Inhibitors of the Hepatitis C Virus Polymerase; Mode of Action and Resistance

The hepatitis C virus (HCV) is a pandemic human pathogen posing a substantial health and economic burden in both developing and developed countries. Controlling the spread of HCV through behavioural prevention strategies has met with limited success and vaccine development remains slow. The development of antiviral therapeutic agents has also been challenging, primarily due to the lack of efficient cell culture and animal models for all HCV genotypes, as well as the large genetic diversity between HCV strains. On the other hand, the use of interferon-α-based treatments in combination with the guanosine analogue, ribavirin, achieved limited success, and widespread use of these therapies has been hampered by prevalent side effects. For more than a decade, the HCV RNA-dependent RNA polymerase (RdRp) has been targeted for antiviral development. Direct acting antivirals (DAA) have been identified which bind to one of at least six RdRp inhibitor-binding sites, and are now becoming a mainstay of highly effective and well tolerated antiviral treatment for HCV infection. Here we review the different classes of RdRp inhibitors and their mode of action against HCV. Furthermore, the mechanism of antiviral resistance to each class is described, including naturally occurring resistance-associated variants (RAVs) in different viral strains and genotypes. Finally, we review the impact of these RAVs on treatment outcomes with the newly developed regimens.     

Histomorphologic Characterization of Noncarious and Caries-Affected Dentin/Adhesive Interfaces

PURPOSE: The purpose of this study was to compare the dentin/adhesive interfacial characteristics when bonding to noncarious as well as caries-affected dentin. MATERIALS AND METHODS: Seven extracted, unerupted, third molars were sectioned into halves. Artificial caries was created on one-half of each tooth, leaving the other half as a control. Dentin surfaces were treated with UNO adhesive according to the manufacturer's instructions for the wet-bonding technique and under environmental conditions present in the oral cavity. Dentin/adhesive interface sections of each half-tooth were stained with Goldner's trichrome, a classic bone stain, and examined using light microscopy. The width of exposed collagen was measured directly from photomicrographs, and adhesive penetration was analyzed qualitatively. RESULTS: The degree and extent to which the adhesive encapsulated the demineralized dentin matrix were reflected in the color difference in the stained sections with the noncarious dentin sections showing a degree of collagen encapsulation superior to that of the caries-affected dentin sections. The overall mean widths of exposed collagen were significantly (p < or = .05) greater at the caries-affected dentin/adhesive interface, 8.6 (1.7) microm, as compared with those at the noncarious dentin/adhesive interface, 6.0 (1.5) microm. CONCLUSIONS: The morphologic characteristics of the caries-affected dentin/interface suggest an increase in the exposed collagen zone and a decrease in the quality of the adhesive infiltration when compared with noncarious dentin. The evidence suggests that dentin substrate characteristics have a significant effect on the dentin/adhesive interface structure.     

History of Articulators: Henry L. "Harry" Page and the Transograph

The intention of this article is to introduce the reader to the Transograph from a historical perspective. The technical data presented are intended to help the reader understand the design of this unique instrument and how it was programmed, but will not provide the reader a thorough understanding of this philosophy. The article seeks neither to defend nor criticize the principles of Transographics.     

Introducing dental students to clinical patient care: The complete denture prosthodontics transition clinic

Using complete denture treatment as an introduction to clinical patient care for dental students, the purposes of the Complete Denture Prosthodontics Transition Clinic at the University of Colorado School of Dentistry are to reduce the time lapse between the preclinical complete denture prosthodontics course and the first denture patient experience, and to encourage development of student self-confidence and skills. In the 2002 spring semester, faculty at the University of Colorado School of Dentistry initiated the Complete Denture Prosthodontics Transition Clinic for DS-II (second-year) dental students, as an introduction to clinical patient care. Each patient was assigned to a team of two dental students. Three Division of Prosthodontics faculty members staffed each clinic session, providing a student-to-faculty ratio of approximately 6.6:1 and a patient-to-faculty ratio of approximately 3.3:1. All DS-II students in the Class of 2004 delivered their first complete dentures no later than 8 months (average, 184 days) after the last day of the preclinical complete denture prosthodontics course. The time from the diagnostic appointment through the denture placement appointment averaged 39 days for patients treated in this program, compared with an average of 98 days or more for previous classes. The program was successful in achieving the goal of reducing the time lapse between the preclinical complete denture prosthodontics course and the first denture patient experience.     

Making clinical decisions for dental care: concepts to consider

Clinical decisions are often made with incomplete information, yet patient care decisions are made every day. Patients vary clinically, uncertainty exists in diagnostic and prognostic information, and many preventive and treatment alternatives have not been formally assessed for their effectiveness. Because scientific information will never answer all clinical questions, clinical decisions are partially based on probabilistic information.
This paper describes how to apply clinical decision making to diagnosing and managing dental caries and periodontal diseases. By using explicit information to quantify probabilities and outcomes, clinical decision making analyzes decisions made under uncertain conditions and the uncertain impact of clinical information.
Clinical decision making incorporates concepts for preventing, diagnosing and treating dental caries and periodontal diseases: risk assessment, evidence-based dentistry, and multiple oral health outcomes. This information can serve as a tool for clinicians to augment clinical judgment and expertise.     

A new index for evaluating horizontal skeletal discrepancies and predicting treatment outcomes

The cephalometric measurement known as Wits appraisal (AOBO) was studied to determine its importance in diagnosis, treatment, and prediction of treatment success. The Wits appraisal is used primarily to identify unreliable ANB values (those that do not accurately reflect the degree of horizontal jaw discrepancy, ie, those that differ greatly from the AOBO value). Therefore, differences between AOBO and ANB also were evaluated. Because neither measurement alone can assess jaw discrepancies with total accuracy, they were combined, plotted on a scattergram, and divided into equal zones to create a new index of horizontal skeletal discrepancies and treatment predictability. Pretreatment values correspond to treatment difficulty, and posttreatment values correspond to the effectiveness of treatment. Treatment time for each zone also was evaluated. We were able to draw several conclusions from this study. First, combining AOBO and ANB values results in a more accurate measurement of treatment difficulty. These combined values also can be used to predict both treatment time and the success of treatment for horizontal discrepancies. Second, the AOBO value predicts variations in treatment time at each ANB value. Finally, adding ANB and AOBO values and then dividing the total yields zones that represent statistically significant differences in treatment times and percentages of success. The zones also correlate with the difference between AOBO and ANB measurements.