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PURPOSE: Brain metastases (BM) occur in 15-35% of patients with metastatic breast cancer, conferring poor prognosis and impairing quality of life. Clinical scores have been developed to classify patients according to their prognosis. We aimed to check the utility of the Breast Graded Prognostic Assessment (B-GPA) and its modified version (mB-GPA) and compare them in routine clinical practice. METHODS: This is an ambispective study including all patients with breast cancer BM treated in a single cancer comprehensive center. We analyzed the overall survival (OS) from BM diagnosis until death. The Kaplan-Meier method and Cox proportional hazard regression model were used in the analyses. ROC curves were performed to compare both scores. RESULTS: We included 169 patients; median age was 50 years. HER2-positive and triple negative patients were 33.7% and 20.7%, respectively. At the last follow-up, 90% of the patients had died. Median OS was 12 months (95% confidence interval 8.0-16.0 months). OS was worse in patients with > 3 BM and in patients with triple negative subtype. CONCLUSIONS: In our series, we confirm that B-GPA and mB-GPA scores correlated with prognosis. ROC curves showed that B-GPA and mB-GPA have similar prognostic capabilities, slightly in favor of mB-GPA.

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OBJECTIVE: To explore whether the IFNL3/4 rs12979860 genotype may influence serum levels or production of interferon-inducible protein-10 (IP-10) by peripheral blood mononuclear cells from patients with systemic lupus erythematosus (SLE). METHODS: Sixty-six patients with SLE and 22 healthy blood donors (controls) were included. The IFNL3/4 rs12979860 polymorphism was genotyped by real-time polymerase chain reaction. IP-10 levels in sera supernatants of IFNα stimulated peripheral blood mononuclear cells were measured by enzime-linked immunosorbent assay. RESULTS: Allelic frequencies were CC (29%), CT (52%) and TT (20%) in SLE, and CC (32%), CT (41%) and TT (27%) in healthy controls. Median serum IP-10 levels were higher in SLE patients than in controls (190.8 versus 118.1 pg/ml; p < 0.001), particularly in those with high disease activity (278.5 versus 177.2 pg/ml; p = 0.037). However, serum IP-10 levels were not influenced by IFNL3/4 genotypes. Higher IP-10 production by peripheral blood mononuclear cells was found in both SLE patients (median 519.3 versus 207.6 pg/ml; p = 0.012) and controls (median 454.0 versus 201.7 pg/ml; p = 0.034) carrying the IFNL3/4 C allele compared with carriers of the T allele. CONCLUSIONS: Although IFNL3/4 rs12979860 allele C does not appear to influence serum IP-10 levels in SLE, it plays an important role in the production of IP-10 by peripheral blood mononuclear cells after IFNα stimulation.

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OBJECTIVE: The study aims to investigate the ovarian reserve in premenopausal women with antiphospholipid syndrome (APS) and to evaluate whether it is associated with cumulative organ damage or the risk of clinical complications. METHODS: This single-center study was conducted in 23 premenopausal female patients (10 with primary APS and 13 with secondary APS) and 24 healthy volunteers. Serum anti-Müllerian hormone (AMH) levels were measured by enzyme-linked immunoassay. Disease-specific organ damage (DIAPS score) and the risk of clinical complications (aGAPSS score) were additionally evaluated in APS patients. RESULTS: Serum AMH levels were similar in APS patients (median 6.06, interquartile range 4.31-7.54 ng/ml) and in controls (4.87, 2.64-6.40 ng/ml; P = 0.116), and no differences were observed between the primary (6.60, 5.49-8.88 ng/ml) and secondary (6.06, 3.91-7.30 ng/ml; P = 0.532) forms of the syndrome. In individuals with APS, serum AMH levels correlated inversely with the aGAPSS score (rho-0.421, 95% confidence intervals -0.716 to -0.001; P = 0.045), while no associations were observed with the DIAPS score (rho-0.001, -0.423 to 0.422; P = 0.996). CONCLUSIONS: Ovarian reserve is not reduced in premenopausal women with APS. In addition, serum AMH levels may reflect the risk of APS-related clinical complications but not the burden of disease-specific organ damage.

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OBJECTIVE: The objective was to assess the proportion of Th1, Th2 and Th17 phenotypes in senescent CD4+CD28null cells from patients with systemic lupus erythematosus (SLE) and its association with the pattern of joint involvement. METHODS: This cross-sectional study was performed in SLE patients with erosive arthritis (rhupus) or nondeforming, nonerosive arthritis. Total CD4+CD28null cells as well as the proportion of these cells expressing T-bet, GATA3 or RORγt were analyzed by color-flow cytometry. Serum osteopontin levels were measured by ELISA. RESULTS: Eighteen SLE patients (nine with rhupus and nine with nonerosive arthritis) were studied. The percentage of CD4+CD28null/CD4+ cells (17.7%, 10.3-25.0% versus 9.4%, 8.1-22.4%; P = 0.386) as well as the osteopontin levels (5800, 5,134-5995 pg/ml versus 5578, 5171-5717 pg/ml; P > 0.05) were similar in both groups. A higher percentage of CD4+CD28nullT-bet+ cells (42.8%, 33.5-53.4% versus 30.0%, 23.3-34.2%) but a lower percentage of CD4+CD28nullGATA3+ cells (3.1%, 1.7-5.6% versus 6.2%, 2.6-18.4%) was observed in patients with rhupus than in their counterparts ( P = 0.016). The frequency of CD4+CD28nullRORγt+ cells was similar between groups. CONCLUSIONS: In patients with rhupus, senescent CD4+CD28null cells are preferentially polarized to a Th1 phenotype, whereas this is partial towards Th2 in lupus patients with a nonerosive arthritis pattern.

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RESUMEN Introducción: El comportamiento caótico de la dinámica cardiaca normal y aguda ha sido caracterizado en el contexto de la teoría de los sistemas dinámicos y la geometría fractal. Objetivo: Desarrollar una nueva metodología diagnóstica para la evaluación de la dinámica cardiaca en pacientes de UCI, durante 16 horas. Metodología: Este es un estudio en pacientes ingresados a Cuidados Intensivos posquirúrgicos (UCI) y sujetos sanos, tomando un total de 47 registros electrocardiográficos continuos y/o Holter, normales y con patología aguda, evaluados en 16 horas. Se desarrolló una inducción con dos dinámicas normales y tres de UCI; a partir de los valores máximos y mínimos de la frecuencia cardiaca/hora y total de latidos/hora, registrados durante 16 horas se construyeron atractores para evaluar sus espacios de ocupación y dimensión fractal, con el fin de establecer diferencias e igualdades respecto a estados normales y patológicos. Se realizaron medidas de sensibilidad y especificidad con las dinámicas restantes para comparar el diagnostico matemático con el diagnóstico clínico. Resultados: Los espacios de ocupación de los atractores cardiacos diferencian dinámicas cardiacas normales de dinámicas con enfermedad crónica y aguda, detectando además dinámicas patológicas con valores superiores a los límites de normalidad, logrando valores de sensibilidad de 0,937 y especificidad del 1. Conclusión: se estableció una nueva metodología de evaluación de la dinámica cardiaca de utilidad para el seguimiento clínico en pacientes de UCI.

ABSTRACT Introduction: The chaotic behavior of normal and acute cardiac dynamics has been characterized in the context of theory of dynamical systems and fractal geometry. Objective: to establish a new diagnostic method for assessing cardiac dynamics in ICU patients, for 16 hours. Methodology: This is a study in post-surgical patients admitted to intensive care (ICU) and in healthy subjects, taking a total of 47 continuous electrocardiographic recordings and/ or Holter, normal and acute pathology, evaluated in 16 hours. Induction with two normal and three UCI dynamics was developed; from the maximum and minimum values of the heart/time and total frequency of beats/minute for 16 hours recorded attractors they were constructed to assess their areas of occupation and fractal dimension, in order to establish differences and equalities regarding normal states and pathological. Sensitivity and specificity measurements were performed with the remaining dynamic to compare mathematical diagnosis with clinical diagnosis. Results: Space occupancy heart attractors differ dynamic normal cardiac dynamics with chronic and acute illness, in addition detecting dynamic pathological with above normal limits values, achieving sensitivity values of 0.937 and specificity of 1. Conclusion: a new methodology for evaluating cardiac dynamics useful for clinical monitoring in ICU patients was established.

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Introducción: La teoría de sistemas dinámicos establece medidas cuantitativas de evolución de los sistemas mediante la construcción de atractores. Medidas de ocupación espacial de atractores cardiacos en el espacio fractal de Box Counting diferenciaron normalidad y enfermedad crónica de enfermedad aguda. Objetivo: Aplicar la metodología desarrollada para evaluar matemáticamente el estado cardiaco de Holter con diferentes patologías, confirmando la aplicabilidad de esta metodología para la detección de dinámicas agudas mediante medidas de concordancia estadística respecto al Gold Standard. Metodología: Se analizaron 170 Holter, incluyendo normales, crónicos y en estado agudo. Se construyeron simulaciones de la totalidad de la dinámica basada en número de latidos y frecuencia mínima y máxima cada hora durante 21 horas, para construir atractores en el espacio de fases. Se calculó la dimensión fractal de los atractores evaluando su ocupación espacial en el espacio de Box Counting, estableciendo cuáles corresponden a normalidad y enfermedad aguda de acuerdo con resultados matemáticos previos. Se comparó el diagnóstico matemático con el diagnóstico convencional del Holter, tomado como Gold Standard, estableciendo valores de sensibilidad, especificidad y coeficiente Kappa. Resultados: La dimensión fractal no logró evidenciar diferencias cuantitativas mientras que la metodología detectó en todos los casos dinámicas normales y en estado agudo independientemente de la patología, logrando valores de sensibilidad, especificidad, valor predictivo positivo y negativo de 100%, y coeficiente Kappa de 1. Conclusiones: Se confirmó la capacidad de la metodología físico-matemática para detectar dinámicas agudas independientemente de la patología asociada, confirmando una auto-organización acausal de la dinámica del sistema cuya evaluación permite establecer medidas de aplicabilidad clínica.

Introduction: Dynamic systems theory provides quantitative measures of evolution of systems by building attractors. Spatial occupation measures of cardiac attractors in fractal Box Counting space differentiated normality and chronic disease from acute illness. Objective: To apply the developed methodology to evaluate mathematically the cardiac status of Holter with different pathologies, confirming the applicability of this methodology for the detection of acute dynamic by statistical measures of agreement regarding the Gold Standard. Methodology: 170 Holter, including normal, chronic and in acute states were evaluated. Simulations were constructed the entire dynamic based on the number of beats and the minimum and maximum frequencies every hour for 21 hours, to build attractors in the phase space. The fractal dimension of attractors is calculated, evaluating the spatial occupation in the Box Counting space, establishing which corresponds to normal setting and acute disease in accordance with previous mathematical results. Mathematical diagnosis was compared with conventional diagnostic Holter, taken as the Gold Standard, setting sensitivity, specificity, positive and negative predictive value and Kappa coefficient. Results: The fractal dimension failed to show quantitative differences while the methodology detected in all cases normal dynamics and acute state independently of the disease, achieving sensitivity, specificity, positive and negative predictive value of 100% and a Kappa 1. Conclusions: the ability of the physical-mathematical methodology to detect acute dynamic regardless of the associated pathology was confirmed, as well as an acausal self-organization of the system dynamics, which allows for assessment of clinical applicability measures.

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In this paper we study the validity of the total power fluctuation theorem spent on a Brownian harmonic oscillator when the system is driven out of equilibrium through the drag of the potential minimum. The theorem is first proved for an ordinary harmonic oscillator in two cases: The first one considers the particle in a thermal bath under the action of Gaussian white noise, and in the second one the drift is provided by an additional external Gaussian colored noise satisfying the characteristics of an Ornstein-Uhlenbeck process. We go further, by considering a charged harmonic oscillator under the action of an electromagnetic field. The theorem is also proven as in the two cases given above. In both of those cases, we illustrate the theorem for a uniform motion of the trap potential minimum and show that in the presence of external colored noise, the theorem is only valid in the stationary state.

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El propósito de este ensayo es describir como se concibe a la persona desde la mirada de la corriente antropológica del personalismo que posibilite comprender su anclaje en el cuidado de enfermería en situaciones de cronicidad. Para ello, el grupo de investigación Bienestar y Cronicidad de la Escuela Nacional de Enfermería y Obstetricia rescata el concepto persona y plantea la exigencia de superar el egoísmo individualista, el determinismo positivista y el totalitarismo muy común en los servicios de salud para asumir una actitud crítica frente a las situaciones sociales y políticas actuales que perturban valores esenciales como la dignidad o la relación interpersonal. De la misma forma, con el desarrollo tecnológico actual, la globalización y la modificación de valores, se considera a la persona un objeto más del engranaje social lo que hace compleja la práctica del cuidado y la investigación de enfermería. Lo interesante de considerar a la persona desde la corriente del personalismo es ver cómo desde Santo Tomas de Aquino hasta finales del siglo XX, su abordaje se centra en el valor intrínseco de la persona humana para que las enfermeras la consideren desde esta perspectiva máxime si sufre una enfermedad crónica. El trabajo está elaborado en tres partes. La introducción que precisa algunos aspectos de contexto; una segunda parte donde se revisa las posturas de varios filósofos adscritos al personalismo que ofrecen su concepto de persona y se concluye cómo en una relación de cuidado, la persona es lo más importante siempre y cuando se atienda su naturaleza humana, espiritual, libre, capaz de construir su universo; por ello también es una invitación a renovar o en el mejor de los casos, a reflexionar en el concepto persona en el actual desarrollo de la investigación en enfermería.

The purpose of this essay is to describe as conceived the person from the point of view of current anthropological of personalism enabling understand its anchorage in nursing care in chronic situations. Therefore, the Chronicity and Welfare Research Group of the Escuela Nacional de Enfermería y Obstetricia rescues the concept person and raises the need to overcome selfishness individualistic, positivist determinism and totalitarianism common in health services to take a critical attitude address the current social and political situations that disrupt essential values such as dignity or interpersonal relationships. Moreover, current technological development, globalization and the changing values, the person is considered an object more than the gear making complex social care practice and nursing research. Interesting thing about to consider the person from the current of personalism is see from St. Thomas Aquinas until twentieth century, his approach focuses on the intrinsic value of the human person for nurses to consider in this perspective more so if it has a chronic disease. The work is produced in three parts. A brief introduction which attempts to clarify some aspects of context, a second part where is reviewed the positions of several philosophers about the concept person and concludes that in a relationship of care, the person is most importantly provided be heeded their nature human, spiritual, free, able to build his universe; this is also an invitation to renew or in the best of cases, to reflect the concept of person in the current development of nurse's investigation.

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Objective: To know the frequency of environmental mycobacterium isolations in Chile in the year 2008. Methods: 600 AFB (acid fast bacilli) positive cultures from 22 laboratories of Tuberculosis Bacteriology of the different Network Health Services that constitute the Tuberculosis Control Program of the country were studied, during four months at 2008. 545 (90.8 percent) were pulmonary and 55 (9.2 percent) extra pulmonary. Acid fast bacilli smears were confirmed by Ziehl Neelsen and identification of mycobacteria species or complex were identified by traditional tests according to Runyon classification and biochemical tests, genetic probes and pattern analysis restriction (PRA). Results: 585 cultures were appropriated for inclusion in the study. In 91.3 percent (n = 534) of the cases Mycobacterium tuberculosis was isolated while 0.3 percent was Mycobacterium bovis subspecie BCG (n = 3) and 8.4 percent (n = 48) corresponded to environmental mycobacterium. Of the latter, Mycobacterium kansasii (2.6 percent), Mycobacterium avium-intracellulare (1.5 percent) and Mycobacterium chelonae (1.0 percent) were the most commonly isolated. Conclusion: According to the figures of this study and comparing them with studies of previous years (1988 and 1998) it is concluded that the number of environmental mycobacterium isolated has been relatively constant during the last decade, as well as the species, more commonly isolated.

Objetivos: Conocer la frecuencia de aislamientos de micobacterias ambientales en Chile en el año 2008. Material y Métodos: Se recibieron 600 cultivos desde 22 laboratorios de Bacteriología de la Tuberculosis de los distintos Servicios de Salud de la red que comprende el Programa de Control de la Tuberculosis del país, durante un período de cuatro meses del año 2008. Quinientos cuarenta y cinco (90,8 por ciento) correspondieron a localización pulmonar y 55 (9,2 por ciento) a extrapulmonar. Se confirmó la alcohol-ácido resistencia por tinción de Ziehl Neelsen y para la identificación de especies o complejos micobacterianos se utilizaron pruebas tradicionales y bioquímicas de acuerdo al criterio de clasificación de Runyon, sondas genéticas y análisis de patrones de restricción (PRA). Resultados: De los 600 cultivos recibidos, 585fueron aptos para ser incluidos en el estudio. De éstos, en el 91,3 por ciento (n = 534) de los casos se aisló Mycobacterium tuberculosis, en un 0,3 por ciento Mycobacterium bovis subespecie BCG (n = 3) y un 8,4 por ciento (n = 48) correspondió a micobacterias ambientales. De estas últimas, Mycobacterium kansasii (2,6 por ciento), Mycobacterium avium-intracellulare (1,5 por ciento) y Mycobacterium chelonae (1,0 por ciento) fueron las más comúnmente aisladas. Conclusiones: De acuerdo a las cifras obtenidas en este estudio y comparadas con estudios de años anteriores (1988 y 1998) se concluye que el número de aislamientos de micobacterias ambientales permaneció relativamente constante esta última década, como también las especies más comúnmente aisladas.

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OBJECTIVE: To assess the impact of different doses of anti-interferon gamma (anti-IFNγ) F(ab')2 fragments, administered prophylactically, on survival and on serum concentration of cytokines in a murine model of sepsis induced by cecal ligation and puncture (CLP). We further explore the impact of therapeutic administration of the most protective dose on survival. SUBJECTS AND TREATMENT: Balb/c mice were prophylactically treated by the intraperitoneal route with anti-IFNγ initiated 2 h before CLP and every 24 h for a total of five times in each of the following doses: 0.01, 0.1, or 1 mg/kg. Sham and control groups received sterile saline solution in a similar scheme. METHODS: Serum tumor necrosis factor (TNF), interleukin (IL)-1ß, IL-6, IL-10 and IFNγ were measured at 3, 24 and 48 h after CLP by ELISA. Survival curves were compared using a Mantel-Haenzel method. RESULTS: Significant prophylactic protection was found only with 0.01 mg/kg, in association with regulation of IL-1ß and IL-10 concentrations. As therapy, anti-IFNγ fragments were protective only when initiated 24 h after CLP. CONCLUSIONS: Delicate modulation of IFNγ at the correct timing, even when the septic process has begun, is an exciting alternative to explore in the treatment of sepsis.

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