Value of the First Post-Transplant Biopsy for Predicting Long-Term Cardiac Allograft Vasculopathy (CAV) and Graft Failure in Heart Transplant Patients

BACKGROUND: Cardiac allograft vasculopathy (CAV) is the principal cause of long-term graft failure following heart transplantation. Early identification of patients at risk of CAV is essential to target invasive follow-up procedures more effectively and to establish appropriate therapies. We evaluated the prognostic value of the first heart biopsy (median: 9 days post-transplant) versus all biopsies obtained within the first three months for the prediction of CAV and graft failure due to CAV. METHODS AND FINDINGS: In a prospective cohort study, we developed multivariate regression models evaluating markers of atherothrombosis (fibrin, antithrombin and tissue plasminogen activator [tPA]) and endothelial activation (intercellular adhesion molecule-1) in serial biopsies obtained during the first three months post-transplantation from 172 patients (median follow-up = 6.3 years; min = 0.37 years, max = 16.3 years). Presence of fibrin was the dominant predictor in first-biopsy models (Odds Ratio [OR] for one- and 10-year graft failure due to CAV = 38.70, p = 0.002, 95% CI = 4.00-374.77; and 3.99, p = 0.005, 95% CI = 1.53-10.40) and loss of tPA was predominant in three-month models (OR for one- and 10-year graft failure due to CAV = 1.81, p = 0.025, 95% CI = 1.08-3.03; and 1.31, p = 0.001, 95% CI = 1.12-1.55). First-biopsy and three-month models had similar predictive and discriminative accuracy and were comparable in their capacities to correctly classify patient outcomes, with the exception of 10-year graft failure due to CAV in which the three-month model was more predictive. Both models had particularly high negative predictive values (e.g., First-biopsy vs. three-month models: 99% vs. 100% at 1-year and 96% vs. 95% at 10-years). CONCLUSIONS: Patients with absence of fibrin in the first biopsy and persistence of normal tPA in subsequent biopsies rarely develop CAV or graft failure during the next 10 years and potentially could be monitored less invasively. Presence of early risk markers in the transplanted heart may be secondary to ischemia/reperfusion injury, a potentially modifiable factor

Resolución de problemas científicos escolares y promoción de competencias de pensamiento científico. ¿Qué piensan los docentes de química en ejercicio?

In the article the results of an investigation conducted within the framework of the project FONDECYT 1070795 are exposed. The aims of the research were to identify and characterize the representations and knowledge that teachers in service have, from an average level of education, with respect to the competences of scientific thought and problem solution, and the way in which both should be approached. With the use of an intentional sample of 133, teachers selected from a total of 117 who were incorporated to other phases of the research trough the administration of a questionnaire especially designed, was show the predominance of a very fragmented image, sometimes contradictory, about the solution of problems and about relation between competences of scientific thought; this representation incorporates aspects of great value for the formation of the competent students, and at the same time it includes other aspects that in no way favor this formation, according to the present assessments. It is remarkable that both competences for scientific thought and solution of problems are not constituted as a totality and coherent system in the thinking of the teachers who participated in the research. It should be pointed out that we found data that show an oscillating valuation of the subjective character of the problematic situations and the problem itself; these data show, as well, that teachers give a very important role to language. It is stated that teachers give an oscillating value to the fact that students must deal with theories. It should be noted too that their approaches to the algorithmic processes are very vague, and sometimes contradictory.En el artículo se exponen los resultados de una investigación realizada en el marco del proyecto FONDECYT 1070795, cuyo objetivo consistió en identificar y caracterizar las nociones que tienen los profesores de nivel medio respecto a las competencias de pensamiento científico y solución de problemas, y la manera en que ambos deben trabajarse en la enseñanza de la química. Con el empleo de una muestra intencional de 33 profesores, seleccionados de un total de 117 que se incorporaron a otras fases de la investigación y mediante la administración de un cuestionario especialmente diseñado, se logró poner de manifiesto que en ellos predomina una imagen fragmentada y a veces contradictoria de la solución de problemas y de las competencias de pensamiento científico; dicha representación incorpora aspectos de inestimable valor para la formación del estudiante competente, a la vez que incluye otros que en manera alguna favorecen dicha formación en correspondencia con las exigencias actuales. Es notable que competencias de pensamiento científico y solución de problemas no se constituyan como sistema totalmente coherente en la conceptualización de los profesores investigados. Como dato relevante, se constató la oscilante valoración del carácter subjetivo de las situaciones problémicas y los problemas; junto al papel importante que, en opinión de gran parte de los profesores, desempeña el lenguaje, se le otorga un valor oscilante al trabajo con la teoría por parte de los estudiantes; igualmente resulta difusa, y a veces contradictoria, su aproximación a los procesos de algoritmización

Resolución de problemas científicos escolares y promoción de competencias de pensamiento científico. ¿Qué piensan los docentes de química en ejercicio?

En el artículo se exponen los resultados de una investigación realizada en el marco del proyecto FONDECYT 1070795, cuyo objetivo consistió en identificar y caracterizar las nociones que tienen los profesores de nivel medio respecto a las competencias de pensamiento científico y solución de problemas, y la manera en que ambos deben trabajarse en la enseñanza de la química. Con el empleo de una muestra intencional de 33 profesores, seleccionados de un total de 117 que se incorporaron a otras fases de la investigación y mediante la administración de un cuestionario especialmente diseñado, se logró poner de manifiesto que en ellos predomina una imagen fragmentada y a veces contradictoria de la solución de problemas y de las competencias de pensamiento científico; dicha representación incorpora aspectos de inestimable valor para la formación del estudiante competente, a la vez que incluye otros que en manera alguna favorecen dicha formación en correspondencia con las exigencias actuales. Es notable que competencias de pensamiento científico y solución de problemas no se constituyan como sistema totalmente coherente en la conceptualización de los profesores investigados. Como dato relevante, se constató la oscilante valoración del carácter subjetivo de las situaciones problémicas y los problemas; junto al papel importante que, en opinión de gran parte de los profesores, desempeña el lenguaje, se le otorga un valor oscilante al trabajo con la teoría por parte de los estudiantes; igualmente resulta difusa, y a veces contradictoria, su aproximación a los procesos de algoritmización.In the article the results of an investigation conducted within the framework of the project FONDECYT 1070795 are exposed. The aims of the research were to identify and characterize the representations and knowledge that teachers in service have, from an average level of education, with respect to the competences of scientific thought and problem solution, and the way in which both should be approached. With the use of an intentional sample of 133, teachers selected from a total of 117 who were incorporated to other phases of the research trough the administration of a questionnaire especially designed, was show the predominance of a very fragmented image, sometimes contradictory, about the solution of problems and about relation between competences of scientific thought; this representation incorporates aspects of great value for the formation of the competent students, and at the same time it includes other aspects that in no way favor this formation, according to the present assessments. It is remarkable that both competences for scientific thought and solution of problems are not constituted as a totality and coherent system in the thinking of the teachers who participated in the research. It should be pointed out that we found data that show an oscillating valuation of the subjective character of the problematic situations and the problem itself; these data show, as well, that teachers give a very important role to language. It is stated that teachers give an oscillating value to the fact that students must deal with theories. It should be noted too that their approaches to the algorithmic processes are very vague, and sometimes contradictory

LacSwitch® II Regulation of Connexin43 cDNA Expression Enables Gap-Junction Single-Channel Analysis

Metabolic and electrical coupling through gap junction channels is implicated in cell differentiation, tissue homeostasis, and electrotonic propagation of signals in excitable tissues. The characterization of gating properties of these channels requires electrophysiological recordings at both single- and multiple-channel levels. Hence, a system that is able to control connexin expression by external means would provide a useful tool. To regulate the expression of connexins in cells, plasmids encoding a transactivator and/or a lac-operon IPTG response-dependent Cx43 target gene were transfected into communication-deficient N2a neuroblastoma cells. Immunoblotting, dye coupling, and electrophysiological methods revealed that expression of Cx43 in selected clones could be tightly regulated. After 15–20 h of acute induction with IPTG, cell-to-cell communication reached its peak with junctional conductances of 15–30 nS. Chronic induction at specific doses of IPTG produced constant, controlled levels of Cx43 expression, which were reflected by predictable junctional coupling levels. These conditions allowed prolonged recordings from either lowly or highly coupled cells, making lac operon an ideal regulatory system for channel gating studies at a single-channel level

Secuencia de enseñanza y promoción de competencias de pensamiento científico en la Enseñanza del metabolismo en tres profesoras de Biología

Con el propósito de identificar la visión epistemológica sobre la enseñanza de la noción científica de metabolismo, se diseñó un taller de reflexión docente que permitió recoger información sobre las decisiones teórico didácticas de tres profesoras de biología. Para ello, se utilizó como dispositivo de análisis para las profesoras seis fichas de actividades diseñadas por el grupo de investigación. Finalmente se analizan las producciones docentes que nos llevan a decir que las docentes manifiestan una noción de competencia a nivel conceptual. Las producciones docentes están muy condicionadas por la propuesta ministerial; se insiste en el tratamiento del contenido desde el plano instrumental y memorístico, aspectos que dificultan la enseñanza para la promoción de ciertas competencia de pensamiento científico

Defects in Regulation of Local Immune Responses Resulting in Atherosclerosis

Atherosclerosis is nowadays generally accepted as an inflammatory disease but the mechanism of its origin and development have not yet been fully clarified. The present review focuses on the role of the local immune system as one of the key players in the pathogenesis of the complex process. Its part represented by vascular-associated lymphoid tissue (VALT) within the arterial wall participates directly in the vascular wall's homeostatis. Its inordinate activation during ontogenic development of an individual, this formerly defensive and physiologic mechanism transform into a pathological process resulting in an impairing inflammation. Hsp60, CRP and oxidized or otherwise modified LDL are serious candidates for triggering these pathological changes. The principal role is played by anti-Hsp60 antibodies and by shear stress originating on the surface of endothelium due to blood flow. The experimental and clinical data supporting this immunological hypothesis of atherosclerosis are discussed