Background
Intravenous drug administration is associated with potential complications, such as phlebitis. The physiochemical characteristics of the infusate play a very important role in some of ...these problems.
Aim
The aim of this study was to standardize the dilutions of intravenous drugs most commonly used in hospitalized adult patients and to characterize their pH, osmolarity and cytotoxic nature to better guide the selection of the most appropriate vascular access.
Methods
The project was conducted in three phases: (i) standardization of intravenous therapy, which was conducted using a modified double-round Delphi method; (ii) characterization of the dilutions agreed on in the previous phase by means of determining the osmolarity and pH of each of the agreed concentrations, and recording the vesicant nature based on the information in literature; and (iii) algorithm proposal for selecting the most appropriate vascular access, taking into account the information gathered in the previous phases.
Results
In total, 112 drugs were standardized and 307 different admixtures were assessed for pH, osmolarity and vesicant nature. Of these, 123 admixtures (40%), had osmolarity values >600 mOsm/L, pH < 4 or > 9, or were classified as vesicants. In these cases, selection of the most suitable route of infusion and vascular access device is crucial to minimize the risk of phlebitis-type complications.
Conclusions
Increasing safety of intravenous therapy should be a priority in the healthcare settings. Knowing the characteristics of drugs to assess the risk involved in their administration related to their physicochemical nature may be useful to guide decision making regarding the most appropriate vascular access and devices.
The PPARγ coactivator 1 alpha (PGC1α) is a prostate tumor suppressor that controls the balance between anabolism and catabolism. PGC1A downregulation in prostate cancer is causally associated with ...the development of metastasis. Here we show that the transcriptional complex formed by PGC1α and estrogen-related receptor 1 alpha (ERRα) controls the aggressive properties of prostate cancer cells. PGC1α expression significantly decreased migration and invasion of various prostate cancer cell lines. This phenotype was consistent with remarkable cytoskeletal remodeling and inhibition of integrin alpha 1 and beta 4 expression, both
and
. CRISPR/Cas9-based deletion of ERRα suppressed PGC1α regulation of cytoskeletal organization and invasiveness. Mechanistically, PGC1α expression decreased MYC levels and activity prior to inhibition of invasiveness. In addition, PGC1α and ERRα associated at the MYC promoter, supporting the inhibitory activity PGC1α. The inverse correlation between PGC1α-ERRα activity and MYC levels was corroborated in multiple prostate cancer datasets. Altogether, these results support that PGC1α-ERRα functions as a tumor-suppressive transcriptional complex through the regulation of metabolic and signaling events. SIGNIFICANCE: These findings describe how downregulation of the prostate tumor suppressor PGC1 drives invasiveness and migration of prostate cancer cells.
Background: Sarcomas represent an extensive group of malignant diseases affecting mesodermal tissues. Among sarcomas, the clinical management of chondrosarcomas remains a complex challenge, as ...high-grade tumours do not respond to current therapies. Mutations in the isocitrate dehydrogenase (IDH) 1 and 2 genes are among the most common mutations detected in chondrosarcomas and may represent a therapeutic opportunity. The presence of mutated IDH (mIDH) enzymes results in the accumulation of the oncometabolite 2-HG leading to molecular alterations that contribute to drive tumour growth. Methods: We developed a personalized medicine strategy based on the targeted NGS/Sanger sequencing of sarcoma samples (n = 6) and the use of matched patient-derived cell lines as a drug-testing platform. The anti-tumour potential of IDH mutations found in two chondrosarcoma cases was analysed in vitro, in vivo and molecularly (transcriptomic and DNA methylation analyses). Findings: We treated several chondrosarcoma models with specific mIDH1/2 inhibitors. Among these treatments, only the mIDH2 inhibitor enasidenib was able to decrease 2-HG levels and efficiently reduce the viability of mIDH2 chondrosarcoma cells. Importantly, oral administration of enasidenib in xenografted mice resulted in a complete abrogation of tumour growth. Enasidenib induced a profound remodelling of the transcriptomic landscape not associated to changes in the 5 mC methylation levels and its anti-tumour effects were associated with the repression of proliferative pathways such as those controlled by E2F factors. Interpretation: Overall, this work provides preclinical evidence for the use of enasidenib to treat mIDH2 chondrosarcomas. Funding: Supported by the Spanish Research Agency/FEDER (grants PID2022-142020OB-I00; PID2019-106666RB-I00), the ISC III/FEDER (PI20CIII/00020; DTS18CIII/00005; CB16/12/00390; CB06/07/1009; CB19/07/00057); the GEIS group (GEIS-62); and the PCTI (Asturias)/FEDER (IDI/2021/000027).
Sarcomas represent an extensive group of malignant diseases affecting mesodermal tissues. Among sarcomas, the clinical management of chondrosarcomas remains a complex challenge, as high-grade tumours ...do not respond to current therapies. Mutations in the isocitrate dehydrogenase (IDH) 1 and 2 genes are among the most common mutations detected in chondrosarcomas and may represent a therapeutic opportunity. The presence of mutated IDH (mIDH) enzymes results in the accumulation of the oncometabolite 2-HG leading to molecular alterations that contribute to drive tumour growth.
We developed a personalized medicine strategy based on the targeted NGS/Sanger sequencing of sarcoma samples (n = 6) and the use of matched patient-derived cell lines as a drug-testing platform. The anti-tumour potential of IDH mutations found in two chondrosarcoma cases was analysed in vitro, in vivo and molecularly (transcriptomic and DNA methylation analyses).
We treated several chondrosarcoma models with specific mIDH1/2 inhibitors. Among these treatments, only the mIDH2 inhibitor enasidenib was able to decrease 2-HG levels and efficiently reduce the viability of mIDH2 chondrosarcoma cells. Importantly, oral administration of enasidenib in xenografted mice resulted in a complete abrogation of tumour growth. Enasidenib induced a profound remodelling of the transcriptomic landscape not associated to changes in the 5 mC methylation levels and its anti-tumour effects were associated with the repression of proliferative pathways such as those controlled by E2F factors.
Overall, this work provides preclinical evidence for the use of enasidenib to treat mIDH2 chondrosarcomas.
Supported by the Spanish Research Agency/FEDER (grants PID2022-142020OB-I00; PID2019-106666RB-I00), the ISC III/FEDER (PI20CIII/00020; DTS18CIII/00005; CB16/12/00390; CB06/07/1009; CB19/07/00057); the GEIS group (GEIS-62); and the PCTI (Asturias)/FEDER (IDI/2021/000027).
Introducción: Desde hace unos años, la educación asiste a cambios en la formación. Se intenta pasar de una formación basada en la adquisición pasiva de conocimientos teóricos, a otra formación más ...activa, dinámica y reflexiva. La forma ideal de evaluar la capacidad profesional es observar qué hace el médico ante las situaciones habituales en su consulta. Como esto entraña grandes dificultades técnicas, se han diseñado instrumentos que se aproximan bastante a la realidad, como la evaluación clínica objetiva estructurada.
Objetivo: El objetivo fue aplicar una evaluación clínica objetiva estructurada para valorar las habilidades clínicas en estudiantes de quinto semestre.
Método: Se conformó un comité de prueba con 4 docentes del área de formación médica general. Se realizó una tabla de especificaciones de habilidades clínicas para evaluar a los estudiantes con los casos clínicos planificados, fueron incluidas la anamnesis, examen físico, juicio clínico, diagnóstico anatofisiológico, habilidades imagenológicas y comunicación terapéutica. Se diseñaron 4 estaciones, se validó a través del juicio de expertos su contenido y se calculó la validez predictiva de las listas de cotejo. Se aplicó la prueba a 17 estudiantes, se validó el instrumento, se obtuvieron resultados de la estadística descriptiva y se calculó el alfa de Cronbach.
Resultados: El análisis de concordancia del instrumento de evaluación según los expertos, fue aceptable, pues la condición de esencial superó el 80%; la validez predictiva y el alfa de Cronbach en 3 de las estaciones fue significativo, la cardiopatía chagásica fue la mejor evaluada con 97.5 y el alfa de Cronbach general fue de 0.507.
Conclusiones: Los instrumentos utilizados en la evaluación clínica objetiva estructurada tienen la validez y confiabilidad suficiente para ser aplicados en el contexto investigativo y mejorar la calidad de las evaluaciones clínicas, haciéndolas más objetivas y con mayores posibilidades de retroalimentación en el proceso de aprendizaje.
The Canarias InfraRed Camera Experiment (CIRCE) is a near-infrared (1-2.5 micron) imager, polarimeter and low-resolution spectrograph operating as a visitor instrument for the Gran Telescopio ...Canarias 10.4-meter telescope. It was designed and built largely by graduate students and postdocs, with help from the UF astronomy engineering group, and is funded by the University of Florida and the U.S. National Science Foundation. CIRCE is intended to help fill the gap in near-infrared capabilities prior to the arrival of EMIR to the GTC, and will also provide the following scientific capabilities to compliment EMIR after its arrival: high-resolution imaging, narrowband imaging, high-time-resolution photometry, imaging polarimetry, low resolution spectroscopy. In this paper, we review the design, fabrication, integration, lab testing, and on-sky performance results for CIRCE. These include a novel approach to the opto-mechanical design, fabrication, and alignment.
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