Preclinical evaluation of BH3-mimetics targeting MCL-1 (S63845) and BCL-2 (venetoclax) in multiple myeloma

[EN] Multiple myeloma (MM) is a hematologic neoplasm characterized by the proliferation of clonal plasma cells (PCs) in the bone marrow (BM). The substitution of normal BM cells by MM cells results in cytopenias responsible, among other factors, for the immunodeficiency observed in these patients, and also in the production of monoclonal immunoglobulins (Igs) that can lead to renal failure. Other symptoms as hypercalcemia and osteolysis are direct consequences of the interaction of malignant PCs with the BM microenvironment

El uso de ecuaciones específicas de conversión TS-Talla para la estima de la biomasa de peces en balsas de acuicultura someras mediante métodos acústicos

La acuicultura es un sector con demanda creciente en nuestro país y se encuentra en una etapa donde los procesos de producción y comercialización están consolidados. Actualmente, las empresas acuícolas buscan la mejora en la optimización de gastos y el control de la trazabilidad del producto. Para mejorar estos parámetros, es fundamental tener un control exhaustivo sobre el número de peces que se crían en las balsas de cultivo y la biomasa de estas. En primer lugar, para ajustar la dosis de pienso (gasto más relevante en la producción) y en segundo lugar, para mejorar la trazabilidad y el control de la producción final. La hidroacústica ha demostrado ser una técnica eficaz para la determinación de densidad y biomasa de peces, tanto en sistemas de agua dulce como salada. Con este método no intrusivo, se pretende mejorar la fiabilidad de las estimas de densidad y biomasa y reducir el estrés que provocan a los peces los muestreos convencionales. Este trabajo tiene como objetivo la aplicación de esta técnica para la estima de biomasa de peces en balsas de doradas (Sparusaurata) y lubinas (Dicentrarchuslabrax) en esteros. Para ello, se han elaborado ecuaciones que relacionan el TS (dB), cantidad de sonido que devuelve el pez, con la longitud (mm) de los peces, validándose la eficiencia del uso específico de dichas ecuaciones para la estima de la biomasa de peces en sistemas someros

The kinesin spindle protein inhibitor filanesib enhances the activity of pomalidomide and dexamethasone in multiple myeloma

[EN]Kinesin spindle protein inhibition is known to be an effective therapeutic approach in several malignancies. Filanesib (ARRY-520), an inhibitor of this protein, has demonstrated activity in heavily pre-treated multiple myeloma patients. The aim of the work herein was to investigate the activity of filanesib in combination with pomalidomide plus dexamethasone backbone, and the mechanisms underlying the potential synergistic effect. The ability of filanesib to enhance the activity of pomalidomide plus dexamethasone was studied in several in vitro and in vivo models. Mechanisms of this synergistic combination were dissected by gene expression profiling, immunostaining, cell cycle and short interfering ribonucleic acid studies. Filanesib showed in vitro, ex vivo, and in vivo synergy with pomalidomide plus dexamethasone treatment. Importantly, the in vivo synergy observed in this combination was more evident in large, highly proliferative tumors, and was shown to be mediated by the impairment of mitosis transcriptional control, an increase in monopolar spindles, cell cycle arrest and the induction of apoptosis in cells in proliferative phases. In addition, the triple combination increased the activation of the proapoptotic protein BAX, which has previously been associated with sensitivity to filanesib, and could potentially be used as a predictive biomarker of response to this combination. Our results provide preclinical evidence for the potential benefit of the combination of filanesib with pomalidomide and dexamethasone, and supported the initiation of a recently activated trial being conducted by the Spanish Myeloma group which is investigating this combination in relapsed myeloma patients.Array BioPharma, the Spanish ISCIII-FIS and FEDER, the Spanish RTICC, Spanish Association Against Cancer (AECC) and the Regional Council of Castilla y León (Consejería de Medicina y Educación)

Effect of salinity and sex on growth performance of Senegalese sole-

&nbsp;En este trabajo se analiza la influencia de la salinidad y del sexo sobre diferentes par&aacute;metros relacionado con el crecimiento y la morfolog&iacute;a en juveniles de lenguado senegal&eacute;s. Para ello, se criaron un total de 1200 juveniles a cuatro salinidades diferentes (5, 10, 20 y 37 ppt) durante 56 d&iacute;as y se estimaron par&aacute;metros biom&eacute;tricos (peso, SGR, longitud, anchura, &aacute;rea y per&iacute;metro) y de calidad morfol&oacute;gica (excentricidad y elipsidad). Adem&aacute;s, se estimaron niveles de cortisol y de osmolalidad plasm&aacute;tica y se tomaron las muestras para la aplicaci&oacute;n de t&eacute;cnicas gen&oacute;micas. Para este estudio, los animales se identificaron individualmente mediante marcadores electr&oacute;nicos tipo Pit Tags</p

The Current Role of the Heavy/Light Chain Assay in the Diagnosis, Prognosis and Monitoring of Multiple Myeloma: An Evidence-Based Approach.

Despite tremendous progress being made in recent years, multiple myeloma (MM) remains a challenging disease. The laboratory plays a critical role in the overall management of patients. The diagnosis, prognosis, clinical monitoring and evaluation of the response are key moments in the clinical care process. Conventional laboratory methods have been and continue to be the basis of laboratory testing in monoclonal gammopathies, along with the serum free light chain test. However, more accurate methods are needed to achieve new and more stringent clinical goals. The heavy/light chain assay is a relatively new test which can overcome some of the limitations of the conventional methods for the evaluation of intact immunoglobulin MM patients. Here, we report an update of the evidence accumulated in recent years on this method regarding its use in MM

Clinical characterization of brief psychotic disorders triggered by the COVID-19 pandemic: a multicenter observational study.

This study aimed to characterize the clinical profile of patients with brief psychotic disorders (BPD) triggered by the psychosocial distress derived from the COVID-19 crisis. A multicenter study was conducted from March 14 to May 14, 2020 (the peak weeks of the pandemic in Europe). All consecutive patients presenting non-affective psychotic episodes with a duration of untreated psychosis of less than 1 month and whose onset was related to the COVID-19 crisis were recruited, but only those patients meeting Diagnostic Statistical Manual 5th edition (DSM-5) criteria for "BPD with marked stressors" (DSM-5 code: 298.8) during follow-up were finally included. Patients' sociodemographic and clinical characteristics were collected at baseline and summarized with descriptive statistics. During the study period, 57 individuals with short-lived psychotic episodes related to the emotional stress of the COVID-19 pandemic were identified, of whom 33 met DSM-5 criteria for "BPD with marked stressors". The mean age was 42.33 ± 14.04 years, the gender distribution was almost the same, and the majority were rated as having good premorbid adjustment. About a quarter of the patients exhibited suicidal symptoms and almost half presented first-rank schizophrenia symptoms. None of them were COVID-19 positive, but in more than half of the cases, the topic of their psychotic features was COVID-19-related. The coronavirus pandemic is triggering a significant number of BPD cases. Their risk of suicidal behavior, their high relapse rate, and their low temporal stability make it necessary to closely monitor these patients over time