An Ex-Vivo Study Comparing the Accuracy of the E-Connect S+ and Morita Tri Auto ZX2+ Endodontic Handpieces in Root Canal Length Determination.

INTRODUCTION: This ex vivo study evaluated the accuracy of the Electronic Apex Locator (EAL) and Automatic Apical Stop (AAS) functions of the E-Connect S+ and Morita Tri Auto ZX2+ cordless apex locators in determining patency length. METHODS: Sixty-four human teeth with a single root were randomly allocated into E-connect or Morita groups (n = 32). The canals were accessed and preflared, after which a size 15 K-file was inserted into the canal to the major foramen and recorded as the actual length (AL). Matched measurements were taken using the AAS and EAL functions and visually confirmed with confocal microscopy. The variance between canal length (mm), the persons correlation (ρ) between function and AL, and the accuracy (%) of the canal length relative to the AL (Δmm) between devices and functions were assessed. RESULTS: Regardless of device or function, all measurements were within 1±Δmm and correlated strongly (ρ > 0.97) with the AL. When considering a more stringent clinically acceptable range of 0.5±Δmm from the AL, all devices and functions demonstrated similar accuracy levels (84%-94%). However, at lower tolerance ranges, the E-connect device with the EAL function exhibited the highest accuracy. On average, all devices and functions stopped short of the AL (mean Δmm>0). CONCLUSION: The E-Connect S+ and Morita Tri Auto ZX2+ apex locators provided reliable accuracy in determining the position of the major foramen. These findings demonstrate a high level of reproducibility in canal length measurements using both cordless endodontic handpieces, regardless of whether the EAL or AAS functions were employed.

Transplanting supersites of HIV-1 vulnerability.

One strategy for isolating or eliciting antibodies against a specific target region on the envelope glycoprotein trimer (Env) of the human immunodeficiency virus type 1 (HIV-1) involves the creation of site transplants, which present the target region on a heterologous protein scaffold with preserved antibody-binding properties. If the target region is a supersite of HIV-1 vulnerability, recognized by a collection of broadly neutralizing antibodies, this strategy affords the creation of "supersite transplants", capable of binding (and potentially eliciting) antibodies similar to the template collection of effective antibodies. Here we transplant three supersites of HIV-1 vulnerability, each targeted by effective neutralizing antibodies from multiple donors. To implement our strategy, we chose a single representative antibody against each of the target supersites: antibody 10E8, which recognizes the membrane-proximal external region (MPER) on the HIV-1 gp41 glycoprotein; antibody PG9, which recognizes variable regions one and two (V1V2) on the HIV-1 gp120 glycoprotein; and antibody PGT128 which recognizes a glycopeptide supersite in variable region 3 (glycan V3) on gp120. We used a structural alignment algorithm to identify suitable acceptor proteins, and then designed, expressed, and tested antigenically over 100-supersite transplants in a 96-well microtiter-plate format. The majority of the supersite transplants failed to maintain the antigenic properties of their respective template supersite. However, seven of the glycan V3-supersite transplants exhibited nanomolar affinity to effective neutralizing antibodies from at least three donors and recapitulated the mannose9-N-linked glycan requirement of the template supersite. The binding of these transplants could be further enhanced by placement into self-assembling nanoparticles. Essential elements of the glycan V3 supersite, embodied by as few as 3 N-linked glycans and ∼ 25 Env residues, can be segregated into acceptor scaffolds away from the immune-evading capabilities of the rest of HIV-1 Env, thereby providing a means to focus the immune response on the scaffolded supersite.

Clinical evaluation of safety and immunogenicity of PADRE-cytomegalovirus (CMV) and tetanus-CMV fusion peptide vaccines with or without PF03512676 adjuvant.

BACKGROUND: It has been reported that cytomegalovirus (CMV) pp65-specific T cells can protect hematopoietic cell transplant (HCT) recipients from CMV complications. Two candidate CMV peptide vaccines composed of the HLA A*0201 pp65(495-503) cytotoxic CD8(+) T-cell epitope fused to 2 different universal T-helper epitopes (either the synthetic Pan DR epitope [PADRE] or a natural Tetanus sequence) were clinically evaluated for safety and ability to elicit pp65 T cells in HLA A*0201 healthy volunteers. METHODS: Escalating doses (0.5, 2.5, 10 mg) of PADRE or Tetanus pp65(495-503) vaccines with (30 adults) or without (28 adults) PF03512676 adjuvant were administered by subcutaneous injection every 3 weeks for a total of 4 injections. RESULTS: No serious adverse events were reported, although vaccines used in combination with PF03512676 had enhanced reactogenicity. Ex vivo responses were detected by flow cytometry exclusively in volunteers who received the vaccine coadministered with PF03512676. In addition, using a sensitive in vitro stimulation system, vaccine-elicited pp65(495-503) T cells were expanded in 30% of volunteers injected solely with the CMV peptides and in all tested subjects receiving the vaccines coinjected with PF03512676. CONCLUSIONS: Acceptable safety profiles and vaccine-driven expansion of pp65(495-503) T cells in healthy adults support further evaluation of CMV peptide vaccines combined with PF03512676 in the HCT setting. CLINICAL TRIALS REGISTRATION: NCT00722839.

Maintenance of osseointegration utilizing insulin therapy in a diabetic rat model.

BACKGROUND: Normal wound healing processes have been shown to be altered in diabetes, and the effect of the diabetes on bone-to-implant contact (BIC) once osseointegration has been established is still unknown. The purpose of this study was to histologically evaluate the bone-to-implant contact in uncontrolled and insulin-controlled rats in which diabetes was induced following the establishment of osseointegration. METHODS: Thirty-two rats were assigned to eight different treatment groups of four each. Titanium plasma-sprayed (TPS) implants were placed in the femora of each animal, and allowed to osseointegrate for 28 days before diabetic induction. Daily insulin injections were given to four groups of rats and the other four groups received no insulin (uncontrolled). The rats were sacrificed at 1, 2, 3, and 4 months following diabetic induction. RESULTS: The results indicated that at 1, 2, 3, and 4 months, there was more BIC in the insulin-controlled groups compared to the uncontrolled groups. The differences were significantly greater at 2, 3, and 4 months (P < or =0.001). CONCLUSIONS: This study demonstrated that osseointegrated dental implants in insulin-controlled diabetic rats maintained bone-to-implant contacts over a 4-month period. However, boneto- implant contact appears to decrease with time in uncontrolled diabetic rats.