Development and Validation of a Shared Secure Biochemistry Test Bank for Medical, Dental, and Pharmacy Schools.

A shared secure biochemistry test bank (abeQbank) was developed by 61 members of the Association of Biochemistry Educators (ABE) who are from medical, pharmacy, and dental schools. The initial abeQbank contained 305 questions, which were almost all clinical vignettes, and were classified into 9 biochemistry megaThemes with subthemes as determined by ABE workshops 2009-2011. Three medical schools selected 163 board-style abeQbank questions approved by ABE and administered a proctored formative exam using ExamSoft to 97 second-year medical students prior to their USMLE or COMLEX 1 board exam followed by a review session in which students examined their answers and read the rationale for each question. The goals of this project were to (1) provide a resource to biochemistry educators; (2) evaluate the quality of these questions; and (3) ascertain students' relative knowledge in different biochemical concepts. Individual questions and 9 megaTheme groups performed similarly across schools, with the lowest and highest megaThemes ranging from 40 to 70% correct. Five questions were dropped due to miscoding, poor metrics, or questionable distractors requiring a rewrite. The results showed that the examination was strongly reliable with the average KR20 = 0.85, discrimination index and point-biserial > 0.2, and students scoring the examination 8 out of 10 in usefulness. This test bank represents the first attempt by an international biochemistry organization to create a standardized set of questions, with future expansion planned to help standardize the content of biochemistry topics in the curricula.

A searchable database of medical education objectives - creating a comparable gold standard.

BACKGROUND: Medical school curricula strives to teach as much material as can be retained in a limited amount of time. A common "gold standard" resource used building curricula are medical objectives suggested by national societies. Unfortunately these objectives suffer from several functional limitations such as limited accessibility to society members, non-searchable formats (such as nested tables or pdf images), and inability to compare and search across societal objectives for redundancy or gaps. The shift towards integrated curriculums in medical school also highlights the need to access suggested content across classical discipline categories. MAIN BODY: We have codified recommendations from national societies in the United States for medical school objectives in a common tabular format and developed an open access database which can be searched across disciplines and societies. A front end website that allows for searching objectives by keyword while filtering on society or discipline was created. The objectives returned from the initial search can be subsearched by a second term. There is a large range in the format, age, breadth, quantity, and quality of objectives from different societies. Some unique disciplines have overlapping suggested content though most of the content does seem "binnable" by discipline. The choice of metadata for objectives from each given society was also very inconsistent. CONCLUSION: A free and searchable database of medical content to deliver during medical school has been developed with over 13,000 objectives from 18 societies and 22 disciplines at http://data.medobjectives.marian.edu/ . The normalization of the different disciplines' objectives into a common database allows a platform to standardize objectives moving forward. Future work could include adding user accounts to access the database, submission of new objectives, voting up and down suggested objectives, and adding "answers" mapped to objectives. Keyword tagging could allow import of content (e.g. PowerPoints) and outputting of suggested objectives, which would also allow comparison of curriculum across medical schools.

Amyloid-beta Alzheimer targets - protein processing, lipid rafts, and amyloid-beta pores.

Amyloid beta (Aß), the hallmark of Alzheimer's Disease (AD), now appears to be deleterious in its low number aggregate form as opposed to the macroscopic Aß fibers historically seen postmortem. While Alzheimer targets, such as the tau protein, amyloid precursor protein (APP) processing, and immune system activation continue to be investigated, the recent discovery that amyloid beta aggregates at lipid rafts and likely forms neurotoxic pores has led to a new paradigm regarding why past therapeutics may have failed and how to design the next round of compounds for clinical trials. An atomic resolution understanding of Aß aggregates, which appear to exist in multiple conformations, is most desirable for future therapeutic development. The investigative difficulties, structures of these small Aß aggregates, and current therapeutics are summarized in this review.

A virtual library of constrained cyclic tetrapeptides that mimics all four side-chain orientations for over half the reverse turns in the protein data bank.

Reverse turns are often recognition sites for protein/protein interactions and, therefore, valuable potential targets for determining recognition motifs in development of potential therapeutics. A virtual combinatorial library of cyclic tetrapeptides (CTPs) was generated and the bonds in the low-energy structures were overlapped with canonical reverse-turn Calpha-Cbeta bonds (Tran et al., J Comput Aided Mol Des 19(8):551-566, 2005) to determine the utility of CTPs as reverse-turn peptidomimetics. All reverse turns in the Protein Data Bank (PDB) with a crystal structures resolution < or = 3.0 A were classified into the same known canonical reverse-turn Calpha-Cbeta bond clusters (Tran et al., J Comput Aided Mol Des 19(8):551-566, 2005). CTP reverse-turn mimics were compiled that mimicked both the relative orientations of three of the four as well as all four Calpha-Cbeta bonds in the reverse turns of the PDB. 54% of reverse turns represented in the PDB had eight or more CTPs structures that mimicked the orientation of all four of the Calpha-Cbeta bonds in the reverse turn.

c[D-pro-Pro-D-pro-N-methyl-Ala] adopts a rigid conformation that serves as a scaffold to mimic reverse-turns.

Naturally occurring cyclic tetrapeptides (CTPs) such as tentoxin (Halloin et al., Plant Physiol 1970, 45, 310-314; Saad, Phytopathology 1970, 60, 415-418), ampicidin (Darkin-Rattray, Proc Natl Acad Sci USA 1996, 93, 13143-13147), HC-toxin (Walton, Proc Natl Acad Sci USA 1987, 84, 8444-8447), and trapoxin (Yoshida and Sugita, Jpn J Cancer Res 1992, 83, 324-328; Itazaki et al., J Antibiot (Tokyo) 1990, 43, 1524-1532) have a wide range of biological activity and potential use ranging from herbicides (Walton, Proc Natl Acad Sci USA 1987, 84, 8444-8447; Judson, J Agric Food Chem 1987, 35, 451-456) to therapeutics (Loiseau, Biopolymers 2003, 69, 363-385) for malaria (Darkin-Rattray, Proc Natl Acad Sci USA 1996, 93, 13143-13147) and cancer (Yoshida and Sugita, Jpn J Cancer Res 1992, 83, 324-328). To elucidate scaffolds that have few low-energy conformations and could serve as semirigid reverse-turn mimetics, the flexibility of CTPs was determined computationally. Four analogs of cyclic tetraproline c[Pro-pro-Pro-pro] with alternating L- and D-prolines, namely c[pro-Pro-pro-NMe-Ala], c[pip-Pro-pip-Pro], c[pro-Pip-pro-Pro], and c[Ala-Pro-pip-Pro] were synthesized and characterized by NOESY NMR. Both molecular mechanics and Density Functional Theory quantum calculations found these head-to-tail CTPs to be constrained to one or two relatively stable conformations. NMR structures, while not always yielding the same lowest energy conformation as expected by in silico predictions, confirmed only one or two highly populated solution conformations for all four peptides examined. c[pro-Pro-pro-NMe-Ala] was shown to have a single all trans-amide bond conformation from both in silico predictions and NMR characterization, and to be a reverse-turn mimetic by overlapping four Calpha-Cbeta bonds with those for approximately 6.5% (Tran, J Comput Aided Mol Des 2005, 19, 551-566) of reverse-turns in the Protein Data Bank PDB with a RMSD of 0.57 A.