Effect of an Individualized Post-Examination Instructor Remediation on Pharmacy Student Performance in a Biochemistry Course.

Objective. To assess the effectiveness of a post-examination, one-on-one instructor remediation process on student performance in a pharmacy biochemistry course by measuring the degree of score improvement on a subsequent examination. Methods. Students who scored below 70% on any examination were encouraged to meet with the course coordinator. A typical remediation session lasts about 30 minutes, and covers academic preparation, study habits, concept understanding, application, critical thinking, time management, and stress control. Scores in two consecutive examinations were compared between students who underwent remediation and those who did not. All scores were adjusted for level of difficulty. Results. At-risk students with relatively lower scores are more likely to seek remediation. After receiving a score below 70%, students perform better on the next examination regardless of remediation. However, the remediation process results in a statistically significant 43% increase in the degree of improvement in student performance on the next examination. Conclusion. A post-examination, one-on-one remediation is effective in enhancing student performance in the biochemistry course. As this course is one of the two with the highest failure rates in the PharmD program, current intervention might improve student retention.

Targeting Molecular Chaperones for the Treatment of Cystic Fibrosis: Is It a Viable Approach?

Cystic Fibrosis (CF) is largely caused by protein misfolding and the loss of function of a plasma membrane anion channel known as the cystic fibrosis transmembrane conductance regulator (CFTR). The most common CF-causing mutation, F508del, leads to severe conformational defect in CFTR. The cellular chaperone machinery plays an important role in CFTR biogenesis and quality control. Multiple attempts have been made to improve the cell surface functional expression of the mutant CFTR by modulating the expression of components of the cellular chaperone machinery. The efficacy of such an approach has been low largely due to the severe intrinsic folding defects of the F508del CFTR. Moreover, the impact of chaperone perturbation on the chaperone machinery itself and on other physiologically important proteins might lead to potentially severe side effects. Approaches aimed at disrupting chaperone-CFTR interactions show greater efficacy, and are compatible with small-molecule drug discovery and gene therapy. Combination between chaperone modulators and F508del correctors might further enhance potency and specificity. As molecular chaperones play important roles in regulating inflammation and immunity, they can be potential targets for controlling airway infection and inflammation in patients. If such effects can be synergized with chaperone-mediated regulation of CFTR biogenesis and quality control, more efficacious therapeutics will be developed to combat CF lung disease.

Enhancing the Potency of F508del Correction: A Multi-Layer Combinational Approach to Drug Discovery for Cystic Fibrosis.

With better understanding of the cellular and molecular pathophysiology underlying cystic fibrosis (CF), novel drugs are being developed that specifically target the molecular defects of the cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated chloride channel on the plasma membrane that causes CF. Starting with cell-based high-throughput screening, small molecules have been identified that are able to fix specific molecular defects of various disease-causing CFTR mutants. With the successful development of ivacaftor, a "potentiator" that enhances CFTR chloride channel activity, new types of small-molecule compounds that "correct" the misfolding and misprocessing of the most common CF-causing mutation, F508del, are actively being sought for. Recent studies focused on the potential mechanisms of action of some of the investigational CFTR "correctors" shed new light on how the F508del mutant can be targeted in an attempt to ameliorate the clinical symptoms associated with CF. A multi-layer combinational approach has been proposed to achieve the high-potency correction necessary for significant clinical outcome. The mechanistic insights obtained from such studies will shape the future therapeutics development for the vast majority of CF patients.