Near-infrared transillumination with high dynamic range imaging for occlusal caries detection in vitro.

The aim of this study was to assess near-infrared transillumination with high dynamic range imaging (NIRT-HDRI) for occlusal caries detection in vitro and to compare it with visual inspection using the International Caries Detection and Assessment System II (ICDAS) and digital bitewing radiography (BWR). Sixty-one extracted permanent molars with sound or occlusal carious surfaces without severe cavitation were visually assembled. Two examiners assessed twice these surfaces independently using ICDAS, BWR and NIRT-HDRI. The latter was performed with a prototype consisting of two laser sources (780 nm), a CCD sensor and subsequent processing with image analysis software. Thresholds for carious surfaces, enamel and dentin lesions were defined for all methods. Micro-computed tomography served as the reference standard. Linear weighted Kappa analysis of the methods versus the reference at the threshold carious surface, enamel and dentin lesion revealed 0.59/0.08/0.12 for ICDAS, 0.37/- 0.06/0.58 for BWR and 0.33/- 0.01/0.51 for NIRT-HDRI. Sensitivity values at the three thresholds were 0.85/0.78/0.13 for ICDAS, 0.59/0.00/0.69 for BWR and 0.98/0.33/0.78 for NIRT. Specificity values at the three thresholds were 0.70/0.40/1.00 for ICDAS, 0.9./0.96/0.90 for BWR and 0.30/0.65/0.72 for NIRT-HDRI. Reliability analysis revealed substantial agreement for BWR and NIRT and almost perfect agreement for ICDAS. NIRT exhibited a strong ability to identify occlusal dental decay in general; however, it revealed a tendency towards overestimation. Its strength was the detection of dentin caries lesions compared with ICDAS and BWR. NIRT-HDRI seems to be a suitable method to detect hidden dentin caries as a supplement to visual examination.

Author Correction: Chimeric peptidomimetic antibiotics against Gram-negative bacteria.

An Amendment to this paper has been published and can be accessed via a link at the top of the paper.

In-vitro validation of near-infrared reflection for proximal caries detection.

The aim of this study was the in-vitro validation of VistaCam iX HD, which uses near-infrared reflection (NIRR), for proximal caries detection. It was compared with digital bitewing radiography (BWR), and micro-computed tomography (µCT) was used as the reference standard. One-hundred teeth with either sound (n = 54) or carious (n = 46) proximal surfaces were selected using visual-tactile criteria. Images of these surfaces were generated using BWR and NIRR. Evaluation was performed by two examiners, twice, at an interval of 2 weeks. All samples were scanned with a micro-computed tomograph. Thresholds were defined for sound surfaces, and for enamel and dentin lesions, for all methods. Both BWR and NIRR showed moderate sensitivity for the detection of any caries (0.50 for NIRR and 0.53 for BWR). For enamel lesions, sensitivity was lower (0.13 for NIRR and 0.31 for BWR). Specificity was high (≥0.94) in all categories for both methods. Inter-rater reliability ranged from 0.89 to 0.93 and intra-rater reliability from 0.80 to 0.89. Surface evaluation of images generated using NIRR was complicated by overexposed areas; approximately 25% of the images were not clearly interpretable. In conclusion, NIRR and BWR were found to be reproducible methods with comparable diagnostic accuracy. However, NIRR cannot be recommended as a complementary diagnostic method for assessing proximal caries in permanent molars because of problems with image quality and artefacts.

Chimeric peptidomimetic antibiotics against Gram-negative bacteria.

There is an urgent need for new antibiotics against Gram-negative pathogens that are resistant to carbapenem and third-generation cephalosporins, against which antibiotics of last resort have lost most of their efficacy. Here we describe a class of synthetic antibiotics inspired by scaffolds derived from natural products. These chimeric antibiotics contain a ß-hairpin peptide macrocycle linked to the macrocycle found in the polymyxin and colistin family of natural products. They are bactericidal and have a mechanism of action that involves binding to both lipopolysaccharide and the main component (BamA) of the ß-barrel folding complex (BAM) that is required for the folding and insertion of ß-barrel proteins into the outer membrane of Gram-negative bacteria. Extensively optimized derivatives show potent activity against multidrug-resistant pathogens, including all of the Gram-negative members of the ESKAPE pathogens1. These derivatives also show favourable drug properties and overcome colistin resistance, both in vitro and in vivo. The lead candidate is currently in preclinical toxicology studies that-if successful-will allow progress into clinical studies that have the potential to address life-threatening infections by the Gram-negative pathogens, and thus to resolve a considerable unmet medical need.

Fatigue resistance of ultrathin CAD/CAM ceramic and nanoceramic composite occlusal veneers.

OBJECTIVE: The fracture resistance of different ultrathin occlusal computer-aided design/computer-aided manufacturing (CAD/CAM) veneers was investigated under cyclic mechanical loading to restore combined enamel-dentin defects. METHODS: Eighty-four molars were reduced occlusally until extensive dentin exposure occurred with a remaining enamel ring. Twenty-four molars were ground flat for examination of highly standardized specimens, of which 8 were treated with uniformly flat 0.3mm IPS Empress CAD and 0.3 and 0.5mm IPS e.max CAD restorations. Sixty-four molars were anatomically prepared until dentin exposure and were restored using occlusal veneers with fissure/cusp thicknesses of 0.3/0.5mm from 3 different dental CAD/CAM materials: IPS Empress CAD, IPS e.max CAD and Lava Ultimate CAD/CAM. Teeth were etched with 37% phosphoric acid, and occlusal veneers were bonded using an adhesive luting system (Syntac Primer, Adhesive, Heliobond and Variolink II). Specimens were placed under cyclic mechanical loading in a chewing simulator (1 million cycles at 50N) and were examined for cracks after each cyclic loading sequence. The anatomical 0.3/0.5mm IPS e.max CAD specimens experienced an additional 1 million cycles at 100N. Kaplan-Meier survival curves and log-rank tests were used for data analysis. RESULTS: All highly standardized and 0.3/0.5mm IPS e.max CAD specimens tolerated cyclic loading. One anatomical Lava Ultimate CAD/CAM and 10 IPS Empress CAD specimens showed cracks. SIGNIFICANCE: Ultrathin occlusal veneers of lithium disilicate ceramic and nanoceramic composite showed remarkably high fracture strength under cyclic mechanical loading. These veneers might be a tooth substance preserving option for restoring combined dentin-enamel defects.

In vitro validation of near-infrared transillumination at 780 nm for the detection of caries on proximal surfaces.

OBJECTIVES: The aim of the present in vitro study was to determine the ability of Diagnocam to detect caries at an early stage and to compare it with digital radiography. MATERIALS AND METHODS: One hundred twenty proximal surfaces composed equally of sound and decayed surfaces were evaluated by assessing images captured with Diagnocam (Kavo, Biberach, Germany) and digital radiography (DR). All images were assessed twice by two calibrated dentists with a minimum interval of 2 weeks between examinations. The results were compared with µCT scans. RESULTS: Inter-rater reliability showed nearly perfect agreement; a high intra-rater reliability was calculated. Spearman's rank correlation coefficients showed a strong correlation of Diagnocam and µCT (0.82). DR and µCT achieved a slightly lower correlation (0.73). The surfaces were categorized into sound surfaces, enamel lesions, and dentin lesions to determine intraclass correlation coefficients (ICCs), sensitivity and specificity. ICCs between µCT and DR ranged from 0.20 to 0.63. ICCs between Diagnocam and DR were higher in all categories and ranged from 0.56 to 0.83. Sensitivity, specificity, and accuracy of Diagnocam achieved mostly higher values than DR. In detecting enamel lesions, sensitivity was 0.36 for DR and 0.59 for the DC. The areas under the receiver operating characteristic (ROC) curves of Diagnocam were larger than those of DR in all categories. CONCLUSIONS: Diagnocam is more capable of detecting initial proximal lesions than DR and also has a higher sensitivity for dentin lesions. However, caries progression in dentin cannot be reliably determined with Diagnocam. CLINICAL RELEVANCE: Diagnocam may be suitable as a supplement to X-ray diagnostics in clinical use.

Inter- and intraexaminer reliability of bitewing radiography and near-infrared light transillumination for proximal caries detection and assessment.

OBJECTIVES: The purpose of this in vitro study was to evaluate the inter- and intraexaminer reliability of digital bitewing (DBW) radiography and near-infrared light transillumination (NIRT) for proximal caries detection and assessment in posterior teeth. METHODS: From a pool of 85 patients, 100 corresponding pairs of DBW and NIRT images (~1/3 healthy, ~1/3 with enamel caries and ~1/3 with dentin caries) were chosen. 12 dentists with different professional status and clinical experience repeated the evaluation in two blinded cycles. Two experienced dentists provided a reference diagnosis after analysing all images independently. Statistical analysis included the calculation of simple (κ) and weighted Kappa (wκ) values as a measure of reliability. Logistic regression with a backward elimination model was used to investigate the influence of the diagnostic method, evaluation cycle, type of tooth, and clinical experience on reliability. RESULTS: Altogether, inter- and intraexaminer reliability exhibited good to excellent κ and wκ values for DBW radiography (Inter: κ = 0.60/ 0.63; wκ = 0.74/0.76; Intra: κ = 0.64; wκ = 0.77) and NIRT (Inter: κ = 0.74/0.64; wκ = 0.86/0.82; Intra: κ = 0.68; wκ = 0.84). The backward elimination model revealed NIRT to be significantly more reliable than DBW radiography. CONCLUSIONS: This study revealed a good to excellent inter- and intraexaminer reliability for proximal caries detection using DBW and NIRT images. The logistic regression analysis revealed significantly better reliability for NIRT. Additionally, the first evaluation cycle was more reliable according to the reference diagnoses.

Shear bond strength of two adhesives to bovine dentin contaminated with various astringents.

PURPOSE: To investigate the in vitro shear bond strength of two adhesives to bovine dentin contaminated with various astringents. METHODS: 120 adult bovine incisors were collected and cut to obtain 240 specimens. The specimens were randomly divided into a self-etch adhesive group (N = 120) and a total-etch adhesive group (N = 120). Both of the groups were divided into the following six subgroups: the non-contamination group and the contamination groups 25% Al2(SO4)3 (Orbat sensitive), 25% AlCl3 (Racestyptine), 10% AlCl3 (Roeko Gingiva Liquid), 15.5% Fe2(SO4)3 (Astringedent) and AlCl3 Paste (Astringent Retraction Paste, N = 20 in each subgroup). Each astringent was applied for 1 minute to the dentin surface before rinsing with water spray for 20 seconds. The respective adhesive was then applied according to the manufacturer's instructions. Two composite cylinders were shaped with a mold, cured on the dentin surface of each specimen and sheared off after 1 day and 1 week storage. The shear bond strengths (MPa) were recorded and analyzed with ANOVA. Results: In the self-etching adhesive group, all astringents showed negative effects on dentin bonding (P < 0.05). Astringent contamination did not have a negative effect on dentin bonding in the total-etch adhesive group (P > 0.05).

Peptidomimetic antibiotics target outer-membrane biogenesis in Pseudomonas aeruginosa.

Antibiotics with new mechanisms of action are urgently required to combat the growing health threat posed by resistant pathogenic microorganisms. We synthesized a family of peptidomimetic antibiotics based on the antimicrobial peptide protegrin I. Several rounds of optimization gave a lead compound that was active in the nanomolar range against Gram-negative Pseudomonas spp., but was largely inactive against other Gram-negative and Gram-positive bacteria. Biochemical and genetic studies showed that the peptidomimetics had a non-membrane-lytic mechanism of action and identified a homolog of the beta-barrel protein LptD (Imp/OstA), which functions in outer-membrane biogenesis, as a cellular target. The peptidomimetic showed potent antimicrobial activity in a mouse septicemia infection model. Drug-resistant strains of Pseudomonas are a serious health problem, so this family of antibiotics may have important therapeutic applications.

Discovery of novel, highly potent and selective beta-hairpin mimetic CXCR4 inhibitors with excellent anti-HIV activity and pharmacokinetic profiles.

Novel highly potent CXCR4 inhibitors with good pharmacokinetic properties were designed and optimized starting from the naturally occurring beta-hairpin peptide polyphemusin II. The design involved incorporating important residues from polyphemusin II into a macrocyclic template-bound beta-hairpin mimetic. Using a parallel synthesis approach, the potency and ADME properties of the mimetics were optimized in iterative cycles, resulting in the CXCR4 inhibitors POL2438 and POL3026. The inhibitory potencies of these compounds were confirmed in a series of HIV-1 invasion assays in vitro. POL3026 showed excellent plasma stability, high selectivity for CXCR4, favorable pharmacokinetic properties in the dog, and thus has the potential to become a therapeutic compound for application in the treatment of HIV infections (as an entry inhibitor), cancer (for angiogenesis suppression and inhibition of metastasis), inflammation, and in stem cell transplant therapy.