High-resolution dose-response screening using droplet-based microfluidics.

A critical early step in drug discovery is the screening of a chemical library. Typically, promising compounds are identified in a primary screen and then more fully characterized in a dose-response analysis with 7-10 data points per compound. Here, we describe a robust microfluidic approach that increases the number of data points to approximately 10,000 per compound. The system exploits Taylor-Aris dispersion to create concentration gradients, which are then segmented into picoliter microreactors by droplet-based microfluidics. The large number of data points results in IC(50) values that are highly precise (± 2.40% at 95% confidence) and highly reproducible (CV = 2.45%, n = 16). In addition, the high resolution of the data reveals complex dose-response relationships unambiguously. We used this system to screen a chemical library of 704 compounds against protein tyrosine phosphatase 1B, a diabetes, obesity, and cancer target. We identified a number of novel inhibitors, the most potent being sodium cefsulodine, which has an IC(50) of 27 ± 0.83 µM.

[New methods in pharmaceutical research: combinatorial chemistry and high throughput screening]. / Les nouvelles méthodes en recherche pharmaceutique: chimie combinatoire et criblage à haut débit.

New lead-identification methodologies such as high-throughput screening and combinatorial chemistry have been integrated into pharmaceutical research over the past 5-10 years. More rational use in the selection of potential preclinical candidates for some difficult targets has increased the chances of success.

[Academic performance among first year medical students at the School of Medicine, UNAM]. / El desempeño académico de los estudiantes de la Facultad de Medicina en el primer año de la carrera.

OBJECTIVE: [corrected] The academic skills of medical students during their first year (class of 2004) were analyzed. Subjects included gross anatomy, cellular biology, developmental biology, biochemistry and molecular biology, public health I and medical psychology. RESULTS: Results showed that students attending morning classes achieved a higher score than those attending afternoon classes. This fact was even more evident in the hardest subjects such as gross anatomy, biochemistry and molecular biology. It was also noticeable that students' achievement depended on the type of high school they had attended (public or private). The percentage of passing grades for each subject was calculated dividing the percentage of continuous assessment exams' passing grades by the percentage of passing grades given by the professor. CONCLUSIONS: Results showed that the index was close to I in some subjects such as medical psychology and public health, whilst in others such as gross anatomy and cellular biology the range fluctuated from 0.5 to 0.7. We conclude that the passing percentage is lower if it is tested through continuous assessment exams compared with professor's performance appraisals.

El desempeño académico de los estudiantes de la Facultad de Medicina en el primer año de la carrera / Academic performance among first year medical students at the School of Medicine, UNAM

Objetivo: Se analizó el desempeño académico de los estudiantes del primer año de la carrera de Medicina de la generación 2004, en las seis asignaturas que cursaron: anatomía, biología celular y tisular, biología del desarrollo, bioquímica y biología molecular, salud pública I y psicología médica. Resultados: Los resultados mostraron que el desempeño de los alumnos del grupo matutino era superior al del grupo vespertino (p < 0.05); este hecho era más evidente en las asignaturas de mayor índice de dificultad, como anatomía y bioquímica y biología molecular (p < 0.01). Asimismo, se observó que, según el bachillerato de procedencia, ya sea colegios de ciencias y humanidades (CCH), preparatorias o escuelas privadas, el índice de acreditación fue mayor en alumnos de estas últimas. Se calculó el índice de aprobación de cada una de las asignaturas, dividiendo el porcentaje de aprobación en los exámenes departamentales entre el porcentaje de aprobación emitido por el profesor. Conclusión: Los resultados mostraron que en algunas asignaturas el índice era cercano a 1, como psicología médica y salud pública; en cambio, en otras como anatomía y biología celular y tisular los índices fluctuaron entre 0.5 a 0.7, lo que significa que el porcentaje de acreditación es inferior cuando es medido a través de los exámenes departamentales que a través de las evaluaciones del profesor.

OBJECTIVE: The academic skills of medical students during their first year (class of 2004) were analyzed. Subjects included gross anatomy, cellular biology, developmental biology, biochemistry and molecular biology, public health I and medical psychology. RESULTS: Results showed that students attending morning classes achieved a higher score than those attending afternoon classes. This fact was even more evident in the hardest subjects such as gross anatomy, biochemistry and molecular biology. It was also noticeable that students' achievement depended on the type of high school they had attended (public or private). The percentage of passing grades for each subject was calculated dividing the percentage of continuous assessment exams' passing grades by the percentage of passing grades given by the professor. CONCLUSIONS: Results showed that the index was close to I in some subjects such as medical psychology and public health, whilst in others such as gross anatomy and cellular biology the range fluctuated from 0.5 to 0.7. We conclude that the passing percentage is lower if it is tested through continuous assessment exams compared with professor's performance appraisals.