The aim of the study was to evaluate the clinical performance of the nanofiller resin composite Filtek Supreme (3M ESPE) vs the conventional fine hybrid resin composite Tetric Ceram (Ivoclar Vivadent) in stress-bearing posterior cavities. In accordance with a split mouth study design, 50 patients (35.7+/-11.3 years) received at least one pair of Filtek Supreme and Tetric Ceram restorations in each of two comparable class II cavities. To obtain comparability, the adhesive Scotchbond 1 was used for all the restorations. After 2 years, the restorations (total number 112) were scored according to the Ryge criteria. After 2 years (recall rate 100%), the results (%) of the Ryge evaluation for the two groups Filtek Supreme/Tetric Ceram were marginal adaptation: Alfa 96/96, Bravo 2/2, Charlie 2/0, and Delta 0/2; anatomic form: Alfa 98/98, Bravo 0/0, and Charlie 2/2; secondary caries: Alfa 100/100 and Bravo 0/0; marginal discoloration: Alfa 98/100, Bravo 2/0, and Charlie 0/0; surface: Romeo 95/95, Sierra 4/4, Tango 0/0, and Victor 2/2; and color match: Oscar 46/57, Alfa 50/39, Bravo 2/4, and Charlie 2/0. One Tetric Ceram and one Filtek Supreme restoration showed fractures that needed restorative intervention. No severe postoperative sensitivities were reported within the observation period. All restored teeth remained vital; the integrity of all the teeth was scored Alfa. After 2 years, no statistically significant differences (Wilcoxon-Mann-Whitney test) was found between the two restorative materials investigated. Therefore, Filtek Supreme, based on a new nanofiller technology, has proved efficaciousness for clinical use in stress-bearing posterior cavities.

Lead structure discovery mainly focuses on the identification of noncovalently binding ligands. Covalent linkage, however, is an essential binding mechanism for a multitude of successfully marketed drugs, although discovered by serendipity in most cases. We present a concept for the design of fragments covalently binding to proteases. Covalent linkage enables fragment binding unrelated to affinity to shallow protein binding sites and at the same time allows differentiated targeted hit verification and binding location verification through mass spectrometry. We describe a systematic and rational computational approach for the identification of covalently binding fragments from compound collections inhibiting enteroviral 3C protease, a target with high therapeutic potential. By implementing reactive groups potentially forming covalent bonds as a chemical feature in our 3D pharmacophore methodology, covalent binders were discovered by high-throughput virtual screening. We present careful experimental validation of the virtual hits using enzymatic assays and mass spectrometry unraveling a novel, previously unknown irreversible inhibition of the 3C protease by phenylthiomethyl ketone-based fragments. Subsequent synthetic optimization through fragment growing and reactivity analysis against catalytic and noncatalytic cysteines revealed specific irreversible 3C protease inhibition.

Immediately after bonding, less microleakage was observed around the base of metal brackets on human than bovine teeth. These marginal gaps were, however, superficial in both groups, none of them involving deep penetration of dye under the bracket base.