harmful algal blooms. A preliminary study in Sant Andreu de Llavaneres beach (NW Mediterranean) showed the presence of some Vibrio species during a recurrent bloom of the harmful benthic dinoflagellate Ostreopsis cf. ovata. In order to establish the importance of Vibrios in a coastal area of the NW Mediterranean and to study the association with the dinoflagellate, we conducted a sampling monitoring for one year to quantify the concentration of Vibrios both in the water (free-living and attached to particles) and in the epiphytic community of macroalgae. The aims were 1) to evaluate the relative abundance of Vibrio in the epiphytic and in the planktonic bacterial community, 2) to assess the percentage of free-living and attached Vibrios in the planktonic community, and 3) to determine whether the presence of Vibrios is associated with the blooms of the toxic dinoflagellate Ostreopsis or with other environmental parameters. For this purpose, a CARD-FISH molecular probe was applied for the specific detection of bacteria belonging to the genus Vibrio. Cells were quantified and the abundance of both particles and bacteria attached to particles were assessed. The maximum Vibrio concentration (1.3x104 cells ml–1 and 1.4x106 cells g–1 FW, for planktonic and epiphytic samples, respectively) was detected in September. Free-living Vibrios contributed 0.38±0.24% to the total free-living planktonic community and 1.12±0.28% to the epiphytic bacterial community. However, their contribution was particularly high in the planktonic community attached to particles (17.37±20.49%). Although in the planktonic community Vibrio was found preferentially free-living (82.63±20.01%), particles are a niche for Vibrios, since in particles Vibrios may represent up to 72% of the total attached bacterial community. Abundance of planktonic Vibrio was correlated with Ostreopsis concentration and it is likely that they play a role in the wound infections suffered by beach users during the bloom.El género Vibrio incluye a varias bacterias patogénicas que se encuentran en ecosistemas acuáticos. La presencia de Vibrio se ha estimado en muchos ecosistemas mediante técnicas basadas en cultivos. Sin embargo, se conoce poco sobre la contribución de Vibrios en el mar, especialmente en áreas afectadas por proliferaciones algales nocivas. Un estudio preliminar en la playa de Sant Andreu de Llavaneres (Mediterráneo NO) mostró la presencia de algunas especies de Vibrio durante una proliferación recurrente del dinoflagelado béntico nocivo Ostreopsis cf. ovata. Para poder establecer la relevancia de los Vibrios en un área costera del Mediterráneo NO y estudiar su asociación con el dinoflagelado, realizamos un muestreo de monitoreo durante un año para cuantificar la concentración de Vibrios tanto en el agua (de vida libre y adheridos a partículas) y en la comunidad epifítica de macroalgas con los objetivos de 1) evaluar la abundancia relativa de Vibrio en la comunidad bacteriana tanto planctónica como epifítica, 2) estimar el porcentaje de Vibrios de vida libre y adheridos a partículas en la comunidad bacteriana planctónica y 3) determinar si la presencia de Vibrios está relacionada con las proliferaciones del dinoflagelado Ostreopsis o con otros parámetros ambientales. Para este propósito, se aplicó una sonda molecular de CARD-FISH para la detección específica de bacterias pertenecientes al género Vibrio. Se cuantificaron las células y también la abundancia de partículas y de las bacterias adheridas a estas partículas. La máxima concentración de Vibrio (1.3x104 cels ml–1 y 1.4x106 cels g–1 PF, para muestras planctónicas y epifíticas, respectivamente) fue detectada en Septiembre. Los Vibrios de vida libre contribuyeron un 0.38±0.24% al total de la comunidad bacteriana de vida libre y un 1.12±0.28% a la comunidad bacteriana epifítica. Sin embargo, su contribución fue especialmente elevada en la comunidad bacteriana adherida a partículas (17.37±20.49%). Aunque en la comunidad planctónica Vibrio se encontraba preferentemente no adheridos a partículas (82.63±20.01%), las partículas constituyen un nicho para Vibrios, ya que pueden llegar a representar hasta un 72% de la comunidad bacteriana adherida a partículas. La abundancia de Vibrio en el plancton se correlacionó con la concentración de Ostreopsis, y es posible que éstos jueguen un papel en las infecciones de heridas que sufren los bañistas durante las proliferaciones algales

    Significado de la enfermedad y el trasplante de vivo para las personas receptoras de riñón

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    Introducción: En el trasplante renal de donante vivo, la percepción de la situación de enfermedad y la vivencia personal influyen de forma significativa en la adaptación emocional y el afrontamiento de la persona. Objetivo: Conocer el significado que atribuyen las personas con trasplante renal de donante vivo a su enfermedad y a su tratamiento, y detectar si existen cambios antes y después trasplante. Material y Método: Estudio cualitativo fenomenológico. Participaron 7 personas con enfermedad renal que recibieron un trasplante renal de donante vivo preventivo. Se obtuvieron los datos mediante entrevistas semiestructuradas y observación cualitativa. Resultados: Del análisis temático de las entrevistas emergieron tres temas: sin sentimiento de enfermedad (no se sentían enfermos ni a nivel físico ni psicológico); sin necesidad de trasplantarse (la enfermedad no les alteró su vida, pero confiaron en los profesionales y aceptaron la cirugía); y trasplantarse para mantener el mismo modo de vida (para evitar la diálisis y recuperar actividades). Conclusiones: El significado de la enfermedad y del trasplante renal cambian según la etapa (pre o post trasplante) en la que esté el paciente: la identificación de la enfermedad está relacionada con la presencia de sintomatología, con la sintomatología física y con las rutinas de toma de medicación diarias y visitas de seguimiento; y el trasplante renal, significa evitar la diálisis, hacer la misma vida, superar un reto y recuperar la condición física

    Clinical Value of Liquid Biopsy in Patients with FGFR2 Fusion-Positive Cholangiocarcinoma During Targeted Therapy

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    Liquid biopsy; Cholangiocarcinoma; Targeted therapyBiopsia líquida; Colangiocarcinoma; Terapia dirigidaBiòpsia líquida; Colangiocarcinoma; Teràpia dirigidaPurpose: FGFR2 fusions occur in 10% to 15% of patients with intrahepatic cholangiocarcinoma (iCCA), potentially benefiting from FGFR inhibitors (FGFRi). We aimed to assess the feasibility of detecting FGFR2 fusions in plasma and explore plasma biomarkers for managing FGFRi treatment. Experimental design: We conducted a retrospective study in 18 patients with iCCA and known FGFR2 fusions previously identified in tissue samples from prior FGFRi treatment. Both tissue and synchronous plasma samples were analyzed using a custom hybrid capture gene panel with next-generation sequencing (VHIO-iCCA panel) and validated against commercial vendor results. Longitudinal plasma analysis during FGFRi was performed. Subsequently, we explored the correlation between plasma biomarkers, liver enzymes, tumor volume, and clinical outcomes. Results: Sixteen patients (88.9%) were positive for FGFR2 fusion events in plasma. Remarkably, the analysis of plasma suggests that lower levels of ctDNA are linked to clinical benefits from targeted therapy and result in improved progression-free survival and overall survival. Higher concentrations of cell-free DNA before FGFRi treatment were linked to worse overall survival, correlating with impaired liver function and indicating compromised cell-free DNA removal by the liver. Additionally, increased ctDNA or the emergence of resistance mutations allowed earlier detection of disease progression compared with standard radiologic imaging methods. Conclusions: VHIO-iCCA demonstrated accurate detection of FGFR2 fusions in plasma. The integration of information from various plasma biomarkers holds the potential to predict clinical outcomes and identify treatment failure prior to radiologic progression, offering valuable guidance for the clinical management of patients with iCCA.This study was supported by Incyte Corporation (Wilmington, DE; project title: “Identification of FGFR2 alterations by liquid biopsy and correlation with tissue biopsies in patients with cholangiocarcinoma”), the Asociación Española contra el Cáncer (AECC, Spain), and the FERO Foundation. A. Gonzalez-Medina is supported by the grant FJC2019-039770-I funded by Agencia Estatal de Investigación of Ministerio de Ciencia e Innovación (MCIN/AEI/10.13039/501100011033, Spain). R. Pérez-López. is supported by LaCaixa Foundation, a CRIS Foundation Talent Award (TALENT19-05), the FERO Foundation, the Instituto de Salud Carlos III-Investigación en Salud (PI18/01395 and PI21/01019), the Prostate Cancer Foundation (18YOUN19), and the Asociación Española Contra el Cáncer (AECC; PRYCO211023SERR, funding CM). A. Vivancos is supported by the Instituto de Salud Carlos III-investigación en Salud (PI20/01112). Some pictures were created with BioRender

    Cistinosis en pacientes adolescentes y adultos: Recomendaciones para la atención integral de la cistinosis

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    ResumenIntroducciónLa cistinosis es una enfermedad lisosomal minoritaria de expresión sistémica con especial afectación renal y oftalmológica, en la que los pacientes inician terapia renal sustitutiva en la primera década de la vida en ausencia de tratamiento. El pronóstico de la cistinosis depende del diagnóstico precoz, la pronta instauración del tratamiento con cisteamina y el buen cumplimiento terapéutico. La progresión de la enfermedad renal y de las complicaciones extrarrenales y una menor supervivencia, son más acentuadas en pacientes no adherentes.ObjetivoEl objetivo de este trabajo fue la elaboración de unas recomendaciones para la atención integral de la cistinosis y la transición del adolescente a la medicina del adulto, basadas en la experiencia clínica, con el fin de reducir el impacto de la enfermedad y mejorar la calidad de vida y el pronóstico del paciente.MétodoBúsqueda bibliográfica y reuniones de consenso de un equipo multidisciplinar de expertos en la práctica clínica con pacientes afectos de cistinosis (Grupo T-CiS.bcn), procedentes de 5 hospitales localizados en Barcelona.ResultadosEl documento recoge recomendaciones específicas y necesarias para el diagnóstico, tratamiento y seguimiento multidisciplinar de la cistinosis en las siguientes áreas: nefrología, diálisis, trasplante renal, oftalmología, endocrinología, neurología, laboratorio, consejo genético, enfermería y farmacia.ConclusionesDisponer de un documento de referencia para la atención integral de la cistinosis constituye una herramienta de soporte para los profesionales de la salud que asisten a estos pacientes. Los principales pilares en los que se sustenta son: a) el enfoque multidisciplinar, b) la adecuada monitorización de la enfermedad y control de los niveles de cistina intraleucocitarios, c) la importancia de la adherencia al tratamiento con cisteamina y d) la promoción del autocuidado del paciente mediante programas de educación en la enfermedad. Todo ello conducirá, en una segunda fase, a la elaboración de un modelo de transición coordinado entre los servicios de pediatría y de adultos que contemple las necesidades específicas de la cistinosis.AbstractIntroductionCystinosis is a rare lysosomal systemic disease that mainly affects the kidney and the eye. Patients with cystinosis begin renal replacement therapy during the first decade of life in absence of treatment. Prognosis of cystinosis depends on early diagnosis, and prompt starting and good compliance with cysteamine treatment. Kidney disease progression, extra-renal complications and shorter life expectancy are more pronounced in those patients that do not follow treatment.The objective of this work was to elaborate recommendations for the comprehensive care of cystinosis and the facilitation of patient transition from paediatric to adult treatment, based on clinical experience. The goal is to reduce the impact of the disease, and to improve patient quality of life and prognosis.MethodsBibliographic research and consensus meetings among a multidisciplinary professional team of experts in the clinical practice, with cystinotic patients (T-CiS.bcn group) from 5 hospitals located in Barcelona.ResultsThis document gathers specific recommendations for diagnosis, treatment and multidisciplinary follow-up of cystinotic patients in the following areas: nephrology, dialysis, renal transplant, ophthalmology, endocrinology, neurology, laboratory, genetic counselling, nursing and pharmacy.ConclusionsA reference document for the comprehensive care of cystinosis represents a support tool for health professionals who take care of these patients. It is based on the following main pillars: a) a multi-disciplinary approach, b) appropriate disease monitoring and control of intracellular cystine levels in leukocytes, c) the importance of adherence to treatment with cysteamine, and d) the promotion of patient self-care by means of disease education programmes. All these recommendations will lead us, in a second phase, to create a coordinated transition model between paediatric and adult care services which will cover the specific needs of cystinosis

    One-year dietary supplementation with walnuts modifies exosomal miRNA in elderly subjects

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    Purpose: Epidemiological studies and clinical trials support the association of nut consumption with a lower risk of prevalent non-communicable diseases, particularly cardiovascular disease. However, the molecular mechanisms underlying nut benefits remain to be fully described. MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression and play a pivotal role in health and disease. Exosomes are extracellular vesicles released from cells and mediate intercellular communication. Whether nut consumption modulates circulating miRNAs (c-miRNAs) transported in exosomes is poorly described. Methods: Cognitively healthy elderly subjects were randomized to either control (n = 110, abstaining from walnuts) or daily supplementation with walnuts (15% of their total energy, ≈30–60 g/day, n = 101) for 1-year. C-miRNAs were screened in exosomes isolated from 10 samples, before and after supplementation, and identified c-miRNA candidates were validated in the whole cohort. In addition, nanoparticle tracking analysis and lipidomics were assessed in pooled exosomes from the whole cohort. Results: Exosomal hsa-miR-32-5p and hsa-miR-29b-3p were consistently induced by walnut consumption. No major changes in exosomal lipids, nanoparticle concentration or size were found. Conclusion: Our results provide novel evidence that certain c-miRNAs transported in exosomes are modulated by walnut consumption. The extent to which this finding contributes to the benefits of walnuts deserves further research.Fundacion Ramon Areces (CIVP18A3888) Madrid, Spain; the Instituto de Salud Carlos III-Fondo de Investigacion Sanitaria–Fondo Europeo de Desarrollo Regional (grant PI15/01014 and PI18/01152), and the Spanish Agencia Estatal de Investigacion and European Feder Funds (AGL2016-78922-R, PID2019-109369RB-I00, RTI2018-093873-A-I00 and BIO2017-86500-R). AS-V is recipient of the Instituto de Salud Carlos III Miguel Servet II fellowship (grant CP II 17/00029

    Patritumab deruxtecan in HER2-negative breast cancer: part B results of the window-of-opportunity SOLTI-1805 TOT-HER3 trial and biological determinants of early response

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    Patritumab deruxtecan (HER3-DXd) exhibits promising efficacy in breast cancer, with its activity not directly correlated to baseline ERBB3/HER3 levels. This research investigates the genetic factors affecting HER3-DXd's response in women with early-stage hormone receptor-positive and HER2-negative (HR+/HER2-) breast cancer. In the SOLTI-1805 TOT-HER3 trial, a single HER3-DXd dose was administered to 98 patients across two parts: 78 patients received 6.4 mg/kg (Part A), and 44 received a lower 5.6 mg/kg dose (Part B). The CelTIL score, measuring tumor cellularity and infiltrating lymphocytes from baseline to day 21, was used to assess drug activity. Part A demonstrated increased CelTIL score after one dose of HER3-DXd. Here we report CelTIL score and safety for Part B. In addition, the exploratory analyses of part A involve a comprehensive study of gene expression, somatic mutations, copy-number segments, and DNA-based subtypes, while Part B focuses on validating gene expression. RNA analyses show significant correlations between CelTIL responses, high proliferation genes (e.g., CCNE1, MKI67), and low expression of luminal genes (e.g., NAT1, SLC39A6). DNA findings indicate that CelTIL response is significantly associated with TP53 mutations, proliferation, non-luminal signatures, and a distinct DNA-based subtype (DNADX cluster-3). Critically, low HER2DX ERBB2 mRNA, correlates with increased HER3-DXd activity, which is validated through in vivo patient-derived xenograft models. This study proposes chemosensitivity determinants, DNA-based subtype classification, and low ERBB2 expression as potential markers for HER3-DXd activity in HER2-negative breast cancer. Patritumab deruxtecan (HER3-DXd) is a promising therapy for breast cancer, targeting HER3. Here, the authors analyse the genomic factors that affect the response to HER3-DXd in patients with early-stage HER2-negative breast cancer as part of the SOLTI-1805 TOT-HER3 clinical trial and report outcomes for Part B of the trial using lower HER3-DXd dose in patients with HER2-negative breast cancer
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