A Natural-Language-Processing-Based Procedure for Generating Distractors for Multiple-Choice Questions.

One of the most challenging aspects of writing multiple-choice test questions is identifying plausible incorrect response options-i.e., distractors.

Validity of the Health Systems Science Examination: Relationship Between Examinee Performance and Time of Training.

The health systems science (HSS) framework articulates systems-relevant topics that medical trainees must learn to be prepared for physician practice. As new HSS-related curricula are developed, measures demonstrating appropriate levels of reliability and validity are needed. The authors describe a collaborative effort between a consortium of medical schools and the National Board of Medical Examiners to create a multiple-choice HSS examination in the areas of evidence-based medicine/population health, patient safety, quality improvement, and teamwork.

Antitumor activity of a rhenium (I)-diselenoether complex in experimental models of human breast cancer.

Rhenium (I)-diselenother (Re-diselenoether) is a water soluble metal-based compound, combining one atom of rhenium and two atoms of selenium. This compound has been reported to exhibit marked activities against several solid tumor cell lines. We now disclose an improved synthesis of this complex.

Uptake and efflux of rhenium in cells exposed to rhenium diseleno-ether and tissue distribution of rhenium and selenium after rhenium diseleno-ether treatment in mice.

Unlabelled: We proposed a new water-soluble rhenium diseleno-ether compound (with one atom of Re and two atoms of Se) and investigated the uptake of Re into the nucleus of malignant cells in culture exposed to the compound for 48 h and its efflux from the nucleus after a post-exposure period of 48 h, as DNA is the main target of Re. We also studied the distribution of both Re and Se in the main organs after an oral administration of 10 or 40 mg/kg Re diseleno-ether to mice for four weeks, five days-a-week.

Materials And Methods: Re and Se concentrations were assayed by inductively coupled plasma mass spectrometry (ICP-MS).

Combination of three metals for the treatment of cancer: gallium, rhenium and platinum. 1. Determination of the optimal schedule of treatment.

Platinum is well known for its anticancer activity, firstly used as cis-diaminedichloroplatinum (II) (CDDP), with a wide range of activity. Its main mechanism of action involves its binding to DNA. Gallium, another metal, has also demonstrated apoptotic effects on malignant cells, but through interaction with targets other than DNA, such as the membrane, cytoskeleton and proteasome, and on enzyme activities.

Developing an in-training examination for fellows: the experience of the American Society of Clinical Oncology.

The American Society of Clinical Oncology (ASCO) developed its own test -- the Medical Oncology In-Training Examination (MedOnc ITE) -- as a tool to assess trainees' knowledge of the clinical oncology subspecialty, establish consistency in educational standards across training programs, identify areas of strength and weakness in individual programs, and stimulate intraprogrammatic reading and discussion. The Accreditation Council for Graduate Medical Education Outcome Project provided additional incentive for ASCO to develop an ITE. The examination was developed in 4 years.

Inhibitors of strand transfer that prevent integration and inhibit human T-cell leukemia virus type 1 early replication.

The replication of the retrovirus human T-cell leukemia virus type 1 (HTLV-1) is linked to the development of lymphoid malignancies and inflammatory diseases. Data from in vitro, ex vivo, and in vivo studies have revealed that no specific treatment can prevent or block HTLV-1 replication and therefore that there is no therapy for the prevention and/or treatment of HTLV-1-associated diseases in infected individuals. HTLV-1 and human immunodeficiency virus type 1 (HIV-1) integrases, the enzymes that specifically catalyze the integration of these retroviruses in host cell DNA, share important structural properties, suggesting that compounds that inhibit HIV-1 integration could also inhibit HTLV-1 integration.

Experimental/theoretical electrostatic properties of a styrylquinoline-type HIV-1 integrase inhibitor and its progenitors.

We have established that polyhydroxylated styrylquinolines are potent inhibitors of HIV-1 integrase (IN). Among them, we have identified (E)-8-hydroxy-2-[2-(4,5-dihydroxy-3-methoxyphenyl)-ethenyl]-7-quinolinecarboxylic acid (1) as a promising lead. Previous molecular dynamics simulations and docking procedures have shown that the inhibitory activity involves one or two metal cations (Mg2+), which are present in the vicinity of the active center of the enzyme.

New HIV-1 replication inhibitors of the styryquinoline class bearing aroyl/acyl groups at the C-7 position: synthesis and biological activity.

Novel variants of HIV-1 replication inhibitors of the styrylquinoline class harboring aroyl/acyl group at the C-7 position have been synthesized. In sharp contrast with styrylquinolines bearing a carboxylic acid group at C-7, these compounds proved to be inactive toward HIV-1 integrase in in vitro assays.

A methodology to study intracellular distribution of nanoparticles in brain endothelial cells.

Cell internalisation and intracellular distribution of PEG-coated polyhexadecylcyanoacrylate (PEG-PHDCA) nanoparticles in rat brain endothelial cells (RBEC) have been investigated. A cell fractionation method has been developed based on the selective permeabilisation of RBEC plasma membrane by digitonin. By interacting with membrane cholesterol, digitonin creates pores allowing the release of soluble and diffusible species outside the cell.

7-Carboxylato-8-hydroxy-2-methylquinolinium monohydrate and 7-carboxy-8-hydroxy-2-methylquinolinium chloride monohydrate at 100 K.

Both 7-carboxylato-8-hydroxy-2-methylquinolinium monohydrate, C11H9NO3.H2O, (I), and 7-carboxy-8-hydroxy-2-methylquinolinium chloride monohydrate, C11H10NO3+.Cl-.

Negative preclinical results with stealth nanospheres-encapsulated Doxorubicin in an orthotopic murine brain tumor model.

Previous results have shown that PEG-coated poly(hexadecylcyanoacrylate) (PEG-PHDCA) nanospheres displayed a significant accumulation within an orthotopic 9L gliosarcoma model, after i.v. administration to rats.

Asymmetric Michael reaction involving chiral imines/secondary enamines: stereocontrolled synthesis of 2,2-disubstituted tetrahydrothiophen-3-ones.

[reaction: see text] The asymmetric Michael reaction involving a chiral imine derived from 2-methyltetrahydrothiophenone-3-one and enantiopure (R)-1-phenylethylamine with a variety of electrophilic alkenes furnished 2,2-disubstituted tetrahydrothiophenone-3-ones with good yields and excellent stereoselectivity.

Crystallographic/experimental electron density characterizations and reactions with nucleophiles of beta-enaminonitriles possessing a pyrrolobenzazepine core.

In connection with a total synthesis of cephalotaxine (1a), we have examined the addition of various nucleophilic reagents to [ABC] subunits 2 and 7 possessing a pyrrolobenzazepine core. In fact, this reaction implicates invariably the carbonyl group of 2. Regarding the reaction of 7 with nucleophiles, the most striking aspect is the complete lack of reactivity of the enaminonitrile moiety.

Styrylquinolines, integrase inhibitors acting prior to integration: a new mechanism of action for anti-integrase agents.

We have previously shown that styrylquinolines (SQLs) are integrase inhibitors in vitro. They compete with the long terminal repeat substrate for integrase. Here, we describe the cellular mode of action of these molecules.

Linker-modified quinoline derivatives targeting HIV-1 integrase: synthesis and biological activity.

A novel series of HIV-1 integrase inhibitors was synthesized and tested in both in vitro and ex vivo assays. These inhibitors are featured by the presence of a quinoline subunit and an ancillary aromatic ring linked by functionalized spacers such as amide, hydrazide, urea and 1-hydroxyprop-1-en-3-one moiety. Amide derivatives are the most promising ones and could serve as leads for further developments.

Use of the Kohonen neural network for rapid screening of ex vivo anti-HIV activity of styrylquinolines.

Using the Kohonen neural network, the electrostatic potentials on the molecular surfaces of 14 styrylquinoline derivatives were drawn as comparative two-dimensional maps and compared with their known human immunodeficiency virus (HIV)-1 replication blocking potency in cells. A feature of the potential map was discovered to be related with the HIV-1 blocking activity and was used to unmask the activity of further five analogues, previously described but whose cytotoxicity precluded an estimation of their activity, and to predict the activity of 10 new compounds while the experimental data were unknown. The measurements performed later turned out to agree with the predictions.

Stereochemical Aspects in the Asymmetric Michael Addition of Chiral Imines to Substituted Electrophilic Alkenes.

The Michael-type addition of chiral imines, derived from racemic alpha-substituted cyclanones and optically active 1-phenylethylamine, to electrophilic alkenes, in neutral conditions, constitutes one of the most efficient methods for the stereocontrolled construction of quaternary carbon centers. In order to create an additional stereogenic center at the alpha- or beta-position to the quaternary one, the behavior of a variety of alpha- and beta-substituted alkenyl acceptors was examined. In general, these additions are highly regioselective, the alkylation taking place predominantly, if not exclusively, at the more substituted alpha-side of the imine function; however, in some cases (electrophilic alkenes 28 and 49), significant amounts (10-15%) of regioisomeric adducts were obtained.