[Bayesian tragedy, from clinical iatrogenesis to biotechnology]. / La tragedia bayesiana desde la iatrogenia clínica hasta la biotecnología.

Diagnostic algorithms, as well as the biotechnological design, require the calculation of conditional probability, given the presence of certain positive data, in the context of prevalence, sensitivity and specificity; It is necessary to estimate the probability that the patient has a certain disease. Sometimes, with a test of scrutiny, it goes from a probability of 1/1000 to 1/20, constituting a great diagnostic advance, reducing the uncertainty spectacularly; However, the tragedy is that most doctors believe that the probability changed from 0.1% (1/1000) to more than 90%, which is outrageously wrong. Iatrogeny arises from the error in answering the question: "given that the test is positive, what is the probability that the patient has the disease?" In other cases, tragedy is to apply a test to an individual belonging to a subpopulation for which it was not designed. In addition, it is evident that the fascination for the sensitivity avoids the application of less sensitive methods in populations that are abandoned; It is not a matter of making better tests than those that the State does to the patients it attends, but of making less accurate tests for the patients that the State does not attend.

Los algoritmos diagnósticos así como el diseño biotecnológico, requieren del cálculo de la probabilidad condicional, dada la presencia de ciertos datos positivos en el contexto de la prevalencia, de la sensibilidad y de la especificidad, se necesita estimar la probabilidad de que el paciente tenga una determinada enfermedad. A veces, con una prueba de escrutinio se pasa de una probabilidad de 1/1000 a 1/20, constituyendo un gran avance diagnóstico, reduciendo la incertidumbre espectacularmente; sin embargo, la tragedia consiste en que la mayoría de los médicos creen que la probabilidad cambió de 0.1% (1/1000) a más del 90%, lo que es escandalosamente errado. La iatrogenia nace del error al contestar a la pregunta: "Dado que la prueba es positiva, ¿cuál es la probabilidad de que el paciente tenga la enfermedad?" En otros casos lo trágico consiste en aplicar una prueba a un individuo que pertenece a una subpoblación para la que esta no fue diseñada. Adicionalmente, se pone en evidencia que la fascinación por la sensibilidad evita que se apliquen métodos menos sensibles en poblaciones que están abandonadas, pues no se trata de hacer mejores pruebas que las que hace el Estado a los pacientes que atiende, sino de hacer pruebas de menor exactitud a los pacientes que no atiende el Estado.

CCAAT/enhancer binding protein beta is expressed in satellite cells and controls myogenesis.

Upon injury, muscle satellite cells become activated and produce skeletal muscle precursors that engage in myogenesis. We demonstrate that the transcription factor CCAAT/enhancer binding protein beta (C/EBPß) is expressed in the satellite cells of healthy muscle. C/EBPß expression is regulated during myogenesis such that C/EBPß is rapidly and massively downregulated upon induction to differentiate. Furthermore, persistent expression of C/EBPß in myoblasts potently inhibits differentiation at least in part through the inhibition of MyoD protein function and stability. As a consequence, myogenic factor expression, myosin heavy chain expression, and fusogenic activity were reduced in C/EBPß-overexpressing cells. Using knockout models, we demonstrate that loss of Cebpb expression in satellite cells results in precocious differentiation of myoblasts in growth conditions and greater cell fusion upon differentiation. In vivo, loss of Cebpb expression in satellite cells resulted in larger muscle fiber cross-sectional area and improved repair after muscle injury. Our results support the notion that C/EBPß inhibits myogenic differentiation and that its levels must be reduced to allow for activation of MyoD target genes and the progression of differentiation.