Finite element analysis and fracture resistance testing of a new intraradicular post

Objectives: The objective of the present study was to evaluate a prefabricated intraradicular threaded pure titanium post, designed and developed at the Sao Jose dos Campos School of Dentistry - UNESP, Brazil. This new post was designed to minimize stresses observed with prefabricated post systems and to improve cost-benefits. Materials and and methods: Fracture resistance testing of the post/core/root complex, fracture analysis by microscopy and stress analysis by the finite element method were used for post evaluation. The following four prefabricated metal post systems were analyzed: group 1, experimental post; group 2, modification of the experimental post; group 3, Flexi Post, and group 4, Para Post. For the analysis of fracture resistance, 40 bovine teeth were randomly assigned to the four groups (n=10) and used for the fabrication of test specimens simulating the situation in the mouth. The test specimens were subjected to compressive strength testing until fracture in an EMIC universal testing machine. After fracture of the test specimens, their roots were sectioned and analyzed by microscopy. For the finite element method, specimens of the fracture resistance test were simulated by computer modeling to determine the stress distribution pattern in the post systems studied. Results: The fracture test presented the following averages and standard deviation: G1 (45.63 +/- 8.77), G2 (49.98 +/- 7.08), G3 (43.84 +/- 5.52), G4 (47.61 +/- 7.23). Stress was homogenously distributed along the body of the intraradicular post in group 1, whereas high stress concentrations in certain regions were observed in the other groups. These stress concentrations in the body of the post induced the same stress concentration in root dentin. Conclusions: The experimental post (original and modified versions) presented similar fracture resistance and better results in the stress analysis when compared with the commercial post systems tested (08/2008PA/CEP).

Replicative phenotyping adds value to genotypic resistance testing in heavily pre-treated HIV-infected individuals--the Swiss HIV Cohort Study

Background Replicative phenotypic HIV resistance testing (rPRT) uses recombinant infectious virus to measure viral replication in the presence of antiretroviral drugs. Due to its high sensitivity of detection of viral minorities and its dissecting power for complex viral resistance patterns and mixed virus populations rPRT might help to improve HIV resistance diagnostics, particularly for patients with multiple drug failures. The aim was to investigate whether the addition of rPRT to genotypic resistance testing (GRT) compared to GRT alone is beneficial for obtaining a virological response in heavily pre-treated HIV-infected patients. Methods Patients with resistance tests between 2002 and 2006 were followed within the Swiss HIV Cohort Study (SHCS). We assessed patients' virological success after their antiretroviral therapy was switched following resistance testing. Multilevel logistic regression models with SHCS centre as a random effect were used to investigate the association between the type of resistance test and virological response (HIV-1 RNA <50 copies/mL or ≥1.5log reduction). Results Of 1158 individuals with resistance tests 221 with GRT+rPRT and 937 with GRT were eligible for analysis. Overall virological response rates were 85.1% for GRT+rPRT and 81.4% for GRT. In the subgroup of patients with >2 previous failures, the odds ratio (OR) for virological response of GRT+rPRT compared to GRT was 1.45 (95% CI 1.00-2.09). Multivariate analyses indicate a significant improvement with GRT+rPRT compared to GRT alone (OR 1.68, 95% CI 1.31-2.15). Conclusions In heavily pre-treated patients rPRT-based resistance information adds benefit, contributing to a higher rate of treatment success.

Limited clinical benefit of minority K103N and Y181C-variant detection in addition to routine genotypic resistance testing in antiretroviral therapy-naive patients

OBJECTIVE: The presence of minority nonnucleoside reverse transcriptase inhibitor (NNRTI)-resistant HIV-1 variants prior to antiretroviral therapy (ART) has been linked to virologic failure in treatment-naive patients. DESIGN: We performed a large retrospective study to determine the number of treatment failures that could have been prevented by implementing minority drug-resistant HIV-1 variant analyses in ART-naïve patients in whom no NNRTI resistance mutations were detected by routine resistance testing. METHODS: Of 1608 patients in the Swiss HIV Cohort Study, who have initiated first-line ART with two nucleoside reverse transcriptase inhibitors (NRTIs) and one NNRTI before July 2008, 519 patients were eligible by means of HIV-1 subtype, viral load and sample availability. Key NNRTI drug resistance mutations K103N and Y181C were measured by allele-specific PCR in 208 of 519 randomly chosen patients. RESULTS: Minority K103N and Y181C drug resistance mutations were detected in five out of 190 (2.6%) and 10 out of 201 (5%) patients, respectively. Focusing on 183 patients for whom virologic success or failure could be examined, virologic failure occurred in seven out of 183 (3.8%) patients; minority K103N and/or Y181C variants were present prior to ART initiation in only two of those patients. The NNRTI-containing, first-line ART was effective in 10 patients with preexisting minority NNRTI-resistant HIV-1 variant. CONCLUSION: As revealed in settings of case-control studies, minority NNRTI-resistant HIV-1 variants can have an impact on ART. However, the sole implementation of minority NNRTI-resistant HIV-1 variant analysis in addition to genotypic resistance testing (GRT) cannot be recommended in routine clinical settings. Additional associated risk factors need to be discovered.

CRC50151 Resistance Management

Develop nationally agreed, standard methods for insect sample collection, resistance testing, and data management as a basis for a statistically robust and informative national resistance monitoring program.

Anticoagulant resistance in Norway rats (Rattus norvegicus Berk.) in Kent - a VKORC1 single nucleotide polymorphism, tyrosine139phenylalanine, new to the UK

A sample of 10 Norway rats (Rattus norvegicus) was taken for DNA resistance testing from an agricultural site in Kent where applications of the anticoagulant rodenticide bromadiolone had been unsuccessful. All animals tested were homozygous for the single nucleotide VKORC1 polymorphism tyrosine139phenylalanine, or Y139F. This is a common resistance mutation found extensively in France and Belgium but not previously in the UK. Y139F confers a significant level of resistance to first-generation anticoagulants, such as chlorophacinone, and to the second-generation compound bromadiolone. Another compound widely used in the UK, difenacoum, is also thought to be partially resisted by rats which carry Y139F. A silent VKORC1 mutation was also found in all rats tested. The presence of a third important VKORC1 mutation which confers resistance to anticoagulant rodenticides in widespread use in the UK, the others being Y139C and L120Q, further threatens the ability of pest control practitioners to deliver effective rodent control.

Preliminary study of the genetics of resistance in the house mouse

A wild house mouse (Mus domesticus) population originally trapped near Reading, Berkshire, United Kingdom, and maintained as a colony in the laboratory, was subjected to the discriminating feeding period of the warfarin resistance test, as used by Wallace and MacSwiney (1976) and derived from the work of Rowe and Redfern (1964). Eighty percent of this heterogeneous population survived the resistance-test. A similar proportion of the population was found to survive the normally lethal dose of bromadiolone administered by oral gavage. The majority of this population of mice were classified as "warfarin-resistant" and "bromadiolone-resistant." The dose of 10mg.kg-1 of bromadiolone administered by oral gavage appeared to give good discrimination between susceptible and resistant individuals. The results of breeding tests indicate a single dominant gene that confers both "warfarin-resistance" and "bromadiolone-resistance", with complete expression of the resistance genotype in both males and females. Individual mice were classified as to genotype by back-crossing to a homozygous-susceptible strain, and resistance-testing the F1 generation. Separate strains of homozygous-resistant and homozygous-susceptible house mice are now being established.

Resistance to the anticoagulant rodenticides – the deployment of the new molecular methodology to identify mutations of the VKORC1 ‘resistance gene’, and understanding their potential impact on treatment outcome

Anticoagulants rodenticides have already known for over half a century, as effective and safe method of rodent control. However, discovered in 1958 anticoagulant resistance has given us a very important problem for their future long-term use. Laboratory tests provide the main method for identification the different types of anticoagulant resistances, quantify the magnitude of their effect and help us to choose the best pest control strategy. The main important tests are lethal feeding period (LFP) and blood clotting response (BCR) tests. These tests can now be used to quantify the likely effect of the resistance on treatment outcome by providing an estimate of the ‘resistance factor’. In 2004 the gene responsible for anticoagulant resistance (VKORC1) was identified and sequenced. As a result, a new molecular resistance testing methodology has been developed, and a number of resistance mutations, particularly in Norway rats and house mice. Three mutations of the VKORC1 gene in Norway rats have been identified to date that confer a degree of resistance to bromadiolone and difenacoum, sufficient to affect treatment outcome in the field.

Resistance to compression of weakened roots subjected to different root reconstruction protocols

Objective: This study evaluated, in vitro, the fracture resistance of human non-vital teeth restored with different reconstruction protocols. Material and methods: Forty human anterior roots of similar shape and dimensions were assigned to four groups (n=10), according to the root reconstruction protocol: Group I (control): non-weakened roots with glass fiber post; Group II: roots with composite resin by incremental technique and glass fiber post; Group III: roots with accessory glass fiber posts and glass fiber post; and Group IV: roots with anatomic glass fiber post technique. Following post cementation and core reconstruction, the roots were embedded in chemically activated acrylic resin and submitted to fracture resistance testing, with a compressive load at an angle of 45 degrees in relation to the long axis of the root at a speed of 0.5 mm/min until fracture. All data were statistically analyzed with bilateral Dunnett's test (alpha=0.05). Results: Group I presented higher mean values of fracture resistance when compared with the three experimental groups, which, in turn, presented similar resistance to fracture among each other. None of the techniques of root reconstruction with intraradicular posts improved root strength, and the incremental technique was suggested as being the most recommendable, since the type of fracture that occurred allowed the remaining dental structure to be repaired. Conclusion: The results of this in vitro study suggest that the healthy remaining radicular dentin is more important to increase fracture resistance than the root reconstruction protocol.

Effect of two formulations of 10% sodium ascorbate on fracture resistance of endodontically treated tooth submitted to dental bleaching with hydrogen peroxide associated titanium dioxide nanoparticles

Purpose: This study evaluated the effect of 10% sodium ascorbate (10SA), in gel (10SAg) or aqueous solution (10SAs) formulations, on fracture resistance of endodontically treated tooth submitted to dental bleaching procedures with 15% hydrogen peroxide associated with titanium dioxide (15HP-TiO2) nanoparticles and photoactivated by LED-laser. Material and methods: Forty maxillary premolars were endodontically-treated and embedded in acrylic resin up to the cement-enamel junction. The specimens were divided into four groups (n=10): G1 (negative control): no bleaching, coronal access restored with composite resin; G2 (positive control): three dental bleaching sessions using 15HP-TiO2 and LED-laser photoactivation and restored with composite resin (positive control); G3 (10SAg): similar procedures to G2, but applied 10SA, in gel formulation, for 24 hours before restoration; G4 (10SAs): similar procedures to G3, but applied 10SA, in aqueous solution formulation. The 15HP-TiO2 was applied on buccal and lingual surfaces of the crown tooth and inside the pulp chamber and photoactivated by LED-laser. Between each bleaching session, the teeth were maintained in artificial saliva, at 37oC, for 7 days. In sequence, the teeth were submitted to fracture resistance testing using an eletromechanical machine test. The data was analyzed using Kruskal Wallis test (p = 0.05) Results: There are no differences significant among the groups in relation to fracture resistance of endodontically treated teeth (p>0.05). Conclusions: The use of 10% sodium ascorbate, in gel or aqueous solution formulations, did not interfered on the fracture resistance teeth after dental bleaching using 15HP-TiO2 and LED-laser photoactivation.

Fatigue surviving, fracture resistance, shear stress and finite element analysis of glass fiber posts with different diameters

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Effect of different restorative procedures on the fracture resistance of teeth submitted to internal bleaching

The aim of this study was to evaluate the influence of different restorative procedures on the fracture resistance of endodontically treated teeth submitted to intracoronal bleaching. Fifty upper central incisors were distributed into 5 groups: GI - healthy teeth; GII - endodontically treated teeth sealed with Coltosol; GIII - endodontically treated teeth bleached and sealed with Coltosol; GIV - endodontically treated teeth bleached and restored with composite resin; and GV - endodontically treated teeth bleached and restored with a fiberglass post and composite resin. In the bleached specimens, a cervical seal was made prior to bleaching with 38% hydrogen peroxide. The gel was applied on the buccal surface and in the pulp chamber, and was then light-activated for 45 s. This procedure was repeated three times per session for four sessions, and each group was submitted to the restorative procedures described above. The specimens were submitted to fracture resistance testing in a universal testing machine. There were statistically significant differences among the groups (p < 0.05). The mean value found for GIII was the lowest (0.32 kN) and was significantly different from the values found for GI (0.75 kN), GII (0.67 kN), GIV (0.70 kN), and GV (0.72 kN), which were not significantly different from each other (p > 0.05). The restorative procedures using composite resin were found to successfully restore the fracture resistance of endodontically treated and bleached teeth.

Sensitive and rapid detection of ganciclovir resistance by PCR based MALDI-TOF analysis

Cytomegalovirus (CMV) infection is associated with significant morbidity and mortality in transplant recipients. Resistance against ganciclovir is increasingly observed. According to current guidelines, direct drug resistance testing is not always performed due to high costs and work effort, even when resistance is suspected.

Adherence as a Predictor of the Development of Class-Specific Resistance Mutations: The Swiss HIV Cohort Study

Background Non-adherence is one of the strongest predictors of therapeutic failure in HIV-positive patients. Virologic failure with subsequent emergence of resistance reduces future treatment options and long-term clinical success. Methods Prospective observational cohort study including patients starting new class of antiretroviral therapy (ART) between 2003 and 2010. Participants were naïve to ART class and completed ≥1 adherence questionnaire prior to resistance testing. Outcomes were development of any IAS-USA, class-specific, or M184V mutations. Associations between adherence and resistance were estimated using logistic regression models stratified by ART class. Results Of 314 included individuals, 162 started NNRTI and 152 a PI/r regimen. Adherence was similar between groups with 85% reporting adherence ≥95%. Number of new mutations increased with increasing non-adherence. In NNRTI group, multivariable models indicated a significant linear association in odds of developing IAS-USA (odds ratio (OR) 1.66, 95% confidence interval (CI): 1.04-2.67) or class-specific (OR 1.65, 95% CI: 1.00-2.70) mutations. Levels of drug resistance were considerably lower in PI/r group and adherence was only significantly associated with M184V mutations (OR 8.38, 95% CI: 1.26-55.70). Adherence was significantly associated with HIV RNA in PI/r but not NNRTI regimens. Conclusion Therapies containing PI/r appear more forgiving to incomplete adherence compared with NNRTI regimens, which allow higher levels of resistance, even with adherence above 95%. However, in failing PI/r regimens good adherence may prevent accumulation of further resistance mutations and therefore help to preserve future drug options. In contrast, adherence levels have little impact on NNRTI treatments once the first mutations have emerged.

Prevalence of drug-resistance mutations and non-subtype B strains among HIV-infected infants from New York State

Summary: Prevalence studies indicate that transmission of drug-resistant HIV has been rising in the adult population, but data from the perinatally infected pediatric population are limited. In this retrospective study, we sequenced the pol region of HIV from perinatally infected infants diagnosed in New York State in 2001-2002. Analyses of drug resistance, subtype diversity, and perinatal antiretroviral exposure were conducted, and the results were compared with those from a previous study of HIV-infected infants identified in 1998-1999. Eight of 42 infants (19.1%) had provirus carrying at least 1 drug-resistance mutation, an increase of 58% over the 1998-1999 results. Mutations conferring resistance to nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors, and protease inhibitors were detected in 7.1%, 11.9%, and 2.4% of specimens, respectively. Consistent with previous results, perinatal antiretroviral exposure was not associated with drug resistance (P = 0.70). Phylogenetic analysis indicated that 16.7% of infants were infected with a non-subtype B strain of HIV. It seems that drug-resistant and non-subtype B strains of HIV are becoming increasingly common in the perinatally infected population. Our results highlight the value of resistance testing for all HIV-infected infants upon diagnosis and the need to consider subtype diversity in diagnostic and treatment strategies.

Evaluating New Matrix Pooled Testing Methods for Detecting HIV Treatment Failure with and without Covariate Information

Thesis (Master's)--University of Washington, 2016-08