The comfort perception in the critically ill patient from the Kolcaba theoretical model.

BACKGROUND: The stay in a critical care unit (CCU) has a serious impact on physical condition causing numerous discomfort factors such as pain or difficulty in communicating. All of these are associated with possible sequelae following discharge from the Intensive Care Unit (ICU) named post-ICU syndrome. The Kolcaba Comfort Theory allows, from a holistic approach, to identify care needs from the patient's perspective using instruments such as the General Comfort Questionnaire (GCQ). OBJECTIVES: To determine the comfort level of patients admitted to the CCU using the GCQ of Kolcaba and to identify the discomfort factors. METHODS: Cross-sectional descriptive observational prospective study. POPULATION: 580 patients admitted to adult CCU of two high complexity hospitals from June 2015 to March 2020 with stay ≥24 h were interviewed. Descriptive analysis, Student's t-test and ANOVA and multivariate analysis were performed using SPSS v26 and STATA v16. RESULTS: The mean age was 52,62 (16,21), 357 (61,6%) were male and 434 (74,8%) were believers. The type of admission was planned in 322 (55,5%) and the most prevalent reason for admission was surgical 486 (83,8%). The median pain score (NRS) was 3,00 [0-4] and severity score (APACHE II) was 13,26 (5,89), the median length of stay was 4,00 [2-7] days. The mean comfort level was 3,02 (0,31) showing the highest value Reanimation 3.02 (0.30) and the lowest Trauma and Emergency Unit 2.95 (0.38). Statistically significant differences were found between the units in the comfort level of patients >65 years of age (p = 0.029). The Relief comfort type obtained the lowest mean 2.81 (0.33) and the physical context 2.75 (0.41) in the three units. In the multivariate analysis, statistically significant differences were found between the comfort level and the pain level: no pain (p = 0,000) OR 4,361 CI [2,184-8,707], mild pain (p = 0,000) OR 4,007 CI [2,068-7,763], moderate pain (p = 0,007) OR 2,803 CI [1,328-5,913], and the APACHE II score equal to or greater than 10 (p = 0,000) OR 0,472 CI [0,316-0,705]. CONCLUSIONS: The comfort level showed high scores in all three units. The physical and environmental contexts and the relief comfort type negatively affected the perception of comfort. The variables that explained comfort were pain and severity of illness. The evaluation of comfort from the patient's perspective through the GCQ could be considered an indicator of quality of nursing interventions.

Valoración de la repercusión del tabaco en la función pulmonar según el sexo / No disponible

Objetivo: Valorar la posible existencia de diferencias, en función del sexo, de la repercusión del tabaco sobre la función pulmonar. Pacientes y método: Se realizó un estudio descriptivo transversal (primer trimestre 2010), en tres ZBS de Toledo. Los participantes fueron fumadores mayores de 18 años (se excluyeron los pacientes con patología oncológica pulmonar, fibrosis quística, enfermedad pulmonar profesional, disfunciones cognitivas, contraindicaciones para poder realizar una espirometría, y no ser hispano- hablantes). Tras contactar telefónicamente, se citó a los pacientes para realizar una espirometría aprovechando dicha situación para realizar el consejo antitabaco. Si padecían un proceso respiratorio agudo se retrasó la cita diez días tras resolución del cuadro. Se recogió: edad, sexo, edad de inicio de hábito tabáquico, índice tabáquico (IT), función pulmonar- espirometría. Resultados: N= 153. Edad media 49±13,59 años. 61,4% hombres. Edad media inicio del consumo de tabaco 18,18±5,95 (inferior en hombres sin diferencias signifi cativas). Índice tabáquico: mediana 25 (RI 36-15), con diferencias signifi cativas entre sexos (hombres 28 vs mujeres 23; z=-2,107 p<0,05). Los valores medios de los datos espirométricos fueron: CVF: 86,41 (DE 17,44); FEV1: 88,94 (DE 18,09); FEV1/CVF: 85,01 (DE 13,64); MEF25-75: 87,94 (DE 32,42). Existían diferencias signifi cativas entre sexos en los valores medios de CVF, FEV1 y MEF25-75. Un 39,1% tenía un FEV1/CVF < 80 y el 16,99% valores de MEF25-75 <60, sin diferencias por sexos en estos grupos. En hombres, el IT se correlaciona signifi cativamente con CVF (rho: -0,309; p<0,001), FEV1 (rho: -0,320; p<0,001) y MEF25-75 (rho: -0,211; p<0,05), no encontrándose correlaciones significativas entre estos parámetros y el IT en mujeres. Se creó un modelo de regresión lineal entre IT y FEV1 para cada sexo obteniéndose una B= -0,035 en mujeres y una B=-0.182 en varones. Conclusiones: En nuestra muestra, la afectación que produce el tabaco parece ser diferente entre hombres y mujeres, con mayor repercusión en los hombres. Sería necesario realizar nuevos estudios para contrastar estos resultados (AU)

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¿Cómo reparar el daño cerebral isquémico? Utilidad de los modelos experimentales en la búsqueda de respuestas / How to repair an ischemic brain injury? Value of experimental models in search of answers

El objetivo principal de los modelos experimentales de isquemia cerebral es el estudio del daño isquémico cerebral en condiciones fisiológicamente controladas y reproducibles. Los estudios realizados han sido esenciales para establecer nuevos conceptos sobre los mecanismos subyacentes al daño cerebral isquémico tales como la penumbra isquémica, el daño por reperfusión, los mecanismos de muerte celular o la importancia del daño sufrido por las mitocondrias, las células gliales y la sustancia blanca. Sin embargo, debido a la discrepancia entre los estudios experimentales y clínicos respecto a la eficacia de las terapias que tratan de aminorar o revertir el daño isquémico cerebral, existe una polémica creciente en torno a la utilidad clínica de los modelos experimentales de isquemia cerebral. Uno de los principales motivos del fracaso de las diversas estrategias terapéuticas ensayadas en el ámbito clínico es el enfoque teórico reduccionista de la mayoría de los ensayos farmacológicos, que analizan el efecto de una molécula con un mecanismo de acción conocido dentro de una ruta concreta de progresión del daño isquémico. Este abordaje contrasta con la complejidad estructural y funcional del tejido cerebral y la intricada fisiopatología de las alteraciones celulares y moleculares inducidas por la isquemia. Creemos que el objetivo fundamental de los estudios realizados en modelos experimentales de isquemia cerebral debe ser la obtención de conocimientos básicos acerca de los procesos patobiológicos subyacentes al daño isquémico y que los ensayos clínicos no deberían iniciarse con agentes terapéuticos cuyos beneficios hayan sido escasos o inconsistentes en los estudios experimentales (AU)

The major aim of experimental models of cerebral ischemia is to study the cerebral ischemic damage under controlled and reproducible conditions. Experimental studies have been fundamental in the establishment of new concepts regarding the mechanisms underlying the ischemic brain injury, such as the ischemic penumbra, the reperfusion injury, the cell death or the importance of the damage induced on mitochondria, glial cells and white matter. Disagreement between experimental and clinical studies regarding the benefit of drugs to reduce or restore the cerebral ischemic damage has created a growing controversy about the clinical value of the experimental models of cerebral ischemia. One of the major explanations for the failure of the clinical trials is the reductionist approach of most therapies, which are focused on the known effect of a single molecule within a specific pathway of ischemic damage. This philosophy contrasts to the complex morphological design of the cerebral tissue and the complex cellular and molecular physiopathology underlying the ischemic brain injury. We believe that the main objective of studies carried out in experimental models of cerebral ischemic injury must be a better understanding of the fundamental mechanisms underlying progression of the ischemic injury. Clinical trials should not be considered if the benefit obtained in experimental studies is limited or weak (AU)

How to repair an ischemic brain injury? Value of experimental models in search of answers.

The major aim of experimental models of cerebral ischemia is to study the cerebral ischemic damage under controlled and reproducible conditions. Experimental studies have been fundamental in the establishment of new concepts regarding the mechanisms underlying the ischemic brain injury, such as the ischemic penumbra, the reperfusion injury, the cell death or the importance of the damage induced on mitochondria, glial cells and white matter. Disagreement between experimental and clinical studies regarding the benefit of drugs to reduce or restore the cerebral ischemic damage has created a growing controversy about the clinical value of the experimental models of cerebral ischemia. One of the major explanations for the failure of the clinical trials is the reductionist approach of most therapies, which are focused on the known effect of a single molecule within a specific pathway of ischemic damage. This philosophy contrasts to the complex morphological design of the cerebral tissue and the complex cellular and molecular physiopathology underlying the ischemic brain injury. We believe that the main objective of studies carried out in experimental models of cerebral ischemic injury must be a better understanding of the fundamental mechanisms underlying progression of the ischemic injury. Clinical trials should not be considered if the benefit obtained in experimental studies is limited or weak.

[Experimental models of cerebral ischemia]. / Modelos experimentales de isquemia cerebral.

AIM: To provide a summary of the different experimental models of cerebral ischemia designed both under in vivo and in vitro conditions. A clear and concise description of the specific types of brain lesion reproduced by each model is given together with the most frequent technical troubles associated. DEVELOPMENT: Experimental models of cerebral ischemia have contributed substantially to the understanding of the physiopathology of the ischemic brain injury and to test the beneficial effects of new therapies. Outcome of patients suffering from an ischemic stroke has improved considerably with the use of these models, particularly after the introduction of thrombolytic and neuroprotective drugs. Experimental models allow the study of the evolving ischemic brain injury under strict and controlled conditions. Usefulness of experimental models is limited by their reliability, simplicity and reproducibility among different researchers. Small rodents, especially rats, have been the preferred animals used to develop models of cerebral ischemic injury, due to their cerebral physiology and vascularisation which is closer to the human. CONCLUSION: The use of experimental models of cerebral ischemia constitutes the most suitable tool to investigate the physiopathology of this type of injury. However their simplicity prevents an exact reproduction of the cerebral damage observed in clinical settings. This could be the main reason for the discrepancies observed between the therapeutic effect in the experimental and clinical studies.

Modelos experimentales de isquemia cerebral / Experimental models of cerebral ischemia

Objetivo. Revisar los modelos experimentales de isquemia cerebral utilizados en la investigación de la fisiopatología y la terapéutica de esta afección. Se expone de forma clara y sencilla tanto el tipo de lesión cerebral isquémica que cada modelo trata de reproducir como los detalles técnicos específicos para su realización práctica. Desarrollo. Los modelos experimentalesde isquemia cerebral han permitido estudiar la fisiopatología de esta enfermedad bajo condiciones controladas por el investigador y analizar los efectos de nuevas estrategias terapéuticas. El conocimiento adquirido con estos modelos ha mejorado el pronóstico de los pacientes que han sufrido un infarto cerebral isquémico tras la introducción de agentes trombolíticosy neuroprotectores. Para que un modelo sea valioso debe ser fiable y fácil de realizar y debe reflejar lo más fielmente posible las condiciones clínicas que trata de imitar. Debe ser reproducible y tener una baja variabilidad entre individuos (animales) y entre investigadores. Los roedores pequeños, particularmente las ratas, son los animales con los que se han desarrollado la mayoría de estos modelos por tener una fisiología y vascularización cerebral similares a la humana. Conclusión. Los modelos experimentales suponen actualmente la mejor herramienta para el estudio de los mecanismos subyacentes al daño cerebral isquémico, aunque su simplicidad impide reproducir de forma exacta la lesión cerebral observada en la práctica clínica. Ésta puede ser la causa de la discrepancia en la respuesta terapéutica observada entre los estudios experimentalesy los clínicosPST

Aim. To provide a summary of the different experimental models of cerebral ischemia designed both under in vivoand in vitro conditions. A clear and concise description of the specific types of brain lesion reproduced by each model is given together with the most frequent technical troubles associated. Development. Experimental models of cerebral ischemia have contributed substantially to the understanding of the physiopathology of the ischemic brain injury and to test the beneficial effects of new therapies. Outcome of patients suffering from an ischemic stroke has improved considerably with the use of these models, particularly after the introduction of thrombolytic and neuroprotective drugs. Experimental models allow thestudy of the evolving ischemic brain injury under strict and controlled conditions. Usefulness of experimental models is limited by their reliability, simplicity and reproducibility among different researchers. Small rodents, especially rats, have been the preferred animals used to develop models of cerebral ischemic injury, due to their cerebral physiology and vascularisation which is closer to the human. Conclusion. The use of experimental models of cerebral ischemia constitutes the most suitable tool to investigate the physiopathology of this type of injury. However their simplicity prevents an exact reproduction of the cerebral damage observed in clinical settings. This could be the main reason for the discrepancies observed between the therapeutic effect in the experimental and clinical studies

Endoscopia digestiva alta / No disponible

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Endoscopia digestiva alta / No disponible

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Microarray analysis of newly synthesized RNA in cells and animals.

Current methods to analyze gene expression measure steady-state levels of mRNA. To specifically analyze mRNA transcription, we have developed a technique that can be applied in vivo in intact cells and animals. Our method makes use of the cellular pyrimidine salvage pathway and is based on affinity-chromatographic isolation of thiolated mRNA. When combined with data on mRNA steady-state levels, this method is able to assess the relative contributions of mRNA synthesis and degradation/stabilization. It overcomes limitations associated with currently available methods such as mechanistic intervention that disrupts cellular physiology, or the inability to apply the techniques in vivo. Our method was first tested in serum response of cultured fibroblast cells and then applied to the study of renal ischemia reperfusion injury, demonstrating its applicability for whole organs in vivo. Combined with data on mRNA steady-state levels, this method provided a detailed analysis of regulatory mechanisms of mRNA expression and the relative contributions of RNA synthesis and turnover within distinct pathways, and identification of genes expressed at low abundance at the transcriptional level.

Réplica. Impulso bioeléctrico, cuantificaciones sinápticas y de circuitos cerebrales, origen de la vida y composición principal de las neuronas / Reply. Bioelectrical impulse, synaptic and brain circuit quantifications, the origins of life and the main composition of neurons

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Development of a citrus genome-wide EST collection and cDNA microarray as resources for genomic studies.

A functional genomics project has been initiated to approach the molecular characterization of the main biological and agronomical traits of citrus. As a key part of this project, a citrus EST collection has been generated from 25 cDNA libraries covering different tissues, developmental stages and stress conditions. The collection includes a total of 22,635 high-quality ESTs, grouped in 11,836 putative unigenes, which represent at least one third of the estimated number of genes in the citrus genome. Functional annotation of unigenes which have Arabidopsis orthologues (68% of all unigenes) revealed gene representation in every major functional category, suggesting that a genome-wide EST collection was obtained. A Citrus clementina Hort. ex Tan. cv. Clemenules genomic library, that will contribute to further characterization of relevant genes, has also been constructed. To initiate the analysis of citrus transcriptome, we have developed a cDNA microarray containing 12,672 probes corresponding to 6875 putative unigenes of the collection. Technical characterization of the microarray showed high intra- and inter-array reproducibility, as well as a good range of sensitivity. We have also validated gene expression data achieved with this microarray through an independent technique such as RNA gel blot analysis.

[Blood brain barrier: development of a structure which supports the functional heterogeneity of the central nervous system]. / La barrera hematoencefalica: desarrollo de una estructura que permite la heterogeneidad funcional del sistema nervioso central.

AIMS: To analyze the functional reasons justifying the existence of the blood brain barrier with an emphasis on its fundamental role supporting neuroglial coupling. DEVELOPMENT: We review in an integrated manner the contributions of different research areas in physiology and metabolism of the central nervous system which allow to understand the functional need for the existence of the blood brain barrier. In particular, we describe the physiological basis of the metabolic functional coupling and the metabolic interactions between neurons and glial cells, two properties directly derived from the presence of the blood brain barrier. Likewise the blood brain barrier is presented as an important determinant of the heterogeneous activation of cerebral tissue as detected by neuroimaging technologies as positron emission tomography and functional magnetic resonance imaging. CONCLUSIONS: The main function of the blood brain barrier is to maintain a stable composition of the extracellular milieu in nervous tissue. This allows the changes in ionic composition and neurotransmitter concentration in the extracellular milieu, to reflect indirectly the generation of action potentials and the state of neurotransmission of neuronal circuits. Glial cells induce the development of the blood brain barrier and are the main sensors of neuronal function, due to their important take up capacity for extracellular potassium and neurotransmitters. Glial homeostasis of the extracellular milieu is circuit specific, limiting the functional metabolic coupling to discrete regions of the brain and generating the classical pattern of heterogeneous activity in the different modules of the nervous tissue.

La barrera hematoencefálica: desarrollo de una estructura que permite la heterogeneidad funcional del sistema nervioso central / Blood-brain barrier: development of a structure which supports the functional heterogeneity of the central nervous system

Objetivo. Analizar las razones funcionales que justifican la existencia de la barrera hematoencefálica (BHE), con énfasis en su papel crucial como soporte de la unidad funcional neurona-glía.Desarrollo. Se revisan en detalle y de manera integrada las aportaciones de diversas áreas de investigación en fisiología y metabolismo del sistema nervioso central que permiten comprender la necesidad funcional de la existencia de la BHE. En especial, se describen las bases fisiológicas del acoplamiento metabólico-funcional en el tejido nervioso y las interacciones metabólicas entre las neuronas y las células gliales, dos propiedades derivadas directamente de la presencia de la BHE. Se presenta la barrera como un importante determinante de la activación heterogénea del tejido cerebral, detectable mediante tecnologías de neuroimagen funcional, como la tomografía de emisión de positrones y la imagen de resonancia magnética funcional. Conclusiones. La función principal de la BHE es mantener una composición estable del medio extracelular en el tejido nervioso. Esto permite que los cambios de composición iónica y de concentración de neurotransmisores del medio extracelular sean el reflejo indirecto de la generación de potenciales de acción y del estado de neurotransmisión de los circuitos neuronales. Las células gliales inducen el desarrollo de la barrera y son los principales sensores de la función neuronal, debido a su capacidad de recaptación del exceso extracelular de potasio y de neurotransmisores. La homeostasis glial del medio extracelular es específica de circuito, limita el acoplamiento metabólico-funcional a regiones discretas del cerebro y genera el patrón de actividad heterogénea en los diversos módulos del tejido nervioso (AU)

Aims. To analyze the functional reasons justifying the existence of the blood-brain barrier with an emphasis on its fundamental role supporting neuroglial coupling. Development. We review in an integrated manner the contributions of different research areas in physiology and metabolism of the central nervous system which allow to understand the functional need for the existence of the blood-brain barrier. In particular, we describe the physiological basis of the metabolic-functional coupling and the metabolic interactions between neurons and glial cells, two properties directly derived from the presence of the blood-brain barrier. Likewise the blood-brain barrier is presented as an important determinant of the heterogeneous activation of cerebral tissue as detected by neuroimaging technologies as positron emission tomography and functional magnetic resonance imaging. Conclusions. The main function of the blood-brain barrier is to maintain a stable composition of the extracellular milieu in nervous tissue. This allows the changes in ionic composition and neurotransmitter concentration in the extracellular milieu, to reflect indirectly the generation of action potentials and the state of neurotransmission of neuronal circuits. Glial cells induce the development of the blood-brain barrier and are the main sensors of neuronal function, due to their important take up capacity for extracellular potassium and neurotransmitters. Glial homeostasis of the extracellular milieu is circuit-specific, limiting the functional-metabolic coupling to discrete regions of the brain and generating the classical pattern of heterogeneous activity in the different modules of the nervous tissue (AU)

Cytogenetic characterization of two colon cell lines by using conventional G-banding, comparative genomic hybridization, and whole chromosome painting.

The heterogeneous nature of genetic alterations in cancer cells handicaps the full characterization of its occurrence and the analysis of their molecular bases and relation to biological processes. Although many cancer cells are highly aneuploid, in other cases, as in a subset of colorectal carcinomas displaying microsatellite instability, chromosomal aberrations are scarce. The aim of this study was to fully characterize both qualitatively and quantitatively, the karyotypes of two established colon carcinoma cell lines (LoVo and HCT 116) previously reported as being near diploid. An array of complementary cytogenetic techniques were used: G-banding, comparative genome hybridization (CGH), and whole-chromosome painting (WCP). Combinations of these techniques provided an accurate karyotype for the two cell lines: LoVo cells showed 49,XY,t(2;12)(q13;p11.2),+5,+7,+12,i(15)(q10) and HCT 116 cells showed 45,X,-Y,dup(10)(q24q26),der(16)t(8;16)(q13;p13), der(18)t(17;18)(q21;p11.3). Heterogeneity was also observed in both cell lines as shown by G-banding. Chromosomal unbalances determined by CGH (many of them related to structural reorganizations) were characterized by WCP, allowing the reliable identification of those chromosome markers that could not be completely identified by G-banding. We show that combined analysis with classical and molecular cytogenetic techniques provides an accurate map of chromosomal aberrations in these two cell lines not identified in previous investigations.

Prospective assessment of allelic losses at 4p14-16 in colorectal cancer: two mutational patterns and a locus associated with poorer survival.

Previous studies have shown that allelic losses in a locus mapping to the chromosomal region 4p14-16 are indicative of poor prognosis in colorectal cancer. To further characterize the region involved and to confirm earlier observations, we have analyzed losses of heterozygosity (LOH) in nine microsatellite markers spanning this region in a prospective series of 181 colorectal carcinomas. The extent and the nature of the allelic imbalance were also ascertained by comparative genomic hybridization analysis of selected cases. The minimum common deleted region was confined to marker D4S2397 (LOH in 35% of the informative cases). Surrounding markers displayed LOH in 13-25% of informative cases and (other than the D4S2397 marker itself) showed a higher rate of allelic imbalances in association with mutations in the p53 tumor suppressor gene. Tumors with lymph node invasion also displayed increased rates of LOH in most markers. Regarding patient outcome, LOH solely at the D4S2397 locus was indicative of a shorter disease-free survival (P = 0.027). In consequence, two patterns of allelic loss are defined within the 4p14-16 region: (a) gross losses associated with tumor progression and probably attributable to the genomic instability related to the inactivation of the p53 tumor suppressor gene; and (b) specific losses limited to the D4S2397 locus (within an estimated fragment of 2 Mb) and associated with increased tumor aggressiveness. The presence of one or more putative tumor suppressor genes in this region is postulated.

The DNA binding-independent function of the glucocorticoid receptor mediates repression of AP-1-dependent genes in skin.

The glucocorticoid receptor (GR) mediates the biological effects of glucocorticoids (GCs) through activation or repression of gene expression, either by DNA binding or via interaction with other transcription factors, such as AP-1. Work in tissue culture cells on the regulation of AP-1-dependent genes, such as collagenase (MMP-13) and stromelysin (MMP-3) has suggested that the antitumor and antiinflammatory activity of GCs is mediated, at least in part, by GR-mediated downmodulation of AP-1. Here, we have identified phorbol ester-induced expression of MMP-3 and MMP-13 in mouse skin as the first example of an in vivo system to measure negative interference between AP-1 and GR in the animal. Cell type-specific induction of these genes by tumor promoters is abolished by GCs. Importantly, this is also the case in GR(dim) mice expressing a DNA binding-defective mutant version of GR. In contrast, the newly identified target genes in skin, plasma glutathione peroxidase and HSP-27, were induced by GC in wild-type, but not in GR(dim) mice. Thus, these data suggest that the DNA binding-independent function of the GR is dispensable for repression of AP-1 activity in vivo and responsible for the antitumor promoting activity of GCs.

p53 and K-ras gene mutations correlate with tumor aggressiveness but are not of routine prognostic value in colorectal cancer.

PURPOSE: p53 gene and K-ras mutations are among the most common genetic alterations present in colorectal cancer. The prognostic utility of such mutations remains controversial. The purpose of this study was to prospectively evaluate the prognostic significance of p53 and K-ras gene mutations in colorectal cancer. PATIENTS AND METHODS: One hundred forty patients were analyzed. Tumors belonging to the microsatellite mutator phenotype were excluded (n = 8). Mutations at the K-ras and p53 genes were detected and characterized by restriction fragment length polymorphism, single-strand conformation polymorphism, and sequencing, as appropriate. RESULTS: p53 mutations were detected in 66 (50%) and K-ras mutations were detected in 54 (41%) of the 132 patients. In 26 cases (20%), ras and p53 mutations coexisted; in 38 cases (29%), neither mutation was found. Multivariate analysis of the whole population analyzed (n = 132) showed that survival was strongly correlated with the presence of p53 mutations alone or in combination with K-ras mutations (P = .002; log-rank test). When only patients undergoing a radical resection were considered (R0; n = 101), p53 mutations were no longer of prognostic significance. CONCLUSION: p53 mutations alone or in combination with K-ras mutations are correlated with a worse outcome. However, the routine use of these mutations as prognostic markers in the clinical setting is not recommended.